•As of May 27, 2020 there are over 1,678,843 confirmed cases of COVID-19 claiming more than 100,000 lives in the Unites States. Currently there is no known effective therapy or vaccine.•According to ...a protocol-based treatment algorithm, among hospitalized patients, use of hydroxychloroquine alone and in combination with azithromycin was associated with a significant reduction in-hospital mortality compared to not receiving hydroxychloroquine.•Findings of this observational study provide crucial data on experience with hydroxychloroquine therapy, providing necessary interim guidance for COVID-19 therapeutic practice.
The United States is in an acceleration phase of the COVID-19 pandemic. Currently there is no known effective therapy or vaccine for treatment of SARS-CoV-2, highlighting urgency around identifying effective therapies.
The purpose of this study was to evaluate the role of hydroxychloroquine therapy alone and in combination with azithromycin in hospitalized patients positive for COVID-19.
Multi-center retrospective observational study.
The Henry Ford Health System (HFHS) in Southeast Michigan: large six hospital integrated health system; the largest of hospitals is an 802-bed quaternary academic teaching hospital in urban Detroit, Michigan.
Consecutive patients hospitalized with a COVID-related admission in the health system from March 10, 2020 to May 2, 2020 were included. Only the first admission was included for patients with multiple admissions. All patients evaluated were 18 years of age and older and were treated as inpatients for at least 48h unless expired within 24h.
Receipt of hydroxychloroquine alone, hydroxychloroquine in combination with azithromycin, azithromycin alone, or neither.
The primary outcome was in-hospital mortality.
Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4–10 days), median age was 64 years (IQR:53–76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3–53). Overall in-hospital mortality was 18.1% (95% CI:16.6%–19.7%); by treatment: hydroxychloroquine+azithromycin, 157/783 (20.1% 95% CI: 17.3%–23.0%), hydroxychloroquine alone, 162/1202 (13.5% 95% CI: 11.6%–15.5%), azithromycin alone, 33/147 (22.4% 95% CI: 16.0%–30.1%), and neither drug, 108/409 (26.4% 95% CI: 22.2%–31.0%). Primary cause of mortality was respiratory failure (88%); no patient had documented torsades de pointes. From Cox regression modeling, predictors of mortality were age>65 years (HR:2.6 95% CI:1.9–3.3), white race (HR:1.7 95% CI:1.4–2.1), CKD (HR:1.7 95%CI:1.4–2.1), reduced O2 saturation level on admission (HR:1.5 95%CI:1.1–2.1), and ventilator use during admission (HR: 2.2 95%CI:1.4–3.3). Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine+azithromycin 71% compared to neither treatment (p<0.001).
In this multi-hospital assessment, when controlling for COVID-19 risk factors, treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality. Prospective trials are needed to examine this impact.
A rich body of knowledge links biodiversity to ecosystem functioning (BEF), but it is primarily focused on small scales. We review the current theory and identify six expectations for scale ...dependence in the BEF relationship: (1) a nonlinear change in the slope of the BEF relationship with spatial scale; (2) a scale‐dependent relationship between ecosystem stability and spatial extent; (3) coexistence within and among sites will result in a positive BEF relationship at larger scales; (4) temporal autocorrelation in environmental variability affects species turnover and thus the change in BEF slope with scale; (5) connectivity in metacommunities generates nonlinear BEF and stability relationships by affecting population synchrony at local and regional scales; (6) spatial scaling in food web structure and diversity will generate scale dependence in ecosystem functioning. We suggest directions for synthesis that combine approaches in metaecosystem and metacommunity ecology and integrate cross‐scale feedbacks. Tests of this theory may combine remote sensing with a generation of networked experiments that assess effects at multiple scales. We also show how anthropogenic land cover change may alter the scaling of the BEF relationship. New research on the role of scale in BEF will guide policy linking the goals of managing biodiversity and ecosystems.
We address the challenge of scale for biodiversity and ecosystem functioning (BEF) research. We review current theory and identify six expectations for scale dependence in the BEF relationship. We suggest directions for synthesis that combine theoretical and empirical methods and suggest their application to human transformed landscapes.
ABSTRACT
Biological insurance theory predicts that, in a variable environment, aggregate ecosystem properties will vary less in more diverse communities because declines in the performance or ...abundance of some species or phenotypes will be offset, at least partly, by smoother declines or increases in others. During the past two decades, ecology has accumulated strong evidence for the stabilising effect of biodiversity on ecosystem functioning. As biological insurance is reaching the stage of a mature theory, it is critical to revisit and clarify its conceptual foundations to guide future developments, applications and measurements. In this review, we first clarify the connections between the insurance and portfolio concepts that have been used in ecology and the economic concepts that inspired them. Doing so points to gaps and mismatches between ecology and economics that could be filled profitably by new theoretical developments and new management applications. Second, we discuss some fundamental issues in biological insurance theory that have remained unnoticed so far and that emerge from some of its recent applications. In particular, we draw a clear distinction between the two effects embedded in biological insurance theory, i.e. the effects of biodiversity on the mean and variability of ecosystem properties. This distinction allows explicit consideration of trade‐offs between the mean and stability of ecosystem processes and services. We also review applications of biological insurance theory in ecosystem management. Finally, we provide a synthetic conceptual framework that unifies the various approaches across disciplines, and we suggest new ways in which biological insurance theory could be extended to address new issues in ecology and ecosystem management. Exciting future challenges include linking the effects of biodiversity on ecosystem functioning and stability, incorporating multiple functions and feedbacks, developing new approaches to partition biodiversity effects across scales, extending biological insurance theory to complex interaction networks, and developing new applications to biodiversity and ecosystem management.
The biotic mechanisms underlying ecosystem functioning and stability have been extensively—but separately—explored in the literature, making it difficult to understand the relationship between ...functioning and stability. In this study, we used community models to examine how complementarity and selection, the two major biodiversity mechanisms known to enhance ecosystem biomass production, affect ecosystem stability. Our analytic and simulation results show that although complementarity promotes stability, selection impairs it. The negative effects of selection on stability operate through weakening portfolio effects and selecting species that have high productivity but low tolerance to perturbations (“risk-prone” species). In contrast, complementarity enhances stability by increasing portfolio effects and reducing the relative abundance of risk-prone species. Consequently, ecosystem functioning and stability exhibit either a synergy, if complementarity effects prevail, or trade-off, if selection effects prevail. Across species richness levels, ecosystem functioning and stability tend to be positively related, but negative relationships can occur when selection co-varies with richness. Our findings provide novel insights for understanding the functioning-stability relationship, with potential implications for both ecological research and ecosystem management.
Mitral regurgitation (MR) is the most common type of valvular heart disease in patients over the age of 75 in the US. Despite the prevalence of mitral regurgitation in the elderly population, ...however, almost half of patients identified with moderate-severe MR are turned down for traditional open heart surgery due to frailty and other existing co-morbidities. MitraClip (MC) is a recent percutaneous approach to treat mitral regurgitation by placement of MC in the center of the mitral valve to reduce MR. There are currently no computational simulations to elucidate the role of MC on both the fluid and solid mechanics of the mitral valve. Here, we use the Smoothed Particle Hydrodynamics (SPH) approach to study various positional placements of the MC in the mitral valve and its impact on reducing MR. SPH is a particle based (meshless) approach that handles flow through narrow regions quite efficiently. Fluid and surrounding anatomical structure interactions is handled via contact and hence can be used for studying fluid-structure interaction problems such as blood flow with surrounding tissues/structure. This method is available as part of the Abaqus/Explicit solver. Regurgitation was initiated by removing targeted chordae tendineae that are attached to specified leaflets of the mitral valve and, subsequently, MC implants are placed in various locations, starting from the region near where the chordae tendineae were removed and moving away from the location towards the center of the valve. The MC implant location closest to where the chordae tendineae were removed showed the least amount of residual MR post-clip implantation amongst all other locations of MC implant considered. These findings have important implications for strategic placement of the MC depending on the etiology of MR to optimize clinical outcome.
Transition paths, the fleeting trajectories through the transition states that dominate the dynamics of biomolecular folding reactions, encapsulate the critical information about how structure forms. ...Owing to their brief duration, however, they have not previously been observed directly. We measured transition paths for both nucleic acid and protein folding, using optical tweezers to observe the microscopic diffusive motion of single molecules traversing energy barriers. The average transit times and the shapes of the transit-time distributions agreed well with theoretical expectations for motion over the one-dimensional energy landscapes reconstructed for the same molecules, validating the physical theory of folding reactions. These measurements provide a first look at the critical microscopic events that occur during folding, opening exciting new avenues for investigating folding phenomena.
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