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NASA NTRS2004

Reliability Quantification of the Flexure: A Critical Stirling Convertor Component

Uncertainties in the manufacturing, fabrication process, material behavior, loads, and boundary conditions results in the variation of the stresses and strains induced in the flexures and its fatigue life. Past experience and the test data at material coupon levels revealed a significant amount of scatter of the fatigue life. Owing to these facts, the design of the flexure, using conventional approaches based on safety factor or traditional reliability based on similar equipment considerations does not provide a direct measure of reliability. Additionally, it may not be feasible to run actual long term fatigue tests due to cost and time constraints. Therefore it is difficult to ascertain material fatigue strength limit. The objective of the paper is to present a methodology and quantified results of numerical simulation for the reliability of flexures used in the Stirling convertor for their structural performance. The proposed approach is based on application of finite element analysis method in combination with the random fatigue limit model, which includes uncertainties in material fatigue life. Additionally, sensitivity of fatigue life reliability to the design variables is quantified and its use to develop guidelines to improve design, manufacturing, quality control and inspection design process is described.

Shah, Ashwin R.↗

NASA NTRS2004

Gear Performance Improved by Coating

Gears, bearings, and other mechanical elements transmit loads through contacting surfaces. Even if properly designed, manufactured, installed, and maintained, gears and bearings will eventually fail because of the fatigue of the working surfaces. Economical means for extending the fatigue lives of gears and bearings are highly desired, and coatings offer the opportunity to engineer surfaces to extend the fatigue lives of mechanical components. A tungsten-containing diamondlike-carbon coating exhibiting high hardness, low friction, and good toughness was evaluated for application to spur gears. Fatigue testing was done at the NASA Glenn Research Center on both uncoated and coated spur gears. The results showed that the coating extended the surface fatigue lives of the gears by a factor of about 5 relative to the uncoated gears. For the experiments, a lot of spur test gears made from AISI 9310 gear steel were case-carburized and ground to aerospace specifications. The geometries of the 28-tooth, 8-pitch gears were verified as meeting American Gear Manufacturing Association (AGMA) quality class 12. One-half of the gears were randomly selected for coating. The method of coating was selected to achieve desired adherence, toughness, hardness, and low-friction characteristics. First the gears to be coated were prepared by blasting (vapor honing) with Al2O3 particles and cleaning. Then, the gears were provided with a thin adhesion layer of elemental chromium followed by magnetron sputtering of the outer coating consisting of carbon (70 at.%), hydrogen (15 at.%), tungsten (12 at.%), and nickel (3 at.%) (atomic percent at the surface). In total, the coating thickness was about 2.5 to 3 microns. As compared with the steel substrate, the coated surface was harder by a factor of about 2 and had a smaller elastic modulus. All gears were tested using a 5-centistoke synthetic oil, a 10,000-rpm rotation speed, and a hertzian contact stress of at least 1.7 GPa (250 ksi). Tests were run until either surface fatigue occurred or 300 million stress cycles were completed. Tests were run using either a pair of uncoated gears or a pair of coated gears (coated gears mated with uncoated gears were not evaluated). The fatigue test results, shown on Weibull coordinates in the graph, demonstrate that the coating provided substantially longer fatigue lives even though some of the coated gears endured larger stresses. The increase in fatigue life was a factor of about 5 and the statistical confidence for the improvement is high (greater than 99 percent). Examination of the tested gears revealed substantial reductions of total wear for coated gears in comparison to uncoated gears. The coated gear surface topography changed with running, with localized areas of the tooth surface becoming smoother with running. Theories explaining how coatings can extend gear fatigue lives are research topics for coating, tribology, and fatigue specialists. This work was done as a partnership between NASA, the U.S. Army Research Laboratory, United Technologies Research Corporation, and Sikorsky Aircraft.

Krantz, Timothy L.↗

NASA NTRS2007

PillCam(TradeMark), a Noninvasive Endoscopic Device for the Measurement of Gastrointestinal Motility Changes

Introduction: Bioavailability and effectiveness of drugs given by mouth are governed in part by gastrointestinal (GI) motility and function. Microgravity has been shown to decrease GI motility as indicated by a 3 fold increase in gastrointestinal transit time (GITT). The PillCam(TradeMark), an endoscopic camera embedded in a capsule, is a novel noninvasive and unobtrusive device that is used for the diagnosis of GI pathology. The purpose of this study is to evaluate the usefulness of PillCam(TradeMark) as an alternative to the Lactulose Breath Hydrogen Test (LBHT) for estimating GI motility. The sensitivity and applicability of this device for detection and estimation of the effect of promethazine, a deterrent, and caffeine, a prokinetic, on GI motility were also examined. Method: In this semi-randomized cross-over design study, six male and six female subjects were administered the following 4 treatments: PillCam(TradeMark) alone, PillCam(TradeMark)+Lactulose (10g), PillCam(TradeMark)+caffeine (200mg), and PillCam(TradeMark)+Promethazine (50mg). Results: GITT ranged between 1:24 and 7:52 hr:min. Lactulose did not alter GITT. A significant increase in GITT was noticed after administration of PMZ when compared to values from PillCam(TradeMark) treatment alone or PillCam(TradeMark)+Lactulose treatment. No difference in GITT after caffeine treatment was noticed. While there were no gender related differences in GITT after administration of PillCam(TradeMark) or with lactulose, a significant difference (p<.05) between genders was observed after promethazine administration with mean GITT higher in males (5:50 hr:min) than females (4:15 hr:min). Conclusion: The PillCam(TradeMark) capsule is applicable for the determination of GITT using time stamped GI images. It can be successfully used for the assessment of drug induced changes in GI motility and therefore, may be applicable for microgravity and analog environment studies on GI motility and function.

Vaksman, Zahman↗

NASA NTRS2008

Dual-polarized feed antenna apparatus and method of use

An antenna apparatus and method for the interception of randomly polarized electromagnetic waves utilizing a dual polarized antenna which is excited through a cross-slot aperture using two well-isolated orthogonal feeds.

Sarehraz, Mohammad↗

NASA NTRS2009

Dual-polarized feed antenna apparatus and method of use

Sarehraz, Mohammed↗

NASA NTRS2014

High Intensity Exercise Countermeasures does not Prevent Orthostatic Intolerance Following Prolonged Bed Rest

Approximately 20% of Space Shuttle astronauts became presyncopal during operational stand and 80deg head‐up tilt tests, and the prevalence of orthostatic intolerance increases after longer missions. Greater than 60% of the US astronauts participating in Mir and early International Space Station missions experienced presyncope during post‐flight tilt tests, perhaps related to limitations of the exercise hardware that prevented high intensity exercise training until later ISS missions. The objective of this study was to determine whether an intense resistive and aerobic exercise countermeasure program designed to prevent cardiovascular and musculoskeletal deconditioning during 70 d of bed rest (BR), a space flight analog, would protect against post‐BR orthostatic intolerance. METHODS Twenty‐six subjects were randomly assigned to one of three groups: non‐exercise controls (n=11) or one of two exercise groups (ExA, n=8; ExB, n=7). Both ExA and ExB groups performed the same resistive and aerobic exercise countermeasures during BR, but one exercise group received testosterone supplementation while the other received a placebo during BR in a double‐blinded fashion. On 3 d/wk, subjects performed lower body resistive exercise and 30 min of continuous aerobic exercise (≥75% max heart rate). On the other 3 d/wk, subjects performed only highintensity, interval‐style aerobic exercise. Orthostatic intolerance was assessed using a 15‐min 80 head‐up tilt test performed 2 d (BR‐2) before and on the last day of BR (BR70). Plasma volume was measured using carbon monoxide rebreathing on BR‐3 and before rising on the first recovery day (BR+0). The code for the exercise groups has not been broken, and results are reported here without group identification. RESULTS Only one subject became presyncopal during tilt testing on BR‐2, but 7 of 11 (63%) controls, 3 of 8 (38%) ExA, and 4 of 7 (57%) ExB subjects were presyncopal on BR70. Survival analysis of post‐BR tilt tests revealed no differences (p=0.77) between groups. Plasma volume (absolute or relative to body mass index) decreased (p<0.001) from pre to post‐BR, with no differences between groups. CONCLUSIONS These preliminary results corroborate previous reports that the performance of a vigorous exercise countermeasure protocol during BR, even with testosterone supplementation, does not protect against orthostatic intolerance or plasma volume loss. Preventing post‐BR orthostatic intolerance may require additional countermeasures, such as orthostatic stress during BR or end‐of‐BR fluid infusion.

Platts, Steven H.↗

NASA NTRS2022

Mars 2020 Perseverance Rover SHERLOC Instrument Isolation System

The NASA Jet Propulsion Laboratory (JPL) successfully landed the Mars 2020 Perseverance Rover at Jezero Crater on the Martian surface. Perseverance’s main mission objective is to cache Martian rock and regolith samples in hermetically sealed tubes to be brought back to Earth by future missions. To achieve this goal the rover is equipped with a 2-meter-long Robotic Arm (RA) which manipulates the Turret to interact with the surface. The Turret is comprised of science instruments and tools that enable surface sampling and science. The backbone of the Turret hardware is the Rotary Percussive Coring Drill. The science instruments, which are directly mounted to the structural housing of this drill, must be able to withstand not only the launch and entry, descent and landing (EDL) loads of the vehicle but also the dynamic percussive environment, induced by the drill throughout surface operations. This paper discusses the technical hardware design, development and testing of a vibration isolation system to protect the Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) Instrument from these dynamic environments. The hardware design aspect of this problem was limited by both size and mass constraints. The Turret is tightly configured and the physical space in which hardware can reside is restricted due to multiple axes of surface interaction points. Another driving requirement is the extreme range of thermal non-operational environment from -135C to +90C. This, in addition to SHERLOC being a heavier instrument than previously integrated on a turret, made the use of isolation systems employed on previous rover missions problematic. The final design incorporates custom wire mesh springs preloaded within titanium hexapod struts equipped with flexure ends. Custom versions of commercially available wire mesh springs were designed and tested. These custom springs differed in dimension, density and stiffness from the off the shelf options. The newly designed springs went through various stages of flight acceptance testing. Detailed physics-based modeling to understand what loads the isolation system would experience was used to define the test conditions for the springs and entire isolation subsystem. The testing program developed around this was extensive to fully characterize the isolation performance over cleanliness levels, temperature and life. Another major aspect of this work was developing a method of replicating the drill’s percussive environment for performance and life testing of Turret mounted hardware. Attaching the instrument to an operating drill for testing was not a viable option. A method of using a Highly Accelerated Life Test (HALT) table was developed and applied across the project as the most representative and tunable option to physically simulate this new environment. This method, along with launch environment random vibration testing, was used to build an entire dynamic qualification and flight hardware test program. The results of the design, modeling, testing and analysis of the SHERLOC Isolation System is described throughout the following paper.

Krafchak, Todd↗

NASA NTRS2023

Probabilistic Forecasting of Ground Magnetic Perturbation Spikes at Mid-Latitude Stations

The prediction of large fluctuations in the ground magnetic field (dB/dt) is essential for preventing damage from Geomagnetically Induced Currents. Directly forecasting these fluctuations has proven difficult, but accurately determining the risk of extreme events can allow for the worst of the damage to be prevented. Here we trained Convolutional Neural Network models for eight mid-latitude magnetometers to predict the probability that dB/dt will exceed the 99th percentile threshold 30–60 min in the future. Two model frameworks were compared, a model trained using solar wind data from the Advanced Composition Explorer (ACE) satellite, and another model trained on both ACE and SuperMAG ground magnetometer data. The models were compared to examine if the addition of current ground magnetometer data significantly improved the forecasts of dB/dt in the future prediction window. A bootstrapping method was employed using a random split of the training and validation data to provide a measure of uncertainty in model predictions. The models were evaluated on the ground truth data during eight geomagnetic storms and a suite of evaluation metrics are presented. The models were also compared to a persistence model to ensure that the model using both datasets did not over-rely on dB/dt values in making its predictions. Overall, we find that the models using both the solar wind and ground magnetometer data had better metric scores than the solar wind only and persistence models, and was able to capture more spatially localized variations in the dB/dt threshold crossings.

Michael Coughlan↗

NASA NTRSDate not supplied

Imbalanced Multi-layer Cloud Classification with Advanced Baseline Imager (ABI) and CloudSat/CALIPSO Data

Clouds at different altitudes play different roles in Earth’s climate. Comprehensive understanding of overlapping clouds is important for climate and weather prediction. The East Pacific region is where El Ni˜no and La Ni˜na originate and where multi-layer clouds frequently occur. The overlap of clouds at different altitudes in this region increases the classification complexity for cloud-based climatological studies. Unlike prior work in cloud layer classification that assumes single layer or two-layer of clouds, in this work, we consider multi-layer cloud classification with 8 cloud-level classes (clear-sky, high, middle, low, high+middle, high+low, middle+low, high+middle+low). We develop and analyze machine learning models on features extracted from satellite images from the East Pacific regions collected by GOES Advanced Baseline Imager (ABI). These are used to classify CloudSat/CALIPSO observed multi-layer clouds. Due to the imbalanced nature of the data, we investigate the adoption of conventional resampling methods, as well as deep learning methods with data augmentation. In our experiments, we utilize the random forest classifier and Multilayer perceptron classifier with data augmentation methods to reduce the class imbalance during training. With these approaches, we achieve a classification accuracy of 83.6% without exploiting any ancillary information.

machine learning↗

NASA NTRS1974

Random vibrations of linear viscoelastic beams with lumped masses

A method is presented of determining the mean square transversal deflection of an isotropic and homogeneous linear viscoelastic beam having a certain number of lengthwise distributed lumped masses. It is assumed that the beam is acted upon by a stationary random process uniformly distributed along the beam. The method is useful in vibration level control by means of additional lumped masses.

Dinca, F.↗

DOE OSTI2015

Self-consistent Kohn-Sham method based on the adiabatic-connection fluctuation-dissipation theorem and the exact-exchange kernel

A self-consistent Kohn-Sham method based on the adiabatic-connection fluctuation-dissipation (ACFD) theorem, employing the frequency-dependent exact exchange kernel f{sub x} is presented. The resulting SC-exact-exchange-only (EXX)-ACFD method leads to even more accurate correlation potentials than those obtained within the direct random phase approximation (dRPA). In contrast to dRPA methods, not only the Coulomb kernel but also the exact exchange kernel f{sub x} is taken into account in the EXX-ACFD correlation which results in a method that, unlike dRPA methods, is free of self-correlations, i.e., a method that treats exactly all one-electron systems, like, e.g., the hydrogen atom. The self-consistent evaluation of EXX-ACFD total energies improves the accuracy compared to EXX-ACFD total energies evaluated non-self-consistently with EXX or dRPA orbitals and eigenvalues. Reaction energies of a set of small molecules, for which highly accurate experimental reference data are available, are calculated and compared to quantum chemistry methods like Møller-Plesset perturbation theory of second order (MP2) or coupled cluster methods [CCSD, coupled cluster singles, doubles, and perturbative triples (CCSD(T))]. Moreover, we compare our methods to other ACFD variants like dRPA combined with perturbative corrections such as the second order screened exchange corrections or a renormalized singles correction. Similarly, the performance of our EXX-ACFD methods is investigated for the non-covalently bonded dimers of the S22 reference set and for potential energy curves of noble gas, water, and benzene dimers. The computational effort of the SC-EXX-ACFD method exhibits the same scaling of N{sup 5} with respect to the system size N as the non-self-consistent evaluation of only the EXX-ACFD correlation energy; however, the prefactor increases significantly. Reaction energies from the SC-EXX-ACFD method deviate quite little from EXX-ACFD energies obtained non-self-consistently with dRPA orbitals and eigenvalues, and the deviation reduces even further if the Coulomb kernel is scaled by a factor of 0.75 in the dRPA to reduce self-correlations in the dRPA correlation potential. For larger systems, such a non-self-consistent EXX-ACFD method is a competitive alternative to high-level wave-function-based methods, yielding higher accuracy than MP2 and CCSD methods while exhibiting a better scaling of the computational effort than CCSD or CCSD(T) methods. Moreover, EXX-ACFD methods were shown to be applicable in situation characterized by static correlation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2015

A stochastic model and Monte Carlo algorithm for fluctuation-induced H{sub 2} formation on the surface of interstellar dust grains

A stochastic algorithm for simulation of fluctuation-induced kinetics of H{sub 2} formation on grain surfaces is suggested as a generalization of the technique developed in our recent studies [1] where this method was developed to describe the annihilation of spatially separate electrons and holes in a disordered semiconductor. The stochastic model is based on the spatially inhomogeneous, nonlinear integro-differential Smoluchowski equations with random source term. In this paper we derive the general system of Smoluchowski type equations for the formation of H{sub 2} from two hydrogen atoms on the surface of interstellar dust grains with physisorption and chemisorption sites. We focus in this study on the spatial distribution, and numerically investigate the segregation in the case of a source with a continuous generation in time and randomly distributed in space. The stochastic particle method presented is based on a probabilistic interpretation of the underlying process as a stochastic Markov process of interacting particle system in discrete but randomly progressed time instances. The segregation is analyzed through the correlation analysis of the vector random field of concentrations which appears to be isotropic in space and stationary in time.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2014

Photometric redshift analysis in the Dark Energy Survey Science Verification data

In this study, we present results from a study of the photometric redshift performance of the Dark Energy Survey (DES), using the early data from a Science Verification period of observations in late 2012 and early 2013 that provided science-quality images for almost 200 sq. deg. at the nominal depth of the survey. We assess the photometric redshift (photo-z) performance using about 15 000 galaxies with spectroscopic redshifts available from other surveys. These galaxies are used, in different configurations, as a calibration sample, and photo-z's are obtained and studied using most of the existing photo-z codes. A weighting method in a multidimensional colour–magnitude space is applied to the spectroscopic sample in order to evaluate the photo-z performance with sets that mimic the full DES photometric sample, which is on average significantly deeper than the calibration sample due to the limited depth of spectroscopic surveys. In addition, empirical photo-z methods using, for instance, artificial neural networks or random forests, yield the best performance in the tests, achieving core photo-z resolutions σ68 ~ 0.08. Moreover, the results from most of the codes, including template-fitting methods, comfortably meet the DES requirements on photo-z performance, therefore, providing an excellent precedent for future DES data sets.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

DOE OSTI2023

Efficient QAOA Optimization using Directed Restarts and Graph Lookup

Variational Quantum Algorithms (VQA) aim to enhance the capabilities of Noisy Intermediate-Scale Quantum (NISQ) devices. These algorithms utilize parameterized circuits and classical optimizers to iteratively execute circuits with varying parameters. However, VQA faces computational overheads due to repeated iterations and random restarts. Prior work suggests using basic sub-graphs to transfer parameters for the input graph, reducing optimizer overheads but limiting applicability to structured regular graphs. In real-world applications, random irregular graphs are common, and existing methods are not scalable or practical for such graphs. This paper presents a framework that aims to improve random irregular graphs in VQA. The framework uses graph similarity and important features like total edge counts, average edge counts, and variance. It follows an iterative process to choose basis sub-graphs from a small database and adjust parameters accordingly. Classical optimizers then utilize these parameters to determine when to restart and perform gradient descent. This approach increases the chances of reaching global maximum points.

Wang, Meng↗

DOE OSTI2024

Improved Subseasonal Forecasting of Extreme Polar Vortices Using Machine Learning

Our research was focused on forecasting the position and shape of the winter stratospheric polar vortex at a subseasonal timescale of 15 days in advance. To achieve this, we employed both statistical and neural network machine learning techniques. The analysis was performed on 42 winter seasons of reanalysis data provided by NASA giving us a total of 6,342 days of data. The state of the polar vortex for determined by using geometric moments to calculate the centroid latitude and the aspect ratio of an ellipse fit onto the vortex. Timeseries for thirty additional precursors were calculated to help improve the predictive capabilities of the algorithm. Feature importance of these precursors was performed using random forest to measure the predictive importance and the ideal number of precursors. Then, using the precursors identified as important, various statistical methods were tested for predictive accuracy with random forest and nearest neighbor performing the best. An echo state network, a type of recurrent neural network that features sparsely connected hidden layer and a reduced number of trainable parameters that allows for rapid training and testing, was also implemented for the forecasting problem. Hyperparameter tuning was performed for each methods using a subset of the training data. The algorithms were trained and tuned on the first 41 years of data, then tested for accuracy on the final year. In general, the centroid latitude of the polar vortex proved easier to predict than the aspect ratio across all algorithms. Random forest outperformed other statistical forecasting algorithms overall but struggled to predict extreme values. Forecasting from echo state network suggested a strong predictive capability past 15 days, but further work is required to fully realize the potential of recurrent neural network approaches.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2012

ACCELERATION OF VERY SMALL DUST GRAINS DUE TO RANDOM CHARGE FLUCTUATIONS

We study the acceleration of very small dust grains including polycyclic aromatic hydrocarbons arising from electrostatic interactions of dust grains that have charge fluctuating randomly in time. Random charge fluctuations of very small grains due to discrete charging events (i.e., sticking collisions with electrons and ions in plasma, and emission of photoelectrons by UV photons) are simulated using the Monte Carlo (MC) method. The motion of dust grains in randomly fluctuating electric fields induced by surrounding charged grains is studied using MC simulations. We identify the acceleration induced by random charge fluctuations as a dominant acceleration mechanism for very small grains in the diffuse interstellar medium (ISM). We find that this acceleration mechanism is efficient for environments with a low degree of ionization (i.e., large Debye length), where charge fluctuations are slow but have a large amplitude. The implications of the present acceleration mechanism for grain coagulation and shattering in the diffuse ISM and dark clouds are also discussed.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2011

A new class of accelerated kinetic Monte Carlo algorithms

Kinetic ( aka dynamic) Monte Carlo (KMC) is a powerful method for numerical simulations of time dependent evolution applied in a wide range of contexts including biology, chemistry, physics, nuclear sciences, financial engineering, etc. Generally, in a KMC the time evolution takes place one event at a time, where the sequence of events and the time intervals between them are selected (or sampled) using random numbers. While details of the method implementation vary depending on the model and context, there exist certain common issues that limit KMC applicability in almost all applications. Among such is the notorious 'flicker problem' where the same states of the systems are repeatedly visited but otherwise no essential evolution is observed. In its simplest form the flicker problem arises when two states are connected to each other by transitions whose rates far exceed the rates of all other transitions out of the same two states. In such cases, the model will endlessly hop between the two states otherwise producing no meaningful evolution. In most situation of practical interest, the trapping cluster includes more than two states making the flicker somewhat more difficult to detect and to deal with. Several methods have been proposed to overcome or mitigate the flicker problem, exactly or approximately. Of the exact methods, the one proposed by Novotny is perhaps most relevant to our research. Novotny formulates the problem of escaping from a trapping cluster as a Markov system with absorbing states. Given an initial state inside the cluster, it is in principle possible to solve the Master Equation for the time dependent probabilities to find the walker in a given state (transient or absorbing) of the cluster at any time in the future. Novotny then proceeds to demonstrate implementation of his general method to trapping clusters containing the initial state plus one or two transient states and all of their absorbing states. Similar methods have been subsequently proposed in [refs] but applied in a different context. The most serious deficiency of the earlier methods is that size of the trapping cluster size is fixed and often too small to bring substantial simulation speedup. Furthermore, the overhead associated with solving for the probability distribution on the trapping cluster sometimes makes such simulations less efficient than the standard KMC. Here we report on a general and exact accelerated kinetic Monte Carlo algorithm generally applicable to arbitrary Markov models1. Two different implementations are attempted both based on incremental expansion of trapping sub-set of Markov states: (1) numerical solution of the Master Equation with absorbing states and (2) incremental graph reduction followed by randomization. Of the two implementations, the 2nd one performs better allowing, for the first time, to overcome trapping basins spanning several million Markov states. The new method is used for simulations of anomalous diffusion on a 2D substrate and of the kinetics of diffusive 1st order phase transformations in binary alloys. Depending on temperature and (alloy) super-saturation conditions, speedups of 3 to 7 orders of magnitude are demonstrated, with no compromise of simulation accuracy.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2019

Effects of Alcohol Administered with Flibanserin in Healthy Premenopausal Women: A Randomized, Double-Blind, Single-Dose Crossover Study

Abstract Introduction Flibanserin is approved in the United States and Canada for the treatment of hypoactive sexual desire disorder in premenopausal women. Aim The purpose of this trial was to evaluate the safety of concomitant administration of flibanserin with alcohol. Methods In this single-center, randomized, double-blind, single-dose, crossover study, participants were randomly assigned to 1 of 12 sequences to receive each of 7 treatments: flibanserin 100 mg or placebo with ethanol 0.2 g/kg, 0.4 g/kg, or 0.6 g/kg, or flibanserin 100 mg only. Treatments were administered using a worst-case approach that included morning dosing and consumption of alcohol within 10 minutes. Main Outcome Measure The primary end point was the proportion of participants who experienced dizziness, syncope, or hypotension. Safety end points included orthostatic vital signs. Results The study included 96 premenopausal women (mean age 31 ± 8 years). The incidence of dizziness for ethanol + flibanserin was 39.8% for ethanol 0.6 g/kg, 34.1% for 0.4 g/kg, and 27.4% for 0.2 g/kg compared with 31.1% for flibanserin without ethanol. Based on the available vital signs data, there was no effect of ethanol concentration on orthostatic blood pressure, vertigo, or hypotension; no instances of syncope were observed. The overall incidence of adverse events (AEs) was similar when flibanserin was administered alone (96.7%) or with ethanol (90.5–97.6%). Clinical Implications Consumption of the tested amounts of alcohol (0.2–0.6 g/kg) does not have an additive effect on the AE profile of flibanserin 100 mg in healthy premenopausal women. Strengths & Limitations Strengths include the study population (premenopausal women, as indicated for flibanserin) and range of ethanol doses. Limitations include the morning dosing of study medication, which is inconsistent with the bedtime dosing recommended for flibanserin, and the method of handling missing vital sign measurements. Conclusion Co-administration of flibanserin 100 mg with varying doses of ethanol resulted in few AEs of special interest, with no notable alcohol dose response. However, a significantly greater percentage of participants administered flibanserin with 0.6 g/kg and 0.4 g/kg of alcohol were characterized as “Participants in Whom Standing Blood Pressure Was Not Obtained” compared with participants administered flibanserin alone.

Simon, James A.↗