Predicting plasticity in disordered solids from structural indicators

Amorphous solids lack long-range order. Therefore identifying structural defects -- akin to dislocations in crystalline solids -- that carry plastic flow in these systems remains a daunting challenge. By comparing many different structural indicators in computational models of glasses, under a variety of conditions we carefully assess which of these indicators are able to robustly identify the structural defects responsible for plastic flow in amorphous solids. We further demonstrate that the density of defects changes as a function of material preparation and strain in a manner that is highly correlated with the macroscopic material response. Our work represents an important step towards predicting how and when an amorphous solid will fail from its microscopic structure

The FDA-Approved Drug Cobicistat Synergizes with Remdesivir To Inhibit SARS-CoV-2 Replication In Vitro and Decreases Viral Titers and Disease Progression in Syrian Hamsters

Combinations of direct-acting antivirals are needed to minimize drug resistance mutations and stably suppress replication of RNA viruses. Currently, there are limited therapeutic options against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and testing of a number of drug regimens has led to conflicting results. Here, we show that cobicistat, which is an FDA-approved drug booster that blocks the activity of the drug-metabolizing proteins cytochrome P450-3As (CYP3As) and P-glycoprotein (P-gp), inhibits SARS-CoV-2 replication. Two independent cell-to-cell membrane fusion assays showed that the antiviral effect of cobicistat is exerted through inhibition of spike protein-mediated membrane fusion. In line with this, incubation with low-micromolar concentrations of cobicistat decreased viral replication in three different cell lines including cells of lung and gut origin. When cobicistat was used in combination with remdesivir, a synergistic effect on the inhibition of viral replication was observed in cell lines and in a primary human colon organoid. This was consistent with the effects of cobicistat on two of its known targets, CYP3A4 and P-gp, the silencing of which boosted the in vitro antiviral activity of remdesivir in a cobicistat-like manner. When administered in vivo to Syrian hamsters at a high dose, cobicistat decreased viral load and mitigated clinical progression. These data highlight cobicistat as a therapeutic candidate for treating SARS-CoV-2 infection and as a potential building block of combination therapies for COVID-19

Recent advances in understanding hypertension development in sub-Saharan Africa

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the Human Immunodeficiency Virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions, as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies, and (c) policymakers and health advocates to collectively contribute in creating health-promoting environments in Africa

Prevalence of chronic kidney disease in South Asia: a systematic review

Background: Chronic kidney disease (CKD) is becoming a major public health problem around the world. But the prevalence has not been reported in South Asian region as a whole. This study aimed to systematically review the existing data from population based studies in this region to bridge this gap. Methods Articles published and reported prevalence of CKD according to K/DOQI practice guideline in eight South Asian countries between December 1955 and April 2017 were searched, screened and evaluated from seven electronic databases using the PRISMA checklist. CKD was defined as creatinine clearance (CrCl) or GFR less than 60 ml/min/1.73 m2. Results Sixteen population-based studies were found from four South Asian countries (India, Bangladesh, Pakistan and Nepal) that used eGFR to measure CKD. No study was available from Sri Lanka, Maldives, Bhutan and Afghanistan. Number of participants ranged from 301 in Pakistan to 12,271 in India. Majority of the studies focused solely on urban population. Different studies used different equations for measuring eGFR. The prevalence of CKD ranged from 10.6% in Nepal to 23.3% in Pakistan using MDRD equation. This prevalence was higher among older age group people. Equal number of studies reported high prevalence among male and female each. Conclusions This systematic review reported high prevalence of CKD in South Asian countries. The findings of this study will help pertinent stakeholders to prepare suitable policy and effective public health intervention in order to reduce the burden of this deadly disease in the most densely populated share of the globe

Session 2-B: George MacDonald and His Literary Companions

Imbruted Souls in Milton and MacDonald - Larry E. Fink Beginning with classical literature, the motif of humans being turned into animals has been common (Odysseus; men transformed by Circe, some of the stories in Ovid’s Metamorphoses). In English literature, as early as Chaucer we find mentions of a time when “Beestes and brides couden speke and singe.” As a rule, talking animals appear in stories of an innocent time or in stories for children, fulfilling the wish that pets and wild friends could join fully in our play. The effect is nostalgic, humorous, comic, or simply charming. However, when humans become animalized, moral degeneration is usually the theme, and horror the tone. George MacDonald regularly quotes or alludes to Milton. One of his most compelling characters, Lilith, owes much to Milton’s Satan, as I have argued in another paper. Here, I will explore Milton’s concept of the brute – the animal – in contrast to human nature, both created good as portrayed in Paradise Lost, and consider possible connections between Milton’s Comus and MacDonald’s Curdie stories, particularly how brutish behavior turns people – outwardly or inwardly – into animals. Finally, I will examine “The Adventure of Eustace” in The Voyage of the Dawn Treader. David Elginbrod as a Prototype of the Wingfold Trilogy in Connection with Coleridge and a Joan Drakes\u27 Case and Its Influence Upon a Certain Victorian Novelist - Miho Yamaguchi George MacDonald and Oscar Wilde: Two Victorian Nonconformists - Laura Stanife

Paper Session 3-B

Heavenly Hierarchy?: The Redemptive Nature of Hierarchy in Tolkien\u27s Middle-Earth - Richard Cornell Tolkien\u27s Middle-Earth is a highly stratified and hierarchical world. Although some hierarchies (such as those headed by Sauron & Saruman) are oppressive and malevolent, some (such as those headed by Ilúvatar & Aragorn) are enriching and benevolent. This paper will consider the nature and role of hierarchy in Tolkien\u27s Middle-Earth and specifically attend to the ways in which Tolkien shows hierarchy to be good and ennobling. Furthermore, the paper will demonstrate ways that Tolkien\u27s Christian faith shapes his portrait of hierarchy. A brief conclusion will offer some reflections on how this more positive view of hierarchy might be appropriated today in a society that worships egalitarianism and democracy. George MacDonald and J. R. R. Tolkien on Faërie and Fairy Stories - Paul E. Michelson The paper discusses the ideas of George MacDonald and J.R.R. Tolkien on Faërie and Fairy Stories, based on an analysis of MacDonald\u27s essay The Fantastic Imagination, Tolkien\u27s On Fairy-Stories, Tolkien\u27s correspondence, and Tolkien\u27s unpublished introduction to MacDonald\u27s The Golden Key. The Good Catastrophe: Tolkien on the Consolation of the Happy Ending John Stanifer When describing the nature of fairy-stories, Tolkien famously coined the term eucatastrophe ( eu meaning good ) to express the effect of the sudden joyous turn that leads to the story\u27s happy ending regardless of the dark events preceding it. Tolkien applies that word specifically to fairy-stories, but I would like to explore its meaning in relation to other genres and mediums that Tolkien was either unable or unwilling to consider. Classic literature and modern popular culture alike are ripe with the use of the good catastrophe, and this device is well-known by cultures from all parts of the globe. If it seems like a stretch to connect Greek linguistics, fairy-stories, British literature, Japanese film, and Korean TV dramas, come listen and let me have the chance to surprise you by demonstrating how much all of these have in common

Graduate Health Professions Education: An Interdisciplinary University - Community Partnership Model 1996-2001

Introduction: In 1996, East Tennessee State University (ETSU) reinforced its historical commitment to multidisciplinary community engagement by developing a graduate level community partnerships program in the Division of Health Sciences. While the university\u27s earlier health partnership efforts relied primarily on curricular innovation, the approach to graduate health professions education was to seed a series of curricular enhancements and interdisciplinary, community-based learning experiences and service into traditional curricula. This paper presents the experience of one school in crafting a regional network that became the basis of a division-wide graduate level teaching and learning initiative. Innovations and Evaluation: Carefully selected planning and implementation techniques enabled multidisciplinary practitioners and community members from across a 20-county region to participate with university faculty in training ETSU learners in community-based medical care. By year four of the project, curricular enhancements were institutionalized in over five departments across the Division and engaged 1160 medical residents and graduate learners in a give - get model of health education. Programme evaluation methodology was collaboratively defined and documentation of programme effort and outcomes regularly reported and strategically reviewed. Conclusions: Programme evaluation demonstrates mutual benefit to community and university. Faculty involvement in programme activity increased fourfold and community involvement in training of health professions graduate learners increased threefold by year four. Educational innovations were adopted into traditional curricula, thousands of hours of clinical services were provided to underserved communities and the university-community team forged by network links continues to promote multidisciplinary interests through joint public policy endeavors