Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

On the Impact of Electrode Properties and Their Design for Redox Flow Battery Performance

Redox flow batteries (RFBs) are a promising technology for grid energy storage. However, cost reductions are required prior to widespread adoption. Advances in the design and engineering of the electrochemical stack may enable cost reductions for multiple redox chemistries. Porous electrodes are a prime target for improvement of system power to lower cost per kilowatt-hour, as they are responsible for multiple critical functions in the flow cell including providing surfaces for electrochemical reactions, distributing liquid electrolytes, and conducting electrons and heat. However, there is limited knowledge on how to systematically design and implement these materials in emerging RFB applications, leading to the repurposing of available materials that are not tailored for this system, i.e. porous carbon papers or felts. For optimal RFB performance, it is necessary to pretreat carbons prior to use to improve electrode wetting and enhance redox kinetics, yet the impact of thermal pretreatment on electrode properties and the correlation between these properties are not well defined, thus the subsequent influence on performance is nebulous. Gaining a deeper understanding of electrode properties and their influence on performance will enable targeted improvements to electrode platforms, allowing system-specific performance gains. Further, identifying essential electrode properties will guide the development of alternative electrocatalytic material that may enable new systems in which carbon is unstable or is not catalytically active. In this thesis, I will discuss the impact of electrode treatments on RFB performance, combining experimental and computational approaches. First, I investigate the interrelated effects of thermal pretreatment on electrode properties and correlate the changes in these properties with performance. Surface functionalization, wetting, and surface area are identified as the key properties that influence electrode performance. Next, I specifically investigate the impact of 2 surface area on electrode performance. I show that, while thermal treatment adds a significant amount of physical surface area to the electrode, electrochemical species are unable to access a large fraction of this surface area. Further, I use a convection-reaction model to show that even when all surface area is accessible, there is a limit to the surface area that will improve electrode performance. This limit to “useful” surface area is dictated by rate of reaction and transport within the electrode. Finally, I investigate the viability of nickel metal electrodeposition on carbon electrodes to enhance the performance of a novel polysulfide-permanganate flow battery. I show that nickel-deposited carbon electrodes outperform commercially available metal materials, including foams and weaves. The overarching goal of this thesis work is to develop a deeper understanding of the influence that electrode properties have on performance. By continuing to characterize the fundamental kinetic and transport properties within complex porous materials under forced convection, the community will be prepared to design novel material sets well-suited for use in RFBs and other challenging electrochemical environments.Ph.D

Limited Accessibility to Surface Area Generated by Thermal Pretreatment of Electrodes Reduces Its Impact on Redox Flow Battery Performance

Thermal oxidation of carbon electrodes is a common approach to improving flow battery performance. Here, we investigate how thermal pretreatment increases electrode surface area and the effect this added surface area has on electrode performance. Specifically, we rigorously analyze the surface area of Freudenberg H23 carbon paper electrodes, a binder-free model material, by systematically varying pretreatment temperature (400, 450, and 500 °C) and time (0 to 24 h) and evaluating changes in the physical, chemical, and electrochemical properties of the electrodes. We compare physical surface area, measured by a combination of gas adsorption techniques, to surface area measured via electrochemical double layer capacitance. We find good agreement between the two at shorter treatment times (0-3 h); however, at longer treatment times (6-24 h), the surface area measured electrochemically is an underestimate of the physical surface area. Further, we use gas adsorption to measure a pore size distribution and find that the majority of pores are in the micropore range (< 2 nm), and ca. 60% of the added surface area are in the sub-nanometer (< 1 nm) pore size range. We postulate that the solvated radii and imperfect wetting of electrochemical species may hinder active species transport into these recessed regions, explaining the discrepancy between electrochemical and physical surface area. These results are supported with in situ flow cell testing, where single-electrolyte polarization measurements show little improvement with increasing surface area. Further, using a simple convection-reaction model to simulate electrode overpotential as a function of surface area, we find that increasing surface area improves the performance to a point, but the mass transport to and the catalytic activity of the reaction sites offer greater comparative impact. Ultimately, this work aims to inform the design of electrodes that offer maximal accessible surface area to redox species

Effect of shoulder pain on shoulder kinematics during weight-bearing tasks in persons with spinal cord injury

Objective: To assess 3-dimensional scapulothoracic and glenohumeral kinematics between subjects with spinal cord injury and disease (SCI/D) with and without shoulder pain during a weight-relief raise and transfer task. Design: Case-control, repeated-measures analysis of variance. Setting: Movement analysis laboratory. Participants: Subjects (N=43; 23 with clinical signs of impingement and 20 without) between 21 and 65 years of age, at least 1 year after SCI/D (range, 1-43y) resulting in American Spinal Injury Association Impairment Scale T2 motor neurologic level or below, and requiring the full-time use of a manual wheelchair. Interventions: Weight-relief raises and transfer tasks. Main Outcome Measures: An electromagnetic tracking system acquired 3-dimensional position and orientation of the thorax, scapula, and humerus. Dependent variables included angular values for scapular upward and downward rotation, posterior and anterior tilt, and internal and external rotation relative to the thorax, and glenohumeral internal and external rotation relative to the scapula. The mean of 3 trials was collected, and angular values were compared at 3 distinct phases of the weight-relief raise and transfer activity. Comparisons were also made between transfer direction (lead vs trail arm) and across groups. Results: Key findings include significantly increased scapular upward rotation for the pain group during transfer (P=.03). Significant group differences were found for the trailing arm at the lift pivot (phase 2) of the transfer, with the pain group having greater anterior tilt (mean difference ± SE, 5.7°±2. 8°). The direction of transfer also influenced kinematics at the different phases of the activity. Conclusions: Potentially detrimental magnitude and direction of scapular and glenohumeral kinematics during weight-bearing tasks may pose increased risk for shoulder pain or injury in persons with SCI/D. Consideration should be given to rehabilitation strategies that promote favorable scapular kinematics and glenohumeral external rotation. © 2012 American Congress of Rehabilitation Medicine

Elucidating the nuanced effects of thermal pretreatment on carbon paper electrodes for vanadium Redox flow batteries

Sluggish vanadium reaction rates on the porous carbon electrodes typically used in redox flow batteries have prompted research into pretreatment strategies, most notably thermal oxidation, to improve performance. While effective, these approaches have nuanced and complex effects on electrode characteristics hampering the development of explicit structure–function relations that enable quantitative correlation between specific properties and overall electrochemical performance. Here, we seek to resolve these relationships through rigorous analysis of thermally pretreated SGL 29AA carbon paper electrodes using a suite of electrochemical, microscopic, and spectroscopic techniques and culminating in full cell testing. We systematically vary pretreatment temperature, from 400 to 500 °C, while holding pretreatment time constant at 30 h, and evaluate changes in the physical, chemical, and electrochemical properties of the electrodes. We find that several different parameters contribute to observed performance, including hydrophilicity, microstructure, electrochemical surface area, and surface chemistry, and it is important to note that not all of these properties improve with increasing pretreatment temperature. Consequently, while the best overall performance is achieved with a 475 °C pretreatment, this enhancement is achieved from a balance, rather than a maximization, of critical properties. A deeper understanding of the role each property plays in battery performance is the first step toward developing targeted pretreatment strategies that may enable transformative performance improvements

A Potential–dependent Thiele Modulus to Quantify the Effectiveness of Porous Electrocatalysts

Electrochemical reactors often employ high surface area electrocatalysts to accelerate volumetric reaction rates and increase productivity. While electrocatalysts can alleviate kinetic overpotentials, diffusional resistances at the pore-scale often prevent full catalyst utilization. The effect of intraparticle diffusion on the overall reaction rate can be quantified through an effectiveness factor expression governed by the Thiele modulus parameter. This analytical approach is integral to the development of catalytic structures for thermochemical processes and has previously been extended to electrochemical processes by accounting for the relationship between reaction kinetics and electrode overpotential. In this paper, we illustrate the method by deriving the expression for the potential-dependent Thiele modulus and using it to quantify the effectiveness factor for porous electrocatalytic structures. Specifically, we demonstrate the application of this mathematical framework to spherical microparticles as a function of applied overpotential across catalyst properties and reactant characteristics. The relative effects of kinetics and mass transport are related to overall reaction rates, revealing markedly lower catalyst utilization at increasing overpotential. Subsequently, we generalize the analysis to different catalyst shapes and provide guidance on the design of porous catalytic materials for use in electrochemical reactors

Molecular Simulations of Hydrogen Bond Cluster Size and Reorientation Dynamics in Liquid and Glassy Azole Systems

We simulated the dynamics of azole groups (pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, and tetrazole) as neat liquids and tethered via linkers to aliphatic backbones to determine how tethering and varying functional groups affect hydrogen bond networks and reorientation dynamics, both factors which are thought to influence proton conduction. We used the DL_Poly_2 molecular dynamics code with the GAFF force field to simulate tethered systems over the temperature range 200–900 K and the corresponding neat liquids under liquid state temperatures at standard pressure. We computed hydrogen bond cluster sizes; orientational order parameters; orientational correlation functions associated with functional groups, linkers, and backbones; time scales; and activation energies associated with orientational randomization. All tethered systems exhibit a liquid to glassy-solid transition upon cooling from 600 to 500 K, as evidenced by orientational order parameters and correlation functions. Tethering the azoles was generally found to produce hydrogen bond cluster sizes similar to those in untethered liquids and hydrogen bond lifetimes longer than those in liquids. The simulated rates of functional group reorientation decreased dramatically upon tethering. The activation energies associated with orientational randomization agree well with NMR data for tethered imidazole systems at lower temperatures and for tethered 1,2,3-triazole systems at both low- and high-temperature ranges. Overall, our simulations corroborate the notion that tethering functional groups dramatically slows the process of reorientation. We found a linear correlation between gas-phase hydrogen bond energies and tethered functional group reorientation barriers for all azoles except for imidazole, which acts as an outlier because of both atomic charges and molecular structure

Methods—A Potential–Dependent Thiele Modulus to Quantify the Effectiveness of Porous Electrocatalysts

Electrochemical reactors often employ high surface area electrocatalysts to accelerate volumetric reaction rates and increase productivity. While electrocatalysts can alleviate kinetic overpotentials, diffusional resistances at the pore-scale often prevent full catalyst utilization. The effect of intraparticle diffusion on the overall reaction rate can be quantified through an effectiveness factor expression governed by the Thiele modulus parameter. This analytical approach is integral to the development of catalytic structures for thermochemical processes and has previously been extended to electrochemical processes by accounting for the relationship between reaction kinetics and electrode overpotential. In this paper, we illustrate the method by deriving the expression for the potential-dependent Thiele modulus and using it to quantify the effectiveness factor for porous electrocatalytic structures. Specifically, we demonstrate the application of this mathematical framework to spherical microparticles as a function of applied overpotential across catalyst properties and reactant characteristics. The relative effects of kinetics and mass transport are related to overall reaction rates, revealing markedly lower catalyst utilization at increasing overpotential. Subsequently, we generalize the analysis to different catalyst shapes and provide guidance on the design of porous catalytic materials for use in electrochemical reactors.</jats:p

A Comparison of Separators vs. Membranes in Nonaqueous Redox Flow Battery Electrolytes Containing Small Molecule Active Materials

The lack of suitable membranes for nonaqueous electrolytes limits cell capacity and cycle lifetime in organic redox flow cells. Using soluble, stable materials, we sought to compare the best performance that could be achieved with commercially available microporous separators and ion-selective membranes. We use organic species with proven stability to avoid deconvoluting capacity fade due to crossover and/or cell imbalance from materials degradation. We found a trade-off between lifetime and coulombic efficiency: non-selective separators achieve more stable performance but suffer from low coulombic efficiencies, while ion-selective membranes achieve high coulombic efficiencies but experience capacity loss over time. When electrolytes are pre-mixed prior to cycling, coulombic efficiency remains high, but capacity is lost due to cell imbalance, which can be recovered by electrolyte rebalancing. The results of this study highlight the potential for gains in nonaqueous cell performance that may be enabled by suitable membranes.</p

Ultrathin Conformal oCVD PEDOT Coatings on Carbon Electrodes Enable Improved Performance of Redox Flow Batteries

Surface engineering of porous carbon electrodes is an effective strategy to enhance the power output of redox flow batteries (RFBs) and may enable new cost reduction pathways for energy storage. Here, a surface modification strategy that enhances the electrochemical performance of RFBs in iron-based electrolytes is demonstrated. Nanometric films of poly(3,4-ethylenedioxythiophene) (PEDOT) are grown conformally onto carbon cloth electrodes using oxidative chemical vapor deposition (oCVD) and the impact of film properties on electrode performance in model iron-based electrolytes is investigated. Depositing oCVD PEDOT films on the electrode surface is found to reduce ohmic, kinetic, and mass transport resistances, with the highest current densities and lowest resistances observed for electrodes coated with a ≈78 nm thick film. As compared to unmodified electrodes, coated electrodes enhance the maximum obtained current density at an applied overpotential of 350 mV by 6.7× and 3.7× in iron sulfate and iron chloride, respectively. The oCVD PEDOT film described here represents an initial step toward electrode surfaces of tailored activity, selectivity, and wettability for specific RFB chemistries and, more generally, electrochemical systems with liquid-phase reactants