Surfactant Partitioning Dynamics in Freshly Generated Aerosol Droplets.

Aerosol droplets are unique microcompartments with relevance to areas as diverse as materials and chemical synthesis, atmospheric chemistry, and cloud formation. Observations of highly accelerated and unusual chemistry taking place in such droplets have challenged our understanding of chemical kinetics in these microscopic systems. Due to their large surface-area-to-volume ratios, interfacial processes can play a dominant role in governing chemical reactivity and other processes in droplets. Quantitative knowledge about droplet surface properties is required to explain reaction mechanisms and product yields. However, our understanding of the compositions and properties of these dynamic, microscopic interfaces is poor compared to our understanding of bulk processes. Here, we measure the dynamic surface tensions of 14-25 µm radius (11-65 pL) droplets containing a strong surfactant (either sodium dodecyl sulfate or octyl-ß-D-thioglucopyranoside) using a stroboscopic imaging approach, enabling observation of the dynamics of surfactant partitioning to the droplet-air interface on time scales of 10s to 100s of microseconds after droplet generation. The experimental results are interpreted with a state-of-the-art kinetic model accounting for the unique high surface-area-to-volume ratio inherent to aerosol droplets, providing insights into both the surfactant diffusion and adsorption kinetics as well as the time-dependence of the interfacial surfactant concentration. This study demonstrates that microscopic droplet interfaces can take up to many milliseconds to reach equilibrium. Such time scales should be considered when attempting to explain observations of accelerated chemistry in microcompartments.

A randomized controlled trial evaluating the effects of nurse-led triage of 911 calls.

To better connect non-emergent 911 callers to appropriate care, Washington, DC, routed low-acuity callers to nurses. Nurses could provide non-emergent transportation to a health centre, recommend self-care or return callers to the traditional 911 system. Over about one year, 6,053 callers were randomized (1:1) to receive a business-as-usual response (ncontrol = 3,023) or further triage (ntreatment = 3,030). We report on seven of nine outcomes, which were pre-registered ( https://osf.io/xderw ). The proportion of calls resulting in an ambulance dispatch dropped from 97% to 56% (ß = -1.216 (-1.324, -1.108), P < 0.001), and those resulting in an ambulance transport dropped from 73% to 45% (ß = -3.376 (-3.615, -3.137), P < 0.001). Among those callers who were Medicaid beneficiaries, within 24 hours, the proportion of calls resulting in an emergency department visit for issues classified as non-emergent or primary care physician (PCP) treatable dropped from 29.5% to 25.1% (ß = -0.230 (-0.391, -0.069), P < 0.001), and the proportion resulting in the caller visiting a PCP rose from 2.5% to 8.2% (ß = 1.252 (0.889, 1.615), P < 0.001). Over the longer time span of six months, we failed to detect evidence of impacts on emergency department visits, PCP visits or Medicaid expenditures. From a safety perspective, 13 callers randomized to treatment were eventually diagnosed with a time-sensitive illness, all of whom were quickly triaged to an ambulance response. These short-term effects suggest that nurse-led triage of non-emergent calls can safely connect callers to more appropriate, timely care.

Compression of a Stearic Acid Surfactant Layer on Water Investigated by Ambient Pressure X-ray Photoelectron Spectroscopy.

We present a combined Langmuir-Pockels trough and ambient pressure X-ray photoelectron spectroscopy (APXPS) study of the compression of stearic acid surfactant layers on neat water. Changes in the packing density of the molecules are directly determined from C 1s and O 1s APXPS data. The experimental data are fit with a 2D model for the stearic acid coverage. Based on the results of these proof-of-principle experiments, we discuss the remaining challenges that need to be overcome for future investigations of the role of surfactants in heterogeneous chemical reactions at liquid-vapor interfaces in combined Langmuir-Pockels trough and APXPS measurements.

On the Statistical Mechanics of Mass Accommodation at Liquid-Vapor Interfaces.

We propose a framework for describing the dynamics associated with the adsorption of small molecules to liquid-vapor interfaces using an intermediate resolution between traditional continuum theories that are bereft of molecular detail and molecular dynamics simulations that are replete with them. In particular, we develop an effective single particle equation of motion capable of describing the physical processes that determine thermal and mass accommodation probabilities. The effective equation is parametrized with quantities that vary through space away from the liquid-vapor interface. Of particular importance in describing the early time dynamics is the spatially dependent friction, for which we propose a numerical scheme to evaluate from molecular simulation. Taken together with potentials of mean force computable with importance sampling methods, we illustrate how to compute the mass accommodation coefficient and residence time distribution. Throughout, we highlight the case of ozone adsorption in aqueous solutions and its dependence on electrolyte composition.

Interfacial Nanostructure and Hydrogen Bond Networks of Choline Chloride and Glycerol Mixtures Probed with X-ray and Vibrational Spectroscopies.

The molecular distribution at the liquid-vapor interface and evolution of the hydrogen bond interactions in mixtures of glycerol and choline chloride are investigated using X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. Nanoscale depth profiles of supersaturated deep eutectic solvent (DES) mixtures up to ∼2 nm measured by ambient-pressure XPS show the enhancement of choline cation (Ch+) concentration by a factor of 2 at the liquid-vapor interface compared to the bulk. In addition, Raman spectral analysis of a wide range of DES mixtures reveals the conversion of gauche-conformer Ch+ into the anti-conformer in relatively lower ChCl concentrations. Finally, the depletion of Ch+ from the interface (probing depth = 0.4 nm) is demonstrated by aerosol-based velocity map imaging XPS measurements of glyceline and water mixtures. The nanostructure of liquid-vapor interfaces and structural rearrangement by hydration can provide critical insight into the molecular origin of the deep eutectic behavior and gas-capturing application of DESs.

Chemical Kinetics in Microdroplets.

Micrometer-sized compartments play significant roles in driving heterogeneous transformations within atmospheric and biochemical systems as well as providing vehicles for drug delivery and novel reaction environments for the synthesis of industrial chemicals. Many reports now indicate that reaction kinetics are accelerated under microconfinement, for example, in sprays, thin films, droplets, aerosols, and emulsions. These observations are dramatic, posing a challenge to our understanding of chemical reaction mechanisms with potentially significant practical consequences for predicting the complex chemistry in natural systems. Here we introduce the idea of kinetic confinement, which is intended to provide a conceptual backdrop for understanding when and why microdroplet reaction kinetics differ from their macroscale analogs. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 75 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Iodide oxidation by ozone at the surface of aqueous microdroplets.

The oxidation of iodide by ozone occurs at the sea-surface and within sea spray aerosol, influencing the overall ozone budget in the marine boundary layer and leading to the emission of reactive halogen gases. A detailed account of the surface mechanism has proven elusive, however, due to the difficulty in quantifying multiphase kinetics. To obtain a clearer understanding of this reaction mechanism at the air-water interface, we report pH-dependent oxidation kinetics of I- in single levitated microdroplets as a function of [O3] using a quadrupole electrodynamic trap and an open port sampling interface for mass spectrometry. A kinetic model, constrained by molecular simulations of O3 dynamics at the air-water interface, is used to understand the coupled diffusive, reactive, and evaporative pathways at the microdroplet surface, which exhibit a strong dependence on bulk solution pH. Under acidic conditions, the surface reaction is limited by O3 diffusion in the gas phase, whereas under basic conditions the reaction becomes rate limited on the surface. The pH dependence also suggests the existence of a reactive intermediate IOOO- as has previously been observed in the Br- + O3 reaction. Expressions for steady-state surface concentrations of reactants are derived and utilized to directly compute uptake coefficients for this system, allowing for an exploration of uptake dependence on reactant concentration. In the present experiments, reactive uptake coefficients of O3 scale weakly with bulk solution pH, increasing from 4 × 10-4 to 2 × 10-3 with decreasing solution pH from pH 13 to pH 3.

Spiers Memorial Lecture: Water at interfaces.

In this article we discuss current issues in the context of the four chosen subtopics for the meeting: dynamics and nano-rheology of interfacial water, electrified/charged aqueous interfaces, ice interfaces, and soft matter/water interfaces. We emphasize current advances in both theory and experiment, as well as important practical manifestations and areas of unresolved controversy.

Bayesian design and analysis of two-arm cluster randomized trials using assurance.

We consider the design of a two-arm superiority cluster randomized controlled trial (RCT) with a continuous outcome. We detail Bayesian inference for the analysis of the trial using a linear mixed-effects model. The treatment is compared to control using the posterior distribution for the treatment effect. We develop the form of the assurance to choose the sample size based on this analysis, and its evaluation using a two loop Monte Carlo sampling scheme. We assess the proposed approach, considering the effect of different forms of prior distribution, and the number of Monte Carlo samples needed in both loops for accurate determination of the assurance and sample size. Based on this assessment, we provide general advice on each of these choices. We apply the approach to the choice of sample size for a cluster RCT into poststroke incontinence, and compare the resulting sample size to that from assurance based on a Wald test for the treatment effect. The Bayesian approach to design and analysis developed in this article can offer advantages in terms of an increase in the robustness of the chosen sample size to parameter mis-specification and reduced sample sizes if prior information indicates the treatment effect is likely to be larger than the minimal clinically important difference.

Sample size determination for point-of-care COVID-19 diagnostic tests: a Bayesian approach.

BACKGROUND: In a pandemic setting, it is critical to evaluate and deploy accurate diagnostic tests rapidly. This relies heavily on the sample size chosen to assess the test accuracy (e.g. sensitivity and specificity) during the diagnostic accuracy study. Too small a sample size will lead to imprecise estimates of the accuracy measures, whereas too large a sample size may delay the development process unnecessarily. This study considers use of a Bayesian method to guide sample size determination for diagnostic accuracy studies, with application to COVID-19 rapid viral detection tests. Specifically, we investigate whether utilising existing information (e.g. from preceding laboratory studies) within a Bayesian framework can reduce the required sample size, whilst maintaining test accuracy to the desired precision. METHODS: The method presented is based on the Bayesian concept of assurance which, in this context, represents the unconditional probability that a diagnostic accuracy study yields sensitivity and/or specificity intervals with the desired precision. We conduct a simulation study to evaluate the performance of this approach in a variety of COVID-19 settings, and compare it to commonly used power-based methods. An accompanying interactive web application is available, which can be used by researchers to perform the sample size calculations. RESULTS: Results show that the Bayesian assurance method can reduce the required sample size for COVID-19 diagnostic accuracy studies, compared to standard methods, by making better use of laboratory data, without loss of performance. Increasing the size of the laboratory study can further reduce the required sample size in the diagnostic accuracy study. CONCLUSIONS: The method considered in this paper is an important advancement for increasing the efficiency of the evidence development pathway. It has highlighted that the trade-off between lab study sample size and diagnostic accuracy study sample size should be carefully considered, since establishing an adequate lab sample size can bring longer-term gains. Although emphasis is on its use in the COVID-19 pandemic setting, where we envisage it will have the most impact, it can be usefully applied in other clinical areas.

pH jump kinetics in colliding microdroplets: accelerated synthesis of azamonardine from dopamine and resorcinol.

Recent studies report the dramatic acceleration of chemical reactions in micron-sized compartments. In the majority of these studies the exact acceleration mechanism is unknown but the droplet interface is thought to play a significant role. Dopamine reacts with resorcinol to form a fluorescent product azamonardine and is used as a model system to examine how droplet interfaces accelerate reaction kinetics. The reaction is initiated by colliding two droplets levitated in a branched quadrupole trap, which allows the reaction to be observed in individual droplets where the size, concentration, and charge are carefully controlled. The collision of two droplets produces a pH jump and the reaction kinetics are quantified optically and in situ by measuring the formation of azamonardine. The reaction was observed to occur 1.5 to 7.4 times faster in 9-35 micron droplets compared to the same reaction conducted in a macroscale container. A kinetic model of the experimental results suggests that the acceleration mechanism arises from both the more rapid diffusion of oxygen into the droplet, as well as increased reagent concentrations at the air-water interface.

Elucidating the Mechanism for the Reaction of o-Phthalaldehyde with Primary Amines in the Presence of Thiols.

The use of o-phthalaldehyde (OPA) in combination with a thiol reagent is a common method for detecting primary amines in amino acids, peptides, and proteins. Despite its widespread use, the exact reaction mechanism has been debated since the 1980s. Here, we measure the kinetics of the reaction between OPA, alanine, and a dithiol (1,4-dithiolthreitol, DTT) as a function of pH and reagent concentration. Using these new measurements and accompanying kinetic models, we find evidence that the pH dependence of the kinetics arises from both the protonation states of alanine and DTT, the hydration state of OPA, and the unproductive equilibrium with DTT, all of which are pH-dependent. These results support the mechanism originally proposed by Sternson [Rational design and evaluation of improved o-phthalaldehyde-like fluorogenic reagents. Anal. Biochem. 1985, 144, 233-246] and Wong [Reaction of o-phthalaldehyde with alanine and thiols: kinetics and mechanism. J. Am. Chem. Soc. 1985, 107, 6421-6422], in which the primary amine first reacts with OPA, followed by a reaction with the thiol to form the fluorescent isoindole product.

A library of quantitative markers of seizure severity.

OBJECTIVE: Understanding fluctuations in seizure severity within individuals is important for determining treatment outcomes and responses to therapy, as well as assessing novel treatments for epilepsy. Current methods for grading seizure severity rely on qualitative interpretations from patients and clinicians. Quantitative measures of seizure severity would complement existing approaches to electroencephalographic (EEG) monitoring, outcome monitoring, and seizure prediction. Therefore, we developed a library of quantitative EEG markers that assess the spread and intensity of abnormal electrical activity during and after seizures. METHODS: We analyzed intracranial EEG (iEEG) recordings of 1009 seizures from 63 patients. For each seizure, we computed 16 markers of seizure severity that capture the signal magnitude, spread, duration, and postictal suppression of seizures. RESULTS: Quantitative EEG markers of seizure severity distinguished focal versus subclinical seizures across patients. In individual patients, 53% had a moderate to large difference (rank sum r > .3 , p < .05 ) between focal and subclinical seizures in three or more markers. Circadian and longer term changes in severity were found for the majority of patients. SIGNIFICANCE: We demonstrate the feasibility of using quantitative iEEG markers to measure seizure severity. Our quantitative markers distinguish between seizure types and are therefore sensitive to established qualitative differences in seizure severity. Our results also suggest that seizure severity is modulated over different timescales. We envisage that our proposed seizure severity library will be expanded and updated in collaboration with the epilepsy research community to include more measures and modalities.