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CRISPR based editing of SIV proviral DNA in ART treated non-human primatesElimination of HIV DNA from infected individuals remains a challenge in medicine. Here, we demonstrate that intravenous inoculation of SIV-infected macaques, a well-accepted non-human primate model of HIV infection, with adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing construct designed for eliminating proviral SIV DNA, leads to broad distribution of editing molecules and precise cleavage and removal of fragments of the integrated proviral DNA from the genome of infected blood cells and tissues known to be viral reservoirs including lymph nodes, spleen, bone marrow, and brain among others. Accordingly, AAV9-CRISPR treatment results in a reduction in the percent of proviral DNA in blood and tissues. These proof-of-concept observations offer a promising step toward the elimination of HIV reservoirs in the clinic.
Enrollment Management in the Context of Responsibility Center ManagementResponsibility Center Management (RCM) budget models are designed to create financial incentives that encourage expense reduction and revenue generation. This article—a primer on RCM—equips enrollment management leaders and other higher education professionals with the knowledge required to support the attainment of enrollment headcount and net tuition revenue goals.
Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?The unique cytokine signature of COVID-19 might provide clues to disease mechanisms and possible future therapies. Here, we propose a pathogenic model in which the alarmin cytokine, interleukin (IL)-33, is a key player in driving all stages of COVID-19 disease (ie, asymptomatic, mild–moderate, severe–critical, and chronic–fibrotic). In susceptible individuals, IL-33 release by damaged lower respiratory cells might induce dysregulated GATA-binding factor 3-expressing regulatory T cells, thereby breaking immune tolerance and eliciting severe acute respiratory syndrome coronavirus 2-induced autoinflammatory lung disease. Such disease might be initially sustained by IL-33-differentiated type-2 innate lymphoid cells and locally expanded γδ T cells. In severe COVID-19 cases, the IL-33–ST2 axis might act to expand the number of pathogenic granulocyte–macrophage colony-stimulating factor-expressing T cells, dampen antiviral interferon responses, elicit hyperinflammation, and favour thromboses. In patients who survive severe COVID-19, IL-33 might drive pulmonary fibrosis by inducing myofibroblasts and epithelial–mesenchymal transition. We discuss the therapeutic implications of these hypothetical pathways, including use of therapies that target IL-33 (eg, anti-ST2), T helper 17-like γδ T cells, immune cell homing, and cytokine balance.
Duolingo English Test, Revised Version July 2019The Duolingo English Test (DET) is a computer adaptive test of English proficiency that is increasingly used for English-medium university admissions purposes. During the COVID-19 pandemic of 2020, test centers were shut down in many countries, and major tests including the TOEFL iBT and IELTS could not be administered. The DET is an “at home” test, and thus many universities began accepting DET scores as ameasure of applicants’ English proficiency. Because a revised version of the DET was launched in July, 2019, and because of the large increase in universities accepting DET scores, a critical review of the DET is warranted. The current review lauds the accessibility of the test (e.g., it is an inexpensive “at home” test that can be taken anywhere, in less than an hour, with scores returned in 48 hours). However, the test has multiple shortcomings: the test tasks have little in common with the types of language tasks university students engage in; the test does not assess test takers’ academic language ability, discourse level competence, or interactional competence; it is susceptible to cheating and test preparation; and it has a potential for negative washback on learners and learning systems. In addition, there is a lack of independent research validating the use of DET scores for admissions. Given these shortcomings, the use of DET scores cannot be recommended for university admissions purposes.
Individual Hurricane Preparedness During the COVID-19 Pandemic: Insights for Risk Communication and Emergency Management PoliciesClimate change adaptation strategies should anticipate that the 2020 situation which resembles an above average hurricane season coinciding with a pandemic may occur more frequently in the future. This study draws lessons on how individual hurricane preparedness is influenced by a pandemic, which turns out to be a combination of perceptions of flood and pandemic risks that have opposite effects on preparedness behavior. We conducted three waves of surveys during 2019-2020 to monitor hurricane preparedness activities in flood-prone coastal areas in Florida, including a survey of 600 respondents in early June 2020 to obtain insights into households’ risk perceptions and preparedness for this hurricane season under COVID-19. The results show that this hurricane season is dominated by concerns over COVID-19 which influences people’s evacuation intentions. Whereas hotel costs were the main obstacle to evacuating during Hurricane Dorian in 2019, the main evacuation obstacle identified in the 2020 hurricane season is COVID-19. Our statistical analyses that investigates the factors influencing evacuation intentions consistently show that older individuals are less likely to evacuate voluntarily, because they are concerned about becoming infected by COVID-19. We discuss the implications of our findings for adaptation policies that aim to improve hurricane preparedness in situations of a pandemic, such as risk communication and emergency management policies.