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On-Line Analysis of Physiologic and Neurobehavioral Variables During Long-Duration Space Missions

The goal of this project is to develop reliable statistical algorithms for on-line analysis of physiologic and neurobehavioral variables monitored during long-duration space missions. Maintenance of physiologic and neurobehavioral homeostasis during long-duration space missions is crucial for ensuring optimal crew performance. If countermeasures are not applied, alterations in homeostasis will occur in nearly all-physiologic systems. During such missions data from most of these systems will be either continually and/or continuously monitored. Therefore, if these data can be analyzed as they are acquired and the status of these systems can be continually assessed, then once alterations are detected, appropriate countermeasures can be applied to correct them. One of the most important physiologic systems in which to maintain homeostasis during long-duration missions is the circadian system. To detect and treat alterations in circadian physiology during long duration space missions requires development of: 1) a ground-based protocol to assess the status of the circadian system under the light-dark environment in which crews in space will typically work; and 2) appropriate statistical methods to make this assessment. The protocol in Project 1, Circadian Entrainment, Sleep-Wake Regulation and Neurobehavioral will study human volunteers under the simulated light-dark environment of long-duration space missions. Therefore, we propose to develop statistical models to characterize in near real time circadian and neurobehavioral physiology under these conditions. The specific aims of this project are to test the hypotheses that: 1) Dynamic statistical methods based on the Kronauer model of the human circadian system can be developed to estimate circadian phase, period, amplitude from core-temperature data collected under simulated light- dark conditions of long-duration space missions. 2) Analytic formulae and numerical algorithms can be developed to compute the error in the estimates of circadian phase, period and amplitude determined from the data in Specific Aim 1. 3) Statistical models can detect reliably in near real- time (daily) significant alternations in the circadian physiology of individual subjects by analyzing the circadian and neurobehavioral data collected in Project 1. 4) Criteria can be developed using the Kronauer model and the recently developed Jewett model of cognitive -performance and subjective alertness to define altered circadian and neurobehavioral physiology and to set conditions for immediate administration of countermeasures.

Brown, Emery N.↗

VEG-01: Veggie Hardware Verification Testing

The Veggie plant/vegetable production system is scheduled to fly on ISS at the end of2013. Since much of the technology associated with Veggie has not been previously tested in microgravity, a hardware validation flight was initiated. This test will allow data to be collected about Veggie hardware functionality on ISS, allow crew interactions to be vetted for future improvements, validate the ability of the hardware to grow and sustain plants, and collect data that will be helpful to future Veggie investigators as they develop their payloads. Additionally, food safety data on the lettuce plants grown will be collected to help support the development of a pathway for the crew to safely consume produce grown on orbit. Significant background research has been performed on the Veggie plant growth system, with early tests focusing on the development of the rooting pillow concept, and the selection of fertilizer, rooting medium and plant species. More recent testing has been conducted to integrate the pillow concept into the Veggie hardware and to ensure that adequate water is provided throughout the growth cycle. Seed sanitation protocols have been established for flight, and hardware sanitation between experiments has been studied. Methods for shipping and storage of rooting pillows and the development of crew procedures and crew training videos for plant activities on-orbit have been established. Science verification testing was conducted and lettuce plants were successfully grown in prototype Veggie hardware, microbial samples were taken, plant were harvested, frozen, stored and later analyzed for microbial growth, nutrients, and A TP levels. An additional verification test, prior to the final payload verification testing, is desired to demonstrate similar growth in the flight hardware and also to test a second set of pillows containing zinnia seeds. Issues with root mat water supply are being resolved, with final testing and flight scheduled for later in 2013.

Massa, Gioia↗

NASA EOSDIS Data Usage Metrics- Insight and Assessment

NASA's Earth Science Data and Information System (ESDIS) Project collects Earth science data usage metrics on a daily basis through the ESDIS Metrics System (EMS). This includes metrics on distribution of data products, users, data volumes, and number of files, which are key parameters in evaluating system-level performance of any of the Distributed Active Archive Centers (DAACs) encompassed by NASA's Earth Observing System (EOS) Data and Information System (EOSDIS). EOSDIS data usage metrics illustrate the benefits of making NASA data openly available to the public and show a rapid growth in data distribution to a worldwide user community. In fact, each year since 2014 the EOSDIS has distributed over one billion data files of products from EOS satellite, airborne, and in situ observations. An assessment of the long-term trends of data usage metrics and user characterization provides insights into data usability.This study will focus on describing the EMS as a metrics collection tool and will provide a comprehensive analysis of EOSDIS data usage metrics over the last 10 years. This study will also characterize the product distribution metrics by various tools and services, such as Giovanni, the Open-source Project for a Network Data Access Protocol (OPeNDAP), and subsets, to address how these tools/services have extended the usage of data in the EOSDIS collection. Data usage patterns based on discipline and study area will further assist in understanding how EOSDIS data user needs have evolved over time. Results from this study will provide useful information for the DAACs that can help them improve the functionality of their tools and services as well as more efficiently allocate the resources necessary for enhanced access and availability of their data products. Knowledge of these metrics may also benefit user discovery of data in the EOSDIS collection, promote research collaboration, and stimulate new ideas from work and research conducted using specific datasets and data collections.

Kafle, Durga N.↗

Creating the Environment for Exploration Habitats

The Crew and Thermal Systems Division’s (CTSD) 20 Foot Chamber has undergone significant modifications to support NASA’s future human exploration missions to the Moon, Mars, and beyond. Existing chamber systems such as Vacuum/Repress, Heating Ventilation and Air Conditioning (HVAC), and Fire Suppression System (FSS), were upgraded, while new systems such as Air Revitalization and Gas Distribution were added. In addition, the chamber was outfitted with crew quarters, hygiene areas, storage, and workspaces. Teams across the Johnson Space Center (JSC) worked together to overcome the logistical and operational challenges of the planned test parameters. The ultimate goal was to create an analog testbed in which a maximum of 8 human test subjects could safely live and work for at least 11 days in the same conditions (reduced pressures, Oxygen concentrations, etc.) as those expected inside a base spacecraft. This would allow researchers to study the effects of such environments on humans and to validate proposed Prebreathe Protocols to enable the safe performance of surface extravehicular activities (EVAs). Over the last eighteen months, the CTSD Systems Test Branch has performed six tests of varying lengths and atmospheres for both NASA and commercial partners. To date, researchers now have collected data on 48 test subjects in the course of 42 days and over 130 simulated EVAs. This paper will discuss the history of the 20 Foot Chamber, its long road to becoming an analog testbed for human exploration, and the capabilities that make it a unique, world class facility for NASA and commercial human exploration missions. It will provide an overview of past and future testing, and the lessons learned along the way.

Cristina Aurora Anchondo↗

Creating the Environment for Exploration Habitats

The Crew and Thermal Systems Division’s (CTSD) 20 Foot Chamber has undergone significant modifications to support NASA’s future human exploration missions to the Moon, Mars, and beyond. Existing chamber systems such as Vacuum/Repress, Heating Ventilation and Air Conditioning (HVAC), and Fire Suppression System (FSS), were upgraded, while new systems such as Air Revitalization and Gas Distribution were added. In addition, the chamber was outfitted with crew quarters, hygiene areas, storage, and workspaces. Teams across the Johnson Space Center (JSC) worked together to overcome the logistical and operational challenges of the planned test parameters. The ultimate goal was to create an analog testbed in which a maximum of 8 human test subjects could safely live and work for at least 11 days in the same conditions (reduced pressures, Oxygen concentrations, etc.) as those expected inside a base spacecraft. This would allow researchers to study the effects of such environments on humans and to validate proposed Prebreathe Protocols to enable the safe performance of surface extravehicular activities (EVAs). Over the last eighteen months, the CTSD Systems Test Branch has performed six tests of varying lengths and atmospheres for both NASA and commercial partners. To date, researchers now have collected data on 48 test subjects in the course of 42 days and over 130 simulated EVAs. This paper will discuss the history of the 20 Foot Chamber, its long road to becoming an analog testbed for human exploration, and the capabilities that make it a unique, world class facility for NASA and commercial human exploration missions. It will provide an overview of past and future testing, and the lessons learned along the way.

Cristina A Anchondo↗

Creating the Test Environment for Exploration Habitats

The Crew and Thermal Systems Division’s (CTSD) 20 Foot Chamber has undergone significant modifications to support NASA’s future human exploration missions to the Moon, Mars, and beyond. Existing chamber systems such as Vacuum/Repress, Heating Ventilation and Air Conditioning (HVAC), and Fire Suppression System (FSS), were upgraded, while new systems such as Air Revitalization and Gas Distribution were added. In addition, the chamber was outfitted with crew quarters, hygiene areas, storage, and workspaces. Teams across the Johnson Space Center (JSC) worked together to overcome the logistical and operational challenges of the planned test parameters. The ultimate goal was to create an analog testbed in which a maximum of eight human test subjects could safely live and work for at least 11 days in the same conditions (e.g., reduced pressures, oxygen concentrations, and so on) as those expected inside a base spacecraft. This would allow researchers to study the effects of such environments on humans and to validate proposed Prebreathe Protocols to enable the safe performance of surface extravehicular activities (EVAs). Over the last 18 months, the CTSD Systems Test Branch has performed six tests of varying lengths and atmospheres for both NASA and commercial partners. To date, researchers now have collected data on 48 test subjects in the course of 42 days and over 130 simulated EVAs. This paper will discuss the history of the 20 Foot Chamber, its long road to becoming an analog testbed for human exploration, and the capabilities that make it a unique, world class facility for NASA and commercial human exploration missions. It will provide an overview of past and future testing and the lessons learned along the way.

Cristina A Anchondo↗

Creating the Test Environment for Exploration Habitats

The Crew and Thermal Systems Division’s (CTSD) 20 Foot Chamber has undergone significant modifications to support NASA’s future human exploration missions to the Moon, Mars, and beyond. Existing chamber systems such as Vacuum/Repress, Heating Ventilation and Air Conditioning (HVAC), and Fire Suppression System (FSS), were upgraded, while new systems such as Air Revitalization and Gas Distribution were added. In addition, the chamber was outfitted with crew quarters, hygiene areas, storage, and workspaces. Teams across the Johnson Space Center (JSC) worked together to overcome the logistical and operational challenges of the planned test parameters. The ultimate goal was to create an analog testbed in which a maximum of eight human test subjects could safely live and work for at least 11 days in the same conditions (e.g., reduced pressures, oxygen concentrations, and so on) as those expected inside a base spacecraft. This would allow researchers to study the effects of such environments on humans and to validate proposed Prebreathe Protocols to enable the safe performance of surface extravehicular activities (EVAs). Over the last 18 months, the CTSD Systems Test Branch has performed six tests of varying lengths and atmospheres for both NASA and commercial partners. To date, researchers now have collected data on 48 test subjects in the course of 42 days and over 130 simulated EVAs. This paper will discuss the history of the 20 Foot Chamber, its long road to becoming an analog testbed for human exploration, and the capabilities that make it a unique, world class facility for NASA and commercial human exploration missions. It will provide an overview of past and future testing and the lessons learned along the way.

Chris Briggs↗

Identifying Requirements for Effective Human-Automation Teamwork

Previous studies have shown that poorly designed human-automation collaboration, such as poorly designed communication protocols, often leads to problems for the human operators, such as: lack of vigilance, complacency, and loss of skills. These problems often lead to suboptimal system performance. To address this situation, a considerable amount of research has been conducted to improve human-automation collaboration and to make automation function better as a “team player.” Much of this research is based on an understanding of what it means to be a good team player from the perspective of a human team. However, the research is often based on a simplified view of human teams and teamwork. In this study, we sought to better understand the capabilities and limitations of automation from the standpoint of human teams. We first examined human teams to identify the principles for effective teamwork. We next reviewed the research on integrating automation agents and human agents into mixed agent teams to identify the limitations of automation agents to conform to teamwork principles. This research resulted in insights that can lead to more effective human-automation collaboration by enabling a more realistic set of requirements to be developed based on the strengths and limitations of all agents.

99 GENERAL AND MISCELLANEOUS↗

Metabolite, Protein, and Lipid Extraction (MPLEx): a method that simultaneously inactivates Middle East respiratory syndrome coronavirus and allows analysis of multiple host cell components following infection

Mass spectrometry (MS)-based, integrated proteomics, metabolomics, and lipidomics (collectively, multi-omics) studies provide a very detailed snap shot of virus-induced changes to the host following infection and can lead to the identification of novel prophylactic and therapeutic targets for preventing or lessening disease severity. Multi-omics studies with Middle East respiratory syndrome coronavirus (MERS-CoV) are challenging as the requirements of Biosafety Level 3 containment limit the numbers of samples that can be safely managed. To address these issues, the multi-omics sample preparation technique MPLEx (metabolite, protein, and lipid extraction) was developed to partition a single sample into three distinct parts (metabolites, proteins and lipids) for multi-omics analysis, while simultaneously inactivating MERS-CoV by solubilizing and disrupting the viral envelope and denaturing viral proteins. Here we describe the MPLEx protocol, highlight the step of inactivation, and describe the details of downstream processing, instrumental analysis of studies with Middle East respiratory syndrome coronavirus (MERS-CoV) are challenging as the requirements of Biosafety Level 3 containment limit the numbers of samples that can be safely managed. To address these issues, the multi-omics sample preparation technique MPLEx (metabolite, protein, and lipid extraction) was developed to partition a single sample into three distinct parts (metabolites, proteins and lipids) for multi-omics analysis, while simultaneously inactivating MERS-CoV by solubilizing and disrupting the viral envelope and denaturing viral proteins. Here we describe the MPLEx protocol, highlight the step of inactivation, and describe the details of downstream processing, instrumental analysis of the three separate analytes and their subsequent informatics pipelines.

Nicora, Carrie D.↗

Initial Validation of a Simulation System for Studying Interoperability in Future Air Traffic Management Systems

Future air traffic management systems will need to accommodate large numbers of increasingly diverse air vehicles with different operating paradigms. To support this trend, they will digitally share copious amounts of information via a common communication architecture. Operators will deploy programs that create and negotiate flight plans via the architecture’s communication protocols. These programs will autonomously make decisions that must be arbitrated by the architecture and robust to uncertainty. To study interoperability in air traffic management, a new airspace simulation system was composed by integrating a legacy airspace simulation, an air traffic control model, and a new research communication architecture. It was used to evaluate air traffic management concepts by adapting it to handle congested arrival traffic at Newark Liberty International Airport and executing simulations. Results demonstrated the ability of the simulation system to model in detail strategic traffic flow management, predeparture flight planning, and air traffic control working in concert. Subsequent studies can use the simulation system to study interoperability, autonomy, digital communication, and uncertainty in future air traffic management systems.

aircraft scheduling,traffic flow management,autono↗

Initial Validation of a Simulation System for Studying Interoperability in Future Air Traffic Management Systems

Future air traffic management systems will need to accommodate large numbers of increasingly diverse air vehicles with different operating paradigms. To support this trend, they will digitally share copious amounts of information via a common communication architecture. Operators will deploy programs that create and negotiate flight plans via the architecture’s communication protocols. These programs will autonomously make decisions that must be arbitrated by the architecture and robust to uncertainty. To study interoperability in air traffic management, a new airspace simulation system was composed by integrating a legacy airspace simulation, an air traffic control model, and a new research communication architecture. It was used to evaluate air traffic management concepts by adapting it to handle congested arrival traffic at Newark Liberty International Airport and executing simulations. Results demonstrated the ability of the simulation system to model in detail strategic traffic flow management, predeparture flight planning, and air traffic control working in concert. Subsequent studies can use the simulation system to study interoperability, autonomy, digital communication, and uncertainty in future air traffic management systems.

air traffic control↗

Initial Validation of a Simulation System for Studying Interoperability in Future Air Traffic Management Systems

Future air traffic management systems will need to accommodate large numbers of increasingly diverse air vehicles with different operating paradigms. To support this trend, they will digitally share copious amounts of information via a common communication architecture. Operators will deploy programs that create and negotiate flight plans via the architecture’s communication protocols. These programs will autonomously make decisions that must be arbitrated by the architecture and robust to uncertainty. To study interoperability in air traffic management, a new airspace simulation system was composed by integrating a legacy airspace simulation, an air traffic control model, and a new research communication architecture. It was used to evaluate air traffic management concepts by adapting it to handle congested arrival traffic at Newark Liberty International Airport and executing simulations. Results demonstrated the ability of the simulation system to model in detail strategic traffic flow management, predeparture flight planning, and air traffic control working in concert. Subsequent studies can use the simulation system to study interoperability, autonomy, digital communication, and uncertainty in future air traffic management systems.

air traffic control↗

Enabling Model Organism and Commercial Astronaut Data Access Through the NASA Open Science Data Repository

NASA’s Open Science Data Repository (OSDR) brings together omics data from NASA’s GeneLab project and non-omics data, including physiological, phenotypic, imaging, and behavioral data from NASA’s Ames Life Sciences Data Archive (ALSDA) collected from decades of space biology research, providing open and FAIR (findable, accessible, interoperable, and reusable) access of these precious data to scientists world-wide. This rich source of meticulously curated metadata and data from spaceflight and analog studies has been mined by the scientific community resulting in dozens of high impact scientific publications that reveals a complex network of molecular and physiological effects of spaceflight across living systems, from microbes to plants, to mammals. Understanding how these effects translate to the human condition is critical as we move deeper into the era of commercial space travel. However, the integration of data, specifically omics data, from astronauts is particularly challenging due to their sensitive nature. OSDR has risen to this challenge by developing a mechanism to control access to identifiable levels of omics data, such as raw sequence data, while enabling public access to processed, unidentifiable, data and associated metadata that will allow the scientific community to interrogate human astronaut data alongside data from model organisms to begin answering these critical questions. The 2021 SpaceX Inspiration4 (I4) mission collected a comprehensive atlas of biological measurements from four civilian astronauts, providing a wealth of data to characterize the effects of spaceflight on the human body. These data include both non-omics and omics assays such as direct RNA sequencing (RNA-seq), single nuclei ATAC-seq and RNA-seq, metagenomics, proteomics, and comprehensive metabolic and cytokine panels, all of which have been integrated into the OSDR system across no less than 9 studies. Each study has been carefully curated using community-backed OSDR standards for sample and assay level metadata ensuring these data are findable and accessible. In addition to hosting both raw and processed data from the principal investigator team for each assay type, the GeneLab team plans to re-process the I4 omics data using GeneLab’s standard processing pipelines. The GeneLab processed data outputs will allow for comparisons across studies on OSDR and enable visualization of these data through the OSDR data visualization platform thereby enabling data reusability and interoperability. Here we describe the robust privacy and security protocols implemented by OSDR to safeguard sensitive health data from astronauts while facilitating metadata and processed data sharing for research purposes. We further provide a road map for navigating the vast amount of data provided for each I4 study on the OSDR, including experimental design, associated experiments, payloads, and missions, data generation and analysis protocols, and associated scientific articles. Additionally, we illustrate how to interrogate the standardized metadata provided in the sample and assay tables as well as various means to download and access the data including programmatically through the GeneLab Open API (GLOpenAPI). The open access of datasets in NASA’s OSDR provides a unique opportunity for the scientific community, as well as citizen scientists and students, to continue using OSDR resources to further unlock profound insights into the consequences of space travel on the human body. Through implementation of security measures to protect sensitive human data, the OSDR seeks to strengthen the science exchange between the Biological and Physical Sciences Program and the Human Research Program, per recommendation 4-1 of the 2023-2032 Decadal Survey, and encourage further sharing and dissemination of astronaut data to provide the scientific community with the resources needed to lay the groundwork for developing targeted mitigation strategies to help withstand the rigors of long-duration spaceflight.

Amanda Marie Saravia-butler↗

Enabling Model Organism and Commercial Astronaut Data Access Through the NASA Open Science Data Repository

NASA’s Open Science Data Repository (OSDR) brings together omics data from NASA’s GeneLab project and non-omics data, including physiological, phenotypic, imaging, and behavioral data from NASA’s Ames Life Sciences Data Archive (ALSDA) collected from decades of space biology research, providing open and FAIR (findable, accessible, interoperable, and reusable) access of these precious data to scientists world-wide. This rich source of meticulously curated metadata and data from spaceflight and analog studies has been mined by the scientific community resulting in dozens of high impact scientific publications that reveals a complex network of molecular and physiological effects of spaceflight across living systems, from microbes to plants, to mammals. Understanding how these effects translate to the human condition is critical as we move deeper into the era of commercial space travel. However, the integration of data, specifically omics data, from astronauts is particularly challenging due to their sensitive nature. OSDR has risen to this challenge by developing a mechanism to control access to identifiable levels of omics data, such as raw sequence data, while enabling public access to processed, unidentifiable, data and associated metadata that will allow the scientific community to interrogate human astronaut data alongside data from model organisms to begin answering these critical questions. The 2021 SpaceX Inspiration4 (I4) mission collected a comprehensive atlas of biological measurements from four civilian astronauts, providing a wealth of data to characterize the effects of spaceflight on the human body. These data include both non-omics and omics assays such as direct RNA sequencing (RNA-seq), single nuclei ATAC-seq and RNA-seq, metagenomics, proteomics, and comprehensive metabolic and cytokine panels, all of which have been integrated into the OSDR system across no less than 9 studies. Each study has been carefully curated using community-backed OSDR standards for sample and assay level metadata ensuring these data are findable and accessible. In addition to hosting both raw and processed data from the principal investigator team for each assay type, the GeneLab team plans to re-process the I4 omics data using GeneLab’s standard processing pipelines. The GeneLab processed data outputs will allow for comparisons across studies on OSDR and enable visualization of these data through the OSDR data visualization platform thereby enabling data reusability and interoperability. Here we describe the robust privacy and security protocols implemented by OSDR to safeguard sensitive health data from astronauts while facilitating metadata and processed data sharing for research purposes. We further provide a road map for navigating the vast amount of data provided for each I4 study on the OSDR, including experimental design, associated experiments, payloads, and missions, data generation and analysis protocols, and associated scientific articles. Additionally, we illustrate how to interrogate the standardized metadata provided in the sample and assay tables as well as instructions for how to download and access the data. The I4 datasets described here re present the first ever comprehensive collection of commercial astronaut data.

Amanda M Saravia-Butler↗

Storage Conditions of Human Kidney Tissue Sections Affect Spatial Lipidomics Analysis Reproducibility

Lipids often are labile, unstable, and tend to degrade overtime, so it is of the upmost importance to study these molecules in their most native state. In this study, we sought to understand the optimal storage conditions for spatial lipidomic analysis of human kidney tissue sections. Specifically, we evaluated human kidney tissue sections on several different days throughout the span of a week using our established protocol for elucidating lipids using high mass resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). We studied kidney tissue sections stored under five different conditions: open stored at –80 °C, vacuumed sealed and stored at –80 °C, with matrix preapplied before storage at –80 °C, under a nitrogen atmosphere and stored at –80 °C, and at room temperature in a desiccator. Results were compared to data obtained from kidney tissue sections that were prepared and analyzed immediately after cryosectioning. Data was processed using METASPACE. After a week of storage, the sections stored at room temperature showed the largest amount of lipid degradation, while sections stored under nitrogen and at –80 °C retained the greatest number of overlapping annotations in relation to freshly cut tissue. Overall, we found that molecular degradation of the tissue sections was unavoidable over time, regardless of storage conditions, but storing tissue sections in an inert gas at low temperatures can curtail molecular degradation within tissue sections.

60 APPLIED LIFE SCIENCES↗

Bisphosphonate as a Countermeasure to Space Flight-Induced Bone Loss

The purpose of this research is to determine whether anti-resorptive pharmaceuticals such as bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density and bone strength and the increased renal stone risk documented on previous long-duration space flights [1-3]. Losses averaged ~ 1 to 2 percent per month in such regions as the lumbar spine and hip. Although losses showed significant heterogeneity among individuals and between bones within a given subject, space flight-induced bone loss was a consistent finding. More than 90 percent of astronauts and cosmonauts on long-duration flights (average 171 days) aboard Mir and the ISS, had a minimum 5 percent loss in at least one skeletal site, 40 percent of them had a 10 percent or greater loss in at least one skeletal site, and 22 percent of the Mir cosmonauts experienced a 15 to 20 percent loss in at least one site. These losses occurred even though the crewmembers performed time-consuming in-flight exercise regimens. Moreover, a recent study of 16 ISS astronauts using quantitative computed tomography (QCT) demonstrated trabecular bone losses from the hip averaging 2.3 percent per month [4]. These losses were accompanied by significant losses in hip bone strength that may not be recovered quickly [5]. This rapid loss of bone mass results from a combination of increased and uncoupled remodeling, as demonstrated by increased resorption with little or no change in bone formation markers [6-7]. This elevated remodeling rate likely affects the cortical and trabecular architecture and may lead to irreversible changes. In addition to bone loss, the resulting hypercalciuria increases renal stone risk. Therefore, it is logical to attempt to attenuate this increased remodeling with anti-resorption drugs such as bisphosphonates. Success with alendronate was demonstrated in a bed rest study [8]. This work has been extended to space flight and two dosing regimens: 1) an oral dose of 70 mg of alendronate taken weekly during flight or 2) a single intravenous (IV) dose of 4 mg of zoledronic acid given several weeks before flight. Currently the study is focusing on the oral option because of NASA s safety concerns with the IV-administered drug. The protocol requests 10 male or female crewmembers on ISS flights of 90 days or longer. Controls are 16 previous ISS crewmembers with QCT scans of the hip performed by these same investigators. The primary outcome measure for this study is hip trabecular bone mineral density measured by QCT, but other measures of bone mass are performed including peripheral QCT (pQCT) and dual-energy x-ray absorptiometry. Serum and urinary bone markers and renal stone risk measured before, during, and after flight are included. Postflight data are currently being collected from 2 ISS crewmembers. Two additional crewmembers will return this spring after ~6-month missions. To date no untoward effects have been encountered.

Spector, Elisabeth↗

Annealing of focused ion beam damage in gold microcrystals: an in situ Bragg coherent X-ray diffraction imaging study

Focused ion beam (FIB) techniques are commonly used to machine, analyse and image materials at the micro- and nanoscale. However, FIB modifies the integrity of the sample by creating defects that cause lattice distortions. Methods have been developed to reduce FIB-induced strain; however, these protocols need to be evaluated for their effectiveness. Here, non-destructive Bragg coherent X-ray diffraction imaging is used to study the in situ annealing of FIB-milled gold microcrystals. Two non-collinear reflections are simultaneously measured for two different crystals during a single annealing cycle, demonstrating the ability to reliably track the location of multiple Bragg peaks during thermal annealing. The thermal lattice expansion of each crystal is used to calculate the local temperature. This is compared with thermocouple readings, which are shown to be substantially affected by thermal resistance. To evaluate the annealing process, each reflection is analysed by considering facet area evolution, cross-correlation maps of the displacement field and binarized morphology, and average strain plots. The crystal's strain and morphology evolve with increasing temperature, which is likely to be caused by the diffusion of gallium in gold below ~280°C and the self-diffusion of gold above ~280°C. The majority of FIB-induced strains are removed by 380–410°C, depending on which reflection is being considered. These observations highlight the importance of measuring multiple reflections to unambiguously interpret material behaviour.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

A method for patient dose reduction in dynamic contrast enhanced CT study

Purpose: In dynamic contrast enhanced CT (DCE-CT) study, prolonged CT scanning with high temporal resolution is required to give accurate and precise estimates of kinetic parameters. However, such scanning protocol could lead to substantial radiation dose to the patient. A novel method is proposed to reduce radiation dose to patient, while maintaining high accuracy for kinetic parameter estimates in DCE-CT study. Methods: The method is based on a previous investigation that the arterial impulse response (AIR) in DCE-CT study can be predicted using a population-based scheme. In the proposed method, DCE-CT scanning is performed with relatively low temporal resolution, hence, giving rise to reduction in patient dose. A novel method is proposed to estimate the arterial input function (AIF) based on the coarsely sampled AIF. By using the estimated AIF in the tracer kinetic analysis of the coarsely sampled DCE-CT study, the calculated kinetic parameters are able to achieve a high degree of accuracy. The method was tested on a DCE-CT data set of 48 patients with cervical cancer scanned at high temporal resolution. A random cohort of 34 patients was chosen to construct the orthonormal bases of the AIRs via singular value decomposition method. The determined set of orthonormal bases was used to fit the AIFs in the second cohort (14 patients) at varying levels of down sampling. For each dataset in the second cohort, the estimated AIF was used for kinetic analyses of the modified Tofts and adiabatic tissue homogeneity models for each of the down-sampling schemes between intervals from 2 to 15 s. The results were compared with analyses done with the ''raw'' down-sampled AIF. Results: In the first group of 34 patients, there were 11 orthonormal bases identified to describe the AIRs. The AIFs in the second group were estimated in high accuracy based on the 11 orthonormal bases established in the first group along with down-sampled AIFs. Using the 11 orthonormal bases, the estimated AIFs for the second group were found to have an averaged maximal percentage error of 3.4%{+-} 7.5% in all sampling schemes up to 15 s. The results of kinetic analysis with the proposed method compared with down sampling alone showed that the proposed method is superior in maintaining the accuracy in volume transfer constant (K{sup trans} ) after 9 s down-sampling interval, blood volume (v{sub b} ) for almost all down-sampling intervals, and blood flow (F) after 11 s down-sampling interval. The preliminary results suggested that the proposed method is able to support scanning intervals of 10-15 s at a cost of 6.2%-10.0% loss in accuracy of K{sup trans} and 10.9%-19.4% in v{sub b}, and the scanning intervals of 12-15 s at a cost of 9.7%-14.6% for F in DEC-CT studies for patients with cervix cancer. Conclusions: The proposed method of AIF estimation allows low scanning frequency in DCE-CT study to reduce radiation dose to patient, while maintaining relatively high accuracy in the kinetic parameter estimates. The initial results suggested that the method is applicable for DCE-CT studies for patients with cervical cancer.

60 APPLIED LIFE SCIENCES↗