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Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using Ultrasound and Braslet-M Occlusion Cuffs

The objective of this joint U.S. - Russian project was the development and validation of an in-flight methodology to assess a number of cardiac and vascular parameters associated with circulating volume and its manipulation in long-duration space flight. Responses to modified Valsalva and Mueller maneuvers were measured by cardiac and vascular ultrasound (US) before, during, and after temporary volume reduction by means of Braslet-M thigh occlusion cuffs (Russia). Materials and Methods: The study protocol was conducted in 14 sessions on 9 ISS crewmembers, with an average exposure to microgravity of 122 days. Baseline cardiovascular measurements were taken by echocardiography in multiple modes (including tissue Doppler of both ventricles) and femoral and jugular vein imaging on the International Space Station (ISS). The Braslet devices were then applied and measurements were repeated after >10 minutes. The cuffs were then released and the hemodynamic recovery process was monitored. Modified Valsalva and Mueller maneuvers were used throughout the protocol. All US data were acquired by the HDI-5000 ultrasound system aboard the ISS (ATL/Philips, USA) during remotely guided sessions. The study protocol, including the use of Braslet-M for this purpose, was approved by the ISS Human Research Multilateral Review Board (HRMRB). Results: The effects of fluid sequestration on a number of echocardiographic and vascular parameters were readily detectable by in-flight US, as were responses to respiratory maneuvers. The overall volume status assessment methodology appears to be valid and practical, with a decrease in left heart lateral E (tissue Doppler) as one of the most reliable measures. Increase in the femoral vein cross-sectional areas was consistently observed with Braslet application. Other significant differences and trends within the extensive cardiovascular data were also observed. (Decreased - RV and LV preload indices, Cardiac Output, LV E all maneuvers, LV Stroke Volume). Conclusions: This Study: 1) Addressed specific aspects of operational space medicine and space physiology, including assessment of circulating volume disturbances 2) Expanded the applications of diagnostic ultrasound imaging and Doppler techniques in microgravity. 3) Used respiratory maneuvers against the background of acute circulating volume manipulations which appear to enhance our ability to noninvasively detect volume-dependency in a number of cardiac and vascular parameters. 4) Determined that Tei index is not clinically changed therefore contractility not altered in the face of reduced preload. 5) Determined that increased Femoral Vein Area indicating blood being sequestered in lower extremities correlates with reduced preload and cardiac output. 6) That Braslet may be the only feasible means of acutely treating high pressure pulmonary edema in reduced gravity environments.

Hamilton, Douglas↗

In Situ Guided Wave Structural Health Monitoring System

Aircraft engine rotating equipment operates at high temperatures and stresses. Noninvasive inspection of microcracks in those components poses a challenge for nondestructive evaluation. A low-cost, low-profile, high-temperature ultrasonic guided wave sensor was developed that detects cracks in situ. The transducer design provides nondestructive evaluation of structures and materials. A key feature of the sensor is that it withstands high temperatures and excites strong surface wave energy to inspect surface and subsurface cracks. The sol-gel bismuth titanate-based surface acoustic wave (SAW) sensor can generate efficient SAWs for crack inspection. The sensor is very thin (submillimeter) and can generate surface waves up to 540 C. Finite element analysis of the SAW transducer design was performed to predict the sensor behavior, and experimental studies confirmed the results. The sensor can be implemented on structures of various shapes. With a spray-coating process, the sensor can be applied to the surface of large curvatures. It has minimal effect on airflow or rotating equipment imbalance, and provides good sensitivity.

Zhao, George↗

NASA Tech Briefs, January 2001

The topics include: 1) A "Model" of Interactive Engineering; 2) Feature Section: Communications Technology; 3) lnReview; 4) Application Briefs; 5) Submillimeter-Wave Image Sensor; 6) Ultrasonic/Sonic Drill/Corers With Integrated Sensors; 7) Normally Closed, Piezoelectrically Actuated Microvalve; 8) Magnetostrictively Actuated Valves for Cryosurgical Probes; 9) Remote Sensing of Electric Fields in Clouds; 10) Wireless-Communication Headset Subsystem To Enhance Signaling; 11) Power Amplifier With 9 to 13 dB of Gain From 65 to 146 GHz; 12) Humidity Interlock for Protecting a Cooled Laser Crystal; 13) A Lightweight Ambulatory Physiological Monitoring System; 14) Improvements in a Lightning-Measuring Instrument; 15) Broad-Band, Noninvasive Radio-Frequency Current Probe; 16) Web-Based Technology Distributes Lean Models; 17) Software Guides Aeroelastic-Systems Design; and 18) Postprocessing Software for Micromechanics Analysis Code. A Photonics West 2001 Preview Tech Brief supplement to this January 2001 issue is also included.

Source record↗

On-Orbit Evaluation of a New Treadmill Harness for Improved Crewmember Comfort and Load Distribution

The current design of the International Space Station (ISS) Treadmill Harness has been reported to cause pain and discomfort to crewmembers during exercise. The Harness Station Development Test Objective (SDTO) provided participating crewmembers (n = 6) with a new harness design, the "Glenn Harness," to evaluate for comfort and loading as compared to the current Treadmill Harness. A novel suite of load-sensing instrumentation was developed to noninvasively measure load distribution and provided a first-ever quantification of actual dynamic loads during treadmill exercise. In addition, crew debriefs provided feedback on harness preference and overall impressions. Conclusions: Post-flight analysis in returned Glenn Harnesses (n = 3) showed minimal wear and tear. Four of the six subjects found the Glenn Harness to be more comfortable in this on-orbit, side-by-side comparison as measured by the crew comfort questionnaire and crew debriefs. Specific areas for improvement have been identified, and forward recommendations will be provided to the Human Research Program. The protocol developed for the SDTO provided valuable insight into crew comfort issues, design improvements, and loading preferences for exercise harnessing, which lays the groundwork for better harnessing systems and training protocols.

Perusek, G. P.↗

Imaging Modalities Relevant to Intracranial Pressure Assessment in Astronauts

Learning Objectives of this slide presentation are: 1: To review the morphological changes in orbit structures caused by elevated Intracranial Pressure (ICP), and their imaging representation. 2: To learn about the similarities and differences between MRI and sonographic imaging of the eye and orbit. 3: To learn about the role of MRI and sonography in the noninvasive assessment of intracranial pressure in aerospace medicine, and the added benefits from their combined interpretation.

Sargsyan, Ashot E.↗

Pharmacokinetics of Intranasal Scopolamine Gel Formation During Antiorthostatic Bedrest - A Microgravity Analog

Space Motion sickness (SMS) is an age old problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is the most frequently used drug for the treatment of motion sickness (MS) which is currently available in transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability thus allowing precise and reduced dosing options in addition to offering rescue and treatment options. As such, an intranasal gel dosage formulation of scopolamine (INSCOP) was developed and Pharmacokinetics (PK) and bioavailability were determined under IND guidelines. The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostatic bedrest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 and 0.4 mg doses of INSCOP during AMB and ABR in a four-way crossover design. Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose. Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration versus time curve (AUC) during ABR after the 0.4 mg dose. This difference in AUC and Cls at the higher but not the lower dose during ABR may suggest that ABR may affect metabolism and/or clearance at higher doses of INSCOP. These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

Lakshmi, Putcha↗

Generating Control Commands From Gestures Sensed by EMG

An effort is under way to develop noninvasive neuro-electric interfaces through which human operators could control systems as diverse as simple mechanical devices, computers, aircraft, and even spacecraft. The basic idea is to use electrodes on the surface of the skin to acquire electromyographic (EMG) signals associated with gestures, digitize and process the EMG signals to recognize the gestures, and generate digital commands to perform the actions signified by the gestures. In an experimental prototype of such an interface, the EMG signals associated with hand gestures are acquired by use of several pairs of electrodes mounted in sleeves on a subject s forearm (see figure). The EMG signals are sampled and digitized. The resulting time-series data are fed as input to pattern-recognition software that has been trained to distinguish gestures from a given gesture set. The software implements, among other things, hidden Markov models, which are used to recognize the gestures as they are being performed in real time. Thus far, two experiments have been performed on the prototype interface to demonstrate feasibility: an experiment in synthesizing the output of a joystick and an experiment in synthesizing the output of a computer or typewriter keyboard. In the joystick experiment, the EMG signals were processed into joystick commands for a realistic flight simulator for an airplane. The acting pilot reached out into the air, grabbed an imaginary joystick, and pretended to manipulate the joystick to achieve left and right banks and up and down pitches of the simulated airplane. In the keyboard experiment, the subject pretended to type on a numerical keypad, and the EMG signals were processed into keystrokes. The results of the experiments demonstrate the basic feasibility of this method while indicating the need for further research to reduce the incidence of errors (including confusion among gestures). Topics that must be addressed include the numbers and arrangements of electrodes needed to acquire sufficient data; refinements in the acquisition, filtering, and digitization of EMG signals; and methods of training the pattern- recognition software. The joystick and keyboard simulations were chosen for the initial experiments because they are familiar to many computer users. It is anticipated that, ultimately, interfaces would utilize EMG signals associated with movements more nearly natural than those associated with joysticks or keyboards. Future versions of the pattern-recognition software are planned to be capable of adapting to the preferences and day-today variations in EMG outputs of individual users; this capability for adaptation would also make it possible to select gestures that, to a given user, feel the most nearly natural for generating control signals for a given task (provided that there are enough properly positioned electrodes to acquire the EMG signals from the muscles involved in the gestures).

Wheeler, Kevin R.↗

A Vision of Quantitative Imaging Technology for Validation of Advanced Flight Technologies

Flight-testing is traditionally an expensive but critical element in the development and ultimate validation and certification of technologies destined for future operational capabilities. Measurements obtained in relevant flight environments also provide unique opportunities to observe flow phenomenon that are often beyond the capabilities of ground testing facilities and computational tools to simulate or duplicate. However, the challenges of minimizing vehicle weight and internal complexity as well as instrumentation bandwidth limitations often restrict the ability to make high-density, in-situ measurements with discrete sensors. Remote imaging offers a potential opportunity to noninvasively obtain such flight data in a complementary fashion. The NASA Hypersonic Thermodynamic Infrared Measurements Project has demonstrated such a capability to obtain calibrated thermal imagery on a hypersonic vehicle in flight. Through the application of existing and accessible technologies, the acreage surface temperature of the Shuttle lower surface was measured during reentry. Future hypersonic cruise vehicles, launcher configurations and reentry vehicles will, however, challenge current remote imaging capability. As NASA embarks on the design and deployment of a new Space Launch System architecture for access beyond earth orbit (and the commercial sector focused on low earth orbit), an opportunity exists to implement an imagery system and its supporting infrastructure that provides sufficient flexibility to incorporate changing technology to address the future needs of the flight test community. A long term vision is offered that supports the application of advanced multi-waveband sensing technology to aid in the development of future aerospace systems and critical technologies to enable highly responsive vehicle operations across the aerospace continuum, spanning launch, reusable space access and global reach. Motivations for development of an Agency level imagery-based measurement capability to support cross cutting applications that span the Agency mission directorates as well as meeting potential needs of the commercial sector and national interests of the Intelligence, Surveillance and Reconnaissance community are explored. A recommendation is made for an assessment study to baseline current imaging technology including the identification of future mission requirements. Development of requirements fostered by the applications suggested in this paper would be used to identify technology gaps and direct roadmapping for implementation of an affordable and sustainable next generation sensor/platform system.

Horvath, Thomas J.↗

Measuring Humidity in Sealed Glass Encasements

A technique has been devised for measuring the relative humidity levels in the protective helium/water vapor atmosphere in which the Declaration of Independence, the United States Constitution, and the Bill of Rights are encased behind glass panels on display at the National Archives in Washington, DC. The technique is noninvasive: it does not involve penetrating the encasements (thereby risking contamination or damage to the priceless documents) to acquire samples of the atmosphere. The technique could also be applied to similar glass encasements used to protect and display important documents and other precious objects in museums. The basic principle of the technique is straightforward: An encasement is maintained at its normal display or operating temperature (e.g., room temperature) while a portion of its glass front panel is chilled (see Figure 1) until condensed water droplets become visible on the inside of the panel. The relative humidity of the enclosed atmosphere can then be determined as a known function of the dew point, the temperature below which the droplets condense. Notwithstanding the straightforwardness of the basic principle, careful attention to detail is necessary to enable accurate determination of the dew point. In the initial application, the affected portion of the glass panel was cooled by contact with an aluminum plate that was cooled by a thermoelectric module, the exhaust heat of which was dissipated by a heat sink cooled by a fan. A thermocouple was used to measure the interior temperature of the aluminum plate, and six other thermocouples were used to measure the temperatures at six locations on the cooled outer surface of the glass panel (see Figure 2). Thermal grease was applied to the aluminum plate and the thermocouples to ensure close thermal contact. Power was supplied to the thermoelectric module in small increments, based on previous laboratory tests. A small flashlight and a magnifying glass were used to look for water droplets condensing on the inner surface of the glass. The temperature readings of the thermocouples were taken during cool-down and upon observing condensation. In determining the dew point, it was necessary to make a correction for the differences between the temperatures measured on the chilled outer surface of the glass and the temperature of the inner surface, where the condensation took place. The correction was derived from a laboratory test on a measurement setup that was nearly identical, except that the dew location on the inner surface was also instrumented with a thermocouple. The test showed that the temperature at the dew location on the inner surface of the glass panel was 0.9 C above the temperature determined from the measurements on the chilled outer surface of the panel.

West, James W.↗

Pharmacokinetics of Intranasal Scopolamine Gel Formulation During Antiorthostatic Bed Rest, a Microgravity Analog

Statement of Purpose, Innovation or Hypothesis: Space Motion sickness (SMS) is a long-standing problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is frequently used for the treatment of motion sickness (MS), and is available as transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability, thus allowing precise and reduced dosing in addition to offering rescue and treatment options. An intranasal gel dosage formulation of scopolamine (INSCOP) was developed and pharmacokinetics (PK) and bioavailability were determined in clinical trials with human subjects under IND guidelines.Description of Methods and Materials: The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostaticbed rest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 mg and 0.4 mg doses of INSCOP during AMB and ABR in a 4-way crossover design.Data and Results: Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose, Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration-versus-time curve (AUC) during ABR after the 0.4 mg dose.Interpretation, Conclusion or Significance: The difference in AUC and Cls at the higher (0.4 mg) but not the lower dose (0.2 mg) during ABR suggests that ABR may affect metabolism and/or clearance of INSCOP at higher doses . These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

Singh, Rajendra P.↗

Multisensor Instrument for Real-Time Biological Monitoring

The figure schematically depicts an instrumentation system, called a fiber optic-based integration system (FOBIS), that is undergoing development to enable real-time monitoring of fluid cell cultures, bioprocess flows, and the like. The FOBIS design combines a micro flow cytometer (MFC), a microphotometer (MP), and a fluorescence-spectrum- or binding-force-measuring micro-sensor (MS) in a single instrument that is capable of measuring multiple biological parameters simultaneously or sequentially. The fiber-optic-based integration system is so named because the MFC, the MP, and the MS are integrated into a single optical system that is coupled to light sources and photometric equipment via optical fibers. The optical coupling components also include a wavelength-division multiplexer and diffractive optical elements. The FOBIS includes a laserdiode- and fiber-optic-based optical trapping subsystem (optical tweezers ) with microphotometric and micro-sensing capabilities for noninvasive confinement and optical measurement of relevant parameters of a single cell or other particle. Some of the measurement techniques implemented together by the FOBIS have long been used separately to obtain basic understanding of the optical properties of individual cells and other organisms, the optical properties of populations of organisms, and the interrelationships among these properties, physiology of the organisms, and physical processes that govern the media that surround the organisms. For example, flow cytometry yields information on numerical concentrations, cross-sectional areas, and types of cells or other particles. Micro-sensing can be used to measure pH and concentrations of oxygen, carbon dioxide, glucose, metabolites, calcium, and antigens in a cell-culture fluid, thereby providing feedback that can be helpful in improving control over a bioprocess. Microphotometry (including measurements of scattering and fluorescence) can yield further information about optically trapped individual particles. In addition to the multifunctionality not previously available in a single biological monitoring system, the FOBIS offers advantages of low mass, sensitivity, accuracy, portability, low cost, compactness (the overall dimensions of the fully developed FOBIS sensor head are expected to be less than 1 by 1 by 2 cm), and immunity to electromagnetic interference at suboptical frequencies. FOBIS could be useful in a variety of laboratory and field settings in such diverse endeavors as medical, veterinary, and general biological research; medical and veterinary diagnosis monitoring of industrial bioprocesses; and analysis of biological contaminants in air, water, and food.

Zhang, Sean (Zhanxiang)↗

Ambient-Light-Canceling Camera Using Subtraction of Frames

The ambient-light-canceling camera (ALCC) is a proposed near-infrared electronic camera that would utilize a combination of (1) synchronized illumination during alternate frame periods and (2) subtraction of readouts from consecutive frames to obtain images without a background component of ambient light. The ALCC is intended especially for use in tracking the motion of an eye by the pupil center corneal reflection (PCCR) method. Eye tracking by the PCCR method has shown potential for application in human-computer interaction for people with and without disabilities, and for noninvasive monitoring, detection, and even diagnosis of physiological and neurological deficiencies. In the PCCR method, an eye is illuminated by near-infrared light from a lightemitting diode (LED). Some of the infrared light is reflected from the surface of the cornea. Some of the infrared light enters the eye through the pupil and is reflected from back of the eye out through the pupil a phenomenon commonly observed as the red-eye effect in flash photography. An electronic camera is oriented to image the user's eye. The output of the camera is digitized and processed by algorithms that locate the two reflections. Then from the locations of the centers of the two reflections, the direction of gaze is computed. As described thus far, the PCCR method is susceptible to errors caused by reflections of ambient light. Although a near-infrared band-pass optical filter can be used to discriminate against ambient light, some sources of ambient light have enough in-band power to compete with the LED signal. The mode of operation of the ALCC would complement or supplant spectral filtering by providing more nearly complete cancellation of the effect of ambient light. In the operation of the ALCC, a near-infrared LED would be pulsed on during one camera frame period and off during the next frame period. Thus, the scene would be illuminated by both the LED (signal) light and the ambient (background) light during one frame period, and would be illuminated with only ambient (background) light during the next frame period. The camera output would be digitized and sent to a computer, wherein the pixel values of the background-only frame would be subtracted from the pixel values of the signal-plus-background frame to obtain signal-only pixel values (see figure). To prevent artifacts of motion from entering the images, it would be necessary to acquire image data at a rate greater than the standard video rate of 30 frames per second. For this purpose, the ALCC would exploit a novel control technique developed at NASA s Jet Propulsion Laboratory for advanced charge-coupled-device (CCD) cameras. This technique provides for readout from a subwindow [region of interest (ROI)] within the image frame. Because the desired reflections from the eye would typically occupy a small fraction of the area within the image frame, the ROI capability would make it possible to acquire and subtract pixel values at rates of several hundred frames per second considerably greater than the standard video rate and sufficient to both (1) suppress motion artifacts and (2) track the motion of the eye between consecutive subtractive frame pairs.

Morookian, John Michael↗

Optoelectronic Instrument Monitors pH in a Culture Medium

An optoelectronic instrument monitors the pH of an aqueous cell-culture medium in a perfused rotating-wall-vessel bioreactor. The instrument is designed to satisfy the following requirements: It should be able to measure the pH of the medium continuously with an accuracy of 0.1 in the range from 6.5 to 7.5. It should be noninvasive. Any material in contact with the culture medium should be sterilizable as well as nontoxic to the cells to be grown in the medium. The biofilm that inevitably grows on any surface in contact with the medium should not affect the accuracy of the pH measurement. It should be possible to obtain accurate measurements after only one calibration performed prior to a bioreactor cell run. The instrument should be small and lightweight. The instrument includes a quartz cuvette through which the culture medium flows as it is circulated through the bioreactor. The cuvette is sandwiched between light source on one side and a photodetector on the other side. The light source comprises a red and a green light-emitting diode (LED) that are repeatedly flashed in alternation with a cycle time of 5 s. The responses of the photodiode to the green and red LEDs are processed electronically to obtain a quantity proportional to the ratio between the amounts of green and red light transmitted through the medium.

Anderson, Melody M.↗

Online Oxide Contamination Measurement and Purification Demonstration

Liquid metal sodium-potassium (NaK) has advantageous thermodynamic properties indicating its use as a fission reactor coolant for a surface (lunar, martian) power system. A major area of concern for fission reactor cooling systems is system corrosion due to oxygen contaminants at the high operating temperatures experienced. A small-scale, approximately 4-L capacity, simulated fission reactor cooling system employing NaK as a coolant was fabricated and tested with the goal of demonstrating a noninvasive oxygen detection and purification system. In order to generate prototypical conditions in the simulated cooling system, several system components were designed, fabricated, and tested. These major components were a fully-sealed, magnetically-coupled mechanical NaK pump, a graphite element heated reservoir, a plugging indicator system, and a cold trap. All system components were successfully demonstrated at a maximum system flow rate of approximately 150 cc/s at temperatures up to 550 C. Coolant purification was accomplished using a cold trap before and after plugging operations which showed a relative reduction in oxygen content.

Bradley, D. E.↗

Rapid Detection of the Varicella Zoster Virus in Saliva

Varicella zoster virus (VZV) causes chicken pox on first exposure (usually in children), and reactivates from latency causing shingles (usually in adults). Shingles can be extremely painful, causing nerve damage, organ damage, and blindness in some cases. The virus can be life-threatening in immune-compromised individuals. The virus is very difficult to culture for diagnosis, requiring a week or longer. This invention is a rapid test for VZV from a saliva sample and can be performed in a doctor s office. The kit is small, compact, and lightweight. Detec tion is sensitive, specific, and noninvasive (no needles); only a saliva sample is required. The test provides results in minutes. The entire test is performed in a closed system, with no exposure to infectious materials. The components are made mostly of inexpensive plastic injection molded parts, many of which can be purchased off the shelf and merely assembled. All biological waste is contained for fast, efficient disposal. This innovation was made possible because of discovery of a NASA scientists flight experiment showing the presence of VZV in saliva during high stress periods and disease. This finding enables clinicians to quickly screen patients for VZV and treat the ones that show positive results with antiviral medicines. This promotes a rapid recovery, easing of pain and symptoms, and reduces chances of complications from zoster. Screening of high-risk patients could be incorporated as part of a regular physical exam. These patients include the elderly, pregnant women, and immune-compromised individuals. In these patients, VZV can be a life-threatening disease. In both high- and low-risk patients, early detection and treatment with antiviral drugs can dramatically decrease or even eliminate the clinical manifestation of disease.

Pierson, Duane L.↗

Anomaly Detection Techniques with Real Test Data from a Spinning Turbine Engine-Like Rotor

Online detection techniques to monitor the health of rotating engine components are becoming increasingly attractive to aircraft engine manufacturers in order to increase safety of operation and lower maintenance costs. Health monitoring remains a challenge to easily implement, especially in the presence of scattered loading conditions, crack size, component geometry, and materials properties. The current trend, however, is to utilize noninvasive types of health monitoring or nondestructive techniques to detect hidden flaws and mini-cracks before any catastrophic event occurs. These techniques go further to evaluate material discontinuities and other anomalies that have grown to the level of critical defects that can lead to failure. Generally, health monitoring is highly dependent on sensor systems capable of performing in various engine environmental conditions and able to transmit a signal upon a predetermined crack length, while acting in a neutral form upon the overall performance of the engine system.

Abdul-Aziz, Ali↗

Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

Putcha, Lakshmi↗

Functional Near-Infrared Spectroscopy Signals Measure Neuronal Activity in the Cortex

Functional near infrared spectroscopy (fNIRS) is an emerging optical neuroimaging technology that indirectly measures neuronal activity in the cortex via neurovascular coupling. It quantifies hemoglobin concentration ([Hb]) and thus measures the same hemodynamic response as functional magnetic resonance imaging (fMRI), but is portable, non-confining, relatively inexpensive, and is appropriate for long-duration monitoring and use at the bedside. Like fMRI, it is noninvasive and safe for repeated measurements. Patterns of [Hb] changes are used to classify cognitive state. Thus, fNIRS technology offers much potential for application in operational contexts. For instance, the use of fNIRS to detect the mental state of commercial aircraft operators in near real time could allow intelligent flight decks of the future to optimally support human performance in the interest of safety by responding to hazardous mental states of the operator. However, many opportunities remain for improving robustness and reliability. It is desirable to reduce the impact of motion and poor optical coupling of probes to the skin. Such artifacts degrade signal quality and thus cognitive state classification accuracy. Field application calls for further development of algorithms and filters for the automation of bad channel detection and dynamic artifact removal. This work introduces a novel adaptive filter method for automated real-time fNIRS signal quality detection and improvement. The output signal (after filtering) will have had contributions from motion and poor coupling reduced or removed, thus leaving a signal more indicative of changes due to hemodynamic brain activations of interest. Cognitive state classifications based on these signals reflect brain activity more reliably. The filter has been tested successfully with both synthetic and real human subject data, and requires no auxiliary measurement. This method could be implemented as a real-time filtering option or bad channel rejection feature of software used with frequency domain fNIRS instruments for signal acquisition and processing. Use of this method could improve the reliability of any operational or real-world application of fNIRS in which motion is an inherent part of the functional task of interest. Other optical diagnostic techniques (e.g., for NIR medical diagnosis) also may benefit from the reduction of probe motion artifact during any use in which motion avoidance would be impractical or limit usability.

Harrivel, Angela↗