Search

We use the Community Multiscale Air Quality (CMAQv5.4) model to examine the potential impact of particulate nitrate (pNO 3 - ) photolysis on air quality over the Northern Hemisphere. We estimate the photolysis frequency of pNO 3 - by scaling the photolysis frequency of nitric acid (HNO 3 ) with an enhancement factor that varies between 10 and 100 depending on pNO 3 - and sea-salt aerosol concentrations and then perform CMAQ simulations without and with pNO 3 - photolysis to quantify the range of impacts on tropospheric composition. The photolysis of pNO 3 - produces gaseous nitrous acid (HONO) and nitrogen dioxide (NO 2 ) over seawater thereby increasing atmospheric HONO and NO 2 mixing ratios. HONO subsequently undergoes photolysis, producing hydroxyl radicals (OH). The increase in NO 2 and OH alters atmospheric chemistry and enhances the atmospheric ozone (O 3 ) mixing ratio over seawater, which is subsequently transported to downwind continental regions. Seasonal mean model O 3 vertical column densities without pNO 3 - photolysis are lower than the Ozone Monitoring Instrument (OMI) retrievals, while the column densities with the pNO 3 - photolysis agree better with the OMI retrievals of tropospheric O 3 burden. We compare model O 3 mixing ratios with available surface observed data from the U.S., Japan, the Tropospheric Ozone Assessment Report - Phase II, and OpenAQ; and find that the model without pNO 3 - photolysis underestimates the observed data in winter and spring seasons and the model with pNO 3 - photolysis improves the comparison in both seasons, largely rectifying the pronounced underestimation in spring. Compared to measurements from the western U.S., model O 3 mixing ratios with pNO 3 - photolysis agree better with observed data in all months due to the persistent underestimation of O 3 without pNO 3 - photolysis. Compared to the ozonesonde measurements, model O 3 mixing ratios with pNO 3 - photolysis also agree better with observed data than the model O 3 without pNO 3 - photolysis., 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.)

This prospective observational study aimed to determine the proportion of mechanical complications in patients with acute STEMI and assess the associated outcomes. The study was conducted between June'21 and May'22, including 1307 patients. Mechanical complications were evaluated using 2D-Echo. Among the STEMI patients, 17 individuals (1.3 %) experienced mechanical complications. The most prevalent complication was FWR (n = 9), followed by VSR(n = 7) and PMR (n = 1). However, despite their low incidence, mechanical complications carry a significant mortality burden. Mortality rates were higher in older age and female patients., 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., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Future estimates of atmospheric pollutant concentrations serve as critical information for policy makers to formulate current policy indicators to achieve future targets. Tropospheric burden of O 3 is modulated not only by anthropogenic and natural precursor emissions, but also by the downward transport of O 3 associated with stratosphere to troposphere exchange (STE). Hence changes in the estimates of STE and its contributions are key to understand the nature and intensity of future ground level O 3 concentrations. The difference in simulated O 3 mixing ratios with and without the O 3 -Potential Vorticity (PV) parameterization scheme is used to represent the model estimated influence of STE on tropospheric O 3 distributions. Though STE contributions remain constant in Northern hemisphere as a whole, regional differences exist with Europe (EUR) registering increased STE contribution in both spring and winter while Eastern China (ECH) reporting increased contribution in spring in 2050 (RCP8.5) as compared to 2015. Importance of climate change can be deduced from the fact that ECH and EUR recorded increased STE contribution to O 3 in RCP8.5 compared to RCP4.5. Comparison of STE and non-STE meteorological process contributions to O 3 due to climate change revealed that contributions of non-STE processes were highest in summer while STE contributions were highest in winter. EUR reported highest STE contribution while ECH reported highest non-STE contribution. None of the 3 regions show consistent low STE contribution due to future climate change (< 50%) in all seasons indicating the significance of STE to ground level O 3 .

The fourth phase of the Air Quality Model Evaluation International Initiative (AQMEII4) is conducting a diagnostic intercomparison and evaluation of deposition simulated by regional-scale air quality models over North America and Europe. In this study, we analyze annual AQMEII4 simulations performed with the Community Multiscale Air Quality Model (CMAQ) version 5.3.1 over North America. These simulations were configured with both the M3Dry and Surface Tiled Aerosol and Gas Exchange (STAGE) dry deposition schemes available in CMAQ. A comparison of observed and modeled concentrations and wet deposition fluxes shows that the AQMEII4 CMAQ simulations perform similarly to other contemporary regional-scale modeling studies. During summer, M3Dry has higher ozone (O 3 ) deposition velocities (V d ) and lower mixing ratios than STAGE for much of the eastern U.S. while the reverse is the case over eastern Canada and along the West Coast. In contrast, during winter STAGE has higher O 3 V d and lower mixing ratios than M3Dry over most of the southern half of the modeling domain while the reverse is the case for much of the northern U.S. and southern Canada. Analysis of the diagnostic variables defined for the AQMEII4 project, i.e. grid-scale and land-use (LU) specific effective conductances and deposition fluxes for the major dry deposition pathways, reveals generally higher summertime stomatal and wintertime cuticular grid-scale effective conductances for M3Dry and generally higher soil grid-scale effective conductances (for both vegetated and bare soil) for STAGE in both summer and winter. On a domain-wide basis, the stomatal grid-scale effective conductances account for about half of the total O 3 V d during daytime hours in summer for both schemes. Employing LU-specific diagnostics, results show that daytime V d varies by a factor of 2 between LU categories. Furthermore, M3Dry vs. STAGE differences are most pronounced for the stomatal and vegetated soil pathway for the forest LU categories, with M3Dry estimating larger effective conductances for the stomatal pathway and STAGE estimating larger effective conductances for the vegetated soil pathway for these LU categories. Annual domain total O 3 deposition fluxes differ only slightly between M3Dry (74.4 Tg/year) and STAGE (76.2 Tg/yr), but pathway-specific fluxes to individual LU types can vary more substantially on both annual and seasonal scales which would affect estimates of O 3 damages to sensitive vegetation. A comparison of two simulations differing only in their LU classification scheme shows that the differences in LU cause seasonal mean O 3 mixing ratio differences on the order of 1 ppb across large portions of the domain, with the differences generally largest during summer and in areas characterized by the largest differences in the fractional coverages of the forest, planted/cultivated, and grassland LU categories. These differences are generally smaller than the M3Dry vs. STAGE differences outside the summer season but have a similar magnitude during summer. Results indicate that the deposition impacts of LU differences are caused both by differences in the fractional coverages and spatial distributions of different LU categories as well as the characterization of these categories through variables like surface roughness and vegetation fraction in look-up tables used in the land-surface model and deposition schemes. Overall, the analyses and results presented in this study illustrate how the diagnostic grid-scale and LU-specific dry deposition variables adopted for AQMEII4 can provide insights into similarities and differences between the CMAQ M3Dry and STAGE dry deposition schemes that affect simulated pollutant budgets and ecosystem impacts from atmospheric pollution., Competing Interests: Competing Interests The authors declare no competing interests.

We examine the impact of dimethylsulfide (DMS) emissions on sulfate concentrations over the continental U.S. by using the Community Multiscale Air Quality (CMAQ) model version 5.4 and performing annual simulations without and with DMS emissions for 2018. DMS emissions enhance sulfate not only over seawater but also over land, although to a lesser extent. On an annual basis, the inclusion of DMS emissions increase sulfate concentrations by 36% over seawater and 9% over land. The largest impacts over land occur in California, Oregon, Washington, and Florida, where the annual mean sulfate concentrations increase by ~25%. The increase in sulfate causes a decrease in nitrate concentration due to limited ammonia concentration especially over seawater and an increase in ammonium concentration with a net effect of increased inorganic particles. The largest sulfate enhancement occurs near the surface (over seawater) and the enhancement decreases with altitude, diminishing to 10-20% at an altitude of ~5 km. Seasonally, the largest enhancement of sulfate over seawater occurs in summer, and the lowest in winter. In contrast, the largest enhancements over land occur in spring and fall due to higher wind speeds that can transport more sulfate from seawater into land., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

The United States Environmental Protection Agency (US EPA) has developed a set of annual North American emissions data for multiple air pollutants across 18 broad source categories for 2002 through 2017. The sixteen new annual emissions inventories were developed using consistent input data and methods across all years. When a consistent method or tool was not available for a source category, emissions were estimated by scaling data from the EPA's 2017 National Emissions Inventory with scaling factors based on activity data and/or emissions control information. The emissions datasets are designed to support regional air quality modeling for a wide variety of human health and ecological applications. The data were developed to support simulations of the EPA's Community Multiscale Air Quality model but can also be used by other regional scale air quality models. The emissions data are one component of EPA's Air Quality Time Series Project which also includes air quality modeling inputs (meteorology, initial conditions, boundary conditions) and outputs (e.g., ozone, PM 2.5 and constituent species, wet and dry deposition) for the Conterminous US at a 12 km horizontal grid spacing., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2023 The Author(s).)

We analyze hourly PM 2.5 (particles with an aerodynamic diameter of ≤ 2.5 μm) concentrations measured at the U.S. Embassy in Dhaka over the 2016 - 2021 time period and find that concentrations are seasonally dependent with the highest occurring in winter and the lowest in monsoon seasons. Mean winter PM 2.5 concentrations reached ~165-175 μg/m 3 while monsoon concentrations remained ~30-35 μg/m 3 . Annual mean PM 2.5 concentration reached ~5-6 times greater than the Bangladesh annual PM 2.5 standard of 15 μg/m 3 . The number of days exceeding the daily PM 2.5 standard of 65 μg/m 3 in a year approached nearly 50%. Daily-mean PM 2.5 concentrations remained elevated (>65 μg/m 3 ) for more than 80 consecutive days. Night-time concentrations were greater than daytime concentrations. The comparison of results obtained from the Community Multiscale Air Quality (CMAQ) model simulations over the Northern Hemisphere using 108-km horizontal grids with observed data suggests that the model can reproduce the seasonal variation of observed data but underpredicts observed PM 2.5 in winter months with a normalized mean bias of 13-32%. In the model, organic aerosol is the largest component of PM 2.5 , of which secondary organic aerosol plays a dominant role. Transboundary pollution has a large impact on the PM 2.5 concentration in Dhaka, with an annual mean contribution of ~40 μg/m 3 ., 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.

Several locations across the United States in non-compliance with the national standard for ground-level ozone (O 3 ) are thought to have sizeable influences from distant extra-regional emission sources or natural stratospheric O 3 , which complicates design of local emission control measures. To quantify the amount of long-range transported O 3 (LRT O 3 ), its origin, and change over time, we conduct and analyze detailed sensitivity calculations characterizing the response of O 3 to emissions from different source regions across the Northern Hemisphere in conjunction with multi-decadal simulations of tropospheric O 3 distributions and changes. Model calculations show that the amount of O 3 at any location attributable to sources outside North America varies both spatially and seasonally. On a seasonal-mean basis, during 1990-2010, LRT O 3 attributable to international sources steadily increased by 0.06-0.2 ppb yr -1 at locations across the United States and arose from superposition of unequal and contrasting trends in individual source-region contributions, which help inform attribution of the trend evident in O 3 measurements. Contributions of emissions from Europe steadily declined through 2010, while those from Asian emissions increased and remained dominant. Steadily rising NO x emissions from international shipping resulted in increasing contributions to LRT O 3 , comparable to those from Asian emissions in recent years. Central American emissions contribute a significant fraction of LRT O 3 in southwestern United States. In addition to the LRT O 3 attributable to emissions outside of North America, background O 3 across the continental United States is comprised of a sizeable and spatially variable fraction that is of stratospheric origin (29-78%)., Competing Interests: The authors declare no competing financial interest.

Airborne aerosols reduce surface solar radiation through light scattering and absorption (aerosol direct effects, ADEs), influence regional meteorology, and further affect atmospheric chemical reactions and aerosol concentrations. The inhibition of turbulence and the strengthened atmospheric stability induced by ADEs increases surface primary aerosol concentration, but the pathway of ADE impacts on secondary aerosol is still unclear. In this study, the online coupled meteorological and chemistry model (WRF-CMAQ; Weather Research and Forecasting-Community Multiscale Air Quality) with integrated process analysis was applied to explore how ADEs affect secondary aerosol formation through changes in atmospheric dynamics and photolysis processes. The meteorological condition and air quality in the Jing-Jin-Ji area (denoted JJJ, including Beijing, Tianjin, and Hebei Province in China) in January and July 2013 were simulated to represent winter and summer conditions, respectively. Our results show that ADEs through the photolysis pathway inhibit sulfate formation during winter in the JJJ region and promote sulfate formation in July. The differences are attributed to the alteration of effective actinic flux affected by single-scattering albedo (SSA). ADEs through the dynamics pathway act as an equally or even more important route compared with the photolysis pathway in affecting secondary aerosol concentration in both summer and winter. ADEs through dynamics traps formed sulfate within the planetary boundary layer (PBL) which increases sulfate concentration in winter. Meanwhile, the impact of ADEs through dynamics is mainly reflected in the increase of gaseous-precursor concentrations within the PBL which enhances secondary aerosol formation in summer. For nitrate, reduced upward transport of precursors restrains the formation at high altitude and eventually lowers the nitrate concentration within the PBL in winter, while such weakened vertical transport of precursors increases nitrate concentration within the PBL in summer, since nitrate is mainly formed near the surface ground., Competing Interests: Competing interests. The contact author has declared that neither they nor their co-authors have any competing interests.

The two-way coupled Weather Research and Forecasting and Community Multiscale Air Quality (WRF-CMAQ) model has been developed to more realistically represent the atmosphere by accounting for complex chemistry-meteorology feedbacks. In this study, we present a comparative analysis of two-way (with consideration of both aerosol direct and indirect effects) and offline coupled WRF v3.4 and CMAQ v5.0.2 over the contiguous US. Long-term (5 years from 2008 to 2012) simulations using WRF-CMAQ with both offline and two-way coupling modes are carried out with anthropogenic emissions based on multiple years of the U.S. National Emission Inventory and chemical initial and boundary conditions derived from an advanced Earth system model (i.e., a modified version of the Community Earth System Model/Community Atmospheric Model). The comprehensive model evaluations show that both two-way WRF-CMAQ and WRF-only simulations perform well for major meteorological variables such as temperature at 2 m, relative humidity at 2 m, wind speed at 10 m, precipitation (except for against the National Climatic Data Center data), and shortwave and longwave radiation. Both two-way and offline CMAQ also show good performance for ozone (O 3 ) and fine particulate matter (PM 2.5 ). Due to the consideration of aerosol direct and indirect effects, two-way WRF-CMAQ shows improved performance over offline coupled WRF and CMAQ in terms of spatiotemporal distributions and statistics, especially for radiation, cloud forcing, O 3 , sulfate, nitrate, ammonium, elemental carbon, tropospheric O 3 residual, and column nitrogen dioxide (NO 2 ). For example, the mean biases have been reduced by more than 10 W m -2 for shortwave radiation and cloud radiative forcing and by more than 2 ppb for max 8 h O 3 . However, relatively large biases still exist for cloud predictions, some PM 2.5 species, and PM 10 that warrant follow-up studies to better understand those issues. The impacts of chemistry-meteorological feedbacks are found to play important roles in affecting regional air quality in the US by reducing domain-average concentrations of carbon monoxide (CO), O 3 , nitrogen oxide (NO x ), volatile organic compounds (VOCs), and PM 2.5 by 3.1% (up to 27.8%), 4.2% (up to 16.2%), 6.6% (up to 50.9%), 5.8% (up to 46.6%), and 8.6% (up to 49.1%), respectively, mainly due to reduced radiation, temperature, and wind speed. The overall performance of the two-way coupled WRF-CMAQ model achieved in this work is generally good or satisfactory and the improved performance for two-way coupled WRF-CMAQ should be considered along with other factors in developing future model applications to inform policy making., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

The state-of-the-science Community Multiscale Air Quality (CMAQ) Modeling System has recently been extended for hemispheric-scale modeling applications (referred to as H-CMAQ). In this study, satellite-constrained estimation of the degassing SO 2 emissions from 50 volcanoes over the Northern Hemisphere is incorporated into H-CMAQ, and their impact on tropospheric sulfate aerosol ( SO 4 2 - ) levels is assessed for 2010. The volcanic degassing improves predictions of observations from the Acid Deposition Monitoring Network in East Asia (EANET), the United States Clean Air Status and Trends Network (CASTNET), and the United States Integrated Monitoring of Protected Visual Environments (IMPROVE). Over Asia, the increased SO 4 2 - concentrations were seen to correspond to the locations of volcanoes, especially over Japan and Indonesia. Over the USA, the largest impacts that occurred over the central Pacific were caused by including the Hawaiian Kilauea volcano, while the impacts on the continental USA were limited to the western portion during summertime. The emissions of the Soufrière Hills volcano located on the island of Montserrat in the Caribbean Sea affected the southeastern USA during the winter season. The analysis at specific sites in Hawaii and Florida also confirmed improvements in regional performance for modeled SO 4 2 - by including volcanoes SO 2 emissions. At the edge of the western USA, monthly averaged SO 4 2 - enhancements greater than 0.1μgm -3 were noted within the boundary layer (defined as surface to 750hPa) during June- September. Investigating the change on SO 4 2 - concentration throughout the free troposphere revealed that although the considered volcanic SO 2 emissions occurred at or below the middle of free troposphere (500hPa), compared to the simulation without the volcanic source, SO 4 2 - enhancements of more than 10% were detected up to the top of the free troposphere (250hPa). Our model simulations and comparisons with measurements across the Northern Hemisphere indicate that the degassing volcanic SO 2 emissions are an important source and should be considered in air quality model simulations assessing background SO 4 2 - levels and their source attribution.

Air quality modeling for research and regulatory applications often involves executing many emissions sensitivity cases to quantify impacts of hypothetical scenarios, estimate source contributions, or quantify uncertainties. Despite the prevalence of this task, conventional approaches for perturbing emissions in chemical transport models like the Community Multiscale Air Quality (CMAQ) model require extensive offline creation and finalization of alternative emissions input files. This workflow is often time-consuming, error-prone, inconsistent among model users, difficult to document, and dependent on increased hard disk resources. The Detailed Emissions Scaling, Isolation, and Diagnostic (DESID) module, a component of CMAQv5.3 and beyond, addresses these limitations by performing these modifications online during the air quality simulation. Further, the model contains an Emission Control Interface which allows users to prescribe both simple and highly complex emissions scaling operations with control over individual or multiple chemical species, emissions sources, and spatial areas of interest. DESID further enhances the transparency of its operations with extensive error-checking and optional gridded output of processed emission fields. These new features are of high value to many air quality applications including routine perturbation studies, atmospheric chemistry research, and coupling with external models (e.g., energy system models, reduced-form models)., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

The Community Multiscale Air Quality (CMAQ) model version 5.3 (CMAQ53), released to the public in August 2019 and followed by version 5.3.1 (CMAQ531) in December 2019, contains numerous science updates, enhanced functionality, and improved computation efficiency relative to the previous version of the model, 5.2.1 (CMAQ521). Major science advances in the new model include a new aerosol module (AERO7) with significant updates to secondary organic aerosol (SOA) chemistry, updated chlorine chemistry, updated detailed bromine and iodine chemistry, updated simple halogen chemistry, the addition of dimethyl sulfide (DMS) chemistry in the CB6r3 chemical mechanism, updated M3Dry bidirectional deposition model, and the new Surface Tiled Aerosol and Gaseous Exchange (STAGE) bidirectional deposition model. In addition, support for the Weather Research and Forecasting (WRF) model's hybrid vertical coordinate (HVC) was added to CMAQ53 and the Meteorology-Chemistry Interface Processor (MCIP) version 5.0 (MCIP50). Enhanced functionality in CMAQ53 includes the new Detailed Emissions Scaling, Isolation and Diagnostic (DESID) system for scaling incoming emissions to CMAQ and reading multiple gridded input emission files. Evaluation of CMAQ531 was performed by comparing monthly and seasonal mean daily 8 h average (MDA8) O 3 and daily PM 2.5 values from several CMAQ531 simulations to a similarly configured CMAQ521 simulation encompassing 2016. For MDA8 O 3 , CMAQ531 has higher O 3 in the winter versus CMAQ521, due primarily to reduced dry deposition to snow, which strongly reduces wintertime O 3 bias (2-4 ppbv monthly average). MDA8 O 3 is lower with CMAQ531 throughout the rest of the year, particularly in spring, due in part to reduced O 3 from the lateral boundary conditions (BCs), which generally increases MDA8 O 3 bias in spring and fall ( 0.5 μg m -3 ). For daily 24 h average PM 2.5 , CMAQ531 has lower concentrations on average in spring and fall, higher concentrations in summer, and similar concentrations in winter to CMAQ521, which slightly increases bias in spring and fall and reduces bias in summer. Comparisons were also performed to isolate updates to several specific aspects of the modeling system, namely the lateral BCs, meteorology model version, and the deposition model used. Transitioning from a hemispheric CMAQ (HCMAQ) version 5.2.1 simulation to a HCMAQ version 5.3 simulation to provide lateral BCs contributes to higher O 3 mixing ratios in the regional CMAQ simulation in higher latitudes during winter (due to the decreased O 3 dry deposition to snow in CMAQ53) and lower O 3 mixing ratios in middle and lower latitudes year-round (due to reduced O 3 over the ocean with CMAQ53). Transitioning from WRF version 3.8 to WRF version 4.1.1 with the HVC resulted in consistently higher (1.0-1.5 ppbv) MDA8 O 3 mixing ratios and higher PM 2.5 concentrations (0.1-0.25 μg m -3 ) throughout the year. Finally, comparisons of the M3Dry and STAGE deposition models showed that MDA8 O 3 is generally higher with M3Dry outside of summer, while PM 2.5 is consistently higher with STAGE due to differences in the assumptions of particle deposition velocities to non-vegetated surfaces and land use with short vegetation (e.g., grasslands) between the two models. For ambient NH 3 , STAGE has slightly higher concentrations and smaller bias in the winter, spring, and fall, while M3Dry has higher concentrations and smaller bias but larger error and lower correlation in the summer., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

US background (US-B) ozone (O 3 ) is the O 3 that would be present in the absence of US anthropogenic (US-A) emissions. US-B O 3 varies by location and season and can make up a large, sometimes dominant, portion of total O 3 . Typically, US-B O 3 is quantified using a chemical transport model (CTM) though results are uncertain due to potential errors in model process descriptions and inputs, and there are significant differences in various model estimates of US-B O 3 . We develop and apply a method to fuse observed O 3 with US-B O 3 simulated by a regional CTM (CMAQ). We apportion the model bias as a function of space and time to US-B and US-A O 3 . Trends in O 3 bias are explored across different simulation years and varying model scales. We found that the CTM US-B O 3 estimate was typically biased low in spring and high in fall across years (2016-2017) and model scales. US-A O 3 was biased high on average, with bias increasing for coarser resolution simulations. With the application of our data fusion bias adjustment method, we estimate a 28% improvement in the agreement of adjusted US-B O 3 . Across the four estimates, we found annual mean CTM-simulated US-B O 3 ranging from 30 to 37 ppb with the spring mean ranging from 32 to 39 ppb. After applying the bias adjustment, we found annual mean US-B O 3 ranging from 32 to 33 ppb with the spring mean ranging from 37 to 39 ppb.

Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) treated with immune checkpoint inhibitors (ICIs) are at risk of pneumonitis as well as pneumonia (combined henceforth as ICI-related pulmonary complications). Little is known about the cellular and molecular mechanisms underlying ICI-related pulmonary complications. We characterized lymphocytes from bronchoalveolar lavage (BAL) fluid and peripheral blood from seven AML/MDS patients with pulmonary symptoms after ICI-based therapy (ICI group) and four ICI-naïve AML/MDS patients with extracellular bacterial or fungal pneumonias (controls). BAL T cells in the ICI group were clonally expanded, and BAL IFNγ + IL-17 - CD8 + T and CXCR3 + CCR6 + Th17/Th1 cells were enriched in the ICI group. Our data suggest that these cells may play a critical role in the pathophysiology of ICI-related pulmonary complications. Understanding of these cell populations may also provide predictive and diagnostic biomarkers of ICI-related pulmonary complications, eventually enabling differentiation of pneumonitis from pneumonia in AML/MDS patients receiving ICI-based therapies., Competing Interests: SN has received research support from Kite/Gilead, Cellectis, Poseida, Merck, Acerta, Karus, BMS, Unum Therapeutics, Allogene, and Precision Biosciences; served as consultant and advisory board member for Kite/Gilead, Celgene, Novartis, Unum Therapeutics, Pfizer, Merck, Precision Biosciences, Cell Medica, Incyte, Allogene, Calibr, and Legend Biotech; and has patents related to cell therapy. ND has received research funding from Daiichi Sankyo, Bristol-Myers Squibb, Pfizer, Karyopharm, Sevier, Genentech, and ImmunoGen and has served in a consulting or advisory role for Daiichi Sankyo, Bristol-Myers Squibb, Pfizer, Novartis, Celgene, AbbVie, and Agios. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kim, Sheshadri, Shannon, Kontoyiannis, Kantarjian, Garcia-Manero, Ravandi, Im, Boddu, Bashoura, Balachandran, Evans, Faiz, Ruiz Vazquez, Divenko, Mathur, Tippen, Gumbs, Neelapu, Naing, Wang, Diab, Futreal, Nurieva and Daver.)

Background: It has been reported that patients attending the emergency department with other pathologies may not have received optimal medical care due to the lockdown measures in the early phase of the COVID-19 pandemic., Methods: This was a retrospective study of patients presenting with cardiovascular emergencies to four tertiary regional emergency departments in western India during the government implementation of complete lockdown., Results: 25.0% of patients during the lockdown period and 17.4% of patients during the pre-lockdown period presented outside the window period (presentation after 12 hours of symptom onset) compared with only 6% during the pre-COVID period. In the pre-COVID period, 46.9% of patients with ST elevation myocardial infarction underwent emergent catheterisation, while in the pre-lockdown and lockdown periods, these values were 26.1% and 18.8%, respectively. The proportion of patients treated with intravenous thrombolytic therapy increased from 18.4% in the pre-COVID period to 32.3% in the post-lockdown period. Inhospital mortality for acute coronary syndrome (ACS) increased from 2.69% in the pre-COVID period to 7.27% in the post-lockdown period. There was also a significant decline in emergency admissions for non-ACS conditions, such as acute decompensated heart failure and high degree or complete atrioventricular block., Conclusion: The COVID-19 pandemic has led to delays in patients seeking care for cardiac problems and also affected the use of optimum therapy in our institutions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Green infrastructure (GI) implementation can benefit an urban environment by reducing the impacts of urban stormwater on aquatic ecosystems and human health. However, few studies have systematically analyzed the biophysical effects on regional meteorology and air quality that are triggered by changes in the urban vegetative coverage. In this study we use a state-of-the-art high-resolution air quality model to simulate the effects of a hypothetically feasible vegetation-focused GI implementation scenario in Kansas City, MO/KS on regional meteorology and air quality. Full year simulations are conducted for both the base case and GI land use scenarios using two different land surface models (LSMs) schemes inside the meteorological model. While the magnitudes of the changes in air quality due to the GI implementation differ using the two LSMs, the model outputs consistently showed increases in summertime PM 2.5 (1.1 μg m -3 , approximately 10% increase using NOAH LSM), which occurred mostly during the night and arose from the primary components, due to the cooler surface temperatures and the decreased planetary boundary layer height (PBLH). Both the maximum daily 8-hour average ozone and 1 h daily maximum O 3 during summertime, decreased over the downtown areas (maximum decreases of 0.9 and 1.4 ppbv respectively). The largest ozone decreases were simulated to happen during the night, mainly caused by the titration effect of increased NO x concentration from the lower PBLH. These results highlight the region-specific non-linear process feedback from GI on regional air quality, and further demonstrate the need for comprehensive coupled meteorological-air quality modeling systems and necessity of accurate land surface model for studying these impacts., 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., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Regional-scale air quality models are being used for studying the sources, composition, transport, transformation, and deposition of fine particulate matter (PM 2.5 ). The availability of decadal air quality simulations provides a unique opportunity to explore sophisticated model evaluation techniques rather than relying solely on traditional operational evaluations. In this study, we propose a new approach for process-based model evaluation of speciated PM 2.5 using improved complete ensemble empirical mode decomposition with adaptive noise (improved CEEMDAN) to assess how well version 5.0.2 of the coupled Weather Research and Forecasting model-Community Multiscale Air Quality model (WRF-CMAQ) simulates the time-dependent long-term trend and cyclical variations in daily average PM 2.5 and its species, including sulfate (SO 4 ), nitrate (NO 3 ), ammonium (NH 4 ), chloride (Cl), organic carbon (OC), and elemental carbon (EC). The utility of the proposed approach for model evaluation is demonstrated using PM 2.5 data at three monitoring locations. At these locations, the model is generally more capable of simulating the rate of change in the long-term trend component than its absolute magnitude. Amplitudes of the sub-seasonal and annual cycles of total PM 2.5 , SO 4 , and OC are well reproduced. However, the time-dependent phase difference in the annual cycles for total PM 2.5 , OC, and EC reveals a phase shift of up to half a year, indicating the need for proper temporal allocation of emissions and for updating the treatment of organic aerosols compared to the model version used for this set of simulations. Evaluation of sub-seasonal and interannual variations indicates that CMAQ is more capable of replicating the sub-seasonal cycles than interannual variations in magnitude and phase.

Regional air quality models are widely being used to understand the spatial extent and magnitude of the ozone non-attainment problem and to design emission control strategies needed to comply with the relevant ozone standard through direct emission perturbations. In this study, we examine the manageable portion of ground-level ozone using two simulations of the Community Multiscale Air Quality (CMAQ) model for the year 2010 and a probabilistic analysis approach involving 29 years (1990-2018) of historical ozone observations. The modeling results reveal that the reduction in the peak ozone levels from total elimination of anthropogenic emissions within the model domain is around 13-21 ppb for the 90th-100th percentile range of the daily maximum 8-hr ozone concentrations across the contiguous United States (CONUS). Large reductions in the 4th highest 8-hr ozone are seen in the regions of West (interquartile range (IQR) of 17-33%), South (IQR 22-34%), Central (IQR 19-31%), Southeast (IQR 25-34%), and Northeast (IQR 24-37%). However, sites in the western portion of the domain generally show smaller reductions even when all anthropogenic emissions are removed, possibly due to the strong influence of global background ozone, including sources such as intercontinental ozone transport, stratospheric ozone intrusions, wildfires, and biogenic precursor emissions. Probabilistic estimates of the exceedances for several hypothetical thresholds of the 4th highest 8-hr ozone indicate that, in some areas, exceedances of such hypothetical thresholds may occur even with no anthropogenic emissions due to the ever-present atmospheric stochasticity and the current global tropospheric ozone burden. Implications : Because air pollution is intricately linked to adverse health effects, National Ambient Air Quality Standards (NAAQS) have been established for criteria pollutants to safeguard human health and the environment. Areas not in compliance with the relevant standards are required to develop plans and policies to reduce their air pollution levels. Regional-scale air quality models are currently being used routinely to inform policies to identify the emissions reduction required to meet and maintain the NAAQS throughout the country. This paper examines the feasibility of the 4th highest ozone, which is used to derive the ozone design value for NAAQS, complying with various current and hypothetical 8-hr ozone thresholds over CONUS based on the information embedded in 29 years of historical ozone observations and two modeling scenarios with and without anthropogenic emissions loading.

Background: Nearly one third of all major congenital anomalies are due to congenital heart disease (CHD). Globally the prevalence of CHD in adults varies from 0.66 to 40.0 per 1000 study population. In India the prevalence of CHD is 1.09 to 543 per 1000 study population. CHD is a major global health burden because of increased mortality and morbidity associated with it. Early diagnosis and management can be helpful in improving survival rates, quality of life and prognosis in patients suffering from CHD., Aims and Objectives: The aim of this study was to assess the echocardiographic profile of CHD in Western Rajasthan, India in population above 12 years of age., Methods: This retrospective study was carried out at department of Cardiology and Pediatrics of Dr. S. N. Medical College and attached group of hospitals in Jodhpur, Rajasthan, India. The presence of CHD among all patients above 12 years of age who underwent transthoracic echocardiography over a period of around 4 years from July 2014 to April 2018 was analyzed., Results: A total of 256 patients above 12 years of age were identified as having CHD out of the 33,228 patients who underwent echocardiography during the study period, thus giving a prevalence of 7.7 per 1000 study population. Amongst the total diagnosed CHD cases, 137 (53.52%) patients were male with male to female ratio of 1.15:1. CHDs were diagnosed more commonly between 13 to 24 years of age (54.69%). The commonest type of CHD in the present study was atrial septal defect (27.34%) whereas the most common cyanotic CHD was tetralogy of Fallot (10.94%)., Conclusion: Prevalence of CHD in study cohort of age more than 12 years in Western Rajasthan, India was 7.7 per 1000 study population. Profile of CHDs in the present study was similar to that in published literature. We propose to do larger and targeted studies in this age group because many CHDs will become inoperable or even if operated will leave some or other cardiac dysfunction beyond adolescence., (© Journal of the Association of Physicians of India 2011.)

We implement oceanic dimethylsulfide (DMS) emissions and its atmospheric chemical reactions into the Community Multiscale Air Quality (CMAQv53) model and perform annual simulations without and with DMS chemistry to quantify its impact on tropospheric composition and air quality over the Northern Hemisphere. DMS chemistry enhances both sulfur dioxide (SO 2 ) and sulfate ( S O 4 2 - ) over seawater and coastal areas. It enhances annual mean surface SO 2 concentration by +46 pptv and S O 4 2 - by +0.33 μg/m 3 and decreases aerosol nitrate concentration by -0.07 μg/m 3 over seawater compared to the simulation without DMS chemistry. The changes decrease with altitude and are limited to the lower atmosphere. Impacts of DMS chemistry on S O 4 2 - are largest in the summer and lowest in the fall due to the seasonality of DMS emissions, atmospheric photochemistry and resultant oxidant levels. Hydroxyl and nitrate radical-initiated pathways oxidize 75% of the DMS while halogen-initiated pathways oxidize 25%. DMS chemistry leads to more acidic particles over seawater by decreasing aerosol pH. Increased S O 4 2 - from DMS enhances atmospheric extinction while lower aerosol nitrate reduces the extinction so that the net effect of DMS chemistry on visibility tends to remain unchanged over most of the seawater.

The relationship between attachment loss and occlusal trauma has been debated for many years. When a patient presents with advanced periodontal disease, a decision has to be made on whether the teeth can be saved or extracted. In this treatment example, the decision process in therapeutic planning for a patient with stage IV periodontal disease is discussed. The main dilemma is whether the patient should receive a prosthodontic reconstruction supported by osseointegrated implants or by periodontally compromised natural teeth. It is assumed that implants do better than teeth over the long term based on firm documentation in the literature, but this article describes why a periodontal prosthesis is still a viable treatment option.

The downward transport of ozone (O 3 ) stemming from the stratosphere-to-troposphere exchange (STE) can be a significant contributor to background O 3 . Such enhancement of background O 3 may also influence ground-level PM 2.5 , particularly in polluted regions which have abundant precursor emissions. In this study, we quantified the STE impact on tropospheric O 3 and its subsequent influence on surface PM 2.5 across the northern hemisphere. The sensitivity analyses was conducted by using a comprehensive hemispheric atmospheric modeling system. Results suggest the surface PM 2.5 concentration can be considerably enhanced by the STE in polluted regions including East China, East US, and Europe, mostly in winter and spring. In winter, the PM 2.5 concentrations in East China, East US, and Europe are estimated to be enhanced by 1.3%, 3.5% and 5.5% due to the STE. The STE-enhanced PM 2.5 concentrations are typically higher on high pollution days suggesting likely increasing contributions in regions with the growing pollution levels. During the heavy polluted days, the PM 2.5 concentrations in East China can be enhanced by 2.289 μg/m 3 in winter and 2.034 μg/m 3 in spring due to the STE. The STE-enhanced PM 2.5 also exhibits strong diurnal variations following a pattern similar to the total PM 2.5 concentration, with high increasing ratio in the morning and low at afternoon, suggesting that the enhancement is most pronounced during peak pollution events. The STE-enhanced PM 2.5 is exclusively contributed by the increase of nitrate, ammonium, and secondary organic aerosol which in-turn are strongly influenced by the atmospheric oxidation capacity., 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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Case Presentation: We report a patient with the triad of diabetic ketoacidosis, hypertriglyceridemia, and acute pancreatitis associated with computed tomography hypoperfusion complex and adrenal hyperdensity on abdominal imaging - an association not previously reported in diabetic ketoacidosis., Discussion: Presence of computed tomography hypoperfusion complex with hyperdense 'Tubelight adrenals' in a patient with diabetic ketoacidosis is associated with poor prognosis and thus serves to guide clinicians towards early and aggressive management.

The state-of-the-science Community Multiscale Air Quality (CMAQ) modeling system, which has recently been extended for hemispheric-scale modeling applications (referred to as H-CMAQ), is applied to study the trans-Pacific transport, a phenomenon recognized as a potential source of air pollution in the US, during April 2010. The results of this analysis are presented in two parts. In the previous paper (Part 1), model evaluation for tropospheric ozone (O 3 ) was presented and an air mass characterization method was developed. Results from applying this newly established method pointed to the importance of emissions as the factor to enhance the surface O 3 mixing ratio over the US. In this subsequent paper (Part 2), emission impacts are examined based on mathematically rigorous sensitivity analysis using the higher-order decoupled direct method (HDDM) implemented in H-CMAQ. The HDDM sensitivity coefficients indicate the presence of a NO x -sensitive regime during April 2010 over most of the Northern Hemisphere. By defining emission source regions over the US and east Asia, impacts from these emission sources are examined. At the surface, during April 2010, the emission impacts of the US and east Asia are comparable over the western US with a magnitude of about 3ppbv impacts on monthly mean O 3 all-hour basis, whereas the impact of domestic emissions dominates over the eastern US with a magnitude of about 10ppbv impacts on monthly mean O 3 . The positive correlation ( r = 0.63) between surface O 3 mixing ratios and domestic emission impacts is confirmed. In contrast, the relationship between surface O 3 mixing ratios and emission impacts from east Asia exhibits a flat slope when considering the entire US. However, this relationship has strong regional differences between the western and eastern US; the western region exhibits a positive correlation ( r = 0 . 36-0.38), whereas the latter exhibits a flat slope ( r < 0 . 1). Based on the comprehensive evaluation of H-CMAQ, we extend the sensitivity analysis for O 3 aloft. The results reveal the significant impacts of emissions from east Asia on the free troposphere (defined as 750 to 250hPa) over the US (impacts of more than 5ppbv) and the dominance of stratospheric air mass on upper model layer (defined as 250 to 50hPa) over the US (impacts greater than 10ppbv). Finally, we estimate changes of trans-Pacific transport by taking into account recent emission trends from 2010 to 2015 assuming the same meteorological condition. The analysis suggests that the impact of recent emission changes on changes in the contribution of trans-Pacific transport to US O 3 levels was insignificant at the surface level and was small (less than 1ppbv) over the free troposphere.

Stratospheric intrusion and trans-Pacific transport have been recognized as a potential source of tropospheric ozone over the US. The state-of-the-science Community Multiscale Air Quality (CMAQ) modeling system has recently been extended for hemispheric-scale modeling applications (referred to as H-CMAQ). In this study, H-CMAQ is applied to study the stratospheric intrusion and trans-Pacific transport during April 2010. The results will be presented in two companion papers. In this Part 1 paper, model evaluation for tropospheric ozone (O 3 ) is presented. Observations at the surface, by ozonesondes and airplane, and by satellite across the Northern Hemisphere are used to evaluate the model performance for O 3 . H-CMAQ is able to capture surface and boundary layer (defined as surface to 750hPa) O 3 with a normalized mean bias (NMB) of -10%; however, a systematic underestimation with an NMB up to -30% is found in the free troposphere (defined as 750-250hPa). In addition, a new air mass characterization method is developed to distinguish influences of stratosphere-troposphere transport (STT) from the effects of photochemistry on O 3 levels. This method is developed based on the ratio of O 3 and an inert tracer indicating stratospheric O 3 to examine the importance of photochemistry, and sequential intrusion from upper layer. During April 2010, on a monthly average basis, the relationship between surface O 3 mixing ratios and estimated stratospheric air masses in the troposphere show a slight negative slope, indicating that high surface O 3 values are primarily affected by other factors (i.e., emissions), whereas this relationship shows a slight positive slope at elevated sites, indicating that STT has a possible impact at elevated sites. STT shows large day-to-day variations, and STT impacts can either originate from the same air mass over the entire US with an eastward movement found during early April, or stem from different air masses at different locations indicated during late April. Based on this newly established air mass characterization technique, this study can contribute to understanding the role of STT and also the implied importance of emissions leading to high surface O 3 . Further research focused on emissions is discussed in a subsequent paper (Part 2).

Regional-scale air pollution models are routinely being used world-wide for research, forecasting air quality, and regulatory purposes. It is well recognized that there are both reducible (systematic) and irreducible (unsystematic) errors in the meteorology-atmospheric chemistry modeling systems. The inherent (random) uncertainty stems from our inability to properly characterize stochastic variations in atmospheric dynamics and chemistry, and from the incommensurability associated with comparisons of the volume-averaged model estimates with point measurements. Because these stochastic variations are not being explicitly simulated in the current generation of regional-scale meteorology-air quality models, one should expect to find differences between the model estimates and corresponding observations. This paper presents an observation-based methodology to determine the expected errors from current generation regional air quality models even when the model design, physics, chemistry, and numerical analysis, as well as its input data, were "perfect". To this end, the short-term synoptic-scale fluctuations embedded in the daily maximum 8-hr ozone time series are separated from the longer-term forcing using a simple recursive moving average filter. The inherent uncertainty attributable to the stochastic nature of the atmosphere is determined based on 30+ years of historical ozone time series data measured at various monitoring sites in the contiguous United States. The results reveal that the expected root mean square error at the median and 95 th percentile is about 2 ppb and 5 ppb, respectively, even for "perfect" air quality models driven with "perfect" input data. Quantitative estimation of the limit to the model's accuracy will help in objectively assessing the current state-of-the-science in regional air pollution models, measuring progress in their evolution, and providing meaningful and firm targets for improvements in their accuracy relative to ambient measurements., Competing Interests: Competing interests: The authors declare that they have no conflict of interest.

Using lightning flash data from the National Lightning Detection Network with an updated lightning nitrogen oxides (NO x ) emission estimation algorithm in the Community Multiscale Air Quality (CMAQ) model, we estimate the hourly variations in lightning NO x emissions for the summer of 2011 and simulate its impact on distributions of tropospheric ozone (O 3 ) across the continental United States. We find that typical summer-time lightning activity across the U.S. Mountain West States (MWS) injects NO x emissions comparable to those from anthropogenic sources into the troposphere over the region. Comparison of two model simulation cases with and without lightning NO x emissions show that significant amount of ground-level O 3 in the MWS during the summer can be attributed to the lightning NO X emissions. The simulated surface-level O 3 from a model configuration incorporating lightning NO x emissions showed better agreement with the observed values than the model configuration without lightning NO x emissions. The time periods of significant reduction in bias in simulated O 3 between these two cases strongly correlate with the time periods when lightning activity occurred in the region. The inclusion of lightning NO x increased daily maximum 8 h O 3 by up to 17 ppb and improved model performance relative to measured surface O 3 mixing ratios in the MWS region. Analysis of model results in conjunction with lidar measurements at Boulder, Colorado during July 2014 corroborated similar impacts of lightning NO x emissions on O 3 emissions estimated for other summers is comparable to the 2011 air quality. The magnitude of lightning NO x estimates suggesting that summertime surface-level O 3 levels in the MWS region could be significantly influenced by lightning NO x ., Competing Interests: COMPETING INTERESTS The authors declare no competing interests.

Background: Reductions in ambient concentrations of fine particulate matter ( PM 2.5 ) have contributed to reductions in cardiovascular (CV) mortality., Objectives: We examined changes in CV mortality attributed to reductions in emissions from mobile, point, areal, and nonroad sources through changes in concentrations of PM 2.5 and its major components [nitrates, sulfates, elemental carbon (EC), and organic carbon (OC)] in 2,132 U.S. counties between 1990 and 2010., Methods: Using Community Multiscale Air Quality model estimated PM 2.5 total and component concentrations, we calculated population-weighted annual averages for each county. We estimated PM 2.5 total- and component-related CV mortality, adjusted for county-level population characteristics and baseline PM 2.5 concentrations. Using the index of Emission Mitigation Efficiency for primary emission-to-particle pathways, we expressed changes in particle-related mortality in terms of precursor emissions by each sector., Results: PM 2.5 reductions represented 5.7% of the overall decline in CV mortality. Large point source emissions of sulfur dioxide accounted for 6.685 [95% confidence interval (CI): 5.703, 7.667] fewer sulfate-related CV deaths per 100,000 people. Mobile source emissions of primary EC and nitrous oxides accounted for 3.396 (95% CI: 2.772, 4.020) and 3.984 (95% CI: 2.472, 5.496) fewer CV deaths per 100,000 people respectively. Increased EC and OC emissions from areal sources increased carbon-related CV mortality by 0.788 (95% CI: - 0.540 , 2.116) and 0.245 (95% CI: - 0.697 , 1.187) CV deaths per 100,000 people., Discussion: In a nationwide epidemiological study of emission sector contribution to PM 2.5 -related mortality, we found that reductions in sulfur-dioxide emissions from large point sources and nitrates and EC emissions from mobile sources contributed the largest reduction in particle-related mortality rates respectively. https://doi.org/10.1289/EHP5692.

Regulatory T cells (Tregs) are important members of the immune system regulating the host responses to infection and neoplasms. Tregs prevent autoimmune disorders by protecting the host-cells from an immune response, related to the peripheral tolerance. However, tumor cells use Tregs as a shield to protect themselves against anti-tumor immune response. Thus, Tregs are a hurdle in achieving the complete potential of anti-cancer therapies including immunotherapy. This has prompted the development of novel adjuvant therapies that obviate their negative effects thereby enhancing the therapeutic efficacy. Our earlier studies have shown the efficacy of the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG) by reducing the induced Tregs pool and enhance immune stimulation as well as local tumor control. These findings have suggested its potential for enhancing the efficacy of immunotherapy, besides radiotherapy and chemotherapy. This review provides a brief account of the current status of Tregs as a component of the immune-biology of tumors and various preclinical and clinical strategies pursued to obviate the limitations imposed by them in achieving therapeutic efficacy., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Verma et al.)

Multiple myeloma is, in most patients, an incurable cancer. Its precursors can be identified with routine tests setting the stage for early intervention to prevent active myeloma. We investigated the efficacy and safety of pembrolizumab, an antiprogrammed cell death 1 antibody, in smoldering myeloma patients with intermediate/high risk of progression to symptomatic myeloma. Thirteen patients were treated with a median number of 8 cycles. One patient achieved a stringent complete response with bone marrow next-generation sequencing negativity at 10 -4 that is ongoing at 27 months (8%); 11 had stable disease (85%), and 1 progressed (8%). Three patients discontinued therapy due to immune-related adverse events: 2 with transaminitis and 1 due to tubulointerstitial nephritis. Immune profiling of bone marrow samples at baseline showed markers associated with a preexisting immune response in the responder compared with nonresponders and features of increased T-cell exhaustion in nonresponders. Consistent with this, transcriptome sequencing of bone marrow samples at baseline revealed an increased interferon-γ signature in the responder compared with the nonresponders. In summary, our results suggest that smoldering myeloma may be immunogenic in a subset of patients, and therapies that enhance antitumor T-cell responses may be effective in preventing its progression. This trial was registered at www.clinicaltrials.gov as #NCT02603887., (© 2019 by The American Society of Hematology.)

This work describes the lightning nitric oxide (LNO) production schemes in the Community Multiscale Air Quality (CMAQ) model. We first document the existing LNO production scheme and vertical distribution algorithm. We then describe updates that were made to the scheme originally based on monthly National Lightning Detection Network (mNLDN) observations. The updated scheme uses hourly NLDN (hNLDN) observations. These NLDN-based schemes are good for retrospective model applications when historical lightning data are available. For applications when observed data are not available (i.e., air quality forecasts and climate studies that assume similar climate conditions), we have developed a scheme that is based on linear and log-linear parameters derived from regression of multiyear historical NLDN (pNLDN) observations and meteorological model simulations. Preliminary assessment for total column LNO production reveals that the mNLDN scheme overestimates LNO by over 40% during summer months compared with the updated hNLDN scheme that reflects the observed lightning activity more faithfully in time and space. The pNLDN performance varies with year, but it generally produced LNO columns that are comparable to hNLDN and mNLDN, and in most cases it outperformed mNLDN. Thus, when no observed lightning data are available, pNLDN can provide reasonable estimates of LNO emissions over time and space for this important natural NO source that influences air quality regulations., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

Atmospheric oxidation of natural and anthropogenic volatile organic compounds (VOCs) leads to secondary organic aerosol (SOA), which constitutes a major and often dominant component of atmospheric fine particulate matter (PM 2.5 ). Recent work demonstrates that rapid autoxidation of organic peroxy radicals (RO 2 ) formed during VOC oxidation results in highly oxygenated organic molecules (HOM) that efficiently form SOA. As NO x emissions decrease, the chemical regime of the atmosphere changes to one in which RO 2 autoxidation becomes increasingly important, potentially increasing PM 2.5 , while oxidant availability driving RO 2 formation rates simultaneously declines, possibly slowing regional PM 2.5 formation. Using a suite of in situ aircraft observations and laboratory studies of HOM, together with a detailed molecular mechanism, we show that although autoxidation in an archetypal biogenic VOC system becomes more competitive as NO x decreases, absolute HOM production rates decrease due to oxidant reductions, leading to an overall positive coupling between anthropogenic NO x and localized biogenic SOA from autoxidation. This effect is observed in the Atlanta, Georgia, urban plume where HOM is enhanced in the presence of elevated NO, and predictions for Guangzhou, China, where increasing HOM-RO 2 production coincides with increases in NO from 1990 to 2010. These results suggest added benefits to PM 2.5 abatement strategies come with NO x emission reductions and have implications for aerosol-climate interactions due to changes in global SOA resulting from NO x interactions since the preindustrial era., Competing Interests: The authors declare no conflict of interest.

Bromine and iodine chemistry has been updated in the Community Multiscale Air Quality (CMAQ) model to better capture the influence of natural emissions from the oceans on ozone concentrations. Annual simulations were performed using the hemispheric CMAQ model without and with bromine and iodine chemistry. Model results over the Northern Hemisphere show that including bromine and iodine chemistry in CMAQ not only reduces ozone concentrations within the marine boundary layer but also aloft and inland. Bromine and iodine chemistry reduces annual mean surface ozone over seawater by 25%, with lesser ozone reductions over land. The bromine and iodine chemistry decreases ozone concentration without changing the diurnal profile and is active throughout the year. However, it does not have a strong seasonal influence on ozone over the Northern Hemisphere. Model performance of CMAQ is improved by the bromine and iodine chemistry when compared to observations, especially at coastal sites and over seawater. Relative to bromine, iodine chemistry is approximately four times more effective in reducing ozone over seawater over the Northern Hemisphere (on an annual basis). Model results suggest that the chemistry modulates intercontinental transport and lowers the background ozone imported to the United States.

This study assesses the impact of the lightning nitric oxide (LNO) production schemes in the Community Multiscale Air Quality (CMAQ) model on ground-level air quality as well as aloft atmospheric chemistry through detailed evaluation of model predictions of nitrogen oxides (NO x ) and ozone (O 3 ) with corresponding observations for the US. For ground-level evaluations, hourly O 3 and NO x values from the U.S. EPA Air Quality System (AQS) monitoring network are used to assess the impact of different LNO schemes on model prediction of these species in time and space. Vertical evaluations are performed using ozonesonde and P-3B aircraft measurements during the Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER-AQ) campaign conducted in the Baltimore- Washington region during July 2011. The impact on wet deposition of nitrate is assessed using measurements from the National Atmospheric Deposition Program's National Trends Network (NADP NTN). Compared with the Base model (without LNO), the impact of LNO on surface O 3 varies from region to region depending on the Base model conditions. Overall statistics suggest that for regions where surface O 3 mixing ratios are already overestimated, the incorporation of additional NO from lightning generally increased model overestimation of mean daily maximum 8 h (DM8HR) O 3 by 1-2 ppb. In regions where surface O 3 is underestimated by the Base model, LNO can significantly reduce the underestimation and bring model predictions close to observations. Analysis of vertical profiles reveals that LNO can significantly improve the vertical structure of modeled O 3 distributions by reducing underestimation aloft and to a lesser degree decreasing overestimation near the surface. Since the Base model underestimates the wet deposition of nitrate in most regions across the modeling domain with the exception of the Pacific Coast, the inclusion of LNO leads to reduction in biases and errors and an increase in correlation coefficients at almost all the NADP NTN sites. Among the three LNO schemes described in Kang et al. (2019), the hNLDN scheme, which is implemented using hourly observed lightning flash data from National Lightning Detection Network (NLDN), performs best for comparisons with ground-level values, vertical profiles, and wet deposition of nitrate; the mNLDN scheme (the monthly NLDN-based scheme) performed slightly better. However, when observed lightning flash data are not available, the linear regression-based parameterization scheme, pNLDN, provides an improved estimate for nitrate wet deposition compared to the base simulation that does not include LNO., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

Regional-scale air quality models and observations at routine air quality monitoring sites are used to determine attainment/non-attainment of the ozone air quality standard in the United States. In current regulatory applications, a regional-scale air quality model is applied for a base year and a future year with reduced emissions using the same meteorological conditions as those in the base year. Because of the stochastic nature of the atmosphere, the same meteorological conditions would not prevail in the future year. Therefore, we use multi-decadal observations to develop a new method for estimating the confidence bounds for the future ozone design value (based on the 4 th highest value in the daily maximum 8-hr ozone concentration time series, DM8HR) for each emission loading scenario along with the probability of the design value exceeding a given ozone threshold concentration at all monitoring sites in the contiguous United States. To this end, we spectrally decompose the observed DM8HR ozone time series covering the period from 1981 to 2014 using the Kolmogorov-Zurbenko (KZ) filter and examine the variability in the relative strengths of the short-term variations (induced by synoptic-scale weather fluctuations; referred to as synoptic component, SY) and the long-term component (dictated by changes in emissions, seasonality and other slow-changing processes such as climate change; referred to as baseline component, BL). Results indicate that combining the projected change in the ozone baseline level with the adjusted synoptic forcing in historical ozone observations enables us to provide a probabilistic assessment of the efficacy of a selected emissions control strategy in complying with the ozone standard in future years. In addition, attainment demonstration is illustrated with a real-world application of the proposed methodology by using air quality model simulations, thereby helping build confidence in the use of regional-scale air quality models for supporting regulatory policies.

Background: The coronary slow flow phenomenon (CSFP) is an angiographic finding characterized by delayed distal vessel opacification in the absence of significant epicardial coronary stenosis. Although it is well-known to interventional cardiologists for approximately four decades, the etiopathogenesis still remains unclear., Aims and Objectives: In this study, we aimed to determine the clinical, demographic, risk factor and angiographic profile of patients with CSFP., Methods: Clinical, demographic, risk factor and angiographic profile were recorded in all consecutive patients who had undergone coronary angiography between September 2016 and March 2017 and showed features of CSFP and a control group who showed normal coronary flow (NCF). The CSFP was diagnosed on the basis of the corrected thrombolysis in myocardial infarction frame count., Results: CSFP was significantly more prevalent in male patients. Among the traditional risk factors, there was significantly more prevalence of hypertension (31.25% versus 6.67%, p < 0.001), dyslipidemia (40% versus 7.5%, p < 0.001) and history of tobacco use (47.5% versus 10.0%, p < 0.001) in CSFP patients as compared to NCF patients. On multivariable regression analysis hypertension, dyslipidemia, history of smoking and tobacco chewing were found to have independent association with CSFP. Acute coronary syndrome (ACS) was the most common mode of presentation in CSFP patients., Conclusion: CSFP was relatively common among patients who presented with ACS. Hypertension, dyslipidemia, smoking and tobacco chewing can be considered independent risk factors for this phenomenon. Therefore, CSFP should be considered as a pathological entity and not an entirely benign condition., (Copyright © 2018. Published by Elsevier B.V.)

Changing precursor emission patterns in conjunction with stringent health protective air quality standards necessitate accurate quantification of nonlocal contributions to ozone pollution at a location due to atmospheric transport, that by nature predominantly occurs aloft nocturnally. Concerted efforts to characterize ozone aloft on a continuous basis to quantify its contribution to ground-level concentrations, however, are lacking. By applying our classical understanding of air pollution dynamics to analyze variations in widespread surface-level ozone measurements, in conjunction with process-based interpretation from a comprehensive air pollution modeling system and detailed backward-sensitivity calculations that quantitatively link surface-level and aloft pollution, we show that accurate quantification of the amount of ozone in the air entrained from aloft every morning as the atmospheric boundary layer grows is the key missing component for characterizing background pollution at a location, and we propose a cost-effective continuous aloft ozone measurement strategy to address critical scientific gaps in current air quality management. Continuous aloft air pollution measurements can be achieved cost-effectively through leveraging advances in sensor technology and proliferation of tall telecommunications masts. Resultant improvements in ozone distribution characterization at 400-500 m altitude are estimated to be 3-4 times more effective in characterizing the surface-level daily maximum 8-h average ozone (DM8O 3 ) than improvements from surface measurements since they directly quantify the amount of pollution imported to a location and furnish key missing information on processes and sources regulating background ozone and its modulation of ground-level concentrations. Since >80% of the DM8O 3 sensitivity to tropospheric ozone is potentially captured through measurements between 200 and 1200 m altitude (a possible design goal for future remote sensing instrumentation), their assimilation will dramatically improve air quality forecast and health advisories.

Severe and persistent haze pollution involving fine particulate matter (PM 2.5 ) concentrations reaching unprecedentedly high levels across many cities in China poses a serious threat to human health. Although mandatory temporary cessation of most urban and surrounding emission sources is an effective, but costly, short-term measure to abate air pollution, development of long-term crisis response measures remains a challenge, especially for curbing severe urban haze events on a regular basis. Here we introduce and evaluate a novel precision air pollution control approach (PAPCA) to mitigate severe urban haze events. The approach involves combining predictions of high PM 2.5 concentrations, with a hybrid trajectory-receptor model and a comprehensive 3-D atmospheric model, to pinpoint the origins of emissions leading to such events and to optimize emission controls. Results of the PAPCA application to five severe haze episodes in major urban areas in China suggest that this strategy has the potential to significantly mitigate severe urban haze by decreasing PM 2.5 peak concentrations by more than 60% from above 300 μg m -3 to below 100 μg m -3 , while requiring ~30% to 70% less emission controls as compared to complete emission reductions. The PAPCA strategy has the potential to tackle effectively severe urban haze pollution events with economic efficiency.

Stress responses are critical for estrogen (E 2 )-induced apoptosis in E 2 -deprived breast cancer cells. Nuclear factor-kappa B (NF-κB) is an important therapeutic target to prevent stress responses in chronic inflammatory diseases including cancer. However, whether E 2 activates NF-κB to participate in stress-associated apoptosis in E 2 -deprived breast cancer cells is unknown. Here, we demonstrated that E 2 differentially modulates NF-κB activity according to treatment time. E 2 initially has significant potential to suppress NF-κB activation; it completely blocks tumor necrosis factor alpha (TNFα)-induced activation of NF-κB. We found that E 2 preferentially and constantly enhances the expression of the adipogenic transcription factor CCAAT/enhancer binding protein beta (C/EBPβ), which is responsible for the suppression of NF-κB activation by E 2 in MCF-7:5C cells. Interestingly, NF-κB p65 DNA-binding activity is increased when E 2 is administered for 48 h, leading to the induction of TNFα and associated apoptosis. Blocking the nuclear translocation of NF-κB can completely prevent the induction of TNFα and apoptosis induced by E 2 . Further examination revealed that protein kinase RNA-like endoplasmic reticulum kinase (PERK), a stress sensor of unfolded protein response (UPR), plays an essential role in the late activation of NF-κB by E 2 . This modulation between PERK and NF-κB is mainly mediated by a stress responsive transcription factor, transducer and activator of transcription 3 (STAT3), independently of the classic canonical IκBα signaling pathway. Thus, inhibition of PERK kinase activity completely blocks the DNA binding of both STAT3 and NF-κB, thereby preventing induction of NF-κB-dependent genes and E 2 -induced apoptosis. All of these findings suggest that PERK is a key regulator to convey stress signals from the endoplasmic reticulum to the nucleus and illustrate a crucial role for the novel PERK/STAT3/NF-κB/TNFα axis in E 2 -induced apoptosis in E 2 -deprived breast cancer cells., Competing Interests: The authors declare that they have no competing interests.

Lutembacher syndrome is a rare cardiac abnormality characterized by a combination of congenital atrial septal defect (ASD) and acquired rheumatic mitral stenosis (MS). Here we report a case of 18-year-old male with Lutembacher syndrome successfully treated percutaneously with transcatheter Accura balloon valvuloplasty and Amplatzer septal occluder device closure., (© Journal of the Association of Physicians of India 2011.)

Concentrations of both fine particulate matter (PM 2.5 ) and ozone (O 3 ) in the United States (US) have decreased significantly since 1990, mainly because of air quality regulations. Exposure to these air pollutants is associated with premature death. Here we quantify the annual mortality burdens from PM 2.5 and O 3 in the US from 1990 to 2010, estimate trends and inter-annual variability, and evaluate the contributions to those trends from changes in pollutant concentrations, population, and baseline mortality rates. We use a fine-resolution (36 km) self-consistent 21-year simulation of air pollutant concentrations in the US from 1990 to 2010, a health impact function, and annual county-level population and baseline mortality rate estimates. From 1990 to 2010, the modeled population-weighted annual PM 2.5 decreased by 39 %, and summertime (April to September) 1 h average daily maximum O 3 decreased by 9 % from 1990 to 2010. The PM 2.5 -related mortality burden from ischemic heart disease, chronic obstructive pulmonary disease, lung cancer, and stroke steadily decreased by 54% from 123 700 deaths year -1 (95% confidence interval, 70 800-178 100) in 1990 to 58 600 deaths year -1 (24 900-98 500) in 2010. The PM 2.5 -related mortality burden would have decreased by only 24% from 1990 to 2010 if the PM 2.5 concentrations had stayed at the 1990 level, due to decreases in baseline mortality rates for major diseases affected by PM 2.5 . The mortality burden associated with O 3 from chronic respiratory disease increased by 13% from 10 900 deaths year -1 (3700-17 500) in 1990 to 12 300 deaths year -1 (4100-19 800) in 2010, mainly caused by increases in the baseline mortality rates and population, despite decreases in O 3 concentration. The O 3 -related mortality burden would have increased by 55% from 1990 to 2010 if the O 3 concentrations had stayed at the 1990 level. The detrended annual O 3 mortality burden has larger inter-annual variability (coefficient of variation of 12%) than the PM 2.5 -related burden (4%), mainly from the inter-annual variation of O 3 concentration. We conclude that air quality improvements have significantly decreased the mortality burden, avoiding roughly 35 800 (38%) PM 2.5 -related deaths and 4600 (27%) O 3 -related deaths in 2010, compared to the case if air quality had stayed at 1990 levels (at 2010 baseline mortality rates and population)., Competing Interests: Competing interests. The authors declare that they have no conflicts of interest.

Excess deposition (including both wet and dry deposition) of nitrogen and sulfur are detrimental to ecosystems. Recent studies have investigated the spatial patterns and temporal trends of nitrogen and sulfur wet deposition, but few studies have focused on dry deposition due to the scarcity of dry deposition measurements. Here, we use long-term model simulations from the coupled WRF-CMAQ model covering the period from 1990 to 2010 to study changes in spatial distribution as well as temporal trends in total (TDEP), wet (WDEP) and dry deposition (DDEP) of total inorganic nitrogen (TIN) and sulfur (TSO 4 ). We first evaluate the model's performance in simulating WDEP over the U.S. by comparing the model results with observational data from the U.S. National Atmospheric Deposition Program. The coupled model generally underestimates the WDEP of both TIN (including both the oxidized nitrogen deposition-TNO 3 , and the reduced nitrogen deposition-NH X ) and TSO 4 , with better performance in the eastern U.S. than the western U.S. TDEP of both TIN and TSO 4 show significant decreases over the U.S., especially in the east due to the large emission reductions that occurred in that region. The decreasing trends of TIN TDEP are caused by decrease of TNO 3 , and the increasing trends of TIN deposition over the Great Plains and Tropical Wet Forests regions are caused by increases in NH 3 emissions although it should be noted that these increasing trends are not significant. TIN WDEP shows decreasing trends throughout the U.S., except for the Marine West Coast Forest region. TIN DDEP shows significant decreasing trends in the region of Eastern Temperate Forests, Northern Forests, Mediterranean California and Marine West Coast Forest, and significant increasing trends in the region of Tropical Wet Forests, Great Plains and Southern Semi-arid Highlands. For the other three regions (North American Deserts, Temperate Sierras and Northwestern Forested Mountains), the decreasing or increasing trends were not significant. Both the WDEP and DDEP of TSO x have decreases across the U.S., with a larger decreasing trend in the DDEP than that in the WDEP. Across the U.S. during the 1990-2010 period, DDEP of TIN accounted for 58-65% of TDEP of TIN. TDEP of TIN over the U.S. was dominated by deposition of TNO 3 during the first decade, which then shifts to reduced nitrogen (NH X ) dominance after 2003 resulting from combination of NO x emission reductions and NH 3 emission increases. The sulfur DDEP is usually higher than the sulfur WDEP until recent years, as the sulfur DDEP has a larger decreasing trend than WDEP., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

Concentrations of atmospheric trace species in the United States have changed dramatically over the past several decades in response to pollution control strategies, shifts in domestic energy policy and economics, and economic development (and resulting emission changes) elsewhere in the world. Reliable projections of the future atmosphere require models to not only accurately describe current atmospheric concentrations, but to do so by representing chemical, physical and biological processes with conceptual and quantitative fidelity. Only through incorporation of the processes controlling emissions and chemical mechanisms that represent the key transformations among reactive molecules can models reliably project the impacts of future policy, energy and climate scenarios. Efforts to properly identify and implement the fundamental and controlling mechanisms in atmospheric models benefit from intensive observation periods, during which collocated measurements of diverse, speciated chemicals in both the gas and condensed phases are obtained. The Southeast Atmosphere Studies (SAS, including SENEX, SOAS, NOMADSS and SEAC4RS) conducted during the summer of 2013 provided an unprecedented opportunity for the atmospheric modeling community to come together to evaluate, diagnose and improve the representation of fundamental climate and air quality processes in models of varying temporal and spatial scales. This paper is aimed at discussing progress in evaluating, diagnosing and improving air quality and climate modeling using comparisons to SAS observations as a guide to thinking about improvements to mechanisms and parameterizations in models. The effort focused primarily on model representation of fundamental atmospheric processes that are essential to the formation of ozone, secondary organic aerosol (SOA) and other trace species in the troposphere, with the ultimate goal of understanding the radiative impacts of these species in the southeast and elsewhere. Here we address questions surrounding four key themes: gas-phase chemistry, aerosol chemistry, regional climate and chemistry interactions, and natural and anthropogenic emissions. We expect this review to serve as a guidance for future modeling efforts., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.