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At least 73 records · Page 4

Constraints and Opportunities in GCM Model Development

Over the past 30 years climate models have evolved from relatively simple representations of a few atmospheric processes to complex multi-disciplinary system models which incorporate physics from bottom of the ocean to the mesopause and are used for seasonal to multi-million year timescales. Computer infrastructure over that period has gone from punchcard mainframes to modern parallel clusters. Constraints of working within an ever evolving research code mean that most software changes must be incremental so as not to disrupt scientific throughput. Unfortunately, programming methodologies have generally not kept pace with these challenges, and existing implementations now present a heavy and growing burden on further model development as well as limiting flexibility and reliability. Opportunely, advances in software engineering from other disciplines (e.g. the commercial software industry) as well as new generations of powerful development tools can be incorporated by the model developers to incrementally and systematically improve underlying implementations and reverse the long term trend of increasing development overhead. However, these methodologies cannot be applied blindly, but rather must be carefully tailored to the unique characteristics of scientific software development. We will discuss the need for close integration of software engineers and climate scientists to find the optimal processes for climate modeling.

Schmidt, Gavin↗

Analysis by NASA's VESGEN Software of Retinal Blood Vessels Before and After 70-Day Bed Rest: A Retrospective Study

Significant risks for visual impairment associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. Impairments include decreased near visual acuity, posterior globe flattening, choroidal folds, optic disc edema and cotton wool spots. We hypothesize that microgravity-induced fluid shifts result in pathological changes within the retinal blood vessels that precede development of visual and other ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated by NASAs innovative VESsel GENeration Analysis (VESGEN) software for two studies: (1) head-down tilt in human subjects before and after 70 days of bed rest, and (2) U.S. crew members before and after ISS missions. VESGEN analysis in previous research supported by the US National Institutes of Health identified surprising new opportunities to regenerate retinal vessels during early-stage, potentially reversible progression of the visually impairing and blinding disease, diabetic retinopathy.

Vascular↗

X-ray Quasi-Periodic Eruptions from Two Previously Quiescent Galaxies

Quasi-Periodic Eruptions (QPEs) are extreme high-amplitude bursts of X-ray radiation recurring every few hours and originating near the central supermassive black holes in galactic nuclei. It is currently unknown what triggers these events, how long they last and how they are connected to the physical properties of the inner accretion flows. Previously, only two such sources were known, found either serendipitously or in archival data, with emission lines in their optical spectra classifying their nuclei as hosting an actively accreting supermassive black hole. Here we present the detection of QPEs in two further galaxies, obtained with a blind and systematic search over half of the X-ray sky. The optical spectra of these galaxies show no signature of black hole activity, indicating that a pre-existing accretion flow typical of active nuclei is not required to trigger these events. Indeed, the periods, amplitudes and profiles of the newly discovered QPEs are inconsistent with current models that invoke radiation-pressure driven accretion disk instabilities. Instead, QPEs might be driven by an orbiting compact object. Furthermore, their observed properties require the mass of the secondary object to be much smaller than the main body and future X-ray observations may constrain possible changes in the period due to orbital evolution. This scenario could make QPEs a viable candidate for the electromagnetic counterparts of the so-called extreme mass ratio inspirals, with considerable implications for multi-messenger astrophysics and cosmology.

R Arcodia↗

Galileo Probe Measurements of Thermal and Solar Radiation Fluxes in the Jovian Atmosphere

The Galileo probe net flux radiometer (NFR) measured radiation fluxes in Jupiter's atmosphere from about 0.44 to 14 bars, using five spectral channels to separate solar and thermal components. Onboard calibration results confirm that the NFR responded to radiation approximately as expected. NFR channels also responded to a superimposed thermal perturbation, which can be approximately removed using blind channel measurements and physical constraints. Evidence for the expected NH3 cloud was seen in the spectral character of spin-induced modulations of the direct solar beam signals. These results are consistent with an overlying cloud of small NH3 ice particles (0.5-0.75 microns in radius) of optical depth 1.5-2 at 0.5 microns. Such a cloud would have so little effect on thermal fluxes that NFR thermal channels provide no additional constraints on its properties. However, evidence for heating near 0.45 bar in the NFR thermal channels would seem to require either an additional opacity source beyond this small-particle cloud, implying a heterogeneous cloud structure to avoid conflicts with solar modulation results, or a change in temperature lapse rate just above the probe measurements. The large thermal flux levels imply water vapor mixing ratios that are only 6% of solar at 10 bars, but possibly increasing with depth, and significantly subsaturated ammonia at pressures less than 3 bars. If deep NH3 mixing ratios at the probe entry site are 3-4 times ground-based inferences, as suggested by probe radio signal attenuation, then only half as much water is needed to match NFR observations. No evidence of a water cloud was seen near the 5-bar level. The 5-microns thermal channel detected the presumed NH4SH cloud base near 1.35 bars. Effects of this cloud were also seen in the solar channel upflux measurements but not in the solar net fluxes, implying that the cloud is a conservative scatterer of sunlight. The minor thermal signature of this cloud is compatible with particle radii near 3 gm, but it cannot rule out smaller particles. Deeper than about 3 bars, solar channels indicate unexpectedly large absorption of sunlight at wavelengths longer than 0.6 microns, which might be due to unaccounted-for absorption by NH3 between 0.65 and 1.5 microns.

Sromovsky, L. A.↗

Solar Energetic Particles and Space Weather

The solar energetic particles (SEPs) of consequence to space weather are accelerated at shock waves driven out from the Sun by fast coronal mass ejections (CMEs). In the large events, these great shocks fill half of the heliosphere. SEP intensity profiles change appearance with longitude. Events with significant intensities of greater than ten MeV protons occur at an average rate of approx. 13 per year near solar maximum and several events with high intensities of > 100 McV protons occur each decade. As particles stream out along magnetic field lines from a shock near the Sun, they generate waves that scatter subsequent particles. At high intensities, wave growth throttles the flow below the 'streaming limit.' However, if the shock maintains its strength, particle intensities can rise above this limit to a peak when the shock itself passes over the observer creating a 'delayed' radiation hazard, even for protons with energies up to approx. one GeV. The streaming limit makes us blind to the intensities at the oncoming shock, however, heavier elements such as He, O, and Fe probe the shape of the wave spectrum, and variation in abundances of these elements allow us to evade the limit and probe conditions at the shock, with the aid of detailed modeling. At high energies, spectra steepen to form a spectral 'knee'. The location of the proton spectral knee can vary from approx. ten MeV to approx. one GeV, depending on shock conditions, greatly affecting the radiation hazard. Hard spectra are a serious threat to astronauts, placing challenging requirements for shielding, especially on long-duration missions to the moon or Mars.

Reames, Donald V.↗

Galileo Probe Measurements of Thermal and Solar Radiation Fluxes in the Jovian Atmosphere

The Galileo probe net flux radiometer (NFR) measured radiation fluxes in Jupiter's atmosphere from about 0.44 to 14 bars, using five spectral channels to separate solar and thermal components. Onboard calibration results confirm that the NFR responded to radiation approximately as expected. NFR channels also responded to a superimposed thermal perturbation, which can be approximately removed using blind channel measurements and physical constraints. Evidence for the expected NH3 cloud was seen in the spectral character of spin-induced modulations of the direct solar beam signals. These results are consistent with an overlying cloud of small NH3 ice particles (0.5-0.75 microns in radius) of optical depth 1.5-2 at 0.5 microns. Such a cloud would have so little effect on thermal fluxes that NFR thermal channels provide no additional constraints on its properties. However, evidence for heating near 0.45 bar in the NFR thermal channels would seem to require either an additional opacity source beyond this small-particle cloud, implying a heterogeneous-cloud structure to avoid conflicts with solar modulation results, or a change in temperature lapse rate just above the probe measurements. The large thermal flux levels imply water vapor mixing ratios that are only 6% of solar at 10 bars, but possibly increasing with depth, and significantly subsaturated ammonia at pressures less than 3 bars. If deep NH3 mixing ratios at the probe entry site are 3-4 times ground-based inferences, as suggested by probe radio signal attenuation, then only half as much water is needed to match NFR observations. No evidence of a water cloud was seen near the 5-bar level. The 5 microns thermal channel detected the presumed NH4SH cloud base near 1.35 bars. Effects of this cloud were also seen in the solar channel upflux measurements but not in the solar net fluxes, implying that the cloud is a conservative scatterer of sunlight. The minor thermal signature of this cloud is compatible with particle radii near 3 microns, but it cannot rule out smaller particles. Deeper than about 3 bars, solar channels indicate unexpectedly large absorption of sunlight at wavelengths longer than 0.6 microns, which might be due to unaccounted-for absorption by NH3 between 0.65 and 1.5 microns.

Sromovsky, L. A.↗

Mapping by VESGEN of Blood Vessels in the Retinas of ISS Crew Members and Bed Rest Subjects for Increased Understanding of VIIP

Research by NASA has established that significant risks for visual impairment in association with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. Impairments include decreased near visual acuity, posterior globe flattening, choroidal folds, optic disc edema, and cotton wool spots. Much remains to be learned about the etiology of VIIP before effective countermeasures can be developed. Contributions of retinal vascular remodeling to the etiology of VIIP have not yet been investigated, primarily due to the current lack of ophthalmic tools for precisely measuring progressive pathophysiological remodeling of the retinal microvasculature. Although ophthalmic science and clinical practice are now highly sophisticated at detecting indirect, secondary signs of vascular remodeling such as cotton wool spots that arise during the progression of retinal vascular diseases, methods for quantifying direct, primary vascular changes are not yet established. To help develop insightful analysis of retinal vascular remodeling for aerospace medicine, we will map and quantify by our innovative VESsel GENeration Analysis (VESGEN) software the remodeling status of retinal blood vessels in crew members before and after ISS missions, and in healthy human subjects before and after head-down tilt bed rest. For this proof-of-concept study, we hypothesize that pathophysiological remodeling of retinal blood vessels occurs in coordination with microgravity-induced fluid shifts prior to development of visual impairments. VESGEN analysis in previous research supported by the US National Institutes of Health identified surprising new opportunities to regenerate retinal vessels during early-stage progression of the visually impairing, potentially blinding disease, diabetic retinopathy.

ISS Crew↗

Restricted by A Historical Review of Strategies and Organization for Restricted Earth Return of Samples from NASA Planetary Missions

Return of samples from the Moon via the Apollo 11, 12 and 14 missions represented NASA's first attempts into conducting what is now known as Restricted Earth Return. When Apollo returned samples from the moon, there were few of the agencies, legal and organizational structures that exist now. A half a century later, the U.S system has seen changes in legal and organizational structures with the appearance of different agencies and legal requirements. During the Apollo era, U.S. legal and organizational structures, assessed threats to the Earth’s biosphere with a priority towards the risks of effects from extraterrestrial pathogens on humans, though the guiding document, the Baylor Protocol, also considered animal and plant models. This presentation focuses on a review of two main questions: Did the return of samples from the Moon happen at a “sweet spot” in time, where the number of requirements and conservatism was commensurate with the scientific knowns and unknowns? Could the emphasis of risk mitigation on human pathogens during the return of extraterrestrial samples be more about human solipsism, leaving us with a blind spot to sources of pathogens, such as fungi, which could lead to an impact to our biosphere, and we humans, via our food chains and agricultural pathways?

planetary protection↗

The effect of exercise and rest duration on the generation of venous gas bubbles at altitude

BACKGROUND: Decompression, as occurs with aviators and astronauts undergoing high altitude operations or with deep-sea divers returning to surface, can cause gas bubbles to form within the organism. Pressure changes to evoke bubble formation in vivo during depressurization are several orders of magnitude less than those required for gas phase formation in vitro in quiescent liquids. Preformed micronuclei acting as "seeds" have been proposed, dating back to the 1940's. These tissue gas micronuclei have been attributed to a minute gas phase located in hydrophobic cavities, surfactant-stabilized microbubbles, or arising from musculoskeletal activity. The lifetimes of these micronuclei have been presumed to be from a few minutes to several weeks. HYPOTHESIS: The greatest incidence of venous gas emboli (VGE) will be detected by precordial Doppler ultrasound with depressurization immediately following lower extremity exercise, with progressively reduced levels of VGE observed as the interval from exercise to depressurization lengthens. METHODS: In a blinded cross-over design, 20 individuals (15 men, 5 women) at sea level exercised by performing knee-bend squats (150 knee flexes over 10 min, 235-kcal x h(-1)) either at the beginning, middle, or end of a 2-h chair-rest period without an oxygen prebreathe. Seated subjects were then depressurized to 6.2 psia (6,706 m or 22,000 ft altitude equivalent) for 120 min with no exercise performed at altitude. RESULTS: Of the 20 subjects with VGE in the pulmonary artery, 10 demonstrated a greater incidence of bubbles with exercise performed just prior to depressurization, compared with decreasing bubble grades and incidence as the interval of rest increased prior to depressurization. No decompression illness was reported. CONCLUSIONS: There is a significant increase in decompression-induced bubble formation at 6.2 psia when lower extremity exercise is performed just prior to depressurization as compared with longer rest intervals. Analysis indicated that micronuclei half-life is on the order of an hour under these hypobaric conditions.

Controlled Clinical Trial↗

RL-34 ring laser gyro laboratory evaluation for the Deep Space Network antenna application

The overall results of this laboratory evaluation are quite encouraging. The gyro data is in good agreement with the system's overall pointing performance, which is quite close to the technical objectives for the Deep Space Network (DSN) application. The system can be calibrated to the levels required for millidegree levels of pointing performance, and initialization performance is within the required 0.001 degree objective. The blind target acquisition performance is within a factor of two of the 0.0001 degree objective, limited only by a combination of the slow rate (0.5 deg/sec) and the existing production quantization logic (0.38 arc-sec/pulse). Logic circuitry exists to better this performance such that it will better the objective by 50 percent. Representative data with this circuitry has been provided for illustration. Target tracking performance is about twice the one millidegree objective, with several factors contributing. The first factor is the bias stability of the gyros, which is exceptional, but will limit performance to the 0.001 and 0.002 degree range for long tracking periods. The second contributing factor is the accelerometer contributions when the system is elevated. These degrade performance into the 0.003 to 0.004 degree range, which could be improved upon with some additional changes. Finally, we have provided a set of recommendations to improve performance closer to the technical objectives. These recommendations include gyro, electronics, and system configurational changes that form the basis for additional work to achieve the desired performance. In conclusion, we believe that the RL-34 ring laser gyro-based advanced navigation system demonstrated performance consistent with expectations and technical objectives, and it has the potential for even further enhancement for the DSN application.

Source record↗

A Multi-Center Controlled Study of the Acute and Chronic Effects of Cooling Therapy for MS

To determine the acute and chronic effects of cooling therapy on patients with MS using objective functional performance measures and self-assessed measures of fatigue. Cooling demyelinated nerves can reduce conduction block, potentially improving symptoms of MS. Significant acute and chronic effects of cooling have not been demonstrated in a multi-center, controlled, blinded study using objective measures of neurologic function. Patients (N=84) with definite MS, mild to moderate disability (EDSS less than 6.0), and self-reported heat sensitivity were enrolled at 5 study sites. Acute effects of cooling were assessed by randomly assigning subjects to high-dose or low-dose cooling for one hour using an active cooling vest and cap (Life Enhancement Technologies, Santa Clara, CA). Settings were individualized to maintain the cooling garments at 55 F for the high-dose treatment and 70 F for the low-dose treatment. Both patients and examining investigators were blinded to treatment assignments. The MSFC and visual acuity/contrast sensitivity were assessed before and 30 minutes after treatment. The following week, subjects had an identical visit with the alternate cooling treatment. Chronic effects of cooling were assessed by randomly assigning the same subjects to unblinded daily home cooling or observation for 4 weeks. All subjects completed the Rochester Fatigue Diary (RFD) twice weekly and subjective measures of strength, cognition, and energy level daily. At the end of the period, subjects completed the Modified Fatigue Impact Scale (MFIS) and underwent another high-dose cooling session with assessment of the MSFC and vision. After a one-week washout period, subjects crossed over to the alternate 4-week treatment. Oral temperatures were reduced with both acute treatments (0.8 +/- .06 F, high and 0.5 +/- .06 F, low). While mean MSFC did not change significantly during individual cooling sessions, post hoc analysis pooling the 3 high-dose cooling sessions revealed an improvement in MSFC scores (acute phase 0.064 +/- 0.020, p = 0.0013; chronic phase 0.044 +/- 0.021, p = 0.0368) from before to after cooling. The change in MSFC scores during the acute cooling sessions was not related to the extent of change in oral temperatures. Both the RFD score and the MFIS indicate a significantly lower fatigue level during the cooling month compared to observation (RFD, 2.53 +/- 0.83,p = 0.0033; MFIS 7.63 +/- 1.56, p = 0.0001).

Luna, Bernadette↗

Usable Translational Hand Controllers for NASA's Habitability Design Center

This summer I was given the opportunity to work at the Habitability Design Center (HDC). NASA Johnson Space Center's HDC is currently developing Cislunar and Mars spacecraft mockups. I contributed to this effort by designing from scratch low cost, functional translational hand controllers (THCs) that will be used in spacecraft mission simulation in low to medium fidelity exploration spacecraft mockups. This project fell under the category of mechatronics, a combination of mechanical, electrical, and computer engineering. Being an aerospace engineering student, I was out of my comfort zone. And that was a wonderful thing. The autonomy that my mentor, Dr. Robert Howard, allowed me gave me the opportunity to learn by trying, failing, and trying again. This project was not only a professional success for me, but a significant learning experience. I appreciated the freedom that I had to take the time to learn new things for myself rather than blindly follow instructions. I was the sole person working on this project, and was required to work independently to solve the many hardware and software challenges that the project entailed. I researched THCs that have been used on the ISS, the Space Shuttle, and the Orion MPVC and based my design off of these. I worked through many redesigns before finding an optimal configuration of the necessary mechanisms and electrical components for the THC. Once I had a functional hardware design, I dove into the challenge of getting an Arduino Uno, an extremely low cost and easily programmable microcontroller, to behave as a human interface device. The THCs I built needed to be able to integrate to a mission simulation designed by NASA's Graphics and Visualization Lab. This proved to be the most challenging aspect of the project. To accomplish this I learned how to change the firmware of the USB serial converter microcontroller. The process was very complicated as it involved multiple software programs and manual flashing of pins on the Arduino itself. When I successfully achieved the goal I wrote an instructions manual for the process so that the HDC will be able to do this easily in the future for any human interface device they may want to create. I also created a detailed CAD model of my THC design with construction instructions. My THC utilizes three ultrasonic sensors, one for each axis of motion. I wrote a code that stimulates these sensors continuously and feeds back values from each axis ranging from -%100 to %100 of the min/max position in relation to the neutral position of each axis. This was the data that the Graphics and Visualization Lab required to interface with their simulation. I truly enjoyed working in the HDC surrounded by passionate, proactive, and brilliantly creative people. I felt valued and respected as a part of their team. I was given the time and support of my mentor whenever I asked for it. Beyond my positive project experience, I was fortunate enough to be able to take advantage of many of the extra activities that JSC has to offer. I took Russian Phase One during my lunch break every day and can now read Russian and accomplish basic verbal communication. I was heavily involved with the co-tern music video, which led to numerous incredible experiences and friendships. I saw every facility, attended every lecture, and met everyone that I could. I had coffee with Lauri Hansen. I played on an intern volleyball team at the Gilruth. I traveled to Michoud, Stennis, NOLA, and Big Bend National Park. I had the time of my life and I fell in love with JSC. In the next month I will return to Maryland and start my senior year of my undergraduate degree. As I work through it I will remember that all of the studying I do, all of the concentration I give, and all of the sacrifices that I make for school are so that I can work at a place like JSC where I am proud and excited to go into work every day. This internship was an invaluable experience for me, both professionally and personally.

Westbrook, Kimberly↗

Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat

The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation.

NASA Discipline Musculoskeletal↗

The Effects of Chronic Sleep Restriction on Calorie and Macronutrient Intake

Introduction: Chronic sleep restriction (CSR) has been associated with increased calorie intake and increased consumption of fats and carbohydrates, with inconsistent changes in protein. However, the majority of studies have either been observational field studies with no sleep intervention, or laboratory-based studies where food availability may not have reflected participants’ real-world choices. We hypothesized that calorie, fat, and carbohydrate intake would increase during a week of imposed CSR compared to a week of sleep satiation (SS) among individuals living in their home environment. Methods: Twelve healthy participants (6 females) kept a fixed sleep-wake schedule, with a constant waketime, at home for four weeks (actigraphy confirmed compliance). During weeks one and three, participants maintained 9 hours in bed. During weeks two and four, participants were randomly assigned to experimental weeks of 5 and 9 hours of time-in-bed in a crossover design. Participants documented their food consumption during both experimental weeks using a picture-based meal logging application (MealLogger). Intake of calories and macronutrients were classified by two blinded evaluators. Descriptive statistics were calculated in SAS (Cary, NC). Results: Participants averaged 4.43 ± 0.33 (SD) hours of sleep per night during CSR compared to 7.42 ± 0.42 hours during SS. Participants consumed a daily average of 1812 ± 672 kilocalories, 71 ± 31 grams of total fat, 217 ± 69 grams of carbohydrates, and 84 ± 40 grams of protein during CSR, compared to 1682 ± 514 kilocalories, 68 ± 23 grams of total fat, 198 ± 61 grams of carbohydrates, and 77 ± 32 grams of protein during SS. Conclusion: Preliminary descriptive findings suggest that, on average, participants consumed more calories, from an increase in consumption of each macronutrient group, during a week of sleep restriction compared to a week of sleep satiation. Further analysis is needed to determine whether these differences are statistically different and to identify when calories were consumed in each of the experimental conditions.

chronic sleep restriction↗

Dynamic Light-Scattering Probe Used for the Very Early Detection of Cataracts and to Measure Response to Therapy (or Treatment)

Half of all blindness worldwide is due to cataracts, and 34 million Americans over the age of 65 have cataracts. This figure is expected to rise to 70 million by the year 2030. Currently, no medical treatment is available to prevent or halt the progression of a cataract; nor is there any way to reverse a cataract once it has been detected by conventional methods. The only known treatment is surgical removal of the lens. It is estimated that over $5 billion will be spent this year for the treatment of cataract patients in the United States alone. According to Carl Kupfer, M.D., former Director of the National Eye Institute at the National Institutes of Health, "A delay in cataract formation of about 10 years would reduce the prevalence of visually disabling cataracts by about 45 percent." However, this vision remains a dream because of the lack of objective methods that can be used to detect cataracts very early and, hence, can be used for screening potential anticataract drugs. This is about to change. The National Eye Institute and NASA entered into a formal interagency agreement in late 1996 to develop and test a dynamic light-scattering (DLS) device to detect the earliest changes due to cataract formation. The new DLS probe developed by Dr. Ansari at the NASA Glenn Research Center is several orders of magnitude more sensitive than conventional clinical systems. This ultrahigh sensitivity enables the probe to detect the onset of a cataract before it has any effect on vision and allows researchers to test the effectiveness of anticataract drugs in reversing cataracts. This device (see the following illustration) was originally designed to study transport phenomena in microgravity fluid physics experiments onboard the space shuttle orbiters and space station. It will be very useful in testing anticataract drugs to halt or reverse the progression of cataracts during longitudinal clinical trials.

Ansari,Rafat R.↗

By Different Cellular Mechanisms, Lymphatic Vessels Sprout by Endothelial Cell Recruitment Whereas Blood Vessels Grow by Vascular Expansion

The development of effective vascular therapies requires the understanding of all modes of vessel formation contributing to vasculogenesis, angiogenesis (here termed hemangiogenesis) and lymphangiogenesis. We show that lymphangiogenesis proceeds by blind-ended vessel sprouting via recruitment of isolated endothelial progenitor cells to the tips of growing vessels, whereas hemangiogenesis occurs by non-sprouting vessel expansion from the capillary network, during middevelopment in the quail chorioallantoic membrane (CAM). Blood vessels expanded out of capillaries that displayed transient expression of alpha smooth muscle actin (alphaSMA), accompanied by mural recruitment of migratory progenitor cells expressing SMA. Lymphatics and blood vessels were identified by confocal/fluorescence microscopy of vascular endothelial growth factor (VEGF) receptors VEGFR-1 and VEGFR-2, alphaSMA (expressed on CAM blood vessels but not on lymphatics), homeobox transcription factor Prox-1 (specific to CAM lymphatic endothelium), and the quail hematopoetic/vascular marker, QH-1. Expression of VEGFR-1 was highly restricted to blood vessels (primarily capillaries). VEGFR-2 was expressed intensely in isolated hematopoietic cells, lymphatic vessels and moderately in blood vessels. Prox-1 was absent from endothelial progenitor cells prior to lymphatic recruitment. Although vascular endothelial growth factor-165 (VEGF(sub 165)) is a key regulator of numerous cellular processes in hemangiogenesis and vasculogenesis, the role of VEGF(sub 165) in lymphangiogenesis is less clear. Exogenous VEGF(sub 165) increased blood vessel density without changing endogenous modes of vascular/lymphatic vessel formation or marker expression patterns. However, VEGF(sub 165) did increase the frequency of blood vascular anastomoses and strongly induced the antimaturational dissociation of lymphatics from blood vessels, with frequent formation of homogeneous lymphatic networks.

Parsons-Wingerter, Patricia↗

Speech motor control and acute mountain sickness

BACKGROUND: An objective method that accurately quantifies the severity of Acute Mountain Sickness (AMS) symptoms is needed to enable more reliable evaluation of altitude acclimatization and testing of potentially beneficial interventions. HYPOTHESIS: Changes in human articulation, as quantified by timed variations in acoustic waveforms of specific spoken words (voice onset time; VOT), are correlated with the severity of AMS. METHODS: Fifteen volunteers were exposed to a simulated altitude of 4300 m (446 mm Hg) in a hypobaric chamber for 48 h. Speech motor control was determined from digitally recorded and analyzed timing patterns of 30 different monosyllabic words characterized as voiced and unvoiced, and as labial, alveolar, or velar. The Environmental Symptoms Questionnaire (ESQ) was used to assess AMS. RESULTS: Significant AMS symptoms occurred after 4 h, peaked at 16 h, and returned toward baseline after 48 h. Labial VOTs were shorter after 4 and 39 h of exposure; velar VOTs were altered only after 4 h; and there were no changes in alveolar VOTs. The duration of vowel sounds was increased after 4 h of exposure and returned to normal thereafter. Only 1 of 15 subjects did not increase vowel time after 4 h of exposure. The 39-h labial (p = 0.009) and velar (p = 0.037) voiced-unvoiced timed separations consonants and the symptoms of AMS were significantly correlated. CONCLUSIONS: Two objective measures of speech production were affected by exposure to 4300 m altitude and correlated with AMS severity. Alterations in speech production may represent an objective measure of AMS and central vulnerability to hypoxia.

NASA Discipline Space Human Factors↗

Evaluation of Intranasal Scopolamine for the Prevention of Wave Motion Induced Motion Sickness While Maintaining Performance on Operationally Relevant Tasks

Motion sickness represents one of the greatest clinical challenges impacting crew activities during and following g-transitions. Our overall goal is to characterize the effectiveness of motion sickness countermeasures during controlled laboratory experiments using capsule wave motion simulation and during field testing in operational environments. This laboratory study focused on prevention of motion sickness using intranasal scopolamine using a double-blinded repeated measures design in 30 subjects (19M, 11F). Intranasal scopolamine was provided by Defender Pharmaceuticals, Inc. (DPI-386 Nasal Gel, referred to as Inscop) self-administered by a nasal pump (Aptar Pharma) that delivers 0.4 mg dose (0.2 mg / nostril). During each session, subjects were exposed to complex wave motion on a six degree-of-freedom platform that included pitch, roll and heave at provocative stimulus frequencies (0.1-0.25 Hz) while seated in an illuminated cabin deprived of external visual cues. Motion sickness symptoms were compared across treatment and placebo control sessions counterbalanced across subjects and separated by at least one week. The time-to-motion sickness endpoint was based on severe malaise, defined as symptom score of ≥8 points using the Pensacola Diagnostic Index [1]. The bioavailability of scopolamine for each session was estimated from plasma concentrations obtained every 15 min[2]. Side effects during the treatment session were minimal, and performance was not impaired on a test battery including motion perception tracking, tablet-based eye-hand coordination and psychomotor vigilance testing. The plasma concentration remained near-peak levels throughout the 45 min motion sickness testing for most subjects. The percentile ranking on the Motion Sickness Susceptibility Questionnaire [MSSQ, 3]was moderately correlated with the motion sickness time-to-endpoint during the placebo control session (rho = –0.3, p=0.056). Seventeen subjects did not reach an endpoint during their placebo session and were eliminated from subsequent analysis. Another subject was excluded due to insufficient plasma concentration during the treatment session. For the remaining 12 subjects, the change in time-to-motion sickness endpoint between placebo and treatment sessions was moderately correlated with plasma concentration (rho =0.48, p = 0.056), improving on average 4.4 ± 18.4 min, mean ± std with Inscop versus placebo. Our results are consistent with previous findings that intranasal delivery of scopolamine can be effective at reducing motion sickness symptoms with minimal cognitive or sedative side effects. Future work is needed to optimize the delivery of Inscop for rescue (treatment) of symptoms following g-transitions as one of the key advantages of this formulation is self-administration in a suited environment. We will also explore how the combination of Inscop with non-pharmaceutical sensory aids, e.g., vibrotactile feedback of Earth vertical, may further mitigate motion sickness and improve task performance.

S J Wood↗