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Occupational and dietary differences in hydroxylated and methoxylated PBDEs and metals in plasma from Puget Sound, Washington, USA region volunteers

BACKGROUND: Electronic waste (E-waste) recycling is a rapidly growing occupation in the USA with the potential for elevated exposure to flame retardants and metals associated with electronic devices. We previously measured polybrominated diphenyl ethers (PBDEs) in plasma from E-waste workers and found them similar to non-E-waste workers. OBJECTIVES: This study focused on structurally related PBDE derivatives, the hydroxylated (OH-PBDEs) and methoxylated (MeO-PBDEs) forms along with metals known to occur in E-waste. Humans can metabolize PBDEs and some MeO-PBDEs into OH-PBDEs, which is a concern due to greater health risks associated with OH-PBDEs METHODS: We measured 32 different OH-PBDEs and MeO-PBDEs in plasma samples provided by 113 volunteers living in the greater Puget Sound region of Washington State, USA. We measured 14 metals in a subset of 10 E-waste and 10 non-E-waste volunteers. Volunteers were classified based on occupational and dietary habits: work outdoors and weekly consume = 5 seafood servings (outdoor), electronic waste recycling (E-waste) or non-specific indoor occupations (indoor). A two-week food consumption diary was obtained from each volunteer prior to blood sampling. RESULTS: OH-PBDEs were detected in all volunteers varying between 0.27 – 102 ng/g/g-lipid. The MeO-PBDEs were detected in most, but not all volunteers varying between 0 – 60.4 ng/g/g-lipid. E-waste recyclers had OH-PBDE and MeO-PBDE plasma levels that were similar to the indoor group. The outdoor group had significantly higher levels of MeO-PBDEs, but not OH-PBDEs. Comparison of plasma concentrations of BDE-47 with its known hydroxylated metabolites suggested OH-PBDE levels were likely determined by biotransformation and at least two subpopulations identified differing in their apparent rates of OH-PBDE formation. The metals analysis indicated no significant differences between E-waste workers and non-E-waste workers. CONCLUSIONS: Our results indicate E-waste workers do not have elevated plasma levels of these contaminants relative to non-E-waste workers with similar dietary habits.

Schultz, Irvin↗

WE-H-201-03: Enthusiasm and Generosity of Spirit Necessitate a Volunteering Structure to Make Them More Meaningful

The desperate need for radiotherapy in low and mid-income countries (LMICs) has been well documented. Roughly 60 % of the worldwide incidence of cancer occurs in these resource-limited settings and the international community alongside governmental and non-profit agencies have begun publishing reports and seeking help from qualified volunteers. However, the focus of several reports has been on how dire the situation is and the magnitude of the problem, leaving most to feel overwhelmed and unsure as to how to help and why to get involved. This session will help to explain the specific ways that Medical Physicists can uniquely assist in this grand effort to help bring radiotherapy to grossly-underserved areas. Not only can these experts fulfill an important purpose, they also can benefit professionally, academically, emotionally and socially from the endeavor. By assisting others worldwide with their skillset, Medical Physicists can end up helping themselves. Learning Objectives: Understand the need for radiotherapy in LMICs. Understand which agencies are seeking Medical Physicists for help in LMICs. Understand the potential research funding mechanisms are available to establish academic collaborations with LMIC researchers/physicians. Understand the potential social and emotional benefits for both the physicist and the LMIC partners when collaborations are made. Understand the potential for collaboration with other high-income scientists that can develop as the physicist partners with other large institutions to assist LMICs. Wil Ngwa - A recent United Nations Study reports that in developing countries more people have access to cell phones than toilets. In Africa, only 63% of the population has access to piped water, yet, 93% of Africans have cell phone service. Today, these cell phones, Skype, WhatsApp and other information and communication technologies (ICTs) connect us in unprecedented ways and are increasingly recognized as powerful, indispensable to global health. Thanks to ICTs, there are growing opportunities for Medical Physicists to reach out beyond the bunker and impact the world far beyond, without even having to travel. These growing opportunities in global health for Medical Physicists, powered by ICTs, will be highlighted in this presentation, illustrated by high impact examples/models across the globe that are improving patient safety and healthcare outcomes, saving lives. Learning Objectives: Published definitions of global health and the emerging field of global radiation oncology Learn about the transformative potential of ICTs in global radiation oncology care, research and education with focus on Medical Physics Learn about high impact examples of ICT-powered global radiation oncology and the increasing opportunities for participation by Medical Physicists. Yakov Pipman - The number and scope of volunteer Medical Physics activities in support of low-to-middle income countries has been increasing gradually. This happens through a variety of formal channels and to some extent through less formal but personal initiatives. A good deal of effort is dedicated by many, but many more could be recruited through a structured framework to volunteer. We will look into typical volunteer activities and how they fit with organizations already involved in advancing Medical Physics in LMIC. We will identify the range of these organizational activities and their scope to reveal areas of further need. We will point to a few key features of MPWB ( http://www.mpwb.org ) as a volunteering and collaborating structure and how members can get involved and contribute to these efforts at the grass roots level. The goal is that scarce resources can thus be channeled to complement rather than compete with those already in place. Learning Objectives: Understand the strengths and limitations of various organizations that support Medical Physics efforts in LMIC. Learn about ways to volunteer and contribute to Global Health through a grass roots organization focused on Medical Physics in LMIC. Perry Sprawls - With the growing capability and complexity of medical imaging methods in all countries of the world, the expanding role of medical physicists includes optimizing imaging procedures with respect to image quality, radiation dose, and other conflicting factors. With access to appropriate educational resources local medical physicists in all countries can provide direct clinical support and educational for other medical professionals. This is being supported through the process of Collaborative Teaching that combines the capabilities and experience of medical physicists in countries spanning the spectrum of economic, technological, and clinical development. The supporting resources are on the web at: http://www.sprawls.org/resources . Learning Objectives: Identify the medical physics educational needs to support effective and optimized medical imaging procedures. Use collaborative teaching resources to enhance the role of medical physicists in all countries of the world.

60 APPLIED LIFE SCIENCES↗

Self-Management of Patient Body Position, Pose, and Motion Using Wide-Field, Real-Time Optical Measurement Feedback: Results of a Volunteer Study

Purpose: We present the results of a clinical feasibility study, performed in 10 healthy volunteers undergoing a simulated treatment over 3 sessions, to investigate the use of a wide-field visual feedback technique intended to help patients control their pose while reducing motion during radiation therapy treatment. Methods and Materials: An optical surface sensor is used to capture wide-area measurements of a subject's body surface with visualizations of these data displayed back to them in real time. In this study we hypothesize that this active feedback mechanism will enable patients to control their motion and help them maintain their setup pose and position. A capability hierarchy of 3 different level-of-detail abstractions of the measured surface data is systematically compared. Results: Use of the device enabled volunteers to increase their conformance to a reference surface, as measured by decreased variability across their body surfaces. The use of visual feedback also enabled volunteers to reduce their respiratory motion amplitude to 1.7 ± 0.6 mm compared with 2.7 ± 1.4 mm without visual feedback. Conclusions: The use of live feedback of their optically measured body surfaces enabled a set of volunteers to better manage their pose and motion when compared with free breathing. The method is suitable to be taken forward to patient studies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Galaxy Zoo DECaLS: Detailed visual morphology measurements from volunteers and deep learning for 314,000 galaxies

We present Galaxy Zoo DECaLS: detailed visual morphological classifications for Dark Energy Camera Legacy Survey images of galaxies within the SDSS DR8 footprint. Deeper DECaLS images (r = 23.6 versus r = 22.2 from SDSS) reveal spiral arms, weak bars, and tidal features not previously visible in SDSS imaging. To best exploit the greater depth of DECaLS images, volunteers select from a new set of answers designed to improve our sensitivity to mergers and bars. Galaxy Zoo volunteers provide 7.5 million individual classifications over 314 000 galaxies. 140 000 galaxies receive at least 30 classifications, sufficient to accurately measure detailed morphology like bars, and the remainder receive approximately 5. All classifications are used to train an ensemble of Bayesian convolutional neural networks (a state-of-the-art deep learning method) to predict posteriors for the detailed morphology of all 314 000 galaxies. We use active learning to focus our volunteer effort on the galaxies which, if labelled, would be most informative for training our ensemble. When measured against confident volunteer classifications, the trained networks are approximately 99 per cent accurate on every question. Morphology is a fundamental feature of every galaxy; our human and machine classifications are an accurate and detailed resource for understanding how galaxies evolve.

79 ASTRONOMY AND ASTROPHYSICS↗

A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

Highlights: • A human monoclonal antibody against influenza virus was produced from a volunteer. • The antibody was generated from the PBMCs of the volunteer using the fusion method. • The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9). • The antibody targeted a novel epitope in globular head region of the hemagglutinin. • Sequences of the identified epitope are highly conserved among H1 and H9 subtypes. - Abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.

60 APPLIED LIFE SCIENCES↗

Effect of a high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers

Statin use may be limited by muscle side effects. Although incompletely understood to date, their pathophysiology may involve oxidative stress and impairments of mitochondrial function and of muscle Ca{sup 2+} homeostasis. In order to simultaneously assess these mechanisms, 24 male healthy volunteers were randomized to receive either simvastatin for 80 mg daily or placebo for 8 weeks. Blood and urine samples and a stress test were performed at baseline and at follow-up, and mitochondrial respiration and Ca{sup 2+} spark properties were evaluated on a muscle biopsy 4 days before the second stress test. Simvastatin-treated subjects were separated according to their median creatine kinase (CK) increase. Simvastatin treatment induced a significant elevation of aspartate amino transferase (3.38 ± 5.68 vs − 1.15 ± 4.32 UI/L, P < 0.001) and CK (− 24.3 ± 99.1 ± 189.3vs 48.3 UI/L, P = 0.01) and a trend to an elevation of isoprostanes (193 ± 408 vs12 ± 53 pmol/mmol creatinine, P = 0.09) with no global change in mitochondrial respiration, lactate/pyruvate ratio or Ca{sup 2+} sparks. However, among statin-treated subjects, those with the highest CK increase displayed a significantly lower Vmax rotenone succinate and an increase in Ca{sup 2+} spark amplitude vs both subjects with the lowest CK increase and placebo-treated subjects. Moreover, Ca{sup 2+} spark amplitude was positively correlated with treatment-induced CK increase in the whole group (r = 0.71, P = 0.0045). In conclusion, this study further supports that statin induced muscular toxicity may be related to alterations in mitochondrial respiration and muscle calcium homeostasis independently of underlying disease or concomitant medication. -- Highlights: ► Statin use may be limited by side effects, particularly myopathy. ► Statins might impair mitochondrial function and muscle Ca2+ signaling in muscle. ► This was tested among healthy volunteers receiving simvastatin 80 mg daily for 8 weeks. ► CK increase was associated with alterations in Ca2+ sparks and mitochondrial function.

60 APPLIED LIFE SCIENCES↗

Kinetics of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate in blood and of DEHP metabolites in urine of male volunteers after single ingestion of ring-deuterated DEHP

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is suspected to induce antiandrogenic effects in men via its metabolite mono(2-ethylhexyl) phthalate (MEHP). However, there is only little information on the kinetic behavior of DEHP and its metabolites in humans. The toxikokinetics of DEHP was investigated in four male volunteers (28–61 y) who ingested a single dose (645 ± 20 μg/kg body weight) of ring-deuterated DEHP (DEHP-D{sub 4}). Concentrations of DEHP-D{sub 4}, of free ring-deuterated MEHP (MEHP-D{sub 4}), and the sum of free and glucuronidated MEHP-D{sub 4} were measured in blood for up to 24 h; amounts of the monoesters MEHP-D{sub 4}, ring-deuterated mono(2-ethyl-5-hydroxyhexyl) phthalate and ring-deuterated mono(2-ethyl-5-oxohexyl) phthalate were determined in urine for up to 46 h after ingestion. The bioavailability of DEHP-D{sub 4} was surprisingly high with an area under the concentration-time curve until 24 h (AUC) amounting to 50% of that of free MEHP-D{sub 4}. The AUC of free MEHP-D{sub 4} normalized to DEHP-D{sub 4} dose and body weight (AUC/D) was 2.1 and 8.1 times, that of DEHP-D{sub 4} even 50 and 100 times higher than the corresponding AUC/D values obtained earlier in rat and marmoset, respectively. Time courses of the compounds in blood and urine of the volunteers oscillated widely. Terminal elimination half-lives were short (4.3–6.6 h). Total amounts of metabolites in 22-h urine are correlated linearly with the AUC of free MEHP-D{sub 4} in blood, the parameter regarded as relevant for risk assessment. -- Highlights: ► After DEHP intake, DEHP and MEHP in blood show oscillating time courses. ► Dose-related blood levels of DEHP are 50 times higher in humans than in rats. ► Dose-related blood levels of free MEHP are 2 times higher in humans than in rats. ► Elimination of DEHP and its metabolites is short with half-lives of 4.3-6.6 h.

60 APPLIED LIFE SCIENCES↗

Human Dosimetry and Preliminary Tumor Distribution of (superscript)18F-Fluoropaclitaxel in Healthy Volunteers and Newly Diagnosed Breast Cancer Patients Using PET/CT

{sup 18}F-fluoropaclitaxel is a radiolabeled form of paclitaxel, a widely used chemotherapy agent. Preclinical data suggest that {sup 18}F-fluoropaclitaxel may be a reasonable surrogate for measuring the uptake of paclitaxel. As a substrate of P-glycoprotein, a drug efflux pump associated with multidrug resistance, {sup 18}F-fluoropaclitaxel may also be useful in identifying multidrug resistance and predicting tumor response for drugs other than paclitaxel. After informed consent was obtained, 3 healthy volunteers and 3 patients with untreated breast cancer (neoadjuvant chemotherapy candidates, tumor size > 2 cm) received an intravenous infusion of {sup 18}F-fluoropaclitaxel and then underwent PET/CT. Healthy volunteers underwent serial whole-body imaging over an approximately 3-h interval, and organ {sup 18}F residence times were determined from the time-activity curves uncorrected for decay to determine dosimetry. Radiation dose estimates were calculated using OLINDA/EXM software. For breast cancer patients, dynamic imaging of the primary tumor was performed for 60 min, followed by static whole-body scans at 1 and 2 h after injection. Dosimetry calculations showed that the gallbladder received the highest dose (229.50 {mu}Gy/MBq [0.849 rad/mCi]), followed by the small and large intestines (161.26 {mu}Gy/MBq [0.597 rad/mCi] and 184.59 {mu}Gy/MBq [0.683 rad/mCi]). The resultant effective dose was 28.79 {mu}Gy/MBq (0.107 rem/mCi). At approximately 1 h after injection, an average of 42% of the decay-corrected activity was in the gastrointestinal system, with a mean of 0.01% in the tumor. All 3 breast cancer patients showed retention of {sup 18}F-fluoropaclitaxel and ultimately demonstrated a complete pathologic response (no invasive cancer in the breast or axillary nodes) to chemotherapy that included a taxane (either paclitaxel or docetaxel) at surgical resection. The tumor-to-background ratio increased with time to a maximum of 7.7 at 20 min. This study demonstrates the feasibility of using {sup 18}F-fluoropaclitaxel PET/CT tumor imaging and provides radiation dosimetry measurements in humans. Although further study is needed, it is hoped that the measured intratumoral {sup 18}F-fluoropaclitaxel distribution can serve as a surrogate for paclitaxel, and potentially other chemotherapeutic agent retention, in solid tumors.

18F-Fluoropaclitaxel (FPAC)↗

Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers

OBJECTIVES: We sought to determine the relationship between different echocardiographic indices and pulmonary capillary wedge pressures (PCWP) in normal volunteers. BACKGROUND: Indices based on tissue Doppler (TDE) and color M-mode (CMM) echocardiography have been proposed to reflect left (LV) ventricular filling pressures. These include the ratio of early diastolic transmitral velocity (E) to early myocardial velocity measured by TDE (E') and the ratio of E to the wave propagation velocity (Vp) measured from CMM images. These indices, however, have not been validated in normal individuals. METHODS: We studied seven volunteers during two phases of preload altering maneuvers, baseline, with two stages of lower body negative pressure, and repeat baseline with two stages of volume loading. The PCWP obtained from right heart catheterization was compared with diastolic indices using pulsed Doppler, TDE and CMM echocardiography. RESULTS: The PCWP ranged from 2.2 to 23.5 mm Hg. During preload alterations, significant changes in E and septal E' (both p < 0.05) but not lateral E' or Vp were observed. Furthermore, E, septal E' and E/Vp correlated with PCWP (all r > 0.80) but not combined E and TDE indices (both r < 0.15). Within individuals, a similar linear relationship was observed among E/Vp, E and septal E' (average r > 0.80). CONCLUSIONS: In subjects without heart disease, E, septal E' and E/Vp correlate with PCWP. Because the influence of ventricular relaxation is minimized, the ratio E/Vp may be the best overall index of LV filling pressures.

NASA Discipline Cardiopulmonary↗

Global Cloud Cover: Comparison of Satellite, Model, and Volunteer Data

Observing and better understanding clouds and aerosols are priorities in the NASA Earth Science Decadal Survey, US National Climate Assessment, and Intergovernmental Panel on Climate Change Report. The Global Learning & Observations to Benefit the Environment (GLOBE) Program is NASA's largest and longest running citizen science program in the Earth Sciences that collects cloud observations. Since January 2017, NASA GLOBE students and citizen scientists have submitted over 800,000 cloud observations worldwide using both paper-based and smartphone app platforms. In this presentation, we compare satellite, model, and volunteer-reported total cloud cover. The comparison reveals a systematic misreporting of obscured skies (sky not visible due to smoke, dust, haze, etc.) versus overcast skies (100% total cloud cover) by GLOBE participants. We discuss implications for improving procedures for volunteer reporting under overcast and obscured sky conditions, and relevance for reporting extreme air pollution events in areas with little or no formal institutional monitoring networks.

Starke, Matthew↗

Comparison of Anthropomorphic Test Device and human Volunteer Responses in Landing Impact Tests of U.S. Space Vehicles

United States (U.S.) crewed vehicles are being designed to support the National Aeronautics and Space Administration’s (NASA’s) human spaceflight programs. Vehicles must be designed to meet NASA’s occupant protection requirements including landing injury assessment with anthropomorphic test devices (ATDs) and analytical models. However, these tools are limited in capturing all injuries that might occur during spacecraft landings. A NASA study of injuries during Soyuz vehicle landings has shown that analytical models are underpredicting occupant injury. Because of the inherent limitations with our analytical tools, human volunteer impact testing was employed to validate the safety of U.S. crewed vehicles. A total of 84 human volunteer tests in 11 different test orientations and g-levels were completed as part of this effort in collaboration with the Air Force Research Laboratory (AFRL) at Wright-Patterson Air Force Base and the vehicle development companies. Human subjects were tested at various realistic landing loads and in the highest fidelity seat and suit components that were available at the time of testing for two U.S. vehicles. Matched-pair ATD tests in the same test conditions were also conducted with small female and midsized male Hybrid III ATDs. ATDs were fully instrumented. Head accelerations and subjective responses were recorded in human subjects. In some cases, chest accelerations were captured. Responses of the ATDs and humans in matched-pair tests were compared. No ATD tests showed evidence for risk of injury based on NASA occupant protection requirements. Human subjects reported 17 cases of discomfort or pain, 1 human subject was diagnosed with a minor injury that was not evident in the ATD tests. These results provide evidence that ATDs do not capture all potential injury risks, namely lower severity injuries, discomfort, pain, and fit issues. Overall, human testing is beneficial to understanding the true risk of injury to crewmembers during Earth landings.

Teresa Reiber↗

Comparison of Anthropomorphic Test Device and Human Volunteer Responses in Simulated Landing Impact Tests of U.S. Space Vehicles

United States (U.S.) crewed vehicles are being designed to support the National Aeronautics and Space Administration’s (NASA’s) human spaceflight programs. Vehicles must be designed to meet NASA’s occupant protection requirements including landing injury assessment with anthropomorphic test devices (ATDs) and analytical models. However, these tools are limited in capturing all injuries that might occur during spacecraft landings. A NASA study of injuries during Soyuz vehicle landings has shown that analytical models are underpredicting occupant injury. Because of the inherent limitations with our analytical tools, human volunteer impact testing was employed to assess flight-like landing conditions of U.S. crewed vehicles. A total of 84 human volunteer tests in 11 different test orientations and g-levels were completed as part of this effort in collaboration with the Air Force Research Laboratory (AFRL) at Wright-Patterson Air Force Base and U.S. vehicle development companies. Human subjects were tested at various realistic landing loads and in the highest fidelity seat and suit components that were available at the time of testing for two U.S. vehicles. Matched-pair ATD tests in the same test conditions were also conducted with small female and midsized male Hybrid III ATDs. ATDs were fully instrumented. Head accelerations and subjective responses were recorded for human subjects. In some cases, chest accelerations were captured. Responses of the ATDs and humans in matched-pair tests were compared. No ATD tests showed evidence for risk of injury based on NASA occupant protection requirements. Human subjects reported 17 cases of discomfort or pain, and 1 human subject was diagnosed with a minor injury that was not evident in the ATD tests. These results provide evidence that ATDs do not capture all potential injury risks, namely lower severity injuries, discomfort, pain, and fit issues. Overall, human testing is beneficial to understanding the true risk of injury to crewmembers during Earth landings.

Teresa M Reiber↗

Comparison of Anthropomorphic Test Device and Human Volunteer Responses in Simulated Landing Impact Tests of U.S. Space Vehicles

United States (U.S.) crewed vehicles are being designed to support the National Aeronautics and Space Administration’s (NASA’s) human spaceflight programs. Vehicles must be designed to meet NASA’s occupant protection requirements including landing injury assessment with anthropomorphic test devices (ATDs) and analytical models. However, these tools are limited in capturing all injuries that might occur during spacecraft landings. A NASA study of injuries during Soyuz vehicle landings has shown that analytical models are underpredicting occupant injury. Because of the inherent limitations with our analytical tools, human volunteer impact testing was employed to assess flight-like landing conditions of U.S. crewed vehicles. A total of 84 human volunteer tests in 11 different test orientations and g-levels were completed as part of this effort in collaboration with the Air Force Research Laboratory (AFRL) at Wright-Patterson Air Force Base and U.S. vehicle development companies. Human subjects were tested at various realistic landing loads and in the highest fidelity seat and suit components that were available at the time of testing for two U.S. vehicles. Matched-pair ATD tests in the same test conditions were also conducted with small female and midsized male Hybrid III ATDs. ATDs were fully instrumented. Head accelerations and subjective responses were recorded for human subjects. In some cases, chest accelerations were captured. Responses of the ATDs and humans in matched-pair tests were compared. No ATD tests showed evidence for risk of injury based on NASA occupant protection requirements. Human subjects reported 17 cases of discomfort or pain, and 1 human subject was diagnosed with a minor injury that was not evident in the ATD tests. These results provide evidence that ATDs do not capture all potential injury risks, namely lower severity injuries, discomfort, pain, and fit issues. Overall, human testing is beneficial to understanding the true risk of injury to crewmembers during Earth landings.

Teresa M Reiber↗

Comparison of Anthropomorphic Test Device and Human Volunteer Responses in Simulated Landing Impact Tests of U.S. Space Vehicles

United States (U.S.) crewed vehicles are being designed to support the National Aeronautics and Space Administration’s (NASA’s) human spaceflight programs. Vehicles must be designed to meet NASA’s occupant protection requirements including landing injury assessment with anthropomorphic test devices (ATDs) and analytical models. However, these tools are limited in capturing all injuries that might occur during spacecraft landings. A NASA study of injuries during Soyuz vehicle landings has shown that analytical models are underpredicting occupant injury. Because of the inherent limitations with our analytical tools, human volunteer impact testing was employed to assess flight-like landing conditions of U.S. crewed vehicles. A total of 84 human volunteer tests in 11 different test orientations and g-levels were completed as part of this effort in collaboration with the Air Force Research Laboratory (AFRL) at Wright-Patterson Air Force Base and U.S. vehicle development companies. Human subjects were tested at various realistic landing loads and in the highest fidelity seat and suit components that were available at the time of testing for two U.S. vehicles. Matched-pair ATD tests in the same test conditions were also conducted with small female and midsized male Hybrid III ATDs. ATDs were fully instrumented. Head accelerations and subjective responses were recorded for human subjects. In some cases, chest accelerations were captured. Responses of the ATDs and humans in matched-pair tests were compared. No ATD tests showed evidence for risk of injury based on NASA occupant protection requirements. Human subjects reported 17 cases of discomfort or pain, and 1 human subject was diagnosed with a minor injury that was not evident in the ATD tests. These results provide evidence that ATDs do not capture all potential injury risks, namely lower severity injuries, discomfort, pain, and fit issues. Overall, human testing is beneficial to understanding the true risk of injury to crewmembers during Earth landings.

Teresa M Reiber↗

Comparative Prospective Study of Load Distribution Projection Among Patients with Vertebral Fractures Treated with Percutaneous Vertebroplasty and a Control Group of Healthy Volunteers

Purpose: Through a prospective comparison of patients with vertebral fractures and normal population, we illustrate effect of percutaneous vertebroplasty (PV) upon projection of load distribution changes. Methods: Vertebroplasty group (36 symptomatic patients with osteoporotic vertebral fractures) was evaluated on an electronic baropodometer registering projection of weight bearing areas on feet. Load distribution between right and left foot (including rear-front of the same foot) during standing and walking was recorded and compared before (group V1) and the day after (group V2) PV. Control group (30 healthy asymptomatic volunteers-no surgery record) were evaluated on the same baropodometer. Results: Mean value of load distribution difference between rear-front of the same foot was 9.45 ± 6.79 % (54.72–45.28 %) upon standing and 14.76 ± 7.09 % (57.38–42.62 %) upon walking in the control group. Respective load distribution values before PV were 16.52 ± 11.23 and 30.91 ± 19.26 % and after PV were 10.08 ± 6.26 and 14.25 ± 7.68 % upon standing and walking respectively. Mean value of load distribution variation between the two feet was 6.36 and 14.6 % before and 4.62 and 10.4 % after PV upon standing and walking respectively. Comparison of load distribution variation (group V1–V2, group V1-control group) is statistically significant. Comparison of load distribution variation (group V2-control group) is not statistically significant. Comparison of load distribution variation among the two feet is statistically significant during walking but not statistically significant during standing. Conclusions: There is a statistically significant difference when comparing load distribution variation prior vertebroplasty and that of normal population. After vertebroplasty, this difference normalizes in a statistically significant way. PV is efficient on equilibrium-load distribution improvement as well.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Exploiting deep learning and volunteered geographic information for mapping buildings in Kano, Nigeria

Buildings in the developing world are inadequately mapped. Lack of such critical geospatial data adds unnecessary challenges to locating and reaching a large segment of the world’s most vulnerable population, impeding sustainability goals ranging from disaster relief to poverty reduction. Use of volunteered geographic information (VGI) has emerged as a widely accepted source to fill such voids. Despite its promise, availability of building maps for developing countries significantly lags behind demand. We present a new approach, coupling deep convolutional neural networks (CNNs) with VGI for automating building map generation from high-resolution satellite images for Kano state, Nigeria. Specifically, we trained a CNN with VGI building outlines of limited quality and quantity and generated building maps for a 50,000 km 2 area. Resulting maps are in strong agreement with existing settlement maps and require a fraction of the manual input needed for the latter. The VGI-based maps will provide support across multiple facets of socioeconomic development in Kano state, and demonstrates potential advancements in current mapping capabilities in resource constrained countries.

99 GENERAL AND MISCELLANEOUS↗

Establishing reference ranges for circulating biomarkers of drug‐induced liver injury in healthy human volunteers 1

Aims The potential of mechanistic biomarkers to improve prediction of drug‐induced liver injury (DILI) and hepatic regeneration is widely acknowledged. We sought to determine reference intervals for new biomarkers of DILI and regeneration, as well as to characterize their natural variability and impact of diurnal variation. Methods Serum samples from 227 healthy volunteers were recruited as part of a cross‐sectional study; of these, 25 subjects had weekly serial sampling over 3 weeks, while 23 had intensive blood sampling over a 24h period. Alanine aminotransferase (ALT), MicroRNA‐122 (miR‐122), High Mobility Group Box‐1 (HMGB1), total Keratin‐18 (K18), caspase‐cleaved Keratin‐18 (ccK18), Glutamate Dehydrogenase (GLDH) and Macrophage Colony‐Stimulating Factor‐1 (CSF‐1) were assayed. Results Reference intervals were established for each biomarker based on the 97.5% quantile (90% CI) following the assessment of fixed effects in univariate and multivariable models. Intra‐individual variability was found to be non‐significant, and there was no significant impact of diurnal variation. Conclusion Reference intervals for novel DILI biomarkers have been described. An upper limit of a reference range might represent the most appropriate mechanism to utilize these data. These data can now be used to interpret data from exploratory clinical DILI studies and to assist their further qualification as required by regulatory authorities.

Jorgensen, Andrea L. [Department of Health Data Sc↗

Breathing guidance in radiation oncology and radiology: A systematic review of patient and healthy volunteer studies

Purpose: The advent of image-guided radiation therapy has led to dramatic improvements in the accuracy of treatment delivery in radiotherapy. Such advancements have highlighted the deleterious impact tumor motion can have on both image quality and radiation treatment delivery. One approach to reducing tumor motion irregularities is the use of breathing guidance systems during imaging and treatment. These systems aim to facilitate regular respiratory motion which in turn improves image quality and radiation treatment accuracy. A review of such research has yet to be performed; it was therefore their aim to perform a systematic review of breathing guidance interventions within the fields of radiation oncology and radiology. Methods: From August 1–14, 2014, the following online databases were searched: Medline, Embase, PubMed, and Web of Science. Results of these searches were filtered in accordance to a set of eligibility criteria. The search, filtration, and analysis of articles were conducted in accordance with preferred reporting items for systematic reviews and meta-analyses. Reference lists of included articles, and repeat authors of included articles, were hand-searched. Results: The systematic search yielded a total of 480 articles, which were filtered down to 27 relevant articles in accordance to the eligibility criteria. These 27 articles detailed the intervention of breathing guidance strategies in controlled studies assessing its impact on such outcomes as breathing regularity, image quality, target coverage, and treatment margins, recruiting either healthy adult volunteers or patients with thoracic or abdominal lesions. In 21/27 studies, significant (p < 0.05) improvements from the use of breathing guidance were observed. Conclusions: There is a trend toward the number of breathing guidance studies increasing with time, indicating a growing clinical interest. The results found here indicate that further clinical studies are warranted that quantify the clinical impact of breathing guidance, along with the health technology assessment to determine the advantages and disadvantages of breathing guidance.

60 APPLIED LIFE SCIENCES↗