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At least 253 records · Page 14
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Linking Pharmacogenomic Information on Drug Safety and Efficacy with Ethnic Minority Populations

Numerous prescription drugs’ labeling contains pharmacogenomic (PGx) information to aid health providers and patients in the safe and effective use of drugs. However, clinical studies for such PGx biomarkers and related drug doses are generally not conducted in diverse ethnic populations. Thus, it is urgently important to incorporate PGx information with genetic characteristics of racial and ethnic minority populations and utilize it to promote minority health. In this project a bioinformatics approach was developed to enhance the collection of PGx information related to ethnic minorities to pave the way toward understanding the population-wide utility of PGx information. To address this challenge, we first gathered PGx information from drug labels. Second, we extracted data on the allele frequency information of genetic variants in ethnic minority groups from public resources. Then, we collected published research articles on PGx biomarkers and related drugs for reference. Finally, the data were integrated and formatted to build a new PGx database containing information on known drugs and biomarkers for ethnic minority groups. This database provides scientific information needed to evaluate available PGx information to enhance drug dose selection and drug safety for ethnic minority populations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Efficacy of a portable, moderate-resolution, fast-scanning differential mobility analyzer for ambient aerosol size distribution measurements

Abstract. Ambient aerosol size distributions obtained with a compact scanning mobility analyzer, the “Spider” differential mobility analyzer (DMA), are compared to those obtained with a conventional mobility analyzer, with specific attention to the effect of mobility resolution on the measured size distribution parameters. The Spider is a 12 cm diameter radial differential mobility analyzer that spans the 10–500 nm size range with 30 s mobility scans. It achieves its compact size by operating at a nominal mobility resolution R=3 (sheath flow = 0.9 L min−1; aerosol flow = 0.3 L min−1) in place of the higher ratio of sheath flow to aerosol flow commonly used. The question addressed here is whether the lower resolution is sufficient to capture key characteristics of ambient aerosol size distributions. The Spider, operated at R=3 with 30 s up- and downscans, was co-located with a TSI 3081 long-column mobility analyzer, operated at R=10 with a 360 s sampling duty cycle. Ambient aerosol data were collected over 26 consecutive days of continuous operation, in Pasadena, CA. Over the 17–500 nm size range, the two instruments exhibit excellent correlation in the total particle number concentrations and geometric mean diameters, with regression slopes of 1.13 and 1.00, respectively. Our results suggest that particle sizing at a lower resolution than typically employed may be sufficient to obtain key properties of ambient size distributions, at least for these two moments of the size distribution. Moreover, it enables better counting statistics, as the wider transfer function for a given aerosol flow rate results in a higher counting rate.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRS1987

Effects of microgravity on tissue perfusion and the efficacy of astronaut denitrogenation for EVA

A potentially flight-applicable, breath-by-breath method for measuring N2 elimination from human subjects breathing 100 percent O2 for 2-3 hr periods has been developed. The present report describes this development with particular emphasis on required methodological accuracy and its achievement in view of certain properties of mass spectrometer performance. A method for the breath-by-breath analysis of errors in measured N2 elimination profiles is also described.

Gerth, Wayne A.↗
NASA NTRS1992

The efficacy of periodic +Gz exposure in the prevention of bedrest induced orthostatic intolerance

What is the most efficient dosage of periodic exposure to positive 1G(z) during microgravity to maintain a functional upright position after returning to a positive 1G(z) environment? The answer has implications for the type of countermeasures astronauts will be required to perform during long term space flight. Methods: Nine males were subjected to four different positive 1G exposure protocols plus a control protocol ('zero G(z)') during four days of continuous bedrest. The four positive 1G(z) exposures consisted of periodic standing or walking, each for a total period of two or four hours. Each subject was returned for bedrest on five different occasions over a period of approximately one year to obtain data on each of the nine subjects across all four positive 1G(z) treatments and the control. A 30 min tilt test was used to measure orthostatic response during pre and post bedrest. Results: In terms of survival rate (percentage of subjects who did not faint after 30 sec of tilt), four hours of intermittent standing was the only protocol that maintained a rate comparable to pre bedrest levels (87.5 percent). Although the other three positive 1G(z) protocols performed better than the 'zero G(z) control (22.2 percent), only the four hour standing returned post bedrest survival rates to pre bedrest levels. Conclusions: The results will need to be evaluated with regards to a variety of other physiological systems which are known to decondition during microgravitry.

Ludwig, D. A.↗
NASA NTRS2000

Assessment of Countermeasure Efficacy for Long-Term Space Missions

One of the main functions of the upcoming International Space Station (ISS) will be to provide a venue for testing proposed countermeasures for their ability to protect humans from the debilitating effects of longterm space flight. However, several limiting factors preclude an evaluation process similar to that used in clinical trials which traditionally are implemented with large sample sizes of subjects, including control groups, and with blind or double-blind application of treatments according to factorial or other balanced experimental designs. In particular, only very limited numbers of human subjects will be available for actual field testing in the ISS With no more than 125 subjects planned to fly on all ISS missions over 10 years, it is not possible to test extensive combinations of some 15-20 proposed countermeasures. Furthermore because of safety concerns and operational considerations, it is unlikely that anything other than the current best guess at the most effective countermeasure package will ever be used on ISS. In particular, control or placebos will not be allowed. In view of these limitations, historical data and groundbased or animal studies will have to be used to compensate for small sample sizes and lack of controls in the field. As a result, statistical analysis methodology will have to be developed which allows for the integration of these disparate data types into a meaningful evaluation process. The process must be sequential, providing objective rules for deciding through time whether to reject or modify an ineffective countermeasure, or whether to certify one as effective. Additional output should include performance characteristics for all relevant physiological systems, including uncertainty analyses and estimates of accept/reject decision error rates.

Feiveson, Alan H.↗
NASA NTRS2001

The Efficacy of Psychophysiological Measures for Implementing Adaptive Technology

Adaptive automation refers to technology that can change its mode of operation dynamically. Further, both the technology and the operator can initiate changes in the level or mode of automation. The present paper reviews research on adaptive technology. It is divided into three primary sections. In the first section, issues surrounding the development and implementation of adaptive automation are presented. Because physiological-based measures show much promise for implementing adaptive automation, the second section is devoted to examining candidate indices. In the final section, those techniques that show the greatest promise for adaptive automation as well as issues that still need to be resolved are discussed.

Scerbo, Mark W.↗
NASA NTRS1994

Head-Down Suspension Alters Stress-Responsiveness and Feedback Efficacy of 9a-Fludrocortisone in Rats

9a-Fludrocortisone (9aFF) has been used to decrease orthostatic hypotension in astronauts whorl they return to earth after space flight. An earth-based model for weightlessness in space is head-down posture in man and rats. In these studies male rats were suspended head-down or not for 7 days and treated 14 and 2 hours prior to ether stress in the AM with 9aFF (20 micrograms i.u.) at -14 and -2 h or at -2 h with steroid and at -14 h with oil; controls were treated 2x with oil. Rats were decapitated 10 min after ether and ACTH and corticosterone (B) were measured. Both ACTH and B responses were greater in suspended than control rats under all three steroid conditions, and the percentage inhibition of ACTH by 9aFF was similar. Basal activity in the HPA over the 7 d suspension period was probably not elevated since adrenal and thymus weights did not differ in the ambulatory and head down groups. We conclude that headdown suspension facilitates acute stress-induced activity in the HPA axis, but that HPA axis sensitivity to corticosteroid feedback does not change.

Horsley, C. J.↗
NASA NTRS1997

Efficacy of Code Optimization on Cache-based Processors

The current common wisdom in the U.S. is that the powerful, cost-effective supercomputers of tomorrow will be based on commodity (RISC) micro-processors with cache memories. Already, most distributed systems in the world use such hardware as building blocks. This shift away from vector supercomputers and towards cache-based systems has brought about a change in programming paradigm, even when ignoring issues of parallelism. Vector machines require inner-loop independence and regular, non-pathological memory strides (usually this means: non-power-of-two strides) to allow efficient vectorization of array operations. Cache-based systems require spatial and temporal locality of data, so that data once read from main memory and stored in high-speed cache memory is used optimally before being written back to main memory. This means that the most cache-friendly array operations are those that feature zero or unit stride, so that each unit of data read from main memory (a cache line) contains information for the next iteration in the loop. Moreover, loops ought to be 'fat', meaning that as many operations as possible are performed on cache data-provided instruction caches do not overflow and enough registers are available. If unit stride is not possible, for example because of some data dependency, then care must be taken to avoid pathological strides, just ads on vector computers. For cache-based systems the issues are more complex, due to the effects of associativity and of non-unit block (cache line) size. But there is more to the story. Most modern micro-processors are superscalar, which means that they can issue several (arithmetic) instructions per clock cycle, provided that there are enough independent instructions in the loop body. This is another argument for providing fat loop bodies. With these restrictions, it appears fairly straightforward to produce code that will run efficiently on any cache-based system. It can be argued that although some of the important computational algorithms employed at NASA Ames require different programming styles on vector machines and cache-based machines, respectively, neither architecture class appeared to be favored by particular algorithms in principle. Practice tells us that the situation is more complicated. This report presents observations and some analysis of performance tuning for cache-based systems. We point out several counterintuitive results that serve as a cautionary reminder that memory accesses are not the only factors that determine performance, and that within the class of cache-based systems, significant differences exist.

VanderWijngaart, Rob F.↗
NASA NTRS1997

Efficacy of Code Optimization on Cache-Based Processors

In this paper a number of techniques for improving the cache performance of a representative piece of numerical software is presented. Target machines are popular processors from several vendors: MIPS R5000 (SGI Indy), MIPS R8000 (SGI PowerChallenge), MIPS R10000 (SGI Origin), DEC Alpha EV4 + EV5 (Cray T3D & T3E), IBM RS6000 (SP Wide-node), Intel PentiumPro (Ames' Whitney), Sun UltraSparc (NERSC's NOW). The optimizations all attempt to increase the locality of memory accesses. But they meet with rather varied and often counterintuitive success on the different computing platforms. We conclude that it may be genuinely impossible to obtain portable performance on the current generation of cache-based machines. At the least, it appears that the performance of modern commodity processors cannot be described with parameters defining the cache alone.

VanderWijngaart, Rob F.↗
NASA NTRS1998

On the Efficacy of Source Code Optimizations for Cache-Based Systems

Obtaining high performance without machine-specific tuning is an important goal of scientific application programmers. Since most scientific processing is done on commodity microprocessors with hierarchical memory systems, this goal of "portable performance" can be achieved if a common set of optimization principles is effective for all such systems. It is widely believed, or at least hoped, that portable performance can be realized. The rule of thumb for optimization on hierarchical memory systems is to maximize temporal and spatial locality of memory references by reusing data and minimizing memory access stride. We investigate the effects of a number of optimizations on the performance of three related kernels taken from a computational fluid dynamics application. Timing the kernels on a range of processors, we observe an inconsistent and often counterintuitive impact of the optimizations on performance. In particular, code variations that have a positive impact on one architecture can have a negative impact on another, and variations expected to be unimportant can produce large effects. Moreover, we find that cache miss rates - as reported by a cache simulation tool, and confirmed by hardware counters - only partially explain the results. By contrast, the compiler-generated assembly code provides more insight by revealing the importance of processor-specific instructions and of compiler maturity, both of which strongly, and sometimes unexpectedly, influence performance. We conclude that it is difficult to obtain performance portability on modern cache-based computers, and comment on the implications of this result.

VanderWijngaart, Rob F.↗
NASA NTRS2002

The Efficacy of Using Synthetic Vision Terrain-Textured Images to Improve Pilot Situation Awareness

The General Aviation Element of the Aviation Safety Program's Synthetic Vision Systems (SVS) Project is developing technology to eliminate low visibility induced General Aviation (GA) accidents. SVS displays present computer generated 3-dimensional imagery of the surrounding terrain on the Primary Flight Display (PFD) to greatly enhance pilot's situation awareness (SA), reducing or eliminating Controlled Flight into Terrain, as well as Low-Visibility Loss of Control accidents. SVS-conducted research is facilitating development of display concepts that provide the pilot with an unobstructed view of the outside terrain, regardless of weather conditions and time of day. A critical component of SVS displays is the appropriate presentation of terrain to the pilot. An experimental study is being conducted at NASA Langley Research Center (LaRC) to explore and quantify the relationship between the realism of the terrain presentation and resulting enhancements of pilot SA and performance. Composed of complementary simulation and flight test efforts, Terrain Portrayal for Head-Down Displays (TP-HDD) experiments will help researchers evaluate critical terrain portrayal concepts. The experimental effort is to provide data to enable design trades that optimize SVS applications, as well as develop requirements and recommendations to facilitate the certification process. In this part of the experiment a fixed based flight simulator was equipped with various types of Head Down flight displays, ranging from conventional round dials (typical of most GA aircraft) to glass cockpit style PFD's. The variations of the PFD included an assortment of texturing and Digital Elevation Model (DEM) resolution combinations. A test matrix of 10 terrain display configurations (in addition to the baseline displays) were evaluated by 27 pilots of various backgrounds and experience levels. Qualitative (questionnaires) and quantitative (pilot performance and physiological) data were collected during the experimental runs. This paper focuses on the experimental set-up and final physiological results of the TP-HDD simulation experiment. The physiological measures of skin temperature, heart rate, and muscle response, show a decreased engagement (while using the synthetic vision displays as compared to the baseline conventional display) of the sympathetic and somatic nervous system responses which, in turn, indicates a reduced level of mental workload. This decreased level of workload is expected to enable improvement in the pilot's situation and terrain awareness.

Uenking, Michael D.↗