Search

This paper describes the problem of forming work groups. The motivating problem is often described as maximizing the diversity of members within groups, and also as minimizing the differences among groups. We review the formulations of this problem in the literature, paying particular attention to the different criteria that have been suggested. We compare the various criteria by solving a number of test problems using standard techniques and then examining the possibility that using one criterion will produce a result that is desirable on other criteria. Ultimately, we recommend a composite procedure for solving large versions of the group formation problem. Keywords: diversity; heuristic; algorithms

Prompt administration of intravenous (i.v.) dantrolene sodium (DS) is the primary determinant of successful treatment of malignant hyperthermia (MH) syndrome. Because DS has a long reconstitution time for use in treating an MH crisis, we evaluated an alternative technique for hastening the reconstitution. Simulating real-world conditions, with equipment common to the operating room environment, we conducted a randomized, controlled, single-blind study dividing 16 DS vials into 2 equal groups: warm (41 degrees C) and ambient temperature (22 degrees C). With an i.. fluid warmer at 41 degrees C, primed with a 1-L bag of preservative-free sterile water, attached to a 60-mL syringe via a 3-way stopcock, we aspirated and injected the diluent directly into each DS vial. The Icarus effect was clearly demonstrated: warmed diluent vs ambient temperature hastened the reconstitution time for DS. The mean time to particulate-free DS solution suitable for i.v. injection with the warm diluent was 58.88 seconds compared with 93.87 seconds for the ambient temperature group (P <.001). A practical method using a reliable and safe warming device readily available to anesthetists and ubiquitous to the operating room environment speeds the time to administration of DS ultimately reducing morbidity and mortality associated with MH. [ABSTRACT FROM AUTHOR]

Background: Vancomycin has only rarely been implicated as a cause of thrombocytopenia, and there is only limited evidence that this complication is caused by immune mechanisms. We conducted a study to determine whether thrombocytopenia is caused by vancomycin-dependent antibodies in patients being treated with vancomycin.Methods: We identified and characterized vancomycin-dependent, platelet-reactive antibodies in patients who had been referred for testing during a 5-year period because of a clinical suspicion of vancomycin-induced thrombocytopenia. We obtained clinical information about the patients from their referring physicians.Results: Drug-dependent, platelet-reactive antibodies of the IgG class, the IgM class, or both were identified in 34 patients, and clinical follow-up information was obtained from 29 of these patients. The mean nadir platelet count in these patients was 13,600 per cubic millimeter, and severe bleeding occurred in 10 patients (34%). Platelet levels returned to baseline in all 26 surviving patients after vancomycin was stopped. In 15 patients, the drug was continued for 1 to 14 days while other possible causes of thrombocytopenia were investigated. Vancomycin-dependent antibodies were not found in 25 patients who had been given vancomycin and in whom thrombocytopenia did not develop.Conclusions: Severe bleeding can occur in patients with vancomycin-induced immune thrombocytopenia. The detection of vancomycin-dependent antiplatelet antibodies in patients receiving the antibiotic in whom thrombocytopenia develops, and the absence of antibodies in patients given the drug in whom platelet counts remain stable, indicate that these antibodies are the cause of the thrombocytopenia. [ABSTRACT FROM AUTHOR]

The Expedited Modeling of Burn Events Results (EMBER) dataset consists of 36-km grid-spacing Community Multiscale Air Quality (CMAQ) photochemical modeling for the summer of 2023. For emissions, these simulations utilized representative monthly and day-of-week anthropogenic emissions from a recent year and preliminary day-specific 2023 fire emissions derived using BlueSky pipeline. The base model run simulated ozone concentrations across the contiguous US during Apr 11-Sep 29, 2023. Two zero-out model runs simulated ozone levels that would have occurred in the US (1) in the absence of fire emissions ("Zero Fires") and (2) in the absence of only Canadian wildfire emissions ("Zero Canadian Fires"). Fire impacts on ozone were then estimated as the difference between ozone simulated in the base EMBER run compared to the ozone simulated in each of the zero out model runs. EMBER is presented as a screening level dataset due to the emissions limitations and the 36-km grid-spacing used in these simulations.

Prescribed fire is applied across the United States as a fuel treatment to manage the impact of wildfires and restore ecosystems. While the recent application of prescribed fire has largely been confined to the southeastern US, the increase in catastrophic wildfires has accelerated the growth of prescribed fire more broadly. To effectively achieve wildfire risk reduction benefits, which includes reducing the amount of smoke emitted, the area treated by prescribed fire must come into contact with a subsequent wildfire. In this study, we applied timely and consistent geospatially resolved data sets of prescribed fires and wildfires to estimate the rate at which an area treated by prescribed fire encounters a subsequent wildfire. We summarize these encounter rates across time intervals, prescribed fire treatment area, and number of previous prescribed fires and by region. On all U.S. Forest Service lands across the Conterminous US (CONUS) 6.2% of prescribed fire treated area from 2003-2022 encountered a subsequent wildfire in 2004-2023. Encounter rates were highest in western US forests, which tend to be more impacted by wildfire than the eastern US, and lower in the eastern US. Encounter rates increased with treatment area in the southeastern US but were relatively flat in the northwest. For the CONUS, encounter rates increased with longer time intervals, associated with diminished potential for reducing wildfire severity, between prescribed fire and the subsequent wildfire area burned. Our results provide timely information on prescribed fire and wildfire interactions that can be leveraged to optimize analyses of the trade-offs between prescribed fire and wildfire., Competing Interests: The authors declare no competing financial interest., (Not subject to U.S. Copyright. Published 2024 by American Chemical Society.)

Clinical Relevance: There is now an Optometry Council of Australia and New Zealand (OCANZ) accreditation requirement for Australian and Aotearoa New Zealand optometry programs to ensure students can provide culturally safe care for First Nations Peoples. To assist programs, OCANZ developed the Optometry Aboriginal and Torres Strait Islander Health Curriculum Framework (Optometry Framework) ., Background: The objective of this study was to evaluate early progress towards the implementation., Methods: All seven Australian optometry programs were invited to complete a modified version of the OCANZ curriculum mapping tool. Where available, online unit outlines were reviewed to verify and supplement the data. Curriculum maps were synthesised using qualitative content analysis., Results: None of the five participating programs had a standalone Aboriginal and Torres Strait Islander health unit; instead, programs were integrating content into core units. Only 25% of the units with relevant content had a directly related learning outcome. All programs had at least some content that was either directly or indirectly related to each of the Optometry Framework themes, and included some content related to novice and intermediate levels of learning. Four programs had content related to entry to practice levels of learning. The average total duration of directly related content in programs (excluding clinical placements) was 18 hours. Not all programs offered an Aboriginal and Torres Strait Islander health setting clinical placement opportunity. Directly related assessment was minimal in most programs, where the format was predominantly reflective journals or questions within written examinations., Conclusion: Progress has been made in implementing the Optometry Framework ; however, further efforts are required. Programs need to integrate additional directly related learning outcomes, content (particularly entry to practice level learning), and assessment. Further curriculum enhancements will improve the likelihood of optometry students acquiring the necessary capabilities for providing culturally safe care.

Background: Air pollution risk assessments do not generally quantify health impacts using multipollutant risk estimates, but instead use results from single-pollutant or copollutant models. Multipollutant epidemiological models account for pollutant interactions and joint effects but can be computationally complex and data intensive. Risk estimates from multipollutant studies are therefore challenging to implement in the quantification of health impacts., Objectives: Our objective was to conduct a case study using a developmental multipollutant version of the Environmental Benefits Mapping and Analysis Program-Community Edition (BenMAP-CE) to estimate the health impact associated with changes in multiple air pollutants using both a single and multipollutant approach., Methods: BenMAP-CE was used to estimate the change in the number of pediatric asthma emergency department (ED) visits attributable to simulated changes in air pollution between 2011 and 2025 in Atlanta, Georgia, applying risk estimates from an epidemiological study that examined short-term single-pollutant and multipollutant (with and without first-order interactions) exposures. Analyses examined individual pollutants (i.e., ozone, fine particulate matter, carbon monoxide, nitrogen dioxide ( NO 2 ), sulfur dioxide, and particulate matter components) and combinations of these pollutants meant to represent shared properties or predefined sources (i.e., oxidant gases, secondary pollutants, traffic, power plant, and criteria pollutants). Comparisons were made between multipollutant health impact functions (HIF) and the sum of single-pollutant HIFs for the individual pollutants that constitute the respective pollutant groups., Results: Photochemical modeling predicted large decreases in most of the examined pollutant concentrations between 2011 and 2025 based on sector specific (i.e., source-based) estimates of growth and anticipated controls. Estimated number of avoided asthma ED visits attributable to any given multipollutant group were generally higher when using results from models that included interaction terms in comparison with those that did not. We estimated the greatest number of avoided pediatric asthma ED visits for pollutant groups that include NO 2 (i. e., criteria pollutants, oxidants, and traffic pollutants). In models that accounted for interaction, year-round estimates for pollutant groups that included NO 2 ranged from 27.1 [95% confidence interval (CI): 1.6, 52.7; traffic pollutants] to 55.4 (95% CI: 41.8, 69.0; oxidants) avoided pediatric asthma ED visits. Year-round results using multipollutant risk estimates with interaction were comparable to the sum of the single-pollutant results corresponding to most multipollutant groups [e.g., 52.9 (95% CI: 43.6, 62.2) for oxidants] but were notably lower than the sum of the single-pollutant results for some pollutant groups [e.g., 77.5 (95% CI: 66.0, 89.0) for traffic pollutants]., Discussion: Performing a multipollutant health impact assessment is technically feasible but computationally complex. It requires time, resources, and detailed input parameters not commonly reported in air pollution epidemiological studies. Results estimated using the sum of single-pollutant models are comparable to those quantified using a multipollutant model. Although limited to a single study and location, assessing the trade-offs between a multipollutant and single-pollutant approach is warranted. https://doi.org/10.1289/EHP12969.

The Selux Next-Generation Phenotyping (NGP) system (Charlestown, MA) is a new antimicrobial susceptibility testing system that utilizes two sequential assays performed on all wells of doubling dilution series to determine MICs. A multicenter evaluation of the performance of the Selux NGP system compared with reference broth microdilution was conducted following FDA recommendations and using FDA-defined breakpoints. A total of 2,488 clinical and challenge isolates were included; gram-negative isolates were tested against 24 antimicrobials, and gram-positive isolates were tested against 15 antimicrobials. Data is provided for all organism-antimicrobial combinations evaluated, including those that did and did not meet FDA performance requirements. Overall very major error and major error rates were less than 1% (31/3,805 and 107/15,606, respectively), essential agreement and categorical agreement were >95%, reproducibility was ≥95%, and the average time-to-result (from time of assay start to time of MIC result) was 5.65 hours., Competing Interests: Authors K.F., B.R.S., K.R.B., S.M., K.R., A.E., M.S., J.C., J.L., K.D., N.S., G.K., F.C., J.D., A.C., A.L., J.S., K.M., A.V., and E.S. are or have been employed by Selux Diagnostics. A.F., J.S.L., M.J.F., S.E.S., M.P.W., and D.C.H. have consulted for Selux Diagnostics.

Single source contribution to ambient O 3 and PM 2.5 has been estimated with photochemical grid models to support policy demonstrations for National Ambient Air Quality Standards, regional haze, and permit related programs. Limited field data exists to evaluate model representation of the spatial extent and chemical composition of plumes emitted by specific facilities. New tropospheric column measurements of NO 2 and in-plume chemical measurements downwind of specific facilities allows for photochemical model evaluation of downwind plume extent, grid resolution impacts on plume concentration gradients, and source attribution methods. Here, photochemical models were applied with source sensitivity and source apportionment approaches to differentiate single source impacts on NO 2 and O 3 and compare with field study measurements. Source sensitivity approaches (e.g., brute-force difference method and decoupled direct method (DDM)) captured the spatial extent of NO 2 plumes downwind of three facilities and the transition of near-source O 3 titration to downwind production. Source apportionment approaches showed variability in terms of attributing the spatial extent of NO 2 plumes and downwind O 3 production. Each of the Community Multiscale Air Quality (CMAQ) source apportionment options predicted large O 3 contribution from a large industrial facility in the flight transects nearest the facility when measurements and source sensitivity approaches suggest titration was outpacing production. In general, CMAQ DDM tends to attribute more O 3 to boundary inflow and less to within-domain NO X and VOC sources compared to CMAQ source apportionment. The photochemical modeling system was able to capture single source plumes using 1 to 12 km grid resolution with best representation of plume extent and magnitude at the finer resolutions. When modeled at 1 to 12 km grid resolution, primary and secondary PM 2.5 impacts were highest at the source location and decrease as distance increases downwind. The use of coarser grid resolution for single source attribution resulted in predicted impacts highest near the source but lower peak source specific concentrations compared to finer grid resolution simulations because impacts were spread out over a larger area., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Reduced complexity tools that provide a representation of both primarily emitted particulate matter with an aerodynamic diameter less than 2.5 μm (PM 2.5 ), secondarily formed PM 2.5 , and ozone (O 3 ) allow for a quick assessment of many iterations of pollution control scenarios. Here, a new reduced complexity tool, Pattern Constructed Air Pollution Surfaces (PCAPS), that estimates annual average PM 2.5 and seasonal average maximum daily average 8 h (MDA8) O 3 for any source location in the United States is described and evaluated. Typically, reduced complexity tools are not evaluated for skill in predicting change in air pollution by comparison with more sophisticated modeling systems. Here, PCAPS was compared against multiple types of emission control scenarios predicted with state-of-the-science photochemical grid models to provide confidence that the model is realistically capturing the change in air pollution due to changing emissions. PCAPS was also applied with all anthropogenic emissions sources for multiple retrospective years to predict PM 2.5 chemical components for comparison against routine surface measurements. PCAPS predicted similar magnitudes and regional variations in spatial gradients of measured chemical components of PM 2.5 . Model performance for capturing ambient measurements was consistent with other reduced complexity tools. PCAPS also did well at capturing the magnitude and spatial features of changes predicted by photochemical transport models for multiple emissions scenarios for both O 3 and PM 2.5 . PCAPS is a flexible tool that provides source-receptor relationships using patterns of air quality gradients from a training data set of generic modeled sources to create interpolated air pollution gradients for new locations not part of the training database. The flexibility provided for both sources and receptors makes this tool ideal for integration into larger frameworks that provide emissions changes and need estimates of air quality to inform downstream analytics, which often includes an estimate of monetized health effects.

Reduced-form modeling approaches are an increasingly popular way to rapidly estimate air quality and human health impacts related to changes in air pollutant emissions. These approaches reduce computation time by making simplifying assumptions about pollutant source characteristics, transport and chemistry. Two reduced form tools used by the Environmental Protection Agency in recent assessments are source apportionment-based benefit per ton (SA BPT) and source apportionment-based air quality surfaces (SABAQS). In this work, we apply these two reduced form tools to predict changes in ambient summer-season ozone, ambient annual PM 2.5 component species and monetized health benefits for multiple sector-specific emission control scenarios: on-road mobile, electricity generating units (EGUs), cement kilns, petroleum refineries, and pulp and paper facilities. We then compare results against photochemical grid and standard health model-based estimates. We additionally compare monetized PM 2.5 health benefits to values derived from three reduced form tools available in the literature: the Intervention Model for Air Pollution (InMAP), Air Pollution Emission Experiments and Policy Analysis (APEEP) version 2 (AP2) and Estimating Air pollution Social Impact Using Regression (EASIUR). Ozone and PM 2.5 changes derived from SABAQS for EGU scenarios were well-correlated with values obtained from photochemical modeling simulations with spatial correlation coefficients between 0.64 and 0.89 for ozone and between 0.75 and 0.94 for PM 2.5 . SABAQS ambient ozone and PM 2.5 bias when compared to photochemical modeling predictions varied by emissions scenario: SABAQS PM 2.5 changes were overpredicted by up to 46% in one scenario and underpredicted by up to 19% in another scenario; SABAQS seasonal ozone changes were overpredicted by 34% to 83%. All tools predicted total PM 2.5 benefits within a factor of 2 of the full-form predictions consistent with intercomparisons of reduced form tools available in the literature. As reduced form tools evolve, it is important to continue periodic comparison with comprehensive models to identify systematic biases in estimating air pollution impacts and resulting monetized health benefits., Competing Interests: CONFLICTS OF INTEREST There are no conflicts to declare

The Integrated Source Apportionment Method (ISAM) has been revised in the Community Multiscale Air Quality (CMAQ) model. This work updates ISAM to maximize its flexibility, particularly for ozone (O 3 ) modeling, by providing multiple attribution options, including products inheriting attribution fully from nitrogen oxide reactants, fully from volatile organic compound (VOC) reactants, equally from all reactants, or dynamically from NO x or VOC reactants based on the indicator gross production ratio of hydrogen peroxide (H 2 O 2 ) to nitric acid (HNO 3 ). The updated ISAM has been incorporated into the most recent publicly accessible versions of CMAQ (v5.3.2 and beyond). This study's primary objective is to document these ISAM updates and demonstrate their impacts on source apportionment results for O 3 and its precursors. Additionally, the ISAM results are compared with the Ozone Source Apportionment Technology (OSAT) in the Comprehensive Air-quality Model with Extensions (CAMx) and the brute-force method (BF). All comparisons are performed for a 4 km horizontal grid resolution application over the northeastern US for a selected 2 d summer case study (9 and 10 August 2018). General similarities among ISAM, OSAT, and BF results add credibility to the new ISAM algorithms. However, some discrepancies in magnitude or relative proportions among tracked sources illustrate the distinct features of each approach, while others may be related to differences in model formulation of chemical and physical processes. Despite these differences, OSAT and ISAM still provide useful apportionment data by identifying the geographical and temporal contributions of O 3 and its precursors. Both OSAT and ISAM attribute the majority of O 3 and NO x contributions to boundary, mobile, and biogenic sources, whereas the top three contributors to VOCs are found to be biogenic, boundary, and area sources., Competing Interests: Competing interests. The contact author has declared that none of the authors has any competing interests.

Clinical Relevance: Aboriginal and Torres Strait Islander Peoples have the right to the highest attainable standard of health and access to health services without discrimination. To uphold these rights, it is important that optometry students are educated in Aboriginal and Torres Strait Islander health and culturally safe practice., Background: An Aboriginal and Torres Strait Islander health curriculum framework is now mandatory for optometry programs to implement. This study explores the experiences of those involved in implementing this framework and, from their perspectives, what is and is not working., Methods: Heads and educators involved in Aboriginal and Torres Strait Islander health curriculum at Australian optometry programs participated in a mixed-methods study. Information about pedagogy and contextual issues impacting curriculum implementation was collected through surveys and interviews. The design and analysis were underpinned by constructivist grounded theory., Results: Most programs had at least partially implemented components of the curriculum framework. While partnerships were considered essential to success, this remains a work in progress. Authentic learning through clinical placement was considered a priority. Assessment was described as complex and not yet adequately addressed. Only 37% of educators felt fully prepared to teach and 6% to assess this curriculum. More workload allocation, funding and recruitment of Aboriginal and Torres Strait Islander staff and students through institutional commitment and leadership were perceived requirements., Conclusion: Further developing sustainable partnerships where there is reciprocity between optometry programs and Aboriginal and Torres Strait Islander educators and communities is critical to effectively implementing Aboriginal and Torres Strait Islander health curriculum. While clinical placement was considered an important learning experience, the type of experience and whether or not all students should attend require further consideration. Additionally, educators need support for professional development and sharing resources in this emerging field. This will contribute to improving culturally safe practice in optometry.

Widespread population exposure to wildland fire smoke underscores the urgent need for new techniques to characterize fire-derived pollution for epidemiologic studies and to build climate-resilient communities especially for aging populations. Using atmospheric chemical transport modeling, we examined air quality with and without wildland fire smoke PM 2.5 . In 12-km gridded output, the 24-hour average concentration of all-source PM 2.5 in California (2007-2018) was 5.16 μg/m 3 (S.D. 4.66 μg/m 3 ). The average concentration of fire-PM 2.5 in California by year was 1.61 μg/m 3 (~30% of total PM 2.5 ). The contribution of fire-source PM 2.5 ranged from 6.8% to 49%. We define a "smokewave" as two or more consecutive days with modeled levels above 35 μg/m 3 . Based on model-derived fire-PM 2.5 , 99.5% of California's population lived in a county that experienced at least one smokewave from 2007 to 2018, yet understanding of the impact of smoke on the health of aging populations is limited. Approximately 2.7 million (56%) of California residents aged 65+ years lived in counties representing the top 3 quartiles of fire-PM 2.5 concentrations (2007-2018). For each year (2007-2018), grid cells containing skilled nursing facilities had significantly higher mean concentrations of all-source PM 2.5 than cells without those facilities, but they also had generally lower mean concentrations of wildland fire-specific PM 2.5 . Compared to rural monitors in California, model predictions of wildland fire impacts on daily average PM 2.5 carbon (organic and elemental) performed well most years but tended to overestimate wildland fire impacts for high-fire years. The modeling system isolated wildland fire PM 2.5 from other sources at monitored and unmonitored locations, which is important for understanding exposures for aging population in health studies., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Gas phase hydrogen chloride (HCl) was measured at Pasadena and San Joaquin Valley (SJV) ground sites in California during May and June 2010 as part of the CalNex study. Observed mixing ratios were on average 0.83 ppbv at Pasadena, ranging from below detection limit (0.055 ppbv) to 5.95 ppbv, and were on average 0.084 ppbv at SJV with a maximum value of 0.776 ppbv. At both sites, HCl levels were highest during midday and shared similar diurnal variations with HNO 3 . Coupled phase partitioning behavior was found between HCl/Cl - and HNO 3 /NO 3 - using thermodynamic modelling and observations. Regional modeling of Cl - and HCl using CMAQ captures some of the observed relationships but underestimates measurements by a factor of 5 or more. Chloride in the 2.5-10 μm size range in Pasadena was sometimes higher than sea salt abundances, based on co-measured Na + , implying that sources other than sea salt are important. The acid-displacement of HCl/Cl - by HNO 3 /NO 3 - (phase partitioning of semi-volatile acids) observed at the SJV site can only be explained by aqueous phase reaction despite low RH conditions and suggests the temperature dependence of HCl phase partitioning behavior was strongly impacted by the activity coefficient changes under relevant aerosol conditions (e.g., high ionic strength). Despite the influence from activity coefficients, the gas-particle system was found to be well constrained by other stronger buffers and charge balance so that HCl and Cl - concentrations were reproduced well by thermodynamic models.

Amyloidosis is a disorder of protein misfolding and metabolism in which insoluble fibrils are deposited in various tissues, causing organ dysfunction and eventually death. Out of the 60-plus heterogeneous amyloidogenic proteins that have been identified, approximately 30 are associated with human disease. The unifying feature of these proteins is their tendency to form beta-pleated sheets aligned in an antiparallel fashion. These sheets then form rigid, nonbranching fibrils that resist proteolysis, causing mechanical disruption and local oxidative stress in affected organs such as the heart, liver, kidneys, nervous system, and gastrointestinal tract. Here we review the epidemiology of light chain amyloidosis, the staging, and the concomitant prognostication that is critical in determining the appropriate treatment., Competing Interests: The author has no competing interests to declare., (Copyright: © 2022 The Author(s).)

Air pollutant accumulations during wintertime persistent cold air pool (PCAP) events in mountain valleys are of great concern for public health worldwide. Uncertainties associated with the simulated meteorology under stable conditions over complex terrain hinder realistic simulations of air quality using chemical transport models. We use the Community Multiscale Air Quality (CMAQ) model to simulate the gaseous and particulate species for 1 month in January 2011 during the Persistent Cold Air Pool Study (PCAPS) in the Salt Lake Valley (SLV), Utah (USA). Results indicate that the temporal variability associated with the elevated NO x and PM 2.5 concentrations during PCAP events was captured by the model ( r = 0.20 for NO x and r = 0.49 for PM 2.5 ). However, concentrations were not at the correct magnitude (NMB = -35/12% for PM 2.5 during PCAPs/non-PCAPs), where PM 2.5 was underestimated during PCAP events and overestimated during non-PCAP periods. The underestimated PCAP strength is represented by valley heat deficit, which contributed to the underestimated PM 2.5 concentrations compared with observations due to the model simulating more vertical mixing and less stable stratification than what was observed. Based on the observations, the dominant PM 2.5 species were ammonium and nitrate. We provide a discussion that aims to investigate the emissions and chemistry model uncertainties using the nitrogen ratio method and the thermodynamic ammonium nitrate regime method.

Radiological release incidents can potentially contaminate widespread areas with radioactive materials and decontamination efforts are typically focused on populated areas, which means radionuclides may be left in forested areas for long periods of time. Large wildfires in contaminated forested areas have the potential to reintroduce these radionuclides into the atmosphere and cause exposure to first responders and downwind communities. One important radionuclide contaminant released from radiological incidents is radiocesium ( 137 Cs) due to high yields and its long half-life of 30.2 years. An Eulerian 3D photochemical transport model was used to estimate potential ambient impacts of 137 Cs re-emission due to wildfire following hypothetical radiological release scenarios. The Community Multiscale Air Quality (CMAQ) model did well at predicting levels and periods of increased PM2.5 carbon due to wildfire smoke at routine surface monitors in California during the summer of 2016. The model also did well at capturing the extent of the surface mixing layer compared to aerosol lidar measurements. Emissions from a large hypothetical wildfire were introduced into the wildland-urban interface (WUI) impacted by a hypothetical radiological release event. While ambient concentrations tended to be highest near the fire, the highest population committed effective dose equivalent by inhalation to an adult from 137 Cs over an hour was downwind where wind flows moved smoke to high population areas. Seasonal variations in meteorology (wind flows) can result in differential population impacts even in the same metropolitan area. Modeled post-incident ambient levels of 137 Cs both near these wildfires and further downwind in nearby urban areas were well below levels that would necessitate population evacuation or warrant other protective action recommendations such as shelter-in-place. These results suggest that 1) the modeling system captures local to regional scale transport and levels of PM2.5 from wildfire and 2) first responders and downwind population would not be expected to be at elevated risk from the initial inhalathion exposure of 137 Cs re-emission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Atmospheric nitrogen oxide and nitrogen dioxide (NO + NO 2 , together termed as NO X ) estimates from annual photochemical simulations for years 2002-2016 are compared to surface network measurements of NO X and total gas-phase-oxidized reactive nitrogen (NO Y ) to evaluate the Community Multiscale Air Quality (CMAQ) modeling system performance by U.S. region, season, and time of day. In addition, aircraft measurements from 2011 Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality are used to evaluate how emissions, chemical mechanism, and measurement uncertainty each contribute to the overall model performance. We show distinct seasonal and time-of-day patterns in NO X performance. Summertime NO X is overpredicted with bimodal peaks in bias during early morning and evening hours and persisting overnight. The summertime morning NO X bias dropped from between 28% and 57% for earlier years (2002-2012) to between -2% and 7% for later years (2013-2016). Summer daytime NO X tends to be unbiased or underpredicted. In winter, the evening NO X overpredictions remain, but NO X is unbiased or underpredicted overnight, in the morning, and during the day. NO X overpredictions are most pronounced in the Midwestern and Southern United States with Western regions having more of a tendency toward model underpredictions of NO X . Modeled NO X performance has improved substantially over time, reflecting updates to the emission inputs and the CMAQ air quality model. Model performance improvements are largest for years simulated with CMAQv5.1 or later and for emission inventory years 2014 and later, coinciding with reduced onroad NO X emissions from vehicles with newer emission control technologies and improved treatment of chemistry, deposition, and vertical mixing in CMAQ. Our findings suggest that emissions temporalization of specific mobile source sectors have a small impact on model performance, while chemistry updates improve predictions of NO Y but do not improve summertime NO X bias in the Baltimore/DC area. Sensitivity runs performed for different locations across the country suggest that the improvement in summer NO X performance can be attributed to updates in vertical mixing incorporated in CMAQv5.1., Competing Interests: Competing interests The authors have no competing interests.

Formaldehyde (HCHO), a known carcinogen classified as a hazardous pollutant by the United States Environmental Protection Agency (U.S. EPA), is measured through monitoring networks across the U.S. Since these data are limited in spatial and temporal extent, model simulations from the U.S. EPA Community Multiscale Air Quality (CMAQ) model are used to estimate ambient HCHO exposure for the EPA National Air Toxics Assessment (NATA). Here, we employ satellite HCHO retrievals from the Ozone Monitoring Instrument (OMI)-the NASA retrieval developed by the Smithsonian Astrophysical Observatory (SAO), and the European Union Quality Assurance for Essential Climate Variables (QA4ECV) retrieval-to evaluate three CMAQ configurations, spanning the summers of 2011 and 2016, with differing biogenic emissions inputs and chemical mechanisms. These CMAQ configurations capture the general spatial and temporal behavior of both satellite retrievals, but underestimate column HCHO, particularly in the western U.S. In the southeastern U.S., the comparison with OMI HCHO highlights differences in modeled meteorology and biogenic emissions even with differences in satellite retrievals. All CMAQ configurations show low daily correlations with OMI HCHO (r = 0.26 - 0.38), however, we find higher monthly correlations (r = 0.52 - 0.73), and the models correlate best with the OMI-QA4ECV product. Compared to surface observations, we find improved agreement over a 24-hour period compared to afternoon-only, suggesting daily HCHO amounts are captured with more accuracy than afternoon amounts. This work highlights the potential for synergistic improvements in modeling and satellite retrievals to support near-surface HCHO estimates for the NATA and other applications.

Exercise is an established treatment to alleviate pain and improve function among adults with knee osteoarthritis (KOA). However, long-term adherence to exercise is poor and effective approaches to support adherence are limited. Here, we report on an ancillary study to a randomized controlled trial (RCT) where the primary outcome was 2-year adherence to a home based strength-training program. The aims of this current study were to (i) explore experiences, feelings, and perspectives related to long-term adherence to exercise among adults with painful KOA participating in a 2-year RCT, and (ii) identify factors that influenced long-term adherence to exercise. Methods : We purposively recruited 25 subjects and conducted in-depth interviews at the 2-year RCT assessment. In the RCT participants completed a 6-week group exercise program followed by automated telephone calls. Findings : Three conceptual categories describing beliefs about exercise were identified: (1) monitoring; (2) knowledge of how to manage their exercise behaviors; and (3) benefits of exercise. Monitoring provided by peers and instructors during group exercise, and telephone technology were valued by participants. Participants who reported low adherence expressed ambivalence about the benefits of exercise and a desire for more social support. Those who reported high adherence exhibited self-determination and self-efficacy. Conclusions : A novel finding is the conceptual link of self-determination to high adherence to strength-training exercises over 2 years among adults with KOA. Implications for physical therapists include identifying patients' autonomy, competence, and relatedness needs to foster intrinsic control for exercise behavior.

Until recently, air quality impacts from wildfires were predominantly determined based on data from permanent stationary regulatory air pollution monitors. However, low-cost particulate matter (PM) sensors are now widely used by the public as a source of air quality information during wildfires, although their performance during smoke impacted conditions has not been thoroughly evaluated. We collocated three types of low-cost fine PM (PM 2.5 ) sensors with reference instruments near multiple fires in the western and eastern United States (maximum hourly PM 2.5 = 295 µg/m 3 ). Sensors were moderately to strongly correlated with reference instruments (hourly averaged r 2 = 0.52-0.95), but overpredicted PM 2.5 concentrations (normalized root mean square errors, NRMSE = 80-167%). We developed a correction equation for wildfire smoke that reduced the NRMSE to less than 27%. Correction equations were specific to each sensor package, demonstrating the impact of the physical configuration and the algorithm used to translate the size and count information into PM 2.5 concentrations. These results suggest the low-cost sensors can fill in the large spatial gaps in monitoring networks near wildfires with mean absolute errors of less than 10 µg/m 3 in the hourly PM 2.5 concentrations when using a sensor-specific smoke correction equation.

A photochemical model platform for Hawaii, Puerto Rico, and Virgin Islands predicting O 3 , PM 2.5 , and regional haze would be useful to support assessments relevant for the National Ambient Air Quality Standards (NAAQS), Regional Haze Rule, and the Prevention of Significant Deterioration (PSD) program. These areas have not traditionally been modeled with photochemical transport models, but a reasonable representation of meteorology, emissions (natural and anthropogenic), chemistry, and deposition could support air quality management decisions in these areas. Here, a prognostic meteorological model (Weather Research and Forecasting) and photochemical transport (Community Multiscale Air Quality) model were applied for the entire year of 2016 at 27, 9, and 3 km grid resolution for areas covering the Hawaiian Islands and Puerto Rico/Virgin Islands. Model predictions were compared against surface and upper air meteorological and chemical measurements available in both areas. The vertical gradient of temperature, humidity, and winds in the troposphere was well represented. Surface layer meteorological model performance was spatially variable, but temperature tended to be underestimated in Hawaii. Chemically speciated daily average PM 2.5 was generally well characterized by the modeling system at urban and rural monitors in Hawaii and Puerto Rico/Virgin Islands. Model performance was notably impacted by the wildfire emission methodology. Model performance was mixed for hourly SO 2 , NO 2 , PM 2.5 , and CO and was often related to how well local emissions sources were characterized. SO 2 predictions were much lower than measurements at monitors near active volcanos on Hawaii, which was expected since volcanic emissions were not included in these model simulations. Further research is needed to assess emission inventory representation of these areas and how microscale meteorology influenced by the complex land-water and terrain interfaces impacts higher time resolution performance.

Mobile sources emit particulate matter as well as precursors to particulate matter (PM 2.5 ) and ground-level ozone, pollutants known to adversely impact human health. This study uses source-apportionment photochemical air quality modeling to estimate the health burden (expressed as incidence) of an array of PM 2.5 - and ozone-related adverse health impacts, including premature death, attributable to 17 mobile source sectors in the US in 2011 and 2025. Mobile sector-attributable air pollution contributes a substantial fraction of the overall pollution-related mortality burden in the U.S., accounting for about 20% of the PM 2.5 and ozone-attributable deaths in 2011 (between 21 000 and 55 000 deaths, depending on the study used to derive the effect estimate). This value falls to about 13% (between 13 000 and 37 000 deaths) by 2025 due to regulatory and voluntary programs reducing emissions from mobile sources. Similar trends across all morbidity health impacts can also be observed. Emissions from on-road sources are the largest contributor to premature deaths; this is true for both 2011 (between 12 000 and 31 000 deaths) and 2025 (between 6700 and 18 000 deaths). Non-road construction engines, C3 marine engines and emissions from rail also contribute to large portions of premature deaths. Across the 17 mobile sectors modeled, the PM 2.5 -attributable mortality and morbidity burden falls between 2011 and 2025 for 12 sectors and increases for 5. Ozone-attributable mortality and morbidity burden increases between 2011 and 2025 for 10 sectors and falls for 7. These results extend the literature beyond generally aggregated mobile sector health burden toward a representation of highly-resolved source characterization of both current and future health burden. The quantified future mobile source health burden is a novel feature of this analysis and could prove useful for decisionmakers and affected stakeholders.

Objectives: Adults born prematurely have an increased risk of early heart failure. The impact of prematurity on left and right ventricular function has been well documented, but little is known about the impact on the systemic vasculature. The goals of this study were to measure aortic stiffness and the blood pressure response to physiological stressors; in particular, normoxic and hypoxic exercise., Methods: Preterm participants (n = 10) were recruited from the Newborn Lung Project Cohort and matched with term-born, age-matched subjects (n = 12). Aortic pulse wave velocity was derived from the brachial arterial waveform and the heart rate and blood pressure responses to incremental exercise in normoxia (21% O 2 ) or hypoxia (12% O 2 ) were evaluated., Results: Aortic pulse wave velocity was higher in the preterm groups. Additionally, heart rate, systolic blood pressure, and pulse pressure were higher throughout the normoxic exercise bout, consistent with higher conduit artery stiffness. Hypoxic exercise caused a decline in diastolic pressure in this group, but not in term-born controls., Conclusions: In this first report of the blood pressure response to exercise in adults born prematurely, we found exercise-induced hypertension relative to a term-born control group that is associated with increased large artery stiffness. These experiments performed in hypoxia reveal abnormalities in vascular function in adult survivors of prematurity that may further deteriorate as this population ages., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) may necessitate chemotherapy dose reduction, delay, or discontinuation. This pilot study tested feasibility of patient enrollment, CIPN screening, and data collection in cancer patients for a future clinical study that will assess the safety and efficacy of an intervention that may prevent CIPN., Methods: This prospective, observational, single-center, pilot study included adults with newly diagnosed lymphoma or multiple myeloma receiving neurotoxic chemotherapy. Patients were enrolled between September 2016 and February 2017. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire was completed by patients at 3 time points: baseline, week 6, and week 12. The primary outcome was change in the neurotoxicity score between these time points., Results: Of 33 patients approached for consent, 28 (85%) provided consent and were enrolled. The FACT/GOG-Ntx questionnaire was completed by 28 (100%) at baseline, 25 (89%) at week 6, and 24 (86%) at week 12. Average (standard deviation) neurotoxicity scores were 36.5 (6.6) at baseline, 34.0 (8.3) at week 6, and 30.6 (7.6) at week 12. Neurotoxicity scores changed from baseline by - 2.7 points (95% CI - 5.5 to 0.1; p = 0.061) at week 6 and - 6.0 points (95% CI - 5.6 to - 0.8; p = 0.012) at week 12. Clinically meaningful declines (decrease of > 10% from baseline) in neurotoxicity score were detected in 36% (9 of 25) at week 6 and in 67% (16 of 24) at week 12., Conclusion: Sixty-seven percent of patients experienced clinically significant CIPN within 12 weeks of starting chemotherapy. Feasibility metrics for enrollment, consent, CIPN assessment, and follow-up were met.

Policy analysts and researchers often use models to translate expected emissions changes from pollution control policies to estimates of air pollution changes and resulting changes in health impacts. These models can include both photochemical Eulerian grid models or reduced complexity models; these latter models make simplifying assumptions about the emissions-to-air quality relationship as a means of reducing the computational time needed to simulate air quality. This manuscript presents a new database of photochemical- and reduced complexity-modelled changes in annual average particulate matter with aerodynamic diameter less than 2.5 μm and associated health effects and economic values for five case studies representing different emissions control scenarios. The research community is developing an increasing number of reduced complexity models as lower-cost and more expeditious alternatives to full form Eulerian photochemical grid models such as the Comprehensive Air-Quality Model with eXtensions (CAMx) and the Community Multiscale Air Quality (CMAQ) model. A comprehensive evaluation of reduced complexity models can demonstrate the extent to which these tools capture complex chemical and physical processes when representing emission control options. Systematically comparing reduced complexity model predictions to benchmarks from photochemical grid models requires a consistent set of input parameters across all systems. Developing such inputs is resource intensive and consequently the data that we have developed and shared (https://github.com/epa-kpc/RFMEVAL) provide a valuable resource for others to evaluate reduced complexity models. The dataset includes inputs and outputs representing 5 emission control scenarios, including sector-based regulatory policy scenarios focused on on-road mobile sources and electrical generating units (EGUs) as well as hypothetical across-the-board reductions to emissions from cement kilns, refineries, and pulp and paper facilities. Model inputs, outputs, and run control files are provided for the Air Pollution Emission Experiments and Policy Analysis (APEEP) version 2 and 3, Intervention Model for Air Pollution (InMAP), Estimating Air pollution Social Impact Using Regression (EASIUR), and EPA's source apportionment benefit-per-ton reduced complexity models. For comparison, photochemical grid model annual average PM 2.5 output is provided for each emission scenario. Further, inputs are also provided for the Environmental Benefits and Mapping Community Edition (BenMAP-CE) tool to generate county level health benefits and monetized health damages along with output files for benchmarking and intercomparison. Monetized health impacts are also provided from EASIUR and APEEP which can provide these outside the BenMAP-CE framework. The database will allow researchers to more easily compare reduced complexity model predictions against photochemical grid model predictions.

This study sought to retrospectively investigate the outcomes of patients with light-chain amyloidosis (AL) with advanced cardiac involvement who were treated with a strategy of heart transplantation (HT) followed by delayed autologous stem cell transplantation (ASCT) at 1-year posttransplant. Patients with AL amyloidosis with substantial cardiac involvement have traditionally had very poor survival (eg, several months). A few select centers have reported their outcomes for HT followed by a strategy of early ASCT (ie, 6 months) for CA. The outcomes of patients undergoing a delayed strategy have not been reported. All patients with AL amyloidosis at a single institution undergoing evaluation for HT from 2004-2018 were included. Retrospective analyses were performed. Sixteen patients underwent HT (including two combined heart-kidney transplant) for AL amyloidosis. ASCT was performed in a total of nine patients to date at a median 13.5 months (12.8-32.9 months) post-HT. Survival was 87.5% at 1 year and 76.6% at 5 years, comparable to institutional outcomes for nonamyloid HT recipients. In addition to these 16 patients, two patients underwent combined heart-lung transplantation. A strategy of delayed ASCT 1-year post-HT for patients with AL amyloidosis is feasible, safe, and associated with comparable outcomes to those undergoing an earlier ASCT strategy., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Emission inventories are the foundation for cost-effective air quality management activities. In 2005, a report by the public/private partnership North American Research Strategy for Tropospheric Ozone (NARSTO) evaluated the strengths and weaknesses of North American emissions inventories and made recommendations for improving their effectiveness. This paper reviews the recommendation areas and briefly discusses what has been addressed, what remains unchanged, and new questions that have arisen. The findings reveal that all emissions inventory improvement areas identified by the 2005 NARSTO publication have been explored and implemented to some degree. The U.S. National Emissions Inventory has become more detailed and has incorporated new research into previously under-characterized sources such as fine particles and biomass burning. Additionally, it is now easier to access the emissions inventory and the documentation of the inventory via the internet. However, many emissions-related research needs exist, on topics such as emission estimation methods, speciation, scalable emission factor development, incorporation of new emission measurement techniques, estimation of uncertainty, top-down verification, and analysis of uncharacterized sources. A common theme throughout this retrospective summary is the need for increased coordination among stakeholders. Researchers and inventory developers must work together to ensure that planned emissions research and new findings can be used to update the emissions inventory. To continue to address emissions inventory challenges, industry, the scientific community, and government agencies need to continue to leverage resources and collaborate as often as possible. As evidenced by the progress noted, continued investment in and coordination of emissions inventory activities will provide dividends to air quality management programs across the country, continent, and world. Implications : In 2005, a report by the public/private partnership North American Research Strategy for Tropospheric Ozone (NARSTO) evaluated the strengths and weaknesses of North American air pollution emissions inventories. This paper reviews the eight recommendation areas and briefly discusses what has been addressed, what remains unchanged, and new questions that have arisen. Although progress has been made, many opportunities exist for the scientific agencies, industry, and government agencies to leverage resources and collaborate to continue improving emissions inventories.

Alternative medical therapy with multiple intravenous colloidal silver infusions may cause severe illness, including profound copper deficiency-induced anemia and hepatic toxicity. No chelating agent for silver poisoning exists and effective therapy requires apheresis in combination with continuous administration of oral copper., Competing Interests: Each of the authors declare that there is no conflict of interest regarding the publication of this paper.

Cholangiocarcinoma is a highly aggressive and lethal malignancy, with limited treatment options available. Recently, FGFR inhibitors have been developed and utilized in FGFR-mutant cholangiocarcinoma; however, resistance often develops and the genomic determinants of resistance are not fully characterized. We completed whole-exome sequencing (WES) of 11 unique tumor samples obtained from a rapid research autopsy on a patient with FGFR-fusion-positive cholangiocarcinoma who initially responded to the pan-FGFR inhibitor, INCB054828. In vitro studies were carried out to characterize the novel FGFR alteration and secondary FGFR2 mutation identified. Multisite WES and analysis of tumor heterogeneity through subclonal inference identified four genetically distinct cancer cell populations, two of which were only observed after treatment. Additionally, WES revealed an FGFR2 N549H mutation hypothesized to confer resistance to the FGFR inhibitor INCB054828 in a single tumor sample. This hypothesis was corroborated with in vitro cell-based studies in which cells expressing FGFR2-CLIP1 fusion were sensitive to INCB054828 (IC 50 value of 10.16 nM), whereas cells with the addition of the N549H mutation were resistant to INCB054828 (IC 50 value of 1527.57 nM). Furthermore, the FGFR2 N549H secondary mutation displayed cross-resistance to other selective FGFR inhibitors, but remained sensitive to the nonselective inhibitor, ponatinib. Rapid research autopsy has the potential to provide unprecedented insights into the clonal evolution of cancer throughout the course of the disease. In this study, we demonstrate the emergence of a drug resistance mutation and characterize the evolution of tumor subclones within a cholangiocarcinoma disease course., (© 2019 Krook et al.; Published by Cold Spring Harbor Laboratory Press.)

Synthetic peptidomimetics may be designed to mimic functions of antimicrobial peptides, including potentiation of antibiotics, yet possessing improved pharmacological properties. Pairwise screening of 42 synthetic peptidomimetics combined with the antibiotics azithromycin and rifampicin in multidrug-resistant (MDR) Escherichia coli ST131 and Klebsiella pneumoniae ST258 led to identification of two subclasses of α-peptide/β-peptoid hybrids that display synergy with azithromycin and rifampicin (fractional inhibitory concentration indexes of 0.03-0.38). Further screening of the best three peptidomimetics in combination with a panel of 21 additional antibiotics led to identification of peptidomimetics that potentiated ticarcillin/clavulanate and erythromycin against E. coli , and clindamycin against K. pneumoniae . The study of six peptidomimetics was extended to Pseudomonas aeruginosa , confirming synergy with antibiotics for five of them. The most promising compound, H-(Lys-βNPhe) 8 -NH 2 , exerted only a minor effect on the viability of mammalian cells (EC 50 ≥ 124-210 μM), and thus exhibited the highest selectivity toward bacteria. This compound also synergized with rifampicin and azithromycin at sub-micromolar concentrations (0.25-0.5 μM), thereby inducing susceptibility to these antibiotics at clinically relevant concentrations in clinical MDR isolates. This peptidomimetic lead and its analogs constitute promising candidates for efficient repurposing of rifampicin and azithromycin against Gram-negative pathogens.

Wildland fire smoke exposure affects a broad proportion of the U.S. population and is increasing due to climate change, settlement patterns and fire seclusion. Significant public health questions surrounding its effects remain, including the impact on cardiovascular disease and maternal health. Using atmospheric chemical transport modeling, we examined general air quality with and without wildland fire smoke PM 2.5 . The 24-h average concentration of PM 2.5 from all sources in 12-km gridded output from all sources in California (2007-2013) was 4.91 μg/m 3 . The average concentration of fire-PM 2.5 in California by year was 1.22 μg/m 3 (~25% of total PM 2.5 ). The fire-PM 2.5 daily mean was estimated at 4.40 μg/m 3 in a high fire year (2008). Based on the model-derived fire-PM 2.5 data, 97.4% of California's population lived in a county that experienced at least one episode of high smoke exposure ("smokewave") from 2007-2013. Photochemical model predictions of wildfire impacts on daily average PM 2.5 carbon (organic and elemental) compared to rural monitors in California compared well for most years but tended to over-estimate wildfire impacts for 2008 (2.0 μg/m 3 bias) and 2013 (1.6 μg/m 3 bias) while underestimating for 2009 (-2.1 μg/m 3 bias). The modeling system isolated wildfire and PM 2.5 from other sources at monitored and unmonitored locations, which is important for understanding population exposure in health studies. Further work is needed to refine model predictions of wildland fire impacts on air quality in order to increase confidence in the model for future assessments. Atmospheric modeling can be a useful tool to assess broad geographic scale exposure for epidemiologic studies and to examine scenario-based health impacts., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Gram-negative bacterial pathogens are intrinsically resistant to several antibiotics that are not able to penetrate the cell envelope barrier. The aim of this study was to identify peptides that at low concentrations induce susceptibility to these antibiotics in multidrug-resistant (MDR) Gram-negative bacterial strains of clinical relevance. Pairwise screening of 34 diverse peptides and four antibiotics (erythromycin, linezolid, rifampicin and vancomycin) with primary activity against Gram-positive bacteria identified 4 peptides that at submicromolar concentrations conferred susceptibility to rifampicin or erythromycin in Escherichia coli ATCC 25922. The identified peptides exhibited synergy with azithromycin and potentiated clindamycin in MDR E. coli ST131 and Klebsiella pneumoniae ST258. The low cytotoxicity toward eukaryotic cells (IC 50 > 50 µM) observed for two of these peptides (KLWKKWKKWLK-NH 2 and GKWKKILGKLIR-NH 2 ) prompted synthesis and evaluation of the corresponding all-d analogues (D1 and D2), which retained similar synergistic antibacterial profiles. Low concentrations of D1 and D2 in combination with azithromycin and rifampicin inhibited growth of most clinical E. coli, K. pneumoniae and Acinetobacter baumannii strains tested. These data demonstrate that combinatorial screening at low peptide concentrations constitutes an efficient approach to identify clinically relevant peptide-antibiotic combinations. In vivo pharmacokinetic/pharmacodynamic and toxicity studies are needed to further validate the use of the peptides identified in this study for repurposing azithromycin and rifampicin against Gram-negative pathogens., (Copyright © 2018. Published by Elsevier B.V.)

Prescribed grassland fires in the Flint Hills region of central Kansas and northern Oklahoma are a common tool for land management. Local to regional scale impacts on air quality from grassland fires in this region are not well understood, which is important as these types of prescribed fires may increase in the future to preserve broader areas of native grasses in the central U.S. Routine air quality and deposition measurements from sites in and near the Flint Hills were examined for coincident increases during periods of increased prescribed grassland fires. Prescribed fire activity in this region was quantified using satellite detections and multiple publicly available data products of area burned information. March and April comprise over half (41 to 93%) of all annual fire detections in the Flint Hills region seen from satellites between 2007 and 2018 excluding drought years. Annual total fire detections in this region range between 1 and 12 thousand and account for approximately 3% of all fire detections in the contiguous U.S. Annual acres burned ranged from 0.2 to 2 million acres based on U.S. EPA's National Emission Inventory, which accounts for 4 to 38% of grasslands in the area. A comparison of weekly standardized anomalies suggests a relationship between periods of increased grassland fire activity and elevated levels of PM 2.5 organic carbon, elemental carbon, and potassium. Daily 1-hr maximum ozone (O 3 ), ammonia (NH 3 ), sulfur dioxide (SO 2 ), and oxidized nitrogen gases measured at Konza Prairie also had increased levels when prescribed grassland fire activity was highest. This detailed characterization of prescribed fire activity in the Flint Hills and associated air quality impacts will benefit future efforts to understand changes in atmospheric composition due to changing land management practices., (Published by Elsevier B.V.)

By-products of mobile source combustion processes, such as those associated with gasoline- and diesel-powered engines, include direct emissions of particulate matter as well as precursors to particulate matter and ground-level ozone. Human exposure to fine particulate matter with an aerodynamic diameter smaller than 2.5 μm (PM 2.5 ) is associated with increased incidence of premature mortality and morbidity outcomes. This study builds upon recent, detailed source-apportionment air quality modeling to project the health-related benefits of reducing PM 2.5 from mobile sources across the contiguous U.S. in 2025. Updating a previously published benefits analysis approach, we develop national-level benefit per ton estimates for directly emitted PM 2.5 , SO 2 /pSO 4 , and NO X for 16 mobile source sectors spanning onroad vehicles, nonroad engines and equipment, trains, marine vessels, and aircraft. These benefit per ton estimates provide a reduced-form tool for estimating and comparing benefits across multiple mobile source emission scenarios and can be applied to assess the benefits of mobile source policies designed to improve air quality. We found the benefit per ton of directly emitted PM 2.5 in 2025 ranges from $110,000 for nonroad agriculture sources to $700,000 for onroad light duty gas cars and motorcycles (in 2015 dollars and based on an estimate of PM-related mortality derived from the American Cancer Society cohort study). Benefit per ton values for SO 2 /pSO 4 range from $52,000 for aircraft sources (including emissions from ground support vehicles) to $300,000 for onroad light duty diesel emissions. Benefit per ton values for NO X range from $2100 for C1 and C2 marine vessels to $7500 for "nonroad all other" mobile sources, including industrial, logging, and oil field sources. Benefit per ton estimates increase approximately 2.26-fold when using an alternative concentration response function to derive PM 2.5 -related mortality. We also report benefit per ton values for the eastern and western U.S. to account for broad spatial heterogeneity patterns in emissions reductions, population exposure and air quality benefits., (Published by Elsevier B.V.)

Prescribed pasture burning plays a critical role in ecosystem maintenance in tallgrass prairie ecosystems and may contribute to agricultural productivity but can also have negative impacts on air quality. Volatile organic compound (VOC) concentrations were measured immediately downwind of prescribed tallgrass prairie fires in the Flint Hills region of Kansas, United States. The VOC mixture is dominated by alkenes and oxygenated VOCs, which are highly reactive and can drive photochemical production of ozone downwind of the fires. The computed emission factors are comparable to those previous measured from pasture maintenance fires in Brazil. In addition to the emission of large amounts of particulate matter, hazardous air pollutants such as benzene and acrolein are emitted in significant amounts and could contribute to adverse health effects in exposed populations., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest. This document has been subjected to internal Agency review and approved for publication by the United States Environmental Protection Agency. The views expressed in this article are those of the authors and do not represent the views or policies of the U.S. Environmental Protection Agency.

Previous studies have proposed that model performance statistics from earlier photochemical grid model (PGM) applications can be used to benchmark performance in new PGM applications. A challenge in implementing this approach is that limited information is available on consistently calculated model performance statistics that vary spatially and temporally over the U.S. Here, a consistent set of model performance statistics are calculated by year, season, region, and monitoring network for PM 2.5 and its major components using simulations from versions 4.7.1-5.2.1 of the Community Multiscale Air Quality (CMAQ) model for years 2007-2015. The multi-year set of statistics is then used to provide quantitative context for model performance results from the 2015 simulation. Model performance for PM 2.5 organic carbon in the 2015 simulation ranked high (i.e., favorable performance) in the multi-year dataset, due to factors including recent improvements in biogenic secondary organic aerosol and atmospheric mixing parameterizations in CMAQ. Model performance statistics for the Northwest region in 2015 ranked low (i.e., unfavorable performance) for many species in comparison to the 2007-2015 dataset. This finding motivated additional investigation that suggests a need for improved speciation of wildfire PM 2.5 emissions and modeling of boundary layer dynamics near water bodies. Several limitations were identified in the approach of benchmarking new model performance results with previous results. Since performance statistics vary widely by region and season, a simple set of national performance benchmarks (e.g., one or two targets per species and statistic) as proposed previously are inadequate to assess model performance throughout the U.S. Also, trends in model performance statistics for sulfate over the 2007 to 2015 period suggest that model performance for earlier years may not be a useful reference for assessing model performance for recent years in some cases. Comparisons of results from the 2015 base case with results from five sensitivity simulations demonstrated the importance of parameterizations of NH 3 surface exchange, organic aerosol volatility and production, and emissions of crustal cations for predicting PM 2.5 species concentrations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

There is an urgent need for next-generation smoke research and forecasting (SRF) systems to meet the challenges of the growing air quality, health, and safety concerns associated with wildland fire emissions. This review paper presents simulations and experiments of hypothetical prescribed burns with a suite of selected fire behavior and smoke models and identifies major issues for model improvement and the most critical observational needs. The results are used to understand the new and improved capability required for the next-generation SRF systems and to support the design of the Fire and Smoke Model Evaluation Experiment (FASMEE) and other field campaigns. The next-generation SRF systems should have more coupling of fire, smoke, and atmospheric processes to better simulate and forecast vertical smoke distributions and multiple sub-plumes, dynamical and high-resolution fire processes, and local and regional smoke chemistry during day and night. The development of the coupling capability requires comprehensive and spatially and temporally integrated measurements across the various disciplines to characterize flame and energy structure (e.g., individual cells, vertical heat profile and the height of well mixing flaming gases), smoke structure (vertical distributions and multiple sub-plumes), ambient air processes (smoke eddy, entrainment and radiative effects of smoke aerosols), fire emissions (for different fuel types and combustion conditions from flaming to residual smoldering), as well as night-time processes (smoke drainage and super-fog formation).

The Rim Fire was one of the largest wildfires in California history, burning over 250,000 acres during August and September 2013 affecting air quality locally and regionally in the western U.S. Routine surface monitors, remotely sensed data, and aircraft based measurements were used to assess how well the Community Multiscale Air Quality (CMAQ) photochemical grid model applied at 4 and 12 km resolution represented regional plume transport and chemical evolution during this extreme wildland fire episode. Impacts were generally similar at both grid resolutions although notable differences were seen in some secondary pollutants (e.g., formaldehyde and peroxyacyl nitrate) near the Rim fire. The modeling system does well at capturing near-fire to regional scale smoke plume transport compared to remotely sensed aerosol optical depth (AOD) and aircraft transect measurements. Plume rise for the Rim fire was well characterized as the modeled plume top was consistent with remotely sensed data and the altitude of aircraft measurements, which were typically made at the top edge of the plume. Aircraft-based lidar suggests O 3 downwind in the Rim fire plume was vertically stratified and tended to be higher at the plume top, while CMAQ estimated a more uniformly mixed column of O 3 . Predicted wildfire ozone (O 3 ) was overestimated both at the plume top and at nearby rural and urban surface monitors. Photolysis rates were well characterized by the model compared with aircraft measurements meaning aerosol attenuation was reasonably estimated and unlikely contributing to O 3 overestimates at the top of the plume. Organic carbon was underestimated close to the Rim fire compared to aircraft data, but was consistent with nearby surface measurements. Periods of elevated surface PM 2.5 at rural monitors near the Rim fire were not usually coincident with elevated O 3 ., (Published by Elsevier B.V.)

The contribution of precursor emissions from 17 mobile source sectors to ambient ozone and fine particulate matter levels across the U.S. were evaluated, using the CAMx photochemical model, to identify which mobile source sectors are projected to have the largest impacts on air pollution in 2025. Both onroad and nonroad sectors contribute considerably to projected air pollution across much of the country. Summer ozone season ozone contributions between 2 and 5 ppb, which are among the highest levels presented on the maps of mobile source sectors, are largely found in the southeast United States from the onroad sectors, most notably light-duty and heavy-duty vehicles, and along the coastline from the Category 3 (C3) marine sector. Annual average PM 2.5 contributions between 0.5 to 0.9 μg/m 3 , which are among the highest levels presented on the maps of mobile source sectors, are found throughout the Midwest and along portions of the east and west coast from onroad sectors as well as nonroad diesel and rail sectors. Additionally, contributions of precursor emissions to ambient ozone and PM 2.5 levels were evaluated to understand the range of impacts from precursors in the various mobile source sectors. For most mobile source sectors, in most locations, NO X emissions contributed more to ozone than VOC emissions, and secondary PM 2.5 contributed more to ambient PM 2.5 than primary PM 2.5 . The largest ozone levels on the maps showing contributions from mobile source NO X emissions tended to be between 2 and 5 ppb, while the largest ozone levels on the maps showing contributions from mobile source VOC emissions tended to be between 0.9 and 2 ppb, except for southern California where ozone contributions from VOC emissions from onroad light duty vehicles were between 2 and 5 ppb. The largest contributions to ambient PM 2.5 on the maps showing primary and secondary contributions from mobile source sectors tended to be between 0.1 and 0.5 μg/m 3 . The contribution from primary PM 2.5 extended over localized areas (urban-scale) and the contribution from secondary PM 2.5 extended over more regional (multi-state) areas.

Atmospheric models that accurately describe the fate and transport of trace species for the right reasons aid in the development of effective air-quality management strategies that safeguard human health. Controllable emissions facilitate the formation of biogenic secondary organic aerosol (BSOA) to enhance the atmospheric fine particulate matter (PM 2.5 ) burden. Previous modeling with the EPA's Community Multiscale Air Quality (CMAQ) model predicted that anthropogenic primary organic aerosol (POA) emissions had the greatest impact on BSOA. That experiment included formation processes involving semivolatile partitioning but not aerosol liquid water (ALW), a ubiquitous PM constituent. We conduct 17 summertime CMAQ simulations with updated chemistry and evaluate changes in BSOA due to the removal of individual pollutants and source sectors for the contiguous U.S. CMAQ predicts SO 2 from electricity generating units, and mobile source NO X emissions have the largest impacts on BSOA. The removal of anthropogenic NO X , SO 2 , and POA emissions during the simulation reduces the nationally averaged BSOA by 23, 14, and 8% and PM 2.5 by 9.2, 14, and 5.3%, respectively. ALW mass concentrations decrease by 10 and 35% in response to the removal of NO X and SO 2 emissions. This work contributes chemical insight into ancillary benefits of Federal NO X and SO 2 rules that concurrently reduce organic PM 2.5 mass.

Incomplete information regarding emissions from oil and natural gas production has historically made it challenging to characterize the air quality or air pollution-related health impacts for this sector in the United States. Using an emissions inventory for the oil and natural gas sector that reflects information regarding the level and distribution of PM 2.5 and ozone precursor emissions, we simulate annual mean PM 2.5 and summer season average daily 8 h maximum ozone concentrations with the Comprehensive Air-Quality Model with extensions (CAMx). We quantify the incidence and economic value of PM 2.5 and ozone health related effects using the environmental Benefits Mapping and Analysis Program (BenMAP). We find that ambient concentrations of PM 2.5 and ozone, and associated health impacts, are highest in a handful of states including Colorado, Pennsylvania, Texas and West Virginia. On a per-ton basis, the benefits of reducing PM 2.5 precursor emissions from this sector vary by pollutant species, and range from between $6,300 and $320,000, while the value of reducing ozone precursors ranges from $500 to $8,200 in the year 2025 (2015$).