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The impact of heterogeneous uptake of HO2 on aerosol surfaces on radical concentrations and the O3 production regime in Beijing in summertime was investigated. The uptake coefficient of HO2 onto aerosol surfaces, γHO2, was calculated for the AIRPRO campaign in Beijing, in summer 2017, as a function of measured aerosol soluble copper concentration, [Cu2+]eff, aerosol liquid water content, [ALWC], and particulate matter concentration, [PM]. An average γHO2 across the entire campaign of 0.070±0.035 was calculated, with values ranging from 0.002 to 0.15, and found to be significantly lower than the value of γHO2=0.2, commonly used in modelling studies. Using the calculated γHO2 values for the summer AIRPRO campaign, OH, HO2 and RO2 radical concentrations were modelled using a box model incorporating the Master Chemical Mechanism (v3.3.1), with and without the addition of γHO2, and compared to the measured radical concentrations. The rate of destruction analysis showed the dominant HO2 loss pathway to be HO2 + NO for all NO concentrations across the summer Beijing campaign, with HO2 uptake contributing % to the total loss of HO2 on average. This result for Beijing summertime would suggest that under most conditions encountered, HO2 uptake onto aerosol surfaces is not important to consider when investigating increasing O3 production with decreasing [PM] across the North China Plain. At low [NO], however, i.e. ppb, which was often encountered in the afternoons, up to 29 % of modelled HO2 loss was due to HO2 uptake on aerosols when calculated γHO2 was included, even with the much lower γHO2 values compared to γHO2= 0.2, a result which agrees with the aerosol-inhibited O3 regime recently proposed by Ivatt et al. (2022). As such it can be concluded that in cleaner environments, away from polluted urban centres where HO2 loss chemistry is not dominated by NO but where aerosol surface area is high still, changes in PM concentration and hence aerosol surface area could still have a significant effect on both overall HO2 concentration and the O3 production regime. Using modelled radical concentrations, the absolute O3 sensitivity to NOx and volatile organic compounds (VOCs) showed that, on average across the summer AIRPRO campaign, the O3 production regime remained VOC-limited, with the exception of a few days in the afternoon when the NO mixing ratio dropped low enough for the O3 regime to shift towards being NOx-limited. The O3 sensitivity to VOCs, the dominant regime during the summer AIRPRO campaign, was observed to decrease and shift towards a NOx-sensitive regime both when NO mixing ratio decreased and with the addition of aerosol uptake. This suggests that if [NOx] continues to decrease in the future, ozone reduction policies focussing solely on NOx reductions may not be as efficient as expected if [PM] and, hence, HO2 uptake to aerosol surfaces continue to decrease. The addition of aerosol uptake into the model, for both the γHO2 calculated from measured data and when using a fixed value of γHO2=0.2, did not have a significant effect on the overall O3 production regime across the campaign. While not important for this campaign, aerosol uptake could be important for areas of lower NO concentration that are already in a NOx-sensitive regime.

The video game play provides meaningful social interactions through which the participants’ vocabulary can frequently benefit because it utilizes both implicit and explicit learning occasions. The play carries phrases, necessity of communication and task completion where there is an emerging opportunity of integrative learning. Grammar may be deduced from practicing sentence patterns which thus can be anchored into one’s lexicon. Following the latest research data, we attempt to find an answer to which type of video game presents an effective environment for vocabulary acquisition. In our study, we compared 646 video gamer students from five Hungarian secondary schools who completed a receptive vocabulary levels test. It was proven that the action video games have the most significant effect on the participant’s lexical advancement.

OBJECTIVES Bronchiolitis is a viral respiratory infection that can progress to acute respiratory failure. This study evaluated the variability of hospital-wide high-flow nasal cannula (HFNC) usage outside of the ICU and its association with length of stay (LOS) and cost among pediatric patients admitted with bronchiolitis. METHODS This study included patients RESULTS Unadjusted LOS was longer for patients in moderate (MR 1.14; 95% CI 1.11–1.18) and high (MR 1.26; 95% CI 1.22–1.30) NIHU hospitals. Adjusted LOS was longer in moderate (MR 1.03; 95% CI 1.01–1.06), and high (MR 1.08; 95% CI 1.05–1.11) NIHU hospitals. Unadjusted total cost was higher for patients in moderate (MR 1.20; 95% CI 1.16–1.25) and high (MR 1.26; 95% CI 1.22–1.31) NIHU hospitals. Adjusted total cost was higher for patients in moderate (MR 1.05; 95% CI 1.03–1.08), and high (MR 1.05; 95% CI 1.02–1.08) NIHU hospitals. CONCLUSIONS In this study, increased NIHU is associated with increased LOS and total cost.

Those who study macrophage biology struggle with the decision whether to utilize primary macrophages derived directly from mice or opt for the convenience and genetic tractability of immortalized macrophage-like cell lines in in vitro studies. Particularly when it comes to studying phagocytosis and phagosomal maturation-a signature cellular process of the macrophage-many commonly used cell lines are not representative of what occurs in primary macrophages. A system developed by Mark Kamps' group, that utilizes conditionally constitutive activity of Hox transcription factors (Hoxb8 and Hoxa9) to immortalize differentiation-competent myeloid cell progenitors of mice, offers an alternative to the macrophage/macrophage-like dichotomy. In this resource, we will review the use of Hoxb8 and Hoxa9 as hematopoietic regulators to conditionally immortalize murine hematopoietic progenitor cells which retain their ability to differentiate into many functional immune cell types including macrophages, neutrophils, basophils, osteoclasts, eosinophils, dendritic cells, as well as limited potential for the generation of lymphocytes. We further demonstrate that the use of macrophages derived from Hoxb8/Hoxa9 immortalized progenitors and their similarities to bone marrow-derived macrophages. To supplement the existing data, mass spectrometry-based proteomics, flow cytometry, cytology, and in vitro phagosomal assays were conducted on macrophages derived from Hoxb8 immortalized progenitors and compared to bone marrow-derived macrophages and the macrophage-like cell line J774. We additionally propose the use of a standardized nomenclature to describe cells derived from the Hoxb8/Hoxa9 system in anticipation of their expanded use in the study of leukocyte cell biology.

Statistical processing of numerical model output has been a part of both weather forecasting and climate applications for decades. Statistical techniques are used to correct systematic biases in atmospheric model outputs and to represent local effects that are unresolved by the model, referred to as downscaling. Many downscaling techniques have been developed, and it has been difficult to systematically explore the implications of the individual decisions made in the development of downscaling methods. Here we describe a unified framework that enables the user to evaluate multiple decisions made in the methods used to statistically postprocess output from weather and climate models. The Ensemble Generalized Analog Regression Downscaling (En-GARD) method enables the user to select any number of input variables, predictors, mathematical transformations, and combinations for use in parametric or nonparametric downscaling approaches. En-GARD enables explicitly predicting both the probability of event occurrence and the event magnitude. Outputs from En-GARD include errors in model fit, enabling the production of an ensemble of projections through sampling of the probability distributions of each climate variable. We apply En-GARD to regional climate model simulations to evaluate the relative importance of different downscaling method choices on simulations of the current and future climate. We show that choice of predictor variables is the most important decision affecting downscaled future climate outputs, while having little impact on the fidelity of downscaled outcomes for current climate. We also show that weak statistical relationships prevent such approaches from predicting large changes in extreme events on a daily time scale.

Broader spectrum gram-negative antibiotics are commonly utilized empirically for central line-associated bloodstream infections (CLABSI) in febrile short bowel syndrome (SBS) patients receiving home parenteral nutrition compared to those used empirically for inpatient-acquired CLABSI. This analysis reports 57 CLABSI in 22 patients with SBS admitted from the community and 78 inpatient-acquired CLABSI in 76 patients over a 5-year period. Proportional gram-negative CLABSI was similar between the SBS and inpatient-acquired cohorts (43.8% versus 42.3%, respectively, p=0.78). 1.8% and 10.3% (p=0.125) of gram-negative CLABSI were non-susceptible to ceftriaxone and 0% and 3.8% (p=0.52) were non-susceptible to ceftazidime in the SBS and inpatient-acquired cohorts, respectively. In the SBS cohort, home ethanol lock therapy and prior culture results impacted gram-negative pathogen distribution. Broader empiric gram-negative coverage for CLABSI among SBS patients compared to inpatients is unnecessary. Third-generation cephalosporins represent appropriate empiric gram-negative agents for febrile SBS patients presenting from the community to our institution.

Periodontal destruction can be the result of different known and yet-to-be-discovered biological pathways. Recent human genetic association studies have implicated interferon-gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) with high periodontal interleukin (IL)-1β levels and more destructive disease, but mechanistic evidence is lacking. Here, we sought to experimentally validate these observational associations and better understand IFI16 and AIM2's roles in periodontitis.Periodontitis was induced in Ifi204sup-/-/sup(IFI16 murine homolog) and Aim2sup-/-/supmice using the ligature model. Chimeric mice were created to identify the main source cells of Ifi204 in the periodontium. IFI16-silenced human endothelial cells were treated with periodontal pathogens in vitro. Periodontal tissues from Ifi204sup-/-/supmice were evaluated for alveolar bone (micro-CT), cell inflammatory infiltration (MPO+ staining), Il1b (qRT-PCR), and osteoclast numbers (cathepsin K+ staining).Ifi204-deficient micegt; exhibitedgt;20% higher alveolar bone loss than wild-type (WT) (P lt; 0.05), while no significant difference was found in Aim2sup-/-/supmice. Ifi204's effect on bone loss was primarily mediated by a nonbone marrow source and was independent of Aim2. Ifi204-deficient mice had greater neutrophil/macrophage trafficking into gingival tissues regardless of periodontitis development compared to WT. In human endothelial cells, IFI16 decreased the chemokine response to periodontal pathogens. In murine periodontitis, Ifi204 depletion elevated gingival Il1b and increased osteoclast numbers at diseased sites (P lt; 0.05).These findings support IFI16's role as a novel regulator of inflammatory cell trafficking to the periodontium that protects against bone loss and offers potential targets for the development of new periodontal disease biomarkers and therapeutics.

The large reduction in anthropogenic aerosol emissions across China in recent years has improved China’s air quality but also caused changes in radiative forcing. Some studies confirmed the reduction of aerosols over China cause a positive radiative forcing locally and play an important role in Arctic warming. However, few studies have differentiated and quantified the radiative forcing of different aerosol components including BC and sulphate. Here, we aim to understand the reduction of black carbon (BC) and SO2 emissions over China from 2008 to 2016 under a series of policies enacted by the Chinese government and to determine the change in radiative forcing both locally and remotely. We use the Evaluating the Climate and Air Quality Impacts of Short-Lived Pollutants (ECLIPSE) emission inventory to represent China's emissions of the two pollutants during this period and use the United Kingdom Earth System Model (UKESM) v-1 to calculate the individual radiative forcing due to changes in all anthropogenic aerosols, China BC only, and China SO2 only between 2008 and 2016. Finally, we use the temperature coefficients of individual pollutants at different latitude bands to calculate the temperature responses. Our results show the largest reduction of BC over China was from the residential and energy sectors, while the reduction in SO2 emissions from energy and industrial sources were significant. Compared with other inventories, ECLIPSE overestimates the reduction of emissions but shows the same trend. The aerosol radiative forcing over China locally due to the large Chinese emission reductions of BC and SO2 are -0.30±0.01Wm-2 and 1.03±0.07 Wm-2, respectively, which jointly accounts for more than 80% of the total aerosol radiative forcing calculated by the model from all anthropogenic aerosol emission sources. In addition, changes in BC and SO2 over China together contributed to a positive radiative forcing of 0.18 Wm-2 across the North Pacific. However, BC and sulphate are not major contributors to changes in Arctic radiative forcing. The temperature response due to BC (-0.008 ℃) and sulphate (0.060 ℃) is most pronounced locally in the mid-latitudes, while the temperature response in the low and high latitudes is small. This study bridges the gap on changes in radiative forcing due to anthropogenic emissions reductions in China and quantifies the contributions of BC and sulphate aerosols to better understand the impact of air pollution emission control policies on climate.

Objectives A growing body of research is emerging regarding the relationship between parental adverse childhood experiences (ACEs) and negative health, well-being and developmental outcomes in their children. This systematic review seeks to understand the relationship between parental ACEs and the health, well-being and developmental outcomes of their children and whether the relationships differ according to the number and type of parental ACEs. Study design Systematic review. Method The review includes articles published between 2000 and 2021 from studies using quantitative longitudinal methods and multivariate analysis to investigate the relationship between parental ACEs and their offspring's outcomes. Relevant studies were identified through a systematic search of five databases and findings synthesised using a narrative synthesis. This review was registered on PROSPERO (CRD42021274068). Results Nineteen studies met the inclusion criteria and were included in the review. This resulted in a combined population sample of 124,043 parents and 128,400 children. Diversity in measurement of parental ACE exposure and in the type of ACEs measured within the studies precluded a meta-analysis. Offspring of parents exposed to ACEs had a higher risk of a range of negative health, well-being and developmental outcomes. This relationship differs according to the number and type of parental ACEs, with a positive relationship observed between the number of parental ACEs and the risk of negative health, well-being and development outcomes in their children. Conclusions These findings indicate that screening for parental ACEs by health visitors, midwives and other health or social care staff may identify an at-risk population of infants, children and adolescents and improve child outcomes.

POLICY POINTS: Looking for a way to curtail market power abuses in health care and rein in prices, 20 states have restricted most‐favored‐nation (MFN) clauses in some health care contracts. Little is known as to whether restrictions on MFN clauses slow health care price growth. Banning MFN clauses between insurers and hospitals in highly concentrated insurer markets seems to improve competition and lead to lower hospital prices. CONTEXT: Most‐favored‐nation (MFN) contract clauses have recently garnered attention from both Congress and state legislatures looking for ways to curtail market power abuses in health care and rein in prices. In health care, a typical MFN contract clause is stipulated by the insurer and requires a health care provider to grant the insurer the lowest (i.e., the most‐favored) price among the insurers it contracts with. As of August 2020, 20 states restrict the use of MFN clauses in health care contracts (19 states ban their use in at least some health care contracts), with 8 states prohibiting their use between 2010 and 2016. METHODS: Using event study and difference‐in‐differences research designs, we compared prices for a standardized hospital admission in states that banned MFN clauses between 2010 and 2016 with standardized hospital admission prices in states without MFN bans. FINDINGS: Our results show that bans on MFN clauses reduced hospital price growth in metropolitan statistical areas (MSAs) with highly concentrated insurer markets. Specifically, we found that mean hospital prices in MSAs with highly concentrated insurer markets would have been $472 (2.8%) lower in 2016 had the MSAs been in states that banned MFN clauses in 2010. In 2016, the population in our sample that resided in MSAs with highly concentrated insurer markets was just under 75 million (23% of the US population). Hence, banning MFN clauses in all MSAs in our sample with highly concentrated insurer markets in 2010 would have generated savings on hospital expenditures in the range of $2.4 billion per year. CONCLUSIONS: Our empirical findings suggest banning MFN clauses between insurers and providers in highly concentrated insurer markets would improve competition and lead to lower prices and expenditures.

Nitrogen oxides (NOx, NO + NO2) are potent air pollutants which directly impact on human health and which aid the formation of other hazardous pollutants such as ozone (O3) and particulate matter. In this study, we use satellite tropospheric column nitrogen dioxide (TCNO2) data to evaluate the spatiotemporal variability and magnitude of the United Kingdom (UK) bottom-up National Atmospheric Emissions Inventory (NAEI) NOx emissions. Although emissions and TCNO2 represent different quantities, for UK city sources we find a spatial correlation of ∼0.5 between the NAEI NOx emissions and TCNO2 from the high-spatial-resolution TROPOspheric Monitoring Instrument (TROPOMI), suggesting a good spatial distribution of emission sources in the inventory. Between 2005 and 2015, the NAEI total UK NOx emissions and long-term TCNO2 record from the Ozone Monitoring Instrument (OMI), averaged over England, show annually decreasing trends of 4.4 % and 2.2 %, respectively. Top-down NOx emissions were derived in this study by applying a simple mass balance approach to TROPOMI-observed downwind NO2 plumes from city sources. Overall, these top-down estimates were consistent with the NAEI, but for larger cities such as London and Birmingham the inventory is significantly (>25 %) less than the top-down emissions.

Background Diagnostic testing for bacterial etiology of community-acquired pneumonia (CAP) is insensitive. Induced sputum (IS) is an attractive option for the evaluation of the lower respiratory tract. Methods Children aged 0-18 years with CAP were enrolled in the Etiology of Pneumonia in the Community (EPIC) study between 2010 and 2012. Blood and respiratory specimens were assessed by culture and polymerase chain reaction (PCR). The radiographic CAP was determined by a study radiologist. Sputum was induced with hypertonic saline. IS specimen was high quality (HQ) if Gram stain showed >25 white blood and Results Out of 977 children, 916 (94%) children enrolled in Memphis, Tennessee, produced IS; 794 (87%) had radiographic CAP and 174 (19%) were HQ. HQ IS yielded pathogenic bacteria more often than LQ (64% vs 44%; P < .01); however, pathogens were isolated at similar rates in HQ IS in patients with and without radiographic CAP (64% vs. 63%; P = .6). Pathogens from study specimens matched an IS pathogen in only 9/42 (21%) patients with radiographic CAP. Median LOS was similar among patients with radiographic CAP regardless of receipt of IS pathogen-concordant antibiotics (3.1 days), non-pathogen-concordant antibiotics (2.7 days), or no antibiotics (3.2 days; P = .5). Conclusions Bacterial pathogens were isolated from most IS cultures regardless of radiographic CAP and quality of IS. IS cultures infrequently corresponded with sterile site cultures. Isolation of pathogens from pediatric IS reflects oropharyngeal carriage and is insufficient to determine bacterial etiology of CAP.

Anatomy faculty with cadaver-based laboratory courses were presented with a significant challenge in March 2020 to create equivalent learning experiences without cadaveric access. The undergraduate domestic animal anatomy course at the Colorado State University was halfway into a 16-week semester when COVID-19 lockdown orders and the transition to remote instruction began. The new course curriculum was critically evaluated using student surveys and course outcome data. Most students (92.5%) agreed that the transition to online learning was a success; however, students who valued face-to-face lectures prior to March were less likely to perceive the transition as a success. Qualitative and quantitative analyses of survey results suggest that the resources perceived as most helpful for the transition to online learning were not the same as those that helped facilitate animal anatomy learning. Most students (92.5%) agreed that the Virtual Animal Anatomy (VAA) helped them learn anatomy, and 82.2% indicated that the VAA was a valuable resource following the transition to online learning. Additional resources associated with transition success included course instructors, weekly quizzes, written descriptions of anatomical structures and open laboratory sessions. In contrast, those resources associated with facilitating learning included guided quizzes and asynchronous lecture recordings. These findings suggest that the VAA can support online anatomy learning when used in conjunction with other best practices for online teaching.

SNPs associated with human stroke risk have been identified in the intergenic region between Forkhead family transcription factors FOXF2 and FOXQ1 , but we lack a mechanism for the association. FoxF2 is expressed in vascular mural pericytes and is important for maintaining pericyte number and stabilizing small vessels in zebrafish. The stroke-associated SNPs are located in a previously unknown transcriptional enhancer for FOXF2 , functional in human cells and zebrafish. We identify critical enhancer regions for FOXF2 gene expression, including binding sites occupied by transcription factors ETS1, RBPJ, and CTCF. rs74564934, a stroke-associated SNP adjacent to the ETS1 binding site, decreases enhancer function, as does mutation of RPBJ sites. rs74564934 is significantly associated with the increased risk of any stroke, ischemic stroke, small vessel stroke, and elevated white matter hyperintensity burden in humans. Foxf2 has a conserved function cross-species and is expressed in vascular mural pericytes of the vessel wall. Thus, stroke-associated SNPs modulate enhancer activity and expression of a regulator of vascular stabilization, FOXF2 , thereby modulating stroke risk.

In the summer of 2018, Europe experienced an intense heat wave which coincided with several persistent large-scale ozone (O3) pollution episodes. Novel satellite data of lower tropospheric column O3 from the Global Ozone Monitoring Experiment-2 (GOME-2) and Infrared Atmospheric Sounding Interferometer (IASI) on the MetOp satellite showed substantial enhancements in 2018 relative to other years since 2012. Surface observations also showed ozone enhancements across large regions of continental Europe in summer 2018 compared to 2017. Enhancements to surface temperature and the O3 precursor gases carbon monoxide and methanol in 2018 were co-retrieved from MetOp observations by the same scheme. This analysis was supported by the TOMCAT chemistry transport model (CTM) to investigate processes driving the observed O3 enhancements. Through several targeted sensitivity experiments we show that meteorological processes, and emissions to a secondary order, were important for controlling the elevated O3 concentrations at the surface. However, mid-tropospheric (~500 hPa) O3 enhancements were dominated by meteorological processes. We find that contributions from stratospheric O3 intrusions ranged between 15–40 %. Analysis of back trajectories indicates that the import of O3-enriched air masses into Europe originated over the North Atlantic substantially increasing O3 in the 500 hPa layer during summer 2018.

As the third most important greenhouse gas (GHG) after carbon dioxide (CO2) and methane (CH4), tropospheric ozone (O3) is also an air pollutant causing damage to human health and ecosystems. This study brings together recent research on observations and modeling of tropospheric O3 in the Arctic, a rapidly warming and sensitive environment. At different locations in the Arctic, the observed surface O3 seasonal cycles are quite different. Coastal Arctic locations, for example, have a minimum in the springtime due to O3 depletion events resulting from surface bromine chemistry. In contrast, other Arctic locations have a maximum in the spring. The 12 state-of-the-art models used in this study lack the surface halogen chemistry needed to simulate coastal Arctic surface O3 depletion in the springtime; however, the multi-model median (MMM) has accurate seasonal cycles at non-coastal Arctic locations. There is a large amount of variability among models, which has been previously reported, and we show that there continues to be no convergence among models or improved accuracy in simulating tropospheric O3 and its precursor species. The MMM underestimates Arctic surface O3 by 5 % to 15 % depending on the location. The vertical distribution of tropospheric O3 is studied from recent ozonesonde measurements and the models. The models are highly variable, simulating free-tropospheric O3 within a range of ±50 % depending on the model and the altitude. The MMM performs best, within ±8 % for most locations and seasons. However, nearly all models overestimate O3 near the tropopause (∼300 hPa or ∼8 km), likely due to ongoing issues with underestimating the altitude of the tropopause and excessive downward transport of stratospheric O3 at high latitudes. For example, the MMM is biased high by about 20 % at Eureka. Observed and simulated O3 precursors (CO, NOx, and reservoir PAN) are evaluated throughout the troposphere. Models underestimate wintertime CO everywhere, likely due to a combination of underestimating CO emissions and possibly overestimating OH. Throughout the vertical profile (compared to aircraft measurements), the MMM underestimates both CO and NOx but overestimates PAN. Perhaps as a result of competing deficiencies, the MMM O3 matches the observed O3 reasonably well. Our findings suggest that despite model updates over the last decade, model results are as highly variable as ever and have not increased in accuracy for representing Arctic tropospheric O3.