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Air quality management commonly aims to mitigate nitrogen oxide (NOx) emissions from combustion, reducing ozone (O3) and particulate matter (PM) pollution. Despite such ongoing efforts, regulations have recently proven ineffective in rural areas like the Salton Sea Air Basin of Southern California, which routinely violates O3 and PM air quality standards. With over $2 billion in annual agricultural sales and low population density, air quality in the region is likely influenced by the year-round farming activity. We conducted a source apportionment of NOx (an important precursor to both O3 and PM) using nitrogen stable isotopes of ambient NO2, which revealed a significant contribution from soil-emitted NOx to the regional budget. The soil source strength was estimated based on the mean δ15N-NOx from each emission category in the California Air Resources Board's NOx inventory. Our annual average soil emission estimate for the air basin was 11.4 ± 4 tons/d, representing ~ 30% of the extant NOx inventory, 10× larger than the state's inventory for soil emissions. Unconstrained environmental factors such as nutrient availability, soil moisture, and temperature have a first-order impact on soil NOx production in this agriculturally intensive region, with fertilization and irrigation practices likely driving most of the emissions variability. Without spatially and temporally accurate data on fertilizer application rates and irrigation schedules, it is difficult to determine the direct impacts that these variations have on our observations. Nevertheless, comparative analysis with previous studies indicates that soil NOx emissions in the Imperial Valley are likely underrepresented in current inventories, highlighting the need for more detailed and localized observational data to constrain the sizeable and variable emissions from these arid, agricultural soils.

ImportanceMost research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.ObjectiveTo identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.Design, setting, and participantsMulticenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.ExposureSARS-CoV-2 infection.Main outcomes and measuresPASC and 89 prolonged symptoms across 9 symptom domains.ResultsA total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.Conclusions and relevanceThis study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

Immune tolerance is maintained in lymphoid organs (LOs). Despite the presence of complex immune cell networks in non-LOs, it is unknown whether self-tolerance is maintained in these tissues. We developed a technique to restrict genetic recombination to regulatory T cells (Tregs) only in skin. Selective depletion of skin Tregs resulted in T cell-mediated inflammation of hair follicles (HFs). Suppression did not rely on CTLA-4, but instead on high-affinity interleukin-2 (IL-2) receptor expression by skin Tregs, functioning exclusively in a cell-extrinsic manner. In a novel model of HF stem cell (HFSC)-driven autoimmunity, we reveal that skin Tregs immunologically protect the HFSC niche. Finally, we used spatial transcriptomics to identify aberrant IL-2 signaling at stromal-HF interfaces in a rare form of human alopecia characterized by HFSC destruction and alopecia areata. Collectively, these results reveal the fundamental biology of Tregs in skin uncoupled from the systemic pool and elucidate a mechanism of self-tolerance.

ABSTRACT Background Previous studies reveal inconsistent associations between serum lipid traits and the risks of fractures and osteoporosis in the general population. Methods This prospective cohort study analysed data from 414 302 UK Biobank participants (223 060 women and 191 242 men, aged 37–73 years) with serum lipid measurements: apolipoprotein A (Apo A), apolipoprotein B (Apo B), total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), triglycerides (TG) and lipoprotein A (Lp(a)). Multivariable Cox proportional hazard models with penalized cubic splines were used to explore potential nonlinear associations of each lipid trait with the risks of fractures and osteoporosis. Subgroup analyses by age, sex, BMI categories and pre‐existing cardiovascular disease were conducted. Mediation analyses using the g‐formula were performed to quantify to which extent bone mineral density (BMD) may mediate the association between serum lipids and fracture risk. Results Over a median follow‐up period of 13.8 years, 25 918 (6.8%) of the 383 530 participants without prior fracture had incident fracture cases, and 7591 (4.1%) of the 184 919 participants with primary care data and without baseline osteoporosis were diagnosed with osteoporosis. TG had nonlinear associations with fractures and osteoporosis, whereas Apo B, TC and LDL‐C had linear associations. There were also nonlinear associations of Apo A and HDL‐C with fractures. Individuals in the highest quintiles for Apo A (fracture: HR 1.15 [95% CI 1.10, 1.21]; osteoporosis: HR 1.13 [1.02, 1.25]) and HDL‐C (fracture: HR 1.27 [1.20, 1.34]; osteoporosis: HR 1.31 [1.18, 1.46]) were associated with higher risks of fractures and osteoporosis. Conversely, those in the highest quintile for Apo B (fracture: HR 0.85 [0.81, 0.89]; osteoporosis: HR 0.86 [0.79, 0.94]), LDL‐C (fracture: HR 0.89 [0.85, 0.93]; osteoporosis: HR 0.91 [0.83, 1.00]) and TG (fracture: HR 0.78 [0.74, 0.82]; osteoporosis: HR 0.75 [0.68, 0.82]) were associated with lower risks. The associations of Apo A (ratio of HR [RHR] 1.05 [1.02, 1.09]) and HDL‐C (RHR 1.06 [1.03, 1.09]) with fracture risk were more pronounced in men compared to women. Except for TG and Lp(a), the associations between serum lipids and fractures appear to be partially mediated through BMD (mediation proportions: 5.30% to 40.30%), assuming causality. Conclusions Our study reveals a complex interplay between different lipid markers and skeletal health, potentially partially mediated through BMD. Routine lipid profile assessments, including HDL‐C and Apo A among other lipid traits, may be integrated into the strategies for fracture risk stratification.

The identification of photobleaching steps in single molecule fluorescence imaging is a well-established procedure for analysing the stoichiometries of molecular complexes. Nonetheless, the method is challenging with protein fluorophores because of the high levels of noise, rapid bleaching and highly variable signal intensities, all of which complicate methods based on statistical analyses of intensities to identify bleaching steps. It has recently been shown that deep learning by convolutional neural networks can yield an accurate analysis with a relatively short computational time. We describe here an improved use of such an approach that detects bleaching events even in the first time point of observation, and we have included this within an integrated software package incorporating fluorescence spot detection, colocalisation, tracking, FRET and photobleaching step analyses of single molecules or complexes. This package, known as FluoroTensor, is written in Python with a self-explanatory user interface.

Abstract Air quality management commonly aims to mitigate nitrogen oxide (NOx) emissions from combustion, reducing ozone (O3) and particulate matter (PM) pollution. Despite such ongoing efforts, regulations have recently proven ineffective in rural areas like the Salton Sea Air Basin of Southern California, which routinely violates O3 and PM air quality standards. With over $2 billion in annual agricultural sales and low population density, air quality in the region is likely influenced by the year-round farming activity. We conducted a source apportionment of NOx (an important precursor to both O3 and PM) using nitrogen stable isotopes of ambient NO2, which revealed a significant contribution from soil-emitted NOx to the regional budget. The soil source strength was estimated based on the mean δ15N-NOx from each emission category in the California Air Resources Board’s NOx inventory. Our annual average soil emission estimate for the air basin was 11.4 ± 4 tons/d, representing ~ 30% of the extant NOx inventory, 10× larger than the state’s inventory for soil emissions. Unconstrained environmental factors such as nutrient availability, soil moisture, and temperature have a first-order impact on soil NOx production in this agriculturally intensive region, with fertilization and irrigation practices likely driving most of the emissions variability. Without spatially and temporally accurate data on fertilizer application rates and irrigation schedules, it is difficult to determine the direct impacts that these variations have on our observations. Nevertheless, comparative analysis with previous studies indicates that soil NOx emissions in the Imperial Valley are likely underrepresented in current inventories, highlighting the need for more detailed and localized observational data to constrain the sizeable and variable emissions from these arid, agricultural soils.

Objective: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age. Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age. Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable. Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.

Objective: Short-term RCTs have demonstrated that MPH-treatment significantly reduces ADHD-symptoms, but is also associated with adverse events, including sleep problems. However, data on long-term effects of MPH on sleep remain limited. Methods: We performed a 2-year naturalistic prospective pharmacovigilance multicentre study. Participants were recruited into three groups: ADHD patients intending to start MPH-treatment (MPH-group), those not intending to use ADHD-medication (no-MPH-group), and a non-ADHD control-group. Sleep problems were assessed with the Children's-Sleep-Habits-Questionnaire (CSHQ). Results: 1,410 participants were enrolled. Baseline mean CSHQ-total-sleep-scores could be considered clinically significant for the MPH-group and the no-MPH-group, but not for controls. The only group to show a significant increase in any aspect of sleep from baseline to 24-months was the control-group. Comparing the MPH- to the no-MPH-group no differences in total-sleep-score changes were found. Conclusion: Our findings support that sleep-problems are common in ADHD, but don't suggest significant negative long-term effects of MPH on sleep.

The civil service has seen dramatic changes over the last 50 years, symbolized by the shift from Traditional Public Administration, to New Public Management and now New Public Governance. Likewise, the role and nature of people management functions has changed with the development of Strategic HR and Human Resource Development (HRD). Finally, the nature of higher education has changed with a growing emphasis on research impact, knowledge exchange, and industry-academia links such as focusing on employability. In this research we explore the development of the Bahrain Institute for Public Administration's (BIPA) Master in Public Management (MPM) program. Drawing on extensive fieldwork with students, managers, and stakeholders we identify how this program was established, how students were selected, and the implications of their study on the program for the success of the Bahrain government.

Two essential questions for those leading the field of public administration are: What do we teach our students, and how do we train them? As scholars, we pay significant attention to our research, often to the detriment of recognizing the potential for merging our research with teaching through the Scholarship of Teaching and Learning (SoTL). However, given our students' leadership positions, SoTL-related work is vital to their success. In this article, we have come together to reflect on the state of SoTL's work in public administration. Through this reflection, we explore the windows of opportunity for research that we see emerging. Included among these opportunities is the need for research on how we can best serve students in and out of the classroom, as well as research the most effective way of managing our programs. We also see the need for research into faculty development, instructional design, and the return on investment for a public administration degree. Lastly, we argue for improved recognition of the value and contribution of SoTL-related work in tenure and promotion standards.

Objective: The COVID-19 pandemic has disrupted people's lives around the world, including college students. This cross-sectional study aimed to 1) describe psychological distress, coping, and expectancies of undergraduates during COVID-19 "stay-at-home" orders and 2) examine the associations among these variables. Participants and methods: Midwestern US undergraduates (N = 186) completed measures of psychological distress, coping behaviors, and expectancies in March-April 2020 during the initial round of "stay-at-home" orders. Results: Students engaged in approach coping and disease prevention behaviors and had low expectations for contracting COVID-19. Most students reported clinically significant depression or anxiety. Adherence to disease prevention behaviors was associated with less stress but more anxiety. Positive expectancies and approach coping were associated with less distress. Avoidance coping was associated with more distress. Conclusions: This study describes the toll that COVID-19 has had on college students. Continued attention to the mental health of college students during the pandemic is imperative.

Societal Impact Statement The invasive species S. alterniflora and P. australis are fast growing coastal wetland plants sequestering large amounts of carbon in the soil and protect coastlines against erosion and storm surges. In this global analysis, we found that Spartina and Phragmites increase methane but not nitrous oxide emissions, with Phragmites having a lesser effect. The impact of the invasive species on emissions differed greatly among different types of native plant groups, providing valuable information to managers and policymakers during coastal wetland planning and restoration efforts. Further, our estimated net emissions per wetland plant group facilitate regional and national blue carbon estimates. Summary Globally, Spartina alterniflora and Phragmites australis are among the most pervasive invasive plants in coastal wetland ecosystems. Both species sequester large amounts of atmospheric carbon dioxide (CO2) and biogenic carbon in soils but also support production and emission of methane (CH4). In this study, we investigated the magnitude of their net greenhouse gas (GHG) release from invaded and non‐invaded habitats. We conducted a meta‐analysis of GHG fluxes associated with these two species and related soil carbon content and plant biomass in invaded coastal wetlands. Our results show that both invasive species increase CH4 fluxes compared to uninvaded coastal wetlands, but they do not significantly affect CO2 and N2O fluxes. The magnitude of emissions from Spartina and Phragmites differs among native habitats. GHG fluxes, soil carbon and plant biomass of Spartina‐invaded habitats were highest compared to uninvaded mudflats and succulent forb‐dominated wetlands, while being lower compared to uninvaded mangroves (except for CH4). This meta‐analysis highlights the important role of individual plant traits as drivers of change by invasive species on plant‐mediated carbon cycles.

Abstract Egg-laying performance is of great economic importance in poultry, but the underlying genetic mechanisms are still elusive. In this work, we conduct a multi-omics and multi-tissue integrative study in hens with distinct egg production, to detect the hub candidate genes and construct hub molecular networks contributing to egg-laying phenotypic differences. We identifiy three hub candidate genes as egg-laying facilitators: TFPI2, which promotes the GnRH secretion in hypothalamic neuron cells; CAMK2D, which promotes the FSHβ and LHβ secretion in pituitary cells; and OSTN, which promotes granulosa cell proliferation and the synthesis of sex steroid hormones. We reveal key endocrine factors involving egg production by inter-tissue crosstalk analysis, and demonstrate that both a hepatokine, APOA4, and an adipokine, ANGPTL2, could increase egg production by inter-tissue communication with hypothalamic-pituitary-ovarian axis. Together, These results reveal the molecular mechanisms of multi-tissue coordinative regulation of chicken egg-laying performance and provide key insights to avian reproductive regulation.

Abstract Developing high-yielding rice varieties that possess favorable agronomic characteristics and enhanced grain Zn content is crucial in ensuring food security and addressing nutritional needs. This research employed ICIM, IM, and multi-parent population QTL mapping methods to identify important genetic regions associated with traits such as DF, PH, NT, NP, PL, YLD, TGW, GL, GW, Zn, and Fe. Two populations of recombinant inbred lines consisting of 373 lines were phenotyped for agronomic, yield and grain micronutrient traits for three seasons at IRRI, and genotyped by sequencing. Most of the traits demonstrated moderate to high broad-sense heritability. There was a positive relationship between Zn and Fe contents. The principal components and correlation results revealed a significant negative association between YLD and Zn/Fe. ICIM identified 81 QTLs, while IM detected 36 QTLs across populations. The multi-parent population analysis detected 27 QTLs with six of them consistently detected across seasons. We shortlisted eight candidate genes associated with yield QTLs, 19 genes with QTLs for agronomic traits, and 26 genes with Zn and Fe QTLs. Notable candidate genes included CL4 and d35 for YLD, dh1 for DF, OsIRX10, HDT702, sd1 for PH, OsD27 for NP, whereas WFP and OsIPI1 were associated with PL, OsRSR1 and OsMTP1 were associated to TGW. The OsNAS1, OsRZFP34, OsHMP5, OsMTP7, OsC3H33, and OsHMA1 were associated with Fe and Zn QTLs. We identified promising RILs with acceptable yield potential and high grain Zn content from each population. The major effect QTLs, genes and high Zn RILs identified in our study are useful for efficient Zn biofortification of rice.

Abstract Given the existing uncertainty regarding the effectiveness and safety of switching from low-molecular-weight heparin (LMWH) to direct oral anticoagulants (DOACs) in patients with cancer-associated venous thrombosis (CAT), we conducted a comprehensive population-based cohort study utilizing electronic health database in Hong Kong. A total of 4356 patients with CAT between 2010 and 2022 were included, with 1700 (39.0%) patients switching to DOAC treatment. Compared to continuous LMWH treatment, switching to DOACs was associated with a significantly lower risk of hospitalization due to venous thromboembolism (HR: 0.49 [95% CI = 0.35–0.68]) and all-cause mortality (HR: 0.67 [95% CI = 0.61–0.74]), with no significant difference in major bleeding (HR: 1.04 [95% CI = 0.83–1.31]) within six months. These findings provide reassurance regarding the effectiveness and safety of switching from LMWH to DOACs among patients with CAT, including vulnerable patient groups.

Nitrogen dioxide (NO2) plays a pivotal role in the production of secondary pollutants, most importantly ozone (O3) and particulate matter. Regulatory controls have greatly reduced NO2 in cities, where most of the surface monitoring occurs, but the change in rural environments is less certain. Here, we present summertime (June-September) spatio-temporal patterns of NO2 concentrations using satellite and ground observations across California from 2009-2020, quantifying the differences in NO2 trends for five distinct land cover classes: urban, forests, croplands, scrublands (shrublands, savannas, and grasslands), and barren (minimally vegetated) lands. Over urban environments, NO2 columns exhibited continued but weakening downward trends (−3.7 ± 0.3%a−1), which agree fairly well with contemporaneous trends estimated from the surface air quality network (−4.5 ± 0.5%a−1). In rural (i.e., non-urban) parts of the state, however, secular trends are insignificant (0.0-0.4 ± 0.4%a−1) or in the case of remote forests are rapidly on the rise (+4.2 ± 1.2%a−1). Sorting the NO2 columns by air temperature and soil moisture reveals relationships that are commensurate with extant parameterizations but do indicate a stronger temperature dependence. We further find that rapidly rising temperatures and, to a lesser extent, decreasing precipitation in response to climate change are acting to increase soil NO x emissions, explaining about one-third of the observed NO2 rise in non-urban regions across California. Finally, we show that these trends, or their absence, can be attributed predominantly to the dramatic rise in wildfire frequency, especially since the turn of the 21st century.