How stickiness can speed up diffusion in confined systems

The paradigmatic model for heterogeneous media used in diffusion studies is built from reflecting obstacles and surfaces. It is well known that the crowding effect produced by these reflecting surfaces slows the dispersion of Brownian tracers. Here, using a general adsorption desorption model with surface diffusion, we show analytically that making surfaces or obstacles attractive can accelerate dispersion. In particular, we show that this enhancement of diffusion can exist even when the surface diffusion constant is smaller than that in the bulk. Even more remarkably, this enhancement effect occurs when the effective diffusion constant, when restricted to surfaces only, is lower than the effective diffusivity with purely reflecting boundaries. We give analytical formulas for this intriguing effect in periodic arrays of spheres as well as undulating micro-channels. Our results are confirmed by numerical calculations and Monte Carlo simulations

Insular cortex dopamine 1 and 2 receptors in methamphetamine conditioned place preference and aversion: Age and sex differences

Rodent studies have proposed that adolescent susceptibility to substance use is at least partly due to adolescents experiencing reduced aversive effects of drugs compared to adults. We thus investigated methamphetamine (meth) conditioned place preference/aversion (CPP/CPA) in adolescent and adult mice in both sexes using a high dose of meth (3 mg/kg) or saline as controls. Mice tagged with green-fluorescent protein (GFP) at Drd1a or Drd2 were used so that dopamine receptor 1 (D1) and 2 (D2) expression within the insular cortex (insula) could be quantified. There are sex differences in how the density of D1+ and D2+ cells in the insula changes across adolescence that may be related to drug-seeking behaviors. Immunohistochemistry followed by stereology were used to quantify the density of cells with c-Fos and/or GFP in the insula. Unexpectedly, mice showed huge variability in behaviors including CPA, CPP, or no preference or aversion. Females were less likely to show CPP compared to males, but no age differences in behavior were observed. Conditioning with meth increased the number of D2 + cells co-labelled with c-Fos in adults but not in adolescents. D1:D2 ratio also sex- and age-dependently changed due to meth compared to saline. These findings suggest that reduced aversion to meth is unlikely an explanation for adolescent vulnerability to meth use. Sex- and age-specific expressions of insula D1 and D2 are changed by meth injections, which has implications for subsequent meth use

Non-Gaussian diffusion near surfaces

We study the diffusion of finite-size particles confined close to a single wall and in double-wall planar channel geometries. The local diffusion constants are modified near the confining boundaries and depend on the distance to the latter. Displacement parallel to the walls is diffusive as characterized by its second cumulant (the variance), but a non-Gaussian nature can be demonstrated by the fact that its fourth cumulant is non-zero. Establishing a link with the well-known problem of Taylor dispersion, we provide a general expression for the fourth cumulant for general diffusivity tensors and also in the presence of potentials generated by either the walls or externally, for instance due to gravity. We then analyse experimentally and numerically the motion of a colloid in the direction parallel to the wall, for which the measured fourth cumulant is correctly predicted by our theory. This system is a well-controlled physical realization of a Brownian yet non-Gaussian motion generated by a fluctuating diffusivity mechanism for which the local diffusivity is quantified. These results can be used to provide additional tests and constraints for the inference of force maps and local transport properties near surfaces

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

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

Non-Gaussian diffusion near surfaces

We study the diffusion of finite-size particles confined close to a single wall and in double-wall planar channel geometries. The local diffusion constants are modified near the confining boundaries and depend on the distance to the latter. Displacement parallel to the walls is diffusive as characterized by its second cumulant (the variance), but a non-Gaussian nature can be demonstrated by the fact that its fourth cumulant is non-zero. Establishing a link with the well-known problem of Taylor dispersion, we provide a general expression for the fourth cumulant for general diffusivity tensors and also in the presence of potentials generated by either the walls or externally, for instance due to gravity. We then analyse experimentally and numerically the motion of a colloid in the direction parallel to the wall, for which the measured fourth cumulant is correctly predicted by our theory. This system is a well-controlled physical realization of a Brownian yet non-Gaussian motion generated by a fluctuating diffusivity mechanism for which the local diffusivity is quantified. These results can be used to provide additional tests and constraints for the inference of force maps and local transport properties near surfaces.Premières rencontres en environnement complexeMouvement brownien au voisinage d'interfaces mollesCapteur Interférométrique de Contraintes de SurfaceFrottements dans les systèmes complexe

Non-Gaussian diffusion near surfaces

We study the diffusion of finite-size particles confined close to a single wall and in double-wall planar channel geometries. The local diffusion constants are modified near the confining boundaries and depend on the distance to the latter. Displacement parallel to the walls is diffusive as characterized by its second cumulant (the variance), but a non-Gaussian nature can be demonstrated by the fact that its fourth cumulant is non-zero. Establishing a link with the well-known problem of Taylor dispersion, we provide a general expression for the fourth cumulant for general diffusivity tensors and also in the presence of potentials generated by either the walls or externally, for instance due to gravity. We then analyse experimentally and numerically the motion of a colloid in the direction parallel to the wall, for which the measured fourth cumulant is correctly predicted by our theory. This system is a well-controlled physical realization of a Brownian yet non-Gaussian motion generated by a fluctuating diffusivity mechanism for which the local diffusivity is quantified. These results can be used to provide additional tests and constraints for the inference of force maps and local transport properties near surfaces.Premières rencontres en environnement complexeMouvement brownien au voisinage d'interfaces mollesCapteur Interférométrique de Contraintes de SurfaceFrottements dans les systèmes complexe