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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 217 records · Page 12

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↗

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↗

Readying for a Color-Mixed Future Luminous Efficacy on the Horizon

If history repeats itself, lighting 20 years from now will be substantially different than what it is today. Twenty years ago, LEDs were a novelty, not quite ready for use in architectural lighting systems. A little more than 20 years before that, rare-earth tri-phosphor T8 fluorescent lamps were beginning to replace broadband halophosphate T12 fluorescent lamps, which themselves became the predominant source of lumens in the United States around the middle of the last century. At each step in this evolution, new lighting metrics have been developed to address differences in performance, and they in turn guided technology development. For example, in the 1960s, it was CRI and CCT, and more recently it has been LM-79 and TM-30.

Royer, Michael P.↗

Pivotal trial characteristics and types of endpoints used to support Food and Drug Administration rare disease drug approvals between 2013 and 2022

Background/aims Rare disease drug development faces unique challenges, such as genotypic and phenotypic heterogeneity within small patient populations and a lack of established outcome measures for conditions without previously successful drug development programs. These challenges complicate the process of selecting the appropriate trial endpoints and conducting clinical trials in rare diseases. In this descriptive study, we examined novel drug approvals for non-oncologic rare diseases by the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research over the past decade and characterized key regulatory and trial design elements with a focus on the primary efficacy endpoint utilized as the basis of approval. Methods Using the Food and Drug Administration’s Data Analysis Search Host database, we identified novel new drug applications and biologics license applications with orphan drug designation that were approved between 2013 and 2022 for non-oncologic indications. From Food and Drug Administration review documents and other external databases, we examined characteristics of pivotal trials for the included drugs, such as therapeutic area, trial design, and type of primary efficacy endpoints. Differences in trial design elements associated with primary efficacy endpoint type were assessed such as randomization and blinding. Then, we summarized the primary efficacy endpoint types utilized in pivotal trials by therapeutic area, approval pathway, and whether the disease etiology is well defined. Results One hundred and seven drugs that met our inclusion criteria were approved between 2013 and 2022. Assessment of the 107 drug development programs identified 150 pivotal trials that were subsequently analyzed. The pivotal trials were mostly randomized (80%) and blinded (69.3%). Biomarkers (41.1%) and clinical outcomes (42.1%) were commonly utilized as primary efficacy endpoints. Analysis of the use of clinical trial design elements across trials that utilized biomarkers, clinical outcomes, or composite endpoints did not reveal statistically significant differences. The choice of primary efficacy endpoint varied by the drug’s therapeutic area, approval pathway, and whether the indicated disease etiology was well defined. For example, biomarkers were commonly selected as primary efficacy endpoints in hematology drug approvals (70.6%), whereas clinical outcomes were commonly selected in neurology drug approvals (69.6%). Further, if the disease etiology was well defined, biomarkers were more commonly used as primary efficacy endpoints in pivotal trials (44.7%) than if the disease etiology was not well defined (27.3%). Discussion In the past 10 years, numerous novel drugs have been approved to treat non-oncologic rare diseases in various therapeutic areas. To demonstrate their efficacy for regulatory approval, biomarkers and clinical outcomes were commonly utilized as primary efficacy endpoints. Biomarkers were not only frequently used as surrogate efficacy endpoints in accelerated approvals, but also in traditionally approved rare disease drugs. The choice of primary efficacy endpoints varied by therapeutic area, approval pathway, and understanding of disease etiology.

Hong, Kyungwan [Rare Diseases Team, Office of New ↗

A decade of curtailment studies demonstrates a consistent and effective strategy to reduce bat fatalities at wind turbines in North America

Abstract There is a rapid, global push for wind energy installation. However, large numbers of bats are killed by turbines each year, raising concerns about the impacts of wind energy expansion on bat populations. Preventing turbine blades from spinning at low wind speeds, referred to as curtailment, is a method to reduce bat fatalities, but drawing consistent inference across studies has been challenging. We compiled publicly available studies that evaluated curtailment at six wind energy facilities in North America across 10 years. We used meta‐regression of 29 implemented treatments to determine fatality reduction efficacy as well as sources of variation influencing efficacy. We also estimated species‐specific fatality reduction for three species that comprise most fatalities in North America: hoary bat ( Lasiurus cinereus ), eastern red bat ( Lasiurus borealis ) and silver‐haired bat ( Lasionycteris noctivagans ). We found that curtailment reduced total bat fatalities by 33% with every 1.0 ms −1 increase in curtailment wind speed. Estimates of the efficacy for the three target species were similar (hoary bats: 28% per ms −1 , 95% CI: 0.4%–48%, eastern red bats: 32% per ms −1 , 95% CI: 13%–47% and silver‐haired bats: 32% per ms −1 , 95% CI: 3%–53%). Across multiple facilities and years, a 5.0 ms −1 cut‐in speed was estimated to reduce total bat fatalities by an average of 62% (95% CI: 54%–69%). Mortality reductions at individual facilities in any given year were estimated to fall between 33%–79% (95% prediction interval). Inter‐annual differences rather than inter‐site or turbine characteristics accounted for most of the variation in efficacy rates. Species‐specific average mortality reduction at 5.0 ms −1 curtailment wind speed was 48% (95% CI: 24%–64%) for hoary bats, 61% (95% CI: 42%–74%) for eastern red bats and 52% (95% CI: 30%–66%) for silver‐haired bats. Practical implication . curtailment reduced bat mortality at wind turbines in this North American study. Efficacy increased proportionally as curtailment speed is raised, and patterns and rates of efficacy were similar across species. This indicates that curtailment is an effective strategy to reduce bat fatalities at wind energy facilities, but exploration of further refinements could both minimize bat mortality and maximize energy production.

17 WIND ENERGY↗