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"Miller, C"
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Superspreading events in the transmission dynamics of SARS-CoV-2: Opportunities for interventions and control
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 2019 (COVID-19) disease, has moved rapidly around the globe, infecting millions and killing hundreds of thousands. The basic reproduction number, which has been widely used—appropriately and less appropriately—to characterize the transmissibility of the virus, hides the fact that transmission is stochastic, often dominated by a small number of individuals, and heavily influenced by superspreading events (SSEs). The distinct transmission features of SARS-CoV-2, e.g., high stochasticity under low prevalence (as compared to other pathogens, such as influenza), and the central role played by SSEs on transmission dynamics cannot be overlooked. Many explosive SSEs have occurred in indoor settings, stoking the pandemic and shaping its spread, such as long-term care facilities, prisons, meat-packing plants, produce processing facilities, fish factories, cruise ships, family gatherings, parties, and nightclubs. These SSEs demonstrate the urgent need to understand routes of transmission, while posing an opportunity to effectively contain outbreaks with targeted interventions to eliminate SSEs. Here, we describe the different types of SSEs, how they influence transmission, empirical evidence for their role in the COVID-19 pandemic, and give recommendations for control of SARS-CoV-2.
Journal Article
Muscarinic Cholinergic Receptor Agonist and Peripheral Antagonist for Schizophrenia
The muscarinic receptor agonist xanomeline has antipsychotic properties without dopamine blockade. Cholinergic adverse events limit its use. When xanomeline was combined with trospium to limit peripheral effects, scores were better on measures of schizophrenia than were scores with placebo over a period of 5 weeks.
Journal Article
World music : a global journey
\"World Music: A Global Journey, Fourth Edition takes students around the world to experience the diversity of musical expression and cultural traditions. It is known for its breadth in surveying the world's major cultures in a systematic study of world music within a strong pedagogical framework. As one would prepare for any journey, each chapter starts with background preparation, reviewing the historical, cultural, and musical overview of the region. Visits to multiple \"sites\" within a region provide in-depth studies of varied musical traditions. Music analysis begins with an experiential \"first impression\" of the music, followed by an \"aural analysis\" of the sound and prominent musical elements. Finally, students are invited to consider the cultural connections that give the music its meaning and life\"--Back cover.
Book
Mechanism of head-to-head MCM double-hexamer formation revealed by cryo-EM
In preparation for bidirectional DNA replication, the origin recognition complex (ORC) loads two hexameric MCM helicases to form a head-to-head double hexamer around DNA
1
,
2
. The mechanism of MCM double-hexamer formation is debated. Single-molecule experiments have suggested a sequential mechanism, in which the ORC-dependent loading of the first hexamer drives the recruitment of the second hexamer
3
. By contrast, biochemical data have shown that two rings are loaded independently via the same ORC-mediated mechanism, at two inverted DNA sites
4
,
5
. Here we visualize MCM loading using time-resolved electron microscopy, and identify intermediates in the formation of the double hexamer. We confirm that both hexamers are recruited via the same interaction that occurs between ORC and the C-terminal domains of the MCM helicases. Moreover, we identify the mechanism of coupled MCM loading. The loading of the first MCM hexamer around DNA creates a distinct interaction site, which promotes the engagement of ORC at the N-terminal homodimerization interface of MCM. In this configuration, ORC is poised to direct the recruitment of the second hexamer in an inverted orientation, which is suitable for the formation of the double hexamer. Our results therefore reconcile the two apparently contrasting models derived from single-molecule experiments and biochemical data.
Time-resolved electron microscopy reveals the mechanism by which the origin recognition complex loads pairs of MCM helicases around DNA prior to bidirectional replication.
Journal Article
Quantifying the Effect of Anthropogenic Climate Change on Calcifying Plankton
Widely regarded as an imminent threat to our oceans, ocean acidification has been documented in all oceanic basins. Projected changes in seawater chemistry will have catastrophic biotic effects due to ocean acidification hindering biogenic carbonate production, which will in turn lead to substantial changes in marine ecosystems. However, previous attempts to quantify the effect of acidification on planktonic calcifying organisms has relied on laboratory based studies with substantial methodological limitations. This has been overcome by comparing historic plankton tows from the seminal HMS
Challenger
Expedition (1872–1876) with the recent
Tara
Oceans expedition material (2009–2016). Nano CT-scans of selected equatorial Pacific Ocean planktonic foraminifera, have revealed that all modern specimens had up to 76% thinner shells than their historic counterparts. The “
Challenger
Revisited” project highlights the potential of historic ocean collections as a tool to investigate ocean acidification since the early Industrial Revolution. Further analyses of such biotic archives will enable researchers to quantify the effects of anthropogenic climate change across the globe.
Journal Article
Optimal timing of one-shot interventions for epidemic control
The interventions and outcomes in the ongoing COVID-19 pandemic are highly varied. The disease and the interventions both impose costs and harm on society. Some interventions with particularly high costs may only be implemented briefly. The design of optimal policy requires consideration of many intervention scenarios. In this paper we investigate the optimal timing of interventions that are not sustainable for a long period. Specifically, we look at at the impact of a single short-term non-repeated intervention (a “one-shot intervention”) on an epidemic and consider the impact of the intervention’s timing. To minimize the total number infected, the intervention should start close to the peak so that there is minimal rebound once the intervention is stopped. To minimise the peak prevalence, it should start earlier, leading to initial reduction and then having a rebound to the same prevalence as the pre-intervention peak rather than one very large peak. To delay infections as much as possible (as might be appropriate if we expect improved interventions or treatments to be developed), earlier interventions have clear benefit. In populations with distinct subgroups, synchronized interventions are less effective than targeting the interventions in each subcommunity separately.
Journal Article