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After a period of rapidly declining U.S. COVID-19 incidence during January-March 2021, increases occurred in several jurisdictions (1,2) despite the rapid rollout of a large-scale vaccination program. This increase coincided with the spread of more transmissible variants of SARS-CoV-2, the virus that causes COVID-19, including B.1.1.7 (1,3) and relaxation of COVID-19 prevention strategies such as those for businesses, large-scale gatherings, and educational activities. To provide long-term projections of potential trends in COVID-19 cases, hospitalizations, and deaths, COVID-19 Scenario Modeling Hub teams used a multiple-model approach comprising six models to assess the potential course of COVID-19 in the United States across four scenarios with different vaccination coverage rates and effectiveness estimates and strength and implementation of nonpharmaceutical interventions (NPIs) (public health policies, such as physical distancing and masking) over a 6-month period (April-September 2021) using data available through March 27, 2021 (4). Among the four scenarios, an accelerated decline in NPI adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2-3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and deaths. A sharp decline in cases was projected by July 2021, with a faster decline in the high-vaccination scenarios. High vaccination rates and compliance with public health prevention measures are essential to control the COVID-19 pandemic and to prevent surges in hospitalizations and deaths in the coming months.

BackgroundHealthcare-associated infections (HAIs) constitute a significant financial strain on healthcare systems across the world, with surgical site infections (SSIs) being the costliest form. Despite the existence of diverse sources of infection in the operating room (OR), current literature focuses on human and procedural sources of contamination that could lead to an infection. Comparatively, the OR built environment is understudied as a potential disease transmission interface between the environment, patients, and surgical staff. This systematic literature review aims to investigate how the physical characteristics and components of the built environment impact airflow, infection risk, aerosols, particle counts, contamination, and pathogens in operating rooms.Methods and FindingsLiterature searches were conducted in the PubMed and Web of Science Core Collection databases on December 21, 2020, ultimately retrieving 2,965 articles after duplicates were removed. During abstract screening, all abstracts were independently reviewed by two authors and conflicts were resolved by a third author. All articles published since January 1, 2010, that reported primary data investigating an aspect of the built environment inside an OR in relation to airflow, contamination, and/or infection for which the full text in English was available were included. This resulted in the inclusion of 138 articles, which includes studies conducted in ORs during active surgeries, computer modeling studies, and simulations in which a real OR was used for a mock surgical procedure. Six major built environment categories were identified based on the collected literature: OR layout, disinfection systems, surgical lights, doors, ventilation, and portable airflow devices. A survey created on Qualtrics software was used to record the aspect of the built environment and the outcome of each study, as well as the relationship between the two.ConclusionsWhile OR ventilation has been studied extensively, the OR built environment as a whole is understudied in relation to airflow, contamination, and infection. The current literature is inconsistent in both its findings and subsequent recommendations, making it difficult to inform hospital design in the context of SSIs. No articles were identified that discussed respiratory infection transmission in the OR, and very few addressed healthcare worker (HCW) safety in relation to the OR built environment. The significant discrepancies in the literature identified in this review highlight the need for future studies that assess the quality and bias of these studies before firm recommendations can be made. Future work should also focus on addressing the lack information regarding respiratory infection transmission in the OR, especially in the context of HCW safety.

Lay Summary: Competition often occurs among diverse parasites within a single host, but control efforts could change its strength. We examined how the interplay between competition and control could shape the evolution of parasite traits like drug resistance and disease severity.

Significant progress has already been made in development and testing of SARS-CoV-2 vaccines, and Phase III clinical trials have begun for 6 novel vaccine candidates to date. These Phase III trials seek to demonstrate direct benefits of a vaccine on vaccine recipients. However, vaccination is also known to bring about indirect benefits to a population through the reduction of virus circulation. The indirect effects of SARS-CoV-2 vaccination can play a key role in reducing case counts and COVID-19 deaths. To illustrate this point, we show through simulation that a vaccine with strong indirect effects has the potential to reduce SARS-CoV-2 circulation and COVID-19 deaths to a greater extent than an alternative vaccine with stronger direct effects but weaker indirect effects. Protection via indirect effects may be of particular importance in the context of this virus, because elderly individuals are at an elevated risk of death but are also less likely to be directly protected by vaccination due to immune senescence. We therefore encourage ongoing data collection and model development aimed at evaluating the indirect effects of forthcoming SARS-CoV-2 vaccines.

Significant progress has already been made in development and testing of SARS-CoV-2 vaccines, and Phase III clinical trials have begun for 6 novel vaccine candidates to date. These Phase III trials seek to demonstrate direct benefits of a vaccine on vaccine recipients. However, vaccination is also known to bring about indirect benefits to a population through the reduction of virus circulation. The indirect effects of SARS-CoV-2 vaccination can play a key role in reducing case counts and COVID-19 deaths. To illustrate this point, we show through simulation that a vaccine with strong indirect effects has the potential to reduce SARS-CoV-2 circulation and COVID-19 deaths to a greater extent than an alternative vaccine with stronger direct effects but weaker indirect effects. Protection via indirect effects may be of particular importance in the context of this virus, because elderly individuals are at an elevated risk of death but are also less likely to be directly protected by vaccination due to immune senescence. We therefore encourage ongoing data collection and model development aimed at evaluating the indirect effects of forthcoming SARS-CoV-2 vaccines.

In deterministic models of epidemics, there is a host abundance threshold above which the introduction of a few infected individuals leads to a severe epidemic. Studies of weather-driven animal pathogens often assume that abundance thresholds will be overwhelmed by weather-driven stochasticity, but tests of this assumption are lacking. We collected observational and experimental data for a fungal pathogen, Entomophaga maimaiga, that infects the gypsy moth, Lymantria dispar. We used an advanced statistical-computing algorithm to fit mechanistic models to our data, such that different models made different assumptions about the effects of host density and weather on E. maimaiga epizootics (epidemics in animals). We then used Akaike information criterion analysis to choose the best model. In the best model, epizootics are driven by a combination of weather and host density, and the model does an excellent job of explaining the data, whereas models that allow only for weather effects or only for density-dependent effects do a poor job of explaining the data. Density-dependent transmission in our best model produces a host density threshold, but this threshold is strongly blurred by the stochastic effects of weather. Our work shows that host-abundance thresholds may be important even if weather strongly affects transmission, suggesting that epidemiological models that allow for weather have an important role to play in understanding animal pathogens. The success of our model means that it could be useful for managing the gypsy moth, an important pest of hardwood forests in North America.

Explanations for the dynamics of insect outbreaks often focus on natural enemies, on the grounds that parasitoid and pathogen attack rates are high during outbreaks. While natural enemy models can successfully reproduce outbreak cycles, experiments have repeatedly demonstrated the importance of resource quality and abundance. Experiments, however, are rarely invoked in modeling studies. Here we combine mechanistic models, observational data, and field experiments to quantify the roles of parasitoid attacks and resource competition on the jack pine budworm, Choristoneura pinus. By fitting models to a combination of observational and experimental data, we show that parasitoid attacks are the main source of larval budworm mortality at low and intermediate budworm densities but that resource competition is the main source of mortality at high densities. Our results further show that the effects of resource competition become more severe with increasing host tree age and that the effects of parasitoids are moderated by strong competition between parasitoids for hosts. Allowing for these effects in a model of insect outbreaks leads to realistic outbreak cycles, while a host-parasitoid model without resource competition produces an unrealistic stable equilibrium. The effects of resource competition are modulated by tree age, which in turn depends on fire regimes. Our model therefore suggests that increases in fire frequency due to climate change may interact in complex ways with budworm outbreaks. Our work shows that resource competition can be as important as natural enemies in modulating insect outbreaks, while demonstrating the usefulness of high-performance computing in experimental field ecology.

Dense molecular gas and star formation are correlated in galaxies. The effect of low metallicity on this relationship is crucial for interpreting observations of high redshift galaxies, which have lower metallicities than galaxies today. However, it remains relatively unexplored because dense molecular gas tracers like HCN and HCO+ are faint in low metallicity systems. We present Green Bank Telescope observations of HCN(1-0) and HCO+(1-0) on giant molecular cloud (34pc) scales in the nearby low metallicity ($12+\log({\rm O/H})=8.2$) starburst IC 10 and compare them to those in other galaxies. We detect HCN and HCO+ in one and three of five pointings, respectively. The $I_{\rm HCN}/I_{\rm HCO+}$ values are within the range seen in other galaxies, but are most similar to those seen in other low metallicity sources and in starbursts. The detections follow the fiducial $L_{\rm IR}$-$L_{\rm HCN}$ and $L_{\rm IR}$-$L_{\rm HCO+}$ relationships. These trends suggest that HCN and HCO+ can be used to trace dense molecular gas at metallicities of 1/4 $Z_\odot$, to first order. The dense gas fraction is similar to that in spiral galaxies, but lower than that in U/LIRGs. The dense molecular gas star formation efficiency, however, is on the upper end of those in normal galaxies and consistent with those in U/LIRGs. These results suggest that the CO and HCN/HCO+ emission occupy the same relative volumes as at higher metallicity, but that the entire emitting structure is reduced in size. Dense gas mass estimates for high redshift galaxies may need to be corrected for this effect., Comment: Accepted to ApJ

SUMMARY Studies of vulval development in the nematode C. elegans have identified many genes that are involved in cell division and differentiation processes. Some of these encode components of conserved signal transduction pathways mediated by EGF, Notch, and Wnt. To understand how developmental mechanisms change during evolution, we are doing a comparative analysis of vulva formation in C. briggsae, a species that is closely related to C. elegans. Here, we report 14 mutations in 7 Multivulva (Muv) genes in C. briggsae that inhibit inappropriate division of vulval precursors. We have developed a new efficient and cost-effective gene mapping method to localize Muv mutations to small genetic intervals on chromosomes, thus facilitating cloning and functional studies. We demonstrate the utility of our method by determining molecular identities of three of the Muv genes that include orthologs of Cel-lin-1 (ETS) and Cel-lin-31 (Winged-Helix) of the EGF-Ras pathway and Cel-pry-1 (Axin), of the Wnt pathway. The remaining four genes reside in regions that lack orthologs of known C. elegans Muv genes. Inhibitor studies demonstrate that the Muv phenotype of all four new genes is dependent on the activity of the EGF pathway kinase, MEK. One of these, Cbr-lin(gu167), shows modest increase in the expression of Cbr-lin-3/EGF compared to wild type. These results argue that while Cbr-lin(gu167) may act upstream of Cbr-lin-3/EGF, the other three genes influence the EGF pathway downstream or in parallel to Cbr-lin-3. Overall, our findings demonstrate that the genetic program underlying a conserved developmental process includes both conserved and divergent functional contributions.

We compare the structure of molecular gas at $40$ pc resolution to the ability of gas to form stars across the disk of the spiral galaxy M51. We break the PAWS survey into $370$ pc and $1.1$ kpc resolution elements, and within each we estimate the molecular gas depletion time ($\tau_{\rm Dep}^{\rm mol}$), the star formation efficiency per free fall time ($\epsilon_{\rm ff}$), and the mass-weighted cloud-scale (40 pc) properties of the molecular gas: surface density, $\Sigma$, line width, $\sigma$, and $b\equiv\Sigma/\sigma^2\propto\alpha_{\rm vir}^{-1}$, a parameter that traces the boundedness of the gas. We show that the cloud-scale surface density appears to be a reasonable proxy for mean volume density. Applying this, we find a typical star formation efficiency per free-fall time, $\epsilon_{ff} \left( \left< \Sigma_{40pc} \right> \right) \sim 0.3{-}0.36\%$, lower than adopted in many models and found for local clouds. More, the efficiency per free fall time anti-correlates with both $\Sigma$ and $\sigma$, in some tension with turbulent star formation models. The best predictor of the rate of star formation per unit gas mass in our analysis is $b \equiv \Sigma / \sigma^2$, tracing the strength of self gravity, with $\tau_{\rm Dep}^{\rm mol} \propto b^{-0.9}$. The sense of the correlation is that gas with stronger self-gravity (higher $b$) forms stars at a higher rate (low $\tau_{\rm Dep}^{\rm mol}$). The different regions of the galaxy mostly overlap in $\tau_{\rm Dep}^{\rm mol}$ as a function of $b$, so that low $b$ explains the surprisingly high $\tau_{\rm Dep}^{\rm mol}$ found towards the inner spiral arms found by by Meidt et al. (2013)., Comment: Accepted for publication in the Astrophysical Journal, 22 pages, 11 figures, email for access to data table before publication, for high resolution version before publication: http://www.astronomy.ohio-state.edu/~leroy.42/m51_cloudsf.pdf

We explore the use of mm-wave emission line ratios to trace molecular gas density when observations integrate over a wide range of volume densities within a single telescope beam. For observations targeting external galaxies, this case is unavoidable. Using a framework similar to that of Krumholz and Thompson (2007), we model emission for a set of common extragalactic lines from lognormal and power law density distributions. We consider the median density of gas producing emission and the ability to predict density variations from observed line ratios. We emphasize line ratio variations, because these do not require knowing the absolute abundance of our tracers. Patterns of line ratio variations have the prospect to illuminate the high-end shape of the density distribution, and to capture changes in the dense gas fraction and median volume density. Our results with and without a high density power law tail differ appreciably; we highlight better knowledge of the PDF shape as an important area. We also show the implications of sub-beam density distributions for isotopologue studies targeting dense gas tracers. Differential excitation often implies a significant correction to the naive case. We provide tabulated versions of many of our results, which can be used to interpret changes in mm-wave line ratios in terms of changes in the underlying density distributions., 24 pages, 16 figure, Accepted for publication in the Astrophysical Journal, two online tables temporarily available at http://www.astronomy.ohio-state.edu/~leroy.42/densegas_table2.txt and http://www.astronomy.ohio-state.edu/~leroy.42/densegas_table3.txt

Studies of vulval development in the nematode C. elegans have identified many genes that are involved in cell division and differentiation processes. Some of these encode components of conserved signal transduction pathways mediated by EGF, Notch, and Wnt. To understand how developmental mechanisms change during evolution, we are doing a comparative analysis of vulva formation in C. briggsae, a species that is closely related to C. elegans. Here, we report 14 mutations in 7 Multivulva (Muv) genes in C. briggsae that inhibit inappropriate division of vulval precursors. We have developed a new efficient and cost-effective gene mapping method to localize Muv mutations to small genetic intervals on chromosomes, thus facilitating cloning and functional studies. We demonstrate the utility of our method by determining molecular identities of three of the Muv genes that include orthologs of Cel-lin-1 (ETS) and Cel-lin-31 (Winged-Helix) of the EGF-Ras pathway and Cel-pry-1 (Axin), of the Wnt pathway. The remaining four genes reside in regions that lack orthologs of known C. elegans Muv genes. Inhibitor studies demonstrate that the Muv phenotype of all four new genes is dependent on the activity of the EGF pathway kinase, MEK. One of these, Cbr-lin(gu167), shows modest increase in the expression of Cbr-lin-3/EGF compared to wild type. These results argue that while Cbr-lin(gu167) may act upstream of Cbr-lin-3/EGF, the other three genes influence the EGF pathway downstream or in parallel to Cbr-lin-3. Overall, our findings demonstrate that the genetic program underlying a conserved developmental process includes both conserved and divergent functional contributions.