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At least 793 records · Page 44

Combining Machine Learning and Comparative Effectiveness Methodology to Study Primary Care Pharmacotherapy Pathways for Veterans With Depression

Our objective is to demonstrate an innovative method combining machine learning with comparative effectiveness research techniques and to investigate a hitherto unstudied question about the effectiveness of common prescribing patterns. For Operation Enduring Freedom/Operation Iraqi Freedom veterans with major depressive disorder, we generate pharmacotherapy pathways (of antidepressants) using process mining and machine learning. We select the medication episodes that were started at subtherapeutic doses by the first assigned primary care physician and observe the paths that those medication episodes follow. Using 2-stage least squares, we test the effectiveness of starting at a low dose and staying low for longer versus ramping up fast while balancing observable and unobservable characteristics of patients and providers through instrumental variables. We leverage predetermined provider practice patterns as instruments. We collected outpatient pharmacy data for selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, patient and provider characteristics (as control variables), and the instruments for our cohort. All data were extracted for the period between 2006 and 2020. There is a statistically significant positive effect (0.68, 95% CI 0.11–1.25) of “ramping up fast” on engagement in care. When we examine the effect of “ramping up slow”, we see an insignificant negative impact on engagement in care (−0.82, 95% CI −1.89 to 0.25). As expected, the probability of drop-out also seems to have a negative effect on engagement in care (−0.39, 95% CI −0.94 to 0.17). We further validate these results by testing with medication possession ratios calculated periodically as an alternative engagement in care metric. Our findings contradict the “Start low, go slow” adage, indicating that ramping up the dose of an antidepressant faster has a significantly positive effect on engagement in care for our population.

60 APPLIED LIFE SCIENCES↗

Weight control and restraint of laboratory rats

The use of restrained and confined rats in some procedures used in combustion toxicology introduces the problems of obtaining rats of the appropriate size for the apparatus, and of identifying any artifacts resulting from the use of restraint alone. Feeding studies indicate that controlled feeding of fast-growing strains such as the Sprague-Dawley can hold rat size essentially constant for significant periods of time. The undesirable aspects are the need to cage the animals individually, with resultant psychological as well as metabolic effects. Restraint studies of slow-growing strains such as the Fischer 344 indicate that denying access to food and water for periods of several hours at a time interrupts normal gain only temporarily.

Hilado, C. J.↗

Toward Hall MHD Power Generation and Drag Augmentation Using a Coaxial-Electrode Configuration During Hypersonic Entry

Planetary EDL requires that a spacecraft must reduce its relative velocity from multiple km/s to zero for safe landing. The entry phase requires slowing down through an intense hypersonic flight regime (Mach 25 to Mach 5). Magnetohydrodynamics (MHD) is a next-generation concept with a wide untapped set of technologies that can expand planetary exploration capabilities and create more robust entry vehicles by utilizing in-situ resources, increasing control authority, and reducing heat flux. There is therefore a need for an experimentally validated simulation tool for MHD technologies in hypersonic entry.

MHD drag↗

A Plasma Aerocapture and Entry System for Manned Missions and Planetary Deep Space Orbiters

A rapid mission to Mars requires a large change in vehicle velocity upon arrival to establish a stable orbit. This demand is even greater for a Neptune science, requiring many kilometers per second of V. It is clear from past mission studies that a manned Mars mission and deep space planetary orbiters require aerobraking and aerocapture which use aerodynamic drag forces to slow the spacecraft. Aerocapture would enable long term studies of the outer planets and moons that would not be possible with existing braking methodologies. While the ability to utilize these atmospheres to slow down and capture spacecraft would dramatically reduce the cost, launch mass, and travel time, currently planned approaches require significant additional spacecraft mass and risk as the spacecraft must descend deep into the planetary atmosphere in order to produce significant drag on a relatively small aeroshell. The plasma based Magnetoshell being developed in this program holds the potential to perform the desired braking with significantly increased drag and control while dramatically reducing mass. Most importantly, this technology significantly lowers the risk involved with aerocapture thereby making manned planetary missions possible. The fundamental physics of the Magnetoshell is based on demonstrated experimental results. Successful implementation will dramatically decrease radiation exposures, mission risk, launch cost, and launch mass. Implementation of aerobraking by employing a solid deflector or aeroshell as a method for orbit insertion and circularization has been successfully demonstrated in the past, resulting in launch mass savings greater than 50%. In order to reduce the effect of frictional heating and dynamic pressure on the typically fragile aeroshell, or worse solar panels, the braking must be distributed over many orbital passes at a high altitude in the less dense regions of the atmosphere. It can thus take several months for a meter-scale, 1000 kg, aeroshell to execute the many elliptic orbital passes through the atmosphere to achieve the required V. This rather slow method of braking not only reduces frictional heating and dynamic forces, but also avoids unpredictable dynamic behavior due to turbulence, as well as unknown and seasonally variable atmospheric composition and temperature which has led to dangerous, mission-critical events. For exploration class missions such as DRA 5.0 aerocapture and Thermal Protection Systems (TPS) are proposed for breaking at Mars for cargo missions. Traditional aerocapture is considered too risky for manned missions. Even with the enormous mass savings that aerocapture allows, it still requires 80 tons of aeroshell and significantly increased launch mass and propellant. As will be shown, by using Magnetoshells for aerobraking, the DRA 5.0 mission will save 224 metric tons (MT) and greater than $2 B in launch costs. Beyond the dramatic savings for existing mission architectures, a low-mass, risk-free aerocapture system would allow much more rapid missions to Mars and deep space orbiters by allowing direct, faster trajectories. As will be shown, the plasma Magnetoshell Aerobraking, Aerocapture, and Entry System (AAES) not only reduces mass and cost while enabling significant new mission architectures, but also significantly reduces radiation exposures by decreasing trip times.

Manned Missions↗

Eye Movements Reveal Hierarchical Motion Processing

Purpose: In the analysis of visual motion, local features such as orientation are analyzed early in the cortical processing stream (V1), while integration across orientation and space is thought to occur in higher cortical areas such as MT, MST, etc. If all areas provide inputs to eye movement control centers, we would expect that local properties would drive eye movements with relatively short latencies, while global properties would require longer latencies. When such latencies are observed, they can provide information about when (and where?) various stimulus properties are analyzed. Methods: The stimulus employed was an elliptical Gabor patch with a drifting carrier, in which the orientations of the carrier grating and the contrast window were varied independently. We have previously demonstrated that the directional percepts evoked by this stimulus vary between the "grating direction" (the normal to the grating's orientation) and the "window direction", and that similar effects can be observed in reflexive eye movements. Subjects viewed such a stimulus while attempting to maintain steady fixation on the center of the pattern, and the small reflexive eye movements ("stare OKN") were recorded. In the middle of the trial, the orientation of either the grating or the window was rotated smoothly by 30 degrees. Results: Responses to the shift of both grating orientation and window orientation are seen in the average OKN slow phase velocity. Grating rotations produce a rapid OKN rotation to the grating direction (100 ms latency, 300 ms time constant), followed by a slower rebound to the steady state perceived direction midway between the grating and window directions. Window rotations, on the other hand, evoke a slower response (200 ms latency, 500 ms time constant). Conclusions: The results demonstrate multiple cortical inputs to eye movement control: a fast, early input driven by orientation, and a slower input from higher areas sensitive to global stimulus properties.

Mulligan, Jeffrey B.↗

Avoiding Excess Computation in Asynchronous Evolutionary Algorithms

Asynchronous evolutionary algorithms are becoming increasingly popular as a means of making full use of many processors while solving computationally expensive search and optimization problems. These algorithms excel at keeping large clusters fully utilized, but may sometimes inefficiently sample an excess of fast-evaluating solutions at the expense of higher-quality, slow-evaluating ones. We introduce a steady-state parent selection strategy, SWEET (“Selection whilE EvaluaTing”), that sometimes selects individuals that are still being evaluated and allows them to reproduce early. This gives slow-evaluating individuals that have higher fitnesses an increased ability to multiply in the population. We find that SWEET appears effective in simulated take-over time analysis, but that its benefit is confined mostly to early in the run, and our preliminary study on an autonomous vehicle controller problem that involves tuning a spiking neural network proves inconclusive.

Scott, Eric↗

Lower limits for non-radiative recombination loss in organic donor/acceptor complexes

Understanding the factors controlling radiative and non-radiative transition rates for charge transfer states in organic systems is important for applications ranging from organic photovoltaics (OPV) to lasers and LEDs. Here we explore the role of charge-transfer (CT) energetics, lifetimes, and photovoltaic properties in the limit of very slow non-radiative rates by using a model donor/acceptor system with photoluminescence dominated by thermally activated delayed fluorescence (TADF). This blend exhibits an extremely high photoluminescence quantum efficiency (PLQY = ~22%) and comparatively long PL lifetime, while simultaneously yielding appreciable amounts of free charge generation (photocurrent external quantum efficiency EQE of 24%). In solar cells, this blend exhibits non-radiative voltage losses of only ~0.1 V, among the lowest reported for an organic system. Notably, we find that the non-radiative decay rate, k nr , is on the order of 10 5 s -1 , approximately 4–5 orders of magnitude slower than typical OPV blends, thereby confirming that high radiative efficiency and low non-radiative voltage losses are achievable by reducing k nr . Furthermore, despite the high radiative efficiency and already comparatively slow k nr , we find that k nr is nevertheless much faster than predicted by Marcus–Levich–Jortner two-state theory and we conclude that CT-local exciton (LE) hybridization is present. Our findings highlight that it is crucial to evaluate how radiative and non-radiative rates of the LE states individually influence the PLQY of charge-transfer states, rather than solely focusing on the PLQY of the LE. This conclusion will guide material selection in achieving low non-radiative voltage loss in organic solar cells and high luminescence efficiency in organic LEDs.

36 MATERIALS SCIENCE↗

Turbulent Heating in Collisionless Low-beta Plasmas: Imbalance, Landau Damping, and Electron–Ion Energy Partition

An understanding of how turbulent energy is partitioned between ions and electrons in weakly collisional plasmas is crucial for modeling many astrophysical systems. Using theory and simulations of a four-dimensional reduced model of low-beta gyrokinetics (the “Kinetic Reduced Electron Heating Model”), we investigate the dependence of collisionless heating processes on plasma beta and imbalance (normalized cross-helicity). These parameters are important because they control the helicity barrier, the formation of which divides the parameter space into two distinct regimes with remarkably different properties. In the first, at lower beta and/or imbalance, the absence of a helicity barrier allows the cascade of injected power to proceed to small (perpendicular) scales, but its slow cascade rate makes it susceptible to significant electron Landau damping, in some cases leading to a marked steepening of the magnetic spectra on scales above the ion Larmor radius. In the second, at higher beta and/or imbalance, the helicity barrier halts the cascade, confining electron Landau damping to scales above the steep “transition-range” spectral break, resulting in dominant ion heating. We formulate quantitative models of these processes that compare well to simulations in each regime, and combine them with results of previous studies to construct a simple formula for the electron–ion heating ratio as a function of beta and imbalance. This model predicts a “winner takes all” picture of low-beta plasma heating, where a small change in the fluctuations' properties at large scales (the imbalance) can cause a sudden switch between electron and ion heating.

Interplanetary turbulence↗

From IMT Device Measurements to Network-Level Consequences: When Learning Suppresses Beyond-LIF Neuron Dynamics

Emerging neuromorphic devices such as insulator--metal transition (IMT) devices exhibit complex temporal dynamics, including slow internal state memory, hysteresis, and burst-like firing, which are poorly captured by conventional leaky integrate-and-fire (LIF) neurons. However, it remains unclear when such dynamics influence learning and inference at the network level, particularly under commonly used unsupervised plasticity rules. We present a controlled, full-stack co-design study spanning experimental characterization of individual IMT devices, compact neuron model development, and large-scale spiking network simulations with identical architectures and learning rules. Rather than optimizing benchmark accuracy, our goal is to diagnose when neuron-level dynamics survive learning and competition, and when they are suppressed, to inform the co-design of devices, networks, and learning rules that can exploit beyond-LIF complexity.

42 ENGINEERING↗

Contributions of the space program to our knowledge of motion sickness.

A slow rotation room (SRR) was used in a laboratory setting to study experimental motion sickness. This SRR simulates, to some degree, the conditions on a rotating spacecraft. Habitability of the chamber was ascertained by subjects who remained in the room for over a month with experimenters in attendance. Control over stressful accelerations involved regulation of the room's angular velocity and the subject's head rotations. By standardizing the head rotations, the strength of the disturbing stimulus became a function of the room's angular velocity. Mild acute episodes of motion sickness were readily kept under control. Certain techniques demonstrated that a subject's susceptibility may be expressed in terms of the number of head motions at a particular angular velocity to reach a chosen endpoint. Investigations using prolonged exposure used rapid increase in rpm to terminal velocity to evoke symptoms, or incremental increase to terminal velocity to prevent them. The effectiveness of 16 representative antimotion sickness drugs is discussed.

Graybiel, A.↗

Greater Bone Fomation Induction Occurred in Aged Than Young Cancellous Bone Sites

We have determined the differences in the effects of continual prostaglandin E2 (PGE2) treatment in aged (non-growing) and young (growing) cancellous bone sites in 7 month-old Sprague-Dawley rats. The sites involved are the aged Distal Tibial Metaphysis (DTM) with a closed epiphysis and the young Proximal Tibial Metaphysis (PTM) with a slow growing, open epiphysis. The study involved rats treated with 0, 1, 3 or 6 mg PGE2/kg/d for 60, 120 and 180 days. Static and dynamic histomorphometty of percent trabecular area, and tissue-referent bone formation rate (BFR/TV) were determined in both DTM and PTM. In pretreatment controls, the secondary spongiosa of the two metaphyses contain the same amount of cancellous bone (11% in DTM vs. 13% in PTM), but markedly less bone formation in DTM (0.6%/y in DTM vs. 41.5%/y in PTM). After 60 days of 6 mg PGE2/kg/d treatment, %Tb.Ar was increased 607% in DTM and 199% in PTM, BFR/TV was increased to nearly 14 fold in DTM and only 5 fold in PTM. These results indicated the aged metaphysis of the DTM was much more responsive to PGE2 treatment than young, growing metaphysis of the PTM. The results of 120 and 180 days treatment did not significantly differ from 60 days treatment in both sites, indicating that the effect of continuous daily PGE2 treatment were in equilibrium after 60 days. We concluded that aged metaphysis was much more responsive to PGE2 treatment than young growing metaphysis.

Ke, H. Z.↗

Eye Movement Latencies to Direction Change for Different Classes of Motion

In the analysis of visual motion, local features such as orientation are analyzed early in the cortical processing stream (V1), while integration across orientation and space is thought to occur in higher cortical areas such as MT, MST, etc. If all areas provide inputs to eye movement control centers, we would expect that local properties would drive eye movements with relatively short latencies, while global properties would require longer latencies. When such latencies are observed, they can provide information about when (and where?) various stimulus properties are analyzed. To this end, a stimulus was employed in which local and global properties determining perceived direction-of-motion could be manipulated independently: an elliptical Gabor patch with a drifting carrier, with variable orientation of the carrier grating and the contrast window. We have previously demonstrated that the directional percepts evoked by this stimulus vary between the "grating direction" (the normal to the grating's orientation) and the "window direction" (ARVO 91, 94), and that similar effects can be observed in reflexive eye movements (ARVO 95). Subjects viewed such a stimulus while attempting to maintain steady fixation on the center of the pattern, and the small reflexive eye movements ("stare OKN") were recorded. In the middle of the trial, the orientation of either the grating or the window was rotated smoothly by 30 degrees. Responses to the shift of both grating orientation and window orientation are seen in the average OKN slow phase velocity. Grating rotations produce a rapid OKN rotation to the grating direction (100 ms latency, 300 ms time constant), followed by a slower rebound to the steady state perceived direction midway between the grating and window directions. Window rotations, on the other hand, evoke a slower response (200 ms latency, 500 ms time constant). The results demonstrate multiple cortical inputs to eye movement control: a taste early input driven by orientation, and a slower input from higher areas sensitive to global stimulus properties.

Mulligan, Jeffrey B.↗

Guidance for Monitoring Passive Groundwater Remedies Over Extended Time Scales

Passive remediation can be appropriate where natural processes and actions such as institutional controls mitigate exposure to contaminated groundwater, achieving remedial action objectives and protectiveness of human health and the environment. Monitored natural attenuation (MNA) is a prevalent passive remediation strategy supported by a regulatory framework and monitoring design guidance. However, long-term passive remedies are usually selected in combination with at least one active remedy, such as source removal, in situ treatment, or pump-and-treat, functioning as a complementary method for achieving remediation objectives and meeting the applicable statutory and regulatory requirements. However, MNA and existing monitoring guidance primarily target situations where the remedial action objectives are met within a few decades. When time scales for passive remediation extend to many decades (50 years or more), a corresponding change in monitoring strategy is needed to adapt to the extended time scale. This document provides guidance for implementing an extended-scale monitoring (ESM) approach appropriate for long-duration passive remediation. Extended-scale is defined in this document with respect to time (i.e., a long duration of remediation) and a large enough physical scale such that downstream receptors will not be impacted within the remediation timeframe. ESM applies to slow-moving groundwater contaminant plumes and emphasizes monitoring primarily for potential exposure pathways. For this approach, the primary monitoring objective is to demonstrate that the plume diminishes before reaching the receptor zone or point of compliance and/or a receptor does not receive concentrations above the compliance limit. While the overall objectives of protecting human health and the environment are the same as for plumes where remediation can occur over a shorter time period, the time scales between decisions are longer and the dynamics of plume evolution are slower. To this end, a scenario-based strategy is described for different plume and source conditions, defining a containment and receptor zones. The containment zone is the area where the risk of exposure to groundwater contamination can be mitigated (e.g., through institutional controls) during the remediation time period. The receptor zone is defined as the area where exposure to groundwater contamination cannot be mitigated and compliance concentration standards must be met. Within the containment zone, slow plume migration may occur, leading to concentrations that exceed compliance standards. However, where distance to the receptor zone is large relative to plume migration and attenuation rate, this approach can be protective of the receptor zone. Selection of a long-duration passive remedy needs to be based on sufficient understanding of contaminant sources, hydrogeology, and contaminant plumes. A strong technical basis, supported by predictive analysis, is recommended to substantiate that contamination is expected to stay within the containment zone during the active remediation and attainment phase of the remedy, and diminish to meet compliance standards within the extended timeframe prior to reaching the receptor zone (e.g., many decades or even centuries). The ESM approach is based on verification of plume behavior and not on detailed plume dynamics. Monitoring is conducted to confirm expected behavior with an emphasis on exposure pathways to verify that plumes remain contained in areas where the protectiveness objectives can be met. ESM should not be adopted if there is significant risk of the plume extending beyond the containment zone. Given the slow movement within the containment zone, less frequent sampling is required relative to approaches used for conventional-scale remediation.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Phase transitions from the fifth dimension

We study the cosmological transition of 5D warped compactifications, from the high-temperature black-brane phase to the low-temperature Randall-Sundrum I phase. The transition proceeds via percolation of bubbles of IR-brane nucleating from the black-brane horizon. The violent bubble dynamics can be a powerful source of observable stochastic gravitational waves. While bubble nucleation is non-perturbative in 5D gravity, it is amenable to semiclassical treatment in terms of a “bounce” configuration interpolating between the two phases. We demonstrate how such a bounce configuration can be smooth enough to maintain 5D effective field theory control, and how a simple ansatz for it places a rigorous lower-bound on the transition rate in the thin-wall regime, and gives plausible estimates more generally. When applied to the Hierarchy Problem, the minimal Goldberger-Wise stabilization of the warped throat leads to a slow transition with significant supercooling. We demonstrate that a simple generalization of the Goldberger-Wise potential modifies the IR-brane dynamics so that the transition completes more promptly. Supercooling determines the dilution of any (dark) matter abundances generated before the transition, potentially at odds with data, while the prompter transition resolves such tensions. We discuss the impact of the different possibilities on the strength of the gravitational wave signals. Via AdS/CFT duality the warped transition gives a theoretically tractable holographic description of the 4D Composite Higgs (de)confinement transition. Our generalization of the Goldberger-Wise mechanism is dual to, and concretely models, our earlier proposal in which the composite dynamics is governed by separate UV and IR RG fixed points. The smooth 5D bounce configuration we introduce complements the 4D dilaton/radion dominance derivation presented in our earlier work.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

The physics of desiccation cracks 1: Ductile fracturing and dependence on relative humidity

Ductile deformation is ubiquitously found in the shrinkage of geomaterials. The existence of ductility requires elastoplastic mechanics when analyzing the structure deformation under external stress. Here, in this work, we explore the physics of ductile fracturing based on the results from desiccation experiments and triaxial tests. By using the digital image correlation (DIC) method to generate the strain maps of samples undergoing desiccation cracking under different relative humidities, we obtain results showing the previously postulated Cnoidal Wave ductile failure patterns propagating under atmospheric condition-controlled crack velocities. We then correlate these observations with rate-dependent plasticity models calibrated through triaxial tests undergoing several unloading–reloading cycles and velocity stepping. This work demonstrates the necessity to consider ductility in soil cracking, indicating that the formation of crack patterns in soil desiccation is a slow and predictable process.

58 GEOSCIENCES↗

Effect of mass flow rate on gas propagation after vacuum break in a liquid helium cooled tube

Vacuum break in particle accelerators is a major concern due to risks associated with personnel and extensive equipment damage. Continuing research in our lab focuses on the sudden loss of vacuum in the liquid helium cooled beam-line tubes of superconducting particle accelerators. In our previous research, we studied nitrogen gas propagation in a uniform tube system immersed in both normal helium (He I) and superfluid helium (He II). It was observed that He II has a stronger effect in slowing down the gas propagation compared to He I, but this effect was largely due to the variation of the point where condensation and deposition of the nitrogen gas on the tube inner wall. Here, we discuss our modifications to the tube system that now allow us to accurately control the starting location of gas condensation in both the He I and He II experiments. Systematic studies of gas propagation were conducted using this new tube system by varying the nitrogen mass flow rate at the tube inlet.

43 PARTICLE ACCELERATORS↗

Thermalization at low temperatures via weakly damped multisite baths

We study the thermalization properties of one-dimensional open quantum systems coupled to baths at their boundary. The baths are driven to their thermal states via Lindblad operators, while the system undergoes Hamiltonian dynamics. We specifically consider multisite baths and investigate the extent to which the late-time steady state resembles a Gibbs state at some controllable temperature set by the baths. We study three models: a noninteracting fermion model accessible via free-fermion technology, and two interacting models, the XZ model and the chiral clock model, which are accessible via tensor network methods. We show that, by tuning towards the weak coupling and slow relaxation limits, one can engineer low temperatures in the bulk of the system provided the bath size is big enough. Here, we use this capability to study energy transport in the XZ model at lower temperatures than previously reported. Our work paves the way for future studies of interacting open quantum systems at low temperatures.

1-dimensional spin chains↗

Three-level sampler having automated thresholds

A three-level sampler is described that has its thresholds controlled automatically so as to track changes in the statistics of the random process being sampled. In particular, the mean value is removed and the ratio of the standard deviation of the random process to the threshold is maintained constant. The system is configured in such a manner that slow drifts in the level comparators and digital-to-analog converters are also removed. The ratio of the standard deviation to threshold level may be chosen within the constraints of the ratios of two integers N and M. These may be chosen to minimize the quantizing noise of the sampled process.

Jurgens, R. F.↗