The magnitude and pace of photosynthetic recovery after wildfire in California ecosystems.

Wildfire modifies the short- and long-term exchange of carbon between terrestrial ecosystems and the atmosphere, with impacts on ecosystem services such as carbon uptake. Dry western US forests historically experienced low-intensity, frequent fires, with patches across the landscape occupying different points in the fire-recovery trajectory. Contemporary perturbations, such as recent severe fires in California, could shift the historic stand-age distribution and impact the legacy of carbon uptake on the landscape. Here, we combine flux measurements of gross primary production (GPP) and chronosequence analysis using satellite remote sensing to investigate how the last century of fires in California impacted the dynamics of ecosystem carbon uptake on the fire-affected landscape. A GPP recovery trajectory curve of more than five thousand fires in forest ecosystems since 1919 indicated that fire reduced GPP by [Formula: see text] g C m[Formula: see text] y[Formula: see text]([Formula: see text]) in the first year after fire, with average recovery to prefire conditions after [Formula: see text] y. The largest fires in forested ecosystems reduced GPP by [Formula: see text] g C m[Formula: see text] y[Formula: see text] (n = 401) and took more than two decades to recover. Recent increases in fire severity and recovery time have led to nearly [Formula: see text] MMT CO[Formula: see text] (3-y rolling mean) in cumulative forgone carbon uptake due to the legacy of fires on the landscape, complicating the challenge of maintaining California's natural and working lands as a net carbon sink. Understanding these changes is paramount to weighing the costs and benefits associated with fuels management and ecosystem management for climate change mitigation.

Open science priorities for rigorous nature-based climate solutions.

Nature-based climate solutions (NbCS) hold promise, but must be based on the best available science to be successful. We outline key ingredients of open data and science crucial for robust and scalable nature-based climate solutions efforts, as an urgent call to action for academic researchers, nongovernmental organizations, government agencies, and private companies.

Wildfire-induced increases in photosynthesis in boreal forest ecosystems of North America.

Observations of the annual cycle of atmospheric CO2 in high northern latitudes provide evidence for an increase in terrestrial metabolism in Arctic tundra and boreal forest ecosystems. However, the mechanisms driving these changes are not yet fully understood. One proposed hypothesis is that ecological change from disturbance, such as wildfire, could increase the magnitude and change the phase of net ecosystem exchange through shifts in plant community composition. Yet, little quantitative work has evaluated this potential mechanism at a regional scale. Here we investigate how fire disturbance influences landscape-level patterns of photosynthesis across western boreal North America. We use Alaska and Canadian large fire databases to identify the perimeters of wildfires, a Landsat-derived land cover time series to characterize plant functional types (PFTs), and solar-induced fluorescence (SIF) from the Orbiting Carbon Observatory-2 (OCO-2) as a proxy for photosynthesis. We analyze these datasets to characterize post-fire changes in plant succession and photosynthetic activity using a space-for-time approach. We find that increases in herbaceous and sparse vegetation, shrub, and deciduous broadleaf forest PFTs during mid-succession yield enhancements in SIF by 8-40% during June and July for 2- to 59-year stands relative to pre-fire controls. From the analysis of post-fire land cover changes within individual ecoregions and modeling, we identify two mechanisms by which fires contribute to long-term trends in SIF. First, increases in annual burning are shifting the stand age distribution, leading to increases in the abundance of shrubs and deciduous broadleaf forests that have considerably higher SIF during early- and mid-summer. Second, fire appears to facilitate a long-term shift from evergreen conifer to broadleaf deciduous forest in the Boreal Plain ecoregion. These findings suggest that increasing fire can contribute substantially to positive trends in seasonal CO2 exchange without a close coupling to long-term increases in carbon storage.

Challenges in molecular dynamics simulations of heat exchange statistics.

We study heat exchange in temperature-biased metal-molecule-metal molecular junctions by employing the molecular dynamics simulator LAMMPS. Generating the nonequilibrium steady state with Langevin thermostats at the boundaries of the junction, we show that the average heat current across a gold-alkanedithiol-gold nanojunction behaves physically, with the thermal conductance value matching the literature. In contrast, the full probability distribution function for heat exchange, as generated by the simulator, violates the fundamental fluctuation symmetry for entropy production. We trace this failure back to the implementation of the thermostats and the expression used to calculate the heat exchange. To rectify this issue and produce the correct statistics, we introduce single-atom thermostats as an alternative to conventional many-atom thermostats. Once averaging heat exchange over the hot and cold thermostats, this approach successfully generates the correct probability distribution function, which we use to study the behavior of both the average heat current and its noise. We further examine the thermodynamic uncertainty relation in the molecular junction and show that it holds, albeit demonstrating nontrivial trends. Our study points to the need to carefully implement nonequilibrium molecular dynamics solvers in atomistic simulation software tools for future investigations of noise phenomena in thermal transport.

SARS-CoV-2 infection among physicians over time in Ontario, Canada: a population-based retrospective cohort study.

AIM: To assess this risk of SARS-CoV-2 infection among Ontario physicians by specialty and in comparison with non-physician controls during the COVID-19 pandemic. METHODS: In this retrospective cohort study, the primary outcome was incident SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR). Secondary outcomes were hospitalization, use of critical care, and mortality. RESULTS: From March 1, 2020 to December 31, 2022, 6172/30 617 (20%) active Ontario physicians tested positive for SARS-CoV-2. Infection was less likely if physicians were older (OR 0.78 [0.76-0.81] per 10 years), rural residents (OR 0.70 [0.59-0.83]), and lived in more marginalized neighborhoods (OR 0.74 [0.62-0.89]), but more likely if they were female (OR 1.14 [1.07-1.22]), worked in long-term care settings (OR 1.16 [1.02-1.32]), had higher patient volumes (OR 2.05 [1.82-2.30] for highest vs lowest), and were pediatricians (OR 1.25 [1.09-1.44]). Compared with community-matched controls (n=29 763), physicians had a higher risk of infection during the first two waves of the pandemic (OR 1.38 [1.20-1.59]) but by wave 3 the risk was no longer significantly different (OR 0.93 [0.83-1.05]). Physicians were less likely to be hospitalized within 14 days of their first positive PCR test than non-physicians (P<0.0001), but there was no difference in the use of critical care (P=0.48) or mortality (P=0.15). CONCLUSION: Physicians had higher rates of infection than community-matched controls during the first two waves of the pandemic in Ontario, but not from wave 3 onward. Physicians practicing in long-term care facilities and pediatricians were more likely to test positive for SARS-CoV-2 than other physicians.

Inpatient utilization of immune checkpoint inhibitors and clinical outcomes.

INTRODUCTION: Retrospective studies have suggested that patients with poor performance status treated with immune checkpoint inhibitors have shorter overall survival and poorer response rates. This study was undertaken to investigate the possible relationships between inpatient immune checkpoint inhibitor use and clinical outcomes. METHODS: This was a retrospective chart review of cancer patients who received an immune checkpoint inhibitor while hospitalized from 1 January 2016 to 30 December 2020. The primary outcome was 90-day mortality or admission to hospice rate. Secondary outcomes included overall survival, time to death or discharge to hospice, and descriptive summarization of patient characteristics. RESULTS: A total of 52 patients were analyzed. At 90 days, 68.2% of subjects were expired or admitted to hospice (95% CI: 54.7-81%). 90-day overall survival was 47.1%; median survival time was 81 days (95% CI: 28-242 days). The median time to death or hospice was 35 days (95% CI: 24-72 days). The time to death or hospice was shorter for immune checkpoint inhibitor-naive patients compared to those who received immune checkpoint inhibitors prior to admission (29 days, 95% CI: 12-43 days vs. 242 days, 95% CI: 36-1288 days, respectively; HR: 2.74, 95% CI: 1.2-6.25; p = 0.0121). No differences were found when comparing other baseline characteristics. CONCLUSION: A majority of patients who received an immune checkpoint inhibitor while hospitalized were either discharged to hospice or expired by 90 days. An increased rate of death or discharge to hospice was observed for patients who were immune checkpoint inhibitor-naive prior to their admission.

Locating Partial Discharges in Power Transformers with Convolutional Iterative Filtering.

The most common source of transformer failure is in the insulation, and the most prevalent warning signal for insulation weakness is partial discharge (PD). Locating the positions of these partial discharges would help repair the transformer to prevent failures. This work investigates algorithms that could be deployed to locate the position of a PD event using data from ultra-high frequency (UHF) sensors inside the transformer. These algorithms typically proceed in two steps: first determining the signal arrival time, and then locating the position based on time differences. This paper reviews available methods for each task and then propose new algorithms: a convolutional iterative filter with thresholding (CIFT) to determine the signal arrival time and a reference table of travel times to resolve the source location. The effectiveness of these algorithms are tested with a set of laboratory-triggered PD events and two sets of simulated PD events inside transformers in production use. Tests show the new approach provides more accurate locations than the best-known data analysis algorithms, and the difference is particularly large, 3.7X, when the signal sources are far from sensors.

Using remote sensing to quantify the additional climate benefits of California forest carbon offset projects.

Nature-based climate solutions are a vital component of many climate mitigation strategies, including California's, which aims to achieve carbon neutrality by 2045. Most carbon offsets in California's cap-and-trade program come from improved forest management (IFM) projects. Since 2012, various landowners have set up IFM projects following the California Air Resources Board's IFM protocol. As many of these projects approach their 10th year, we now have the opportunity to assess their effectiveness, identify best practices, and suggest improvements toward future protocol revisions. In this study, we used remote sensing-based datasets to evaluate the carbon trends and harvest histories of 37 IFM projects in California. Despite some current limitations and biases, these datasets can be used to quantify carbon accumulation and harvest rates in offset project lands relative to nearby similar "control" lands before and after the projects began. Five lines of evidence suggest that the carbon accumulated in offset projects to date has generally not been additional to what might have otherwise occurred: (1) most forests in northwestern California have been accumulating carbon since at least the mid-1980s and continue to accumulate carbon, whether enrolled in offset projects or not; (2) harvest rates were high in large timber company project lands before IFM initiation, suggesting they are earning carbon credits for forests in recovery; (3) projects are often located on lands with higher densities of low-timber-value species; (4) carbon accumulation rates have not yet increased on lands that enroll as offset projects, relative to their pre-enrollment levels; and (5) harvest rates have not decreased on most project lands since offset project initiation. These patterns suggest that the current protocol should be improved to robustly measure and reward additionality. In general, our framework of geospatial analyses offers an important and independent means to evaluate the effectiveness of the carbon offsets program, especially as these data products continue improving and as offsets receive attention as a climate mitigation strategy.

Simulations of heat transport in single-molecule junctions: Investigations of the thermal diode effect.

With the objective of understanding microscopic principles governing thermal energy flow in nanojunctions, we study phononic heat transport through metal-molecule-metal junctions using classical molecular dynamics (MD) simulations. Considering a single-molecule gold-alkanedithiol-gold junction, we first focus on aspects of method development and compare two techniques for calculating thermal conductance: (i) The Reverse Nonequilibrium MD (RNEMD) method, where heat is inputted and extracted at a constant rate from opposite metals. In this case, the thermal conductance is calculated from the nonequilibrium temperature profile that is created at the junction. (ii) The Approach-to-Equilibrium MD (AEMD) method, with the thermal conductance of the junction obtained from the equilibration dynamics of the metals. In both methods, simulations of alkane chains of a growing size display an approximate length-independence of the thermal conductance, with calculated values matching computational and experimental studies. The RNEMD and AEMD methods offer different insights, and we discuss their benefits and shortcomings. Assessing the potential application of molecular junctions as thermal diodes, alkane junctions are made spatially asymmetric by modifying their contact regions with the bulk, either by using distinct endgroups or by replacing one of the Au contacts with Ag. Anharmonicity is built into the system within the molecular force-field. We find that, while the temperature profile strongly varies (compared with the gold-alkanedithiol-gold junctions) due to these structural modifications, the thermal diode effect is inconsequential in these systems-unless one goes to very large thermal biases. This finding suggests that one should seek molecules with considerable internal anharmonic effects for developing nonlinear thermal devices.

Accurate tracking of forest activity key to multi-jurisdictional management goals: A case study in California.

An essential component of sustainable forest management is accurate monitoring of forest activities. Although monitoring efforts have generally increased for many forests throughout the world, in practice, effective monitoring is complex. Determining the magnitude and location of progress towards sustainability targets can be challenging due to diverse forest operations across multiple jurisdictions, the lack of data standardization, and discrepancies between field inspections and remotely-sensed records. In this work, we used California as a multijurisdictional case study to explore these problems and develop an approach that broadly informs forest monitoring strategies. The State of California recently entered into a shared stewardship agreement with the US Forest Service (USFS) and set a goal to jointly treat one million acres of forest and rangeland annually by 2025. Currently, however, federal and state forest management datasets are disjoint. This work addresses three barriers stymying the use of federal and state archival records to assess management goals. These barriers are: 1) current databases from different jurisdictions have not been combined due to their distinct data collection processes and internal structures; 2) datasets have not been comprehensively analyzed, despite the need to understand the extent of previous treatments as well as the rate of current activity; and 3) the spatial accuracy of archival datasets has not been evaluated against remotely-sensed data. To reduce these barriers, we first aggregated existing archival forest management records between 1984 and 2019 from the USFS' Forest Activity Tracking System (FACTS) and the California Department of Forestry and Fire Protection (CAL FIRE) using a qualitative scalar of treatment intensity. Combined FACTS and CAL FIRE completed footprint acres - defined as unique areas of land where a treatment was completed at any time since 1984 - have decreased since a peak in 2008. At most, 300,000 footprint acres are completed each year, 30% of the million-acre goal. Prescribed fires - defined as direct burning operations - have risen over time, according to the FACTS hazardous fuels dataset but prescribed fire records in CAL FIRE's dataset have rapidly increased since 2016. We also refined the spatial and temporal detail of the aggregated management record using the Continuous Change Detection and Classification algorithm on satellite remote sensing data to produce a state-wide time series map of harvest disturbances. A comparison of the algorithm's refined data to the archival record potentially suggests over-reporting in both FACTS and CAL FIRE's archival datasets. Our integrated dataset provides a better assessment of current treatments and the path towards the 1-million-acre a year goal. The refined dataset leverages the strengths of complementary, albeit imperfect, monitoring strategies from archives and remotely-sensed detection.

Protein profiling in the habenula after chronic (-)-menthol exposure in mice.

The identification of proteins that are altered following nicotine/tobacco exposure can facilitate and positively impact the investigation of related diseases. In this report, we investigated the effects of chronic (-)-menthol exposure in 14 murine brain regions for changes in total ß2 subunit protein levels and changes in epibatidine binding levels using immunoblotting and radioligand binding assays. We identified the habenula as a region of interest due to the region's marked decreases in ß2 subunit and nAChR levels in response to chronic (-)-menthol alone. Thus, we further examined the habenula, a brain region associated with both the reward and withdrawal components of addiction, for additional protein level alterations using mass spectrometry. A total of 552 proteins with altered levels were identified after chronic (-)-menthol exposure. Enriched in the proteins with altered levels after (-)-menthol exposure were proteins associated with signaling, immune systems, RNA regulation, and protein transport. The continuation and expansion of the brain region-specific protein profiling in response to (-)-menthol will provide a better understanding of how this common flavorant in tobacco and e-liquid products may affect addiction and general health.

Fluorescent Silica Nanoparticles to Label Metastatic Tumor Cells in Mineralized Bone Microenvironments.

During breast cancer bone metastasis, tumor cells interact with bone microenvironment components including inorganic minerals. Bone mineralization is a dynamic process and varies spatiotemporally as a function of cancer-promoting conditions such as age and diet. The functional relationship between skeletal dissemination of tumor cells and bone mineralization, however, is unclear. Standard histological analysis of bone metastasis frequently relies on prior demineralization of bone, while methods that maintain mineral are often harsh and damage fluorophores commonly used to label tumor cells. Here, fluorescent silica nanoparticles (SNPs) are introduced as a robust and versatile labeling strategy to analyze tumor cells within mineralized bone. SNP uptake and labeling efficiency of MDA-MB-231 breast cancer cells is characterized with cryo-scanning electron microscopy and different tissue processing methods. Using a 3D in vitro model of marrow-containing, mineralized bone as well as an in vivo model of bone metastasis, SNPs are demonstrated to allow visualization of labeled tumor cells in mineralized bone using various imaging modalities including widefield, confocal, and light sheet microscopy. This work suggests that SNPs are valuable tools to analyze tumor cells within mineralized bone using a broad range of bone processing and imaging techniques with the potential to increase the understanding of bone metastasis.

Anthropogenic and biogenic CO2 fluxes in the Boston urban region.

With the pending withdrawal of the United States from the Paris Climate Accord, cities are now leading US actions toward reducing greenhouse gas emissions. Implementing effective mitigation strategies requires the ability to measure and track emissions over time and at various scales. We report CO2 emissions in the Boston, MA, urban region from September 2013 to December 2014 based on atmospheric observations in an inverse model framework. Continuous atmospheric measurements of CO2 from five sites in and around Boston were combined with a high-resolution bottom-up CO2 emission inventory and a Lagrangian particle dispersion model to determine regional emissions. Our model-measurement framework incorporates emissions estimates from submodels for both anthropogenic and biological CO2 fluxes, and development of a CO2 concentration curtain at the boundary of the study region based on a combination of tower measurements and modeled vertical concentration gradients. We demonstrate that an emission inventory with high spatial and temporal resolution and the inclusion of urban biological fluxes are both essential to accurately modeling annual CO2 fluxes using surface measurement networks. We calculated annual average emissions in the Boston region of 0.92 kg C·m-2·y-1 (95% confidence interval: 0.79 to 1.06), which is 14% higher than the Anthropogenic Carbon Emissions System inventory. Based on the capability of the model-measurement approach demonstrated here, our framework should be able to detect changes in CO2 emissions of greater than 18%, providing stakeholders with critical information to assess mitigation efforts in Boston and surrounding areas.

Brain Region-Specific nAChR and Associated Protein Abundance Alterations Following Chronic Nicotine and/or Menthol Exposure.

The identification of biomarkers that are altered following nicotine/tobacco exposure can facilitate the investigation of tobacco-related diseases. Nicotinic acetylcholine receptors (nAChRs) are pentameric cation channels expressed in the mammalian central and peripheral nervous systems and the neuromuscular junction. Neuronal nAChR subunits (11) have been identified in mammals (α2-7, α9-10, ß2-4). We examined changes in ß2 nAChR subunit protein levels after chronic nicotine, (±)-menthol, or nicotine co-administered with (±)-menthol in nine murine brain regions. Our investigation of ß2 nAChR subunit level changes identified the hypothalamus as a novel region of interest for menthol exposure that demonstrated increased ß2 nAChR levels after (±)-menthol plus nicotine exposure compared to nicotine exposure alone. Using mass spectrometry, we further characterized changes in membrane protein abundance profiles in the hypothalamus to identify potential biomarkers of (±)-menthol plus nicotine exposure and proteins that may contribute to the elevated ß2 nAChR subunit levels. In the hypothalamus, 272 membrane proteins were identified with altered abundances after chronic nicotine plus menthol exposure with respect to chronic nicotine exposure without menthol. A comprehensive investigation of changes in nAChR and non-nAChR protein expression resulting from (±)-menthol plus nicotine in the brain may establish biomarkers to better understand the effects of these drugs on addiction and addiction-related diseases.

Multi-Institution Evaluation of Sequential Gemcitabine and Docetaxel as Rescue Therapy for Nonmuscle Invasive Bladder Cancer.

PURPOSE: Rescue intravesical therapies for patients with bacillus Calmette-Guérin failure nonmuscle invasive bladder cancer remain a critical focus of ongoing research. Sequential intravesical gemcitabine and docetaxel therapy has shown safety and efficacy in 2 retrospective, single institution cohorts. This doublet has since been adopted as an intravesical salvage option at multiple institutions. We report the results of a multi-institutional evaluation of gemcitabine and docetaxel. MATERIALS AND METHODS: Each institution retrospectively reviewed all records of patients treated with intravesical gemcitabine and docetaxel for nonmuscle invasive bladder cancer between June 2009 and May 2018. Only patients with recurrent nonmuscle invasive bladder cancer and a history of bacillus Calmette-Guérin treatment were included in the analysis. If patients were disease-free after induction, maintenance was instituted at the treating physician's discretion. Posttreatment surveillance followed American Urological Association guidelines. Survival analysis was performed using the Kaplan-Meier method and risk factors for treatment failure were assessed with Cox regression models. RESULTS: Overall 276 patients (median age 73 years, median followup 22.9 months) received treatment. Nine patients were unable to tolerate a full induction course. One and 2-year recurrence-free survival rates were 60% and 46%, and high grade recurrence-free survival rates were 65% and 52%, respectively. Ten patients (3.6%) had disease progression on transurethral resection. Forty-three patients (15.6%) went on to cystectomy (median 11.3 months from induction), of whom 11 (4.0%) had progression to muscle invasion. Analysis identified no patient, disease or prior treatment related factors associated with gemcitabine and docetaxel failure. CONCLUSIONS: Intravesical gemcitabine and docetaxel therapy is well tolerated and effective, providing a durable response in patients with recurrent nonmuscle invasive bladder cancer after bacillus Calmette-Guérin therapy. Further prospective study is warranted.

Extensive land cover change across Arctic-Boreal Northwestern North America from disturbance and climate forcing.

A multitude of disturbance agents, such as wildfires, land use, and climate-driven expansion of woody shrubs, is transforming the distribution of plant functional types across Arctic-Boreal ecosystems, which has significant implications for interactions and feedbacks between terrestrial ecosystems and climate in the northern high-latitude. However, because the spatial resolution of existing land cover datasets is too coarse, large-scale land cover changes in the Arctic-Boreal region (ABR) have been poorly characterized. Here, we use 31 years (1984-2014) of moderate spatial resolution (30 m) satellite imagery over a region spanning 4.7 × 106  km2 in Alaska and northwestern Canada to characterize regional-scale ABR land cover changes. We find that 13.6 ± 1.3% of the domain has changed, primarily via two major modes of transformation: (a) simultaneous disturbance-driven decreases in Evergreen Forest area (-14.7 ± 3.0% relative to 1984) and increases in Deciduous Forest area (+14.8 ± 5.2%) in the Boreal biome; and (b) climate-driven expansion of Herbaceous and Shrub vegetation (+7.4 ± 2.0%) in the Arctic biome. By using time series of 30 m imagery, we characterize dynamics in forest and shrub cover occurring at relatively short spatial scales (hundreds of meters) due to fires, harvest, and climate-induced growth that are not observable in coarse spatial resolution (e.g., 500 m or greater pixel size) imagery. Wildfires caused most of Evergreen Forest Loss and Evergreen Forest Gain and substantial areas of Deciduous Forest Gain. Extensive shifts in the distribution of plant functional types at multiple spatial scales are consistent with observations of increased atmospheric CO2 seasonality and ecosystem productivity at northern high-latitudes and signal continental-scale shifts in the structure and function of northern high-latitude ecosystems in response to climate change.

Urban Heat Islets: Street Segments, Land Surface Temperatures, and Medical Emergencies During Heat Advisories.

Objectives. To examine the relationships among environmental characteristics, temperature, and health outcomes during heat advisories at the geographic scale of street segments.Methods. We combined multiple data sets from Boston, Massachusetts, including remotely sensed measures of temperature and associated environmental characteristics (e.g., canopy cover), 911 dispatches for medical emergencies, daily weather conditions, and demographic and physical context from the American Community Survey and City of Boston Property Assessments. We used multilevel models to analyze the distribution of land surface temperature and elevated vulnerability during heat advisories across streets and neighborhoods.Results. A substantial proportion of variation in land surface temperature existed between streets within census tracts (38%), explained by canopy, impervious surface, and albedo. Streets with higher land surface temperature had a greater likelihood of medical emergencies during heat advisories relative to the frequency of medical emergencies during non-heat advisory periods. There was no independent effect of the average land surface temperature of the census tract.Conclusions. The relationships among environmental characteristics, temperature, and health outcomes operate at the spatial scale of the street segment, calling for more geographically precise analysis and intervention. (Am J Public Health. Published online ahead of print May 21, 2020: e1-e8. doi:10.2105/AJPH.2020.305636).

Clearing the surgical backlog caused by COVID-19 in Ontario: a time series modelling study.

BACKGROUND: To mitigate the effects of coronavirus disease 2019 (COVID-19), jurisdictions worldwide ramped down nonemergent surgeries, creating a global surgical backlog. We sought to estimate the size of the nonemergent surgical backlog during COVID-19 in Ontario, Canada, and the time and resources required to clear the backlog. METHODS: We used 6 Ontario or Canadian population administrative sources to obtain data covering part or all of the period between Jan. 1, 2017, and June 13, 2020, on historical volumes and operating room throughput distributions by surgery type and region, and lengths of stay in ward and intensive care unit (ICU) beds. We used time series forecasting, queuing models and probabilistic sensitivity analysis to estimate the size of the backlog and clearance time for a +10% (+1 day per week at 50% capacity) surge scenario. RESULTS: Between Mar. 15 and June 13, 2020, the estimated backlog in Ontario was 148 364 surgeries (95% prediction interval 124 508-174 589), an average weekly increase of 11 413 surgeries. Estimated backlog clearance time is 84 weeks (95% confidence interval [CI] 46-145), with an estimated weekly throughput of 717 patients (95% CI 326-1367) requiring 719 operating room hours (95% CI 431-1038), 265 ward beds (95% CI 87-678) and 9 ICU beds (95% CI 4-20) per week. INTERPRETATION: The magnitude of the surgical backlog from COVID-19 raises serious implications for the recovery phase in Ontario. Our framework for modelling surgical backlog recovery can be adapted to other jurisdictions, using local data to assist with planning.

Policy-Relevant Assessment of Urban CO2 Emissions.

Global fossil fuel carbon dioxide (FFCO2) emissions will be dictated to a great degree by the trajectory of emissions from urban areas. Conventional methods to quantify urban FFCO2 emissions typically rely on self-reported economic/energy activity data transformed into emissions via standard emission factors. However, uncertainties in these traditional methods pose a roadblock to implementation of effective mitigation strategies, independently monitor long-term trends, and assess policy outcomes. Here, we demonstrate the applicability of the integration of a dense network of greenhouse gas sensors with a science-driven building and street-scale FFCO2 emissions estimation through the atmospheric CO2 inversion process. Whole-city FFCO2 emissions agree within 3% annually. Current self-reported inventory emissions for the city of Indianapolis are 35% lower than our optimal estimate, with significant differences across activity sectors. Differences remain, however, regarding the spatial distribution of sectoral FFCO2 emissions, underconstrained despite the inclusion of coemitted species information.

The genetic basis for variation in resistance to infection in the Drosophila melanogaster genetic reference panel.

Individuals vary extensively in the way they respond to disease but the genetic basis of this variation is not fully understood. We found substantial individual variation in resistance and tolerance to the fungal pathogen Metarhizium anisopliae Ma549 using the Drosophila melanogaster Genetic Reference Panel (DGRP). In addition, we found that host defense to Ma549 was correlated with defense to the bacterium Pseudomonas aeruginosa Pa14, and several previously published DGRP phenotypes including oxidative stress sensitivity, starvation stress resistance, hemolymph glucose levels, and sleep indices. We identified polymorphisms associated with differences between lines in both their mean survival times and microenvironmental plasticity, suggesting that lines differ in their ability to adapt to variable pathogen exposures. The majority of polymorphisms increasing resistance to Ma549 were sex biased, located in non-coding regions, had moderately large effect and were rare, suggesting that there is a general cost to defense. Nevertheless, host defense was not negatively correlated with overall longevity and fecundity. In contrast to Ma549, minor alleles were concentrated in the most Pa14-susceptible as well as the most Pa14-resistant lines. A pathway based analysis revealed a network of Pa14 and Ma549-resistance genes that are functionally connected through processes that encompass phagocytosis and engulfment, cell mobility, intermediary metabolism, protein phosphorylation, axon guidance, response to DNA damage, and drug metabolism. Functional testing with insertional mutagenesis lines indicates that 12/13 candidate genes tested influence susceptibility to Ma549. Many candidate genes have homologs identified in studies of human disease, suggesting that genes affecting variation in susceptibility are conserved across species.