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The production of crude oil and natural gas is associated with emissions of air pollutants, such as nitrogen oxides (NOx = NO + NO2) and volatile organic compounds, which are precursors for the formation of ground-level ozone. Knowledge of these emissions is critical to the understanding and mitigation of local air quality. NOx emissions from oil and gas production activities are not well described in commonly used emission inventories, and discrepancies of several factors have been found in the past. Here we present an easy and computationally efficient method to quantify NOx emissions from satellite NO2 observations that can be applied to evaluate common emission inventories and provide timely input for chemistry transport models. Using NO2 columns from the TROPOspheric Monitoring Instrument (TROPOMI), we calculated annually averaged NOx emissions from the divergence of NO2 column fluxes for six oil and gas production regions in the United States. Derived NOx emissions for the years 2018 to 2020 range between 4.8 and 81.1 t/day, and observed trends over time are consistent with changes in industrial activity. To evaluate the method, we compared our results with the fuel-based oil and gas NOx inventory (FOG) and performed sensitivity studies using model output from the Weather Research Forecasting model with Chemistry (WRF-Chem). We found that annually averaged NOx emissions from oil and gas production activities can in most cases be calculated within an uncertainty of 50%, while simultaneously derived emission maps show the spatial distribution of NOx emissions with a high level of detail. For future use, this method can easily be applied globally.

Special Issue: The ENIGMA Consortium: the first 10 years., Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)

Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access) For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large‐scale meta‐ and mega‐analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large‐scale, collaborative studies of mental illness., This review discusses the major challenges facing neuroimaging research of bipolar disorder and highlights the major accomplishments, ongoing challenges and future goals of the ENIGMA Bipolar Disorder Working Group.

Background: Normative modeling is a statistical approach to quantify the degree to which a particular individual-level measure deviates from the pattern observed in a normative reference population. When applied to human brain morphometric measures it has the potential to inform about the significance of normative deviations for health and disease. Normative models can be implemented using a variety of algorithms that have not been systematically appraised. Methods: To address this gap, eight algorithms were compared in terms of performance and computational efficiency using brain regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) collated from 87 international MRI datasets. Performance was assessed with the mean absolute error (MAE) and computational efficiency was inferred from central processing unit (CPU) time. The algorithms evaluated were Ordinary Least Squares Regression (OLSR), Bayesian Linear Regression (BLR), Generalized Additive Models for Location, Scale, and Shape (GAMLSS), Parametric Lambda, Mu, Sigma (LMS), Gaussian Process Regression (GPR), Warped Bayesian Linear Regression (WBLG), Hierarchical Bayesian Regression (HBR), and Multivariable Fractional Polynomial Regression (MFPR). Model optimization involved testing nine covariate combinations pertaining to acquisition features, parcellation software versions, and global neuroimaging measures (i.e., total intracranial volume, mean cortical thickness, and mean cortical surface area). Findings: Statistical comparisons across models at PFDR

Background: Early detection of dementia has become important for interventions that are developed to slow disease progression. Due to technological advancements, healthcare is trending toward using more telehealth screenings due to the convenience it provides patients. In our research, we evaluate the accuracy of a phone-based memory screen at diagnosing mild cognitive impairment. Methods: 181 participants from the Indiana Alzheimer’s Disease Research Center (IADRC)were screened using the Memory and Aging Telephone Screen (MATS) and diagnosed as cognitively normal (CN), subjective cognitive decline (SCD), or mild cognitive impairment (MCI). 177 underwent Rey Auditory Verbal Learning Testing (RAVLT); 103 received Aβ PET scans([18F]florbetapir or [18F]florbetaben); 91 had plasma tau levels measured; and 140 received MRI scans (Freesurfer v6). ANCOVAs were used to evaluate differences between diagnostic groups covarying for age, sex, and education. ROC analysis and logistic regressions were used to predict MCI and Aβ positivity. Partial correlations covarying for sex and age (and education for RAVLT) were conducted to evaluate relationships between MATS scores with RAVLT, brain atrophy, pTau level, and amyloid deposition. Results: MCI patients showed significantly lower MATS scores for immediate (p

Context Multiple clinical evaluation tools exist for adolescent concussion, with various degrees of correlation, presenting challenges for clinicians in identifying which elements of these tools provide the greatest diagnostic utility. Objective To determine the combination of elements from four commonly-used clinical concussion batteries that maximize discrimination of concussed from non-concussed participants. Design Cross-sectional study Setting Suburban school and concussion program of a tertiary care academic center Patients/Participants 166 non-concussed (from a suburban school) and 231 concussed (from the school and concussion program) participants aged 13–19 years Main Outcome Measures Individual elements of the visio-vestibular examination (VVE), Sport Concussion Assessment Tool, 5th Edition (SCAT-5, including the modified balance error scoring system [mBESS]), King-Devick test (K-D), and Post-Concussion Symptom Inventory (PCSI) were evaluated. The sub-components of these tests were grouped into interpretable factors using sparse principal component analysis (sPCA). The 13 resultant factors were combined with clinical covariates into a logistic regression and ranked by frequency of inclusion into the ideal model, and the predictive performance of the ideal model was compared to each of the individual batteries using the area under the receiving operating characteristic curve (AUC). Results A cluster of 4 factors (F1: VVE saccades and vestibulo-ocular reflex; F2: mBESS double leg stance; F3: SCAT-5/PCSI symptoms; F4: K-D completion time) emerged. A model fit with the top factors performed as well as each battery in predicting concussion status (AUC=0.816 [95% CI: 0.731–0.889]), compared to SCAT-5 (AUC=0.784 [95% CI: 0.692–0.866]), PCSI (AUC=0.776 [95% CI: 0.674–0.863]), VVE (AUC=0.711 [95% CI: 0.602–0.814]), and K-D (AUC=0.708 [95% CI: 0.590–0.819]). Conclusions A multifaceted assessment for concussed adolescents, comprised of symptoms, attention, balance, and the visio-vestibular system, is critical. It is likely that current diagnostic batteries measure overlapping domains, and our sPCA analysis demonstrated strategies for streamlining comprehensive concussion assessment across a variety of settings.

A small percentage of universities and colleges conducted mass SARS-CoV-2 testing. However, universal testing is resource-intensive, strains national testing capacity, and false negative tests can encourage unsafe behaviors.A large urban university campus.Virus control centered on three pillars: mitigation, containment, and communication, with testing of symptomatic and a random subset of asymptomatic students.Random surveillance testing demonstrated a prevalence among asymptomatic students of 0.4% throughout the term. There were two surges in cases that were contained by enhanced mitigation and communication combined with targeted testing. Cumulative cases totaled 445 for the term, most resulting from unsafe undergraduate student behavior and among students living off-campus. A case rate of 232/10,000 undergraduates equaled or surpassed several peer institutions that conducted mass testing.An emphasis on behavioral mitigation and communication can control virus transmission on a large urban campus combined with a limited and targeted testing strategy.

Carbonic Anhydrase IX (CAIX) is a major metabolic effector of tumor hypoxia and regulates intra- and extracellular pH and acidosis. Significant advances have been made recently in the development of therapeutic targeting of CAIX. These approaches include antibody-based immunotherapy, as well as use of antibodies to deliver toxic and radioactive payloads. In addition, a large number of small molecule inhibitors which inhibit the enzymatic activity of CAIX have been described. In this commentary, we highlight the current status of strategies targeting CAIX in both the pre-clinical and clinical space, and discuss future perspectives that leverage inhibition of CAIX in combination with additional targeted therapies to enable effective, durable approaches for cancer therapy.

OBJECTIVE: To characterize healthcare and behavioral service providers’ transportation-related discussions with their autistic and non-autistic patients. METHOD: 78 providers completed a cross-sectional survey assessing their transportation discussions with patients. We used Mann–Whitney U tests and chi-square tests to compare differences in provider reports by patient diagnosis. RESULTS: Compared with one in two providers who reported they discuss transportation with non-autistic patients, only one in five have these conversations with their autistic patients. Few (8%) providers felt prepared to assess driving readiness in autistic patients, yet only a quarter refer patients elsewhere. CONCLUSION: There is a critical need to develop resources for use in medical settings to effectively support autistic adolescents’ independence and mobility as they transition into adulthood.

Pathogen traits can vary greatly and impact the ability of a pathogen to persist in a population. Although this variation is fundamental to disease ecology, little is known about the evolutionary pressures that drive these differences, particularly where they interact with host behavior. We hypothesized that host behaviors relevant to different transmission routes give rise to differences in contact network structure, constraining the space over which pathogen traits can evolve to maximize fitness. Our analysis of 232 contact networks across mammals, birds, reptiles, amphibians, arthropods, fish, and mollusks found that contact network topology varies by contact events, most notably in networks that are representative of fluid-exchange transmission. Using infectious disease model simulations, we showed that these differences in network structure suggest pathogens transmitted through fluid-exchange contact events will need traits associated with high transmissibility to successfully proliferate, compared to pathogens that transmit through other types of contact. These findings were supported through a review of known traits of pathogens that transmit in humans. Our work demonstrates that contact network structure may drive the evolution of compensatory pathogen traits according to transmission strategy, providing essential context for understanding pathogen evolution and ecology.

Background To describe post-COVID-19 vaccination [fully vaccinated (FV) and first booster] immune response and occurrence of reinfection ( >90 days from prior infection) in nursing home residents (NHr) with/without evidence of prior SARS-CoV-2 infection. Methods In a longitudinal prospective cohort of 36 NHr from 3 NHs, interviews, chart abstractions, and specimens [blood and anterior nasal swabs (ANs)] were collected at baseline and monthly visits. ANs underwent molecular and BinaxNOW™ antigen testing. Quantitative Meso Scale Discovery platform tested blood specimens for anti-spike (S) protein and anti-nucleocapsid (N) antibodies. In addition, in a subset (n=13), S-specific memory B cells (MBCs) were tested with ELISpot assays. Results The cohort's median age was 72 years; 46% male, 64% White Non-Hispanic, 80% had ≥3 comorbidities, and 29 (81%) had prior SARS-CoV-2 infection. Of 36, 76% received Pfizer-BioNTech and 24% Moderna homologous vaccine. The median distribution of anti-S IgG concentrations among those with prior infection increased 15‒30 days post-FV, remained stable for 90 days, and declined by 120 days. The anti-S IgG remained above the estimated vaccine effectiveness (VE) thresholds published [Pfizer-BioNTech (95% VE: 530 BAU/ml), Moderna (90% VE: 298 BAU/ml)]. Among those without previous infection, anti-S IgG declined after 60 days and stayed near the VE thresholds until a recent infection/booster. Age, sex, and comorbidities had no appreciable impact on anti-S IgG. From enrollment to November 2021, 1of 29 had reinfection. From December 2021 to January 2022, 2 of 7 had a new infection, and 4 of 29 had reinfection, as shown by anti-N IgG rise. Persistently low numbers of total and anti-S MBC were seen across the evaluation, even with post-booster anti-S MBC rise. There was an immediate rise in anti-S IgG concentrations in all participants post-booster, irrespective of recent infection. Conclusion These findings from a NH convenience cohort suggest that prior SARS-CoV-2 infection has a pronounced immunomodulatory enhancing effect on the magnitude and duration of FV immune response. The decline of anti-S antibodies post-FV and rise after booster supported the booster recommendation in this cohort. The low MBC counts indicate immunosenescence in this high-risk population. Disclosures Hollis Houston, BA, Fidelity: Stocks/Bonds.

Background Choosing empiric therapy for patients with community-onset urinary tract infections (CO-UTI) presenting to hospitals for treatment is challenging without understanding local antimicrobial susceptibility patterns. We investigated changes over time in antimicrobial resistance among CO-UTI pathogens and identified patient-level factors associated with higher levels of resistance. Methods We used non-duplicate positive urine cultures in the 2012-2020 Premier Healthcare Database as a proxy for CO-UTI in patients ≥ 18 years old presenting to hospitals receiving care categorized as community-onset inpatient (CO-INPT) or observation/emergency department (OBS/ED). We included cultures positive for Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa obtained within 3 days of admission. Phenotypes investigated include resistance to extended-spectrum cephalosporins (ESC), fluoroquinolones (FLQ), and trimethoprim-sulfamethoxazole (TMP-SX). Logistic regression analyses were performed. Results Among 1,987,605 urine cultures meeting study criteria from 432 hospitals, > 66% were E. coli. Antibiotic resistance (AR) was highest to FLQ among CO-INPT E. coli (31.7%) and P. mirabilis (29.3%) in 2020. ESC resistance increased from 2012 to 2020 among E. coli and K. pneumoniae in both CO-INPT and OBS/ED (p< 0.001). TMP-SX resistance remained > 20% among E. coli in CO-INPT and OBS/ED and P. mirabilis in CO-INPT throughout the study period. All AR phenotypes were significantly higher among CO-INPT than OBS/ED (p< 0.001), and higher among males than females (p< 0.001). FLQ resistance among E. coli, P. mirabilis, and P. aeruginosa was > 20% among males (28.2%, 30.4%, 21.9% respectively) but not females (17.5%, 15.1%, 14.5%) in OBS/ED, while it was > 20% among both males (37.2%, 37.3%, 24.6%) and females (31.2%, 33.9%, 21.9%) in CO-INPT. Figure 1.% Resistance to extended-spectrum cephalosporins by year and acute care setting.Figure 2.% Resistance to fluoroquinolones by year and acute care setting.Figure 3.% Resistance to trimethoprim-sulfamethoxazole by year and acute care setting. Conclusion Resistance to TMP-SX in both CO-INPT and OBS/ED, and FLQ in CO-INPT, was elevated suggesting alternative empiric therapy might be necessary for CO-UTI presenting to hospitals. Increasing resistance to ESC among pathogens in CO-INPT cultures warrants further evaluation of local resistance levels. Gender and need for inpatient therapy are factors to consider in developing local treatment recommendations. Disclosures All Authors: No reported disclosures.

PURPOSE: Older cancer patients are susceptible to long-term effects of chemotherapy, including cancer-related cognitive decline and impairments to quality of life. Taxane-based chemotherapies are associated with physical declines among older women and may negatively impact cognitive performance. We sought to examine whether changes in objective and subjective measures of cognitive performance and well-being differ among older breast cancer survivors as a function of taxane-based chemotherapy treatment regimens. METHODS: Individual-level data was pooled and harmonized from two large prospective studies of older (greater than 60 years) breast cancer survivors. Assessments were conducted prior to systemic therapy and up to 36-months after. Cognitive performance was assessed with objective (working memory, processing speed and executive functions) and subjective tests and physical, emotional and functional well-being was also assessed. RESULTS: One hundred and sixty-seven (M age = 67.3 years) women, with 116 receiving chemotherapy with taxanes and 51 without taxanes contributed data. Declines in subjective cognition for both groups were significant between pre-treatment and 12-month follow-up. Significant improvements were seen on a measure of objective cognition (working memory) from 12 to 36-months. Measures of well-being improved from prior to systemic therapy to 12-months. Longitudinal changes across all measures did not vary as a function of receipt of taxane-based treatment. CONCLUSION: Older women who received treatment with taxanes did not have greater declines in cognitive performance or well-being than women receiving other chemotherapy regimens. Despite older cancer survivors being at greater risk for negative outcomes, treatment with taxane-based chemotherapies does not appear to exacerbate these health consequences.

Current methods to detect recent delta-9-tetrahydrocannabinol (THC) use cannot objectively quantify its psychoactive effects (PE). The Cognalyzer®, an electroencephalography (EEG)-based method, detects and quantifies the strength of THC-induced PE on a scale from 0 to 100%. This study assesses the relationship between the magnitude of Cognalyzer® PE predictions and reported subjective drug effects for 4-h post-cannabis inhalation. Seventy-five participants were enrolled in the study. Prior to ad libitum cannabis inhalation, an EEG recording episode was completed. Immediately after inhalation, the Drug Effects Questionnaire (DEQ) was administered and another EEG recording performed. For 25 participants, the study ended. For 50 participants, assessments were repeated at 30-min intervals for 4 h. EEG files were blinded and analyzed using two versions of the Cognalyzer® algorithm. The relationship between the Cognalyzer® PE level results and the DEQ was assessed using generalized linear models and multiple regression. There were significant PE increases from pre-cannabis for up to 3.5 h. Mean reports of feeling drug effects were > 0 at all post-inhalation time points (p ≤ 0.024). Furthermore, there were significant relationships between the Cognalyzer® PE and self-reported perception of drug effects (p ≤ 0.001). Subgroup analysis showed that Cognalyzer® PE levels were impacted by cannabis use history, subjective ratings of drug effects, oral fluid THC concentration and the cannabis product inhaled. The findings show that the Cognalyzer® can be used to objectively determine the strength of cannabis psychoactive effects that cannabis products create on consumers and how it changes depending on their experience with cannabis. The Cognalyzer® can be used to conduct scientific consumer research to generate trustworthy informational material about the psychoactive experience of cannabis products. For clinical research, the Cognalyzer® can be used to study the pharmacodynamics of cannabinoids or delivery systems, such as nano-emulsifications.

The kinetics of successive reactions of acetylene (C2H2) initiated on either vanadium or iron atomic cations have been investigated under thermal conditions using the variable-ion source and temperature-adjustable selected-ion flow tube apparatus. Consistent with the literature results, the reaction of Fe+ + C2H2 primarily yields Fe+(m/z = (C2H2)3); however, analysis via quantum chemical calculations and statistical modeling shows that the mechanism does not form benzene upon the third acetylene addition. The kinetics are more consistent with successive addition of three acetylene molecules, yielding Fe+(C2H2)3, followed by an addition of a fourth acetylene molecule, initiating cyclotrimerization, yielding either Fe+(C2H2) + neutral benzene or Fe+(Bz) + acetylene, where Bz is a benzene ligand. In contrast, the reaction of V+ + C2H2 yields products via successive associations V+(m/z = (C2H2)n) either with or without a bimolecular step involving loss of one H2 and V+C2(m/z = (C2H2)m), where n and m extend at least up to 11 under conditions of 0.32 Torr at 300 K. Stabilized V+(Bz) is not a significant intermediate in the association mechanism. We propose a plausible mechanism for the generation of neutral benzene in this reaction and compare with the Fe+ results. The reaction steps that produce benzene result in turnover of the single-atom catalyst, and the large hydrocarbons produced that remain associated to the catalyst are proposed to be polycyclic aromatic hydrocarbons.

Stress is a complex life occurrence essential for survival and goal achievement but can be damaging in excess. Because of the high prevalence of stress in North America, a safe supplement that effectively reduces stress is in demand. The objective of this study was to investigate the efficacy and safety of AlphaWave® l-Theanine on whole-scalp and frontal alpha power, midline theta power, and salivary cortisol in healthy, moderately stressed adults. This was a randomized, triple-blind, placebo-controlled, crossover study that consisted of two study periods with a 7-day washout. A single dose of AlphaWave® l-Theanine (200 mg) or placebo was administered. To induce stress, a mental arithmetic test (MAT) was administered before and after the dose. Electroencephalogram, salivary cortisol, blood pressure, heart rate, self-reported stress, adverse events, clinical chemistry, and hematology were assessed to evaluate efficacy and safety. Increases in heart rate, blood pressure, and self-reported stress and state anxiety indicated that participants experienced stress during the MAT. AlphaWave® l-Theanine led to a greater increase in frontal region and whole-scalp alpha power 3 h post-dose compared to placebo (p ≤ 0.050). Within groups, there were increases in alpha power, at 3 h with AlphaWave® l-Theanine, over the whole recording and during the eyes-open portions (p ≤ 0.048) of the alpha task. The changes in alpha wave activity are supported by greater decreases in salivary cortisol 1 h post-dose (p

PurposeOlder cancer survivors required medical care during the COVID-19 pandemic despite infection risks, but there are limited data on medical care in this age group. Methods. We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors ages 60-98 from five US regions (n=321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included self-reported interruptions in ability to see doctors, receive treatment or supportive therapies, or fill prescriptions. Logistic regression models evaluated bivariate and multivariate associations between care disruptions and education, medical, psychosocial and COVID-19-related factors. Multivariate models included age, county COVID-19 rates, comorbidity and post-diagnosis time. Results. There was a high response rate (n=262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were significantly higher with more education (OR 1.23 per one-year increase, 95% CI 1.09-1.39, p =0.001) and greater depression (OR 1.04 per one-point increase in CES-D score, CI 1.003-1.08, p=0.033); tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99 per one-point increase, p=0.012). There was a trend for associations between disruptions and comorbidity (unadjusted OR 1.13 per 1 added comorbidity, 95% CI 0.99-1.29, p=0.07). Adjusting for covariates, only higher education (p=0.001) and tangible social support (p=0.006) remained significantly associated with having care disruptions. Conclusions. Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions.

Volatile chemical products (VCPs) and other non-combustion-related sources have become important for urban air quality, and bottom-up calculations report emissions of a variety of functionalized compounds that remain understudied and uncertain in emissions estimates. Using a new instrumental configuration, we present online measurements of oxygenated organic compounds in a US megacity over a 10 d wintertime sampling period, when biogenic sources and photochemistry were less active. Measurements were conducted at a rooftop observatory in upper Manhattan, New York City, USA using a Vocus chemical ionization time-of-flight mass spectrometer, with ammonium (NH4+) as the reagent ion operating at 1 Hz. The range of observations spanned volatile, intermediate-volatility, and semi-volatile organic compounds, with targeted analyses of ∼150 ions, whose likely assignments included a range of functionalized compound classes such as glycols, glycol ethers, acetates, acids, alcohols, acrylates, esters, ethanolamines, and ketones that are found in various consumer, commercial, and industrial products. Their concentrations varied as a function of wind direction, with enhancements over the highly populated areas of the Bronx, Manhattan, and parts of New Jersey, and included abundant concentrations of acetates, acrylates, ethylene glycol, and other commonly used oxygenated compounds. The results provide top-down constraints on wintertime emissions of these oxygenated and functionalized compounds, with ratios to common anthropogenic marker compounds and comparisons of their relative abundances to two regionally resolved emissions inventories used in urban air quality models.

Introduction This study aims to report on current practice in the management of radial head fractures (RHFs) in the United Kingdom and to review the literature to identify areas for future investigation. Methods A 12-question online survey was sent to 500 surgeon members of the British Elbow and Shoulder Society in 2021. Questions focused on clinical assessment, indications for surgical treatment and willingness to participate in future studies. Descriptive statistical analysis summarised the responses. Results The response rate was 20.4% (n = 102). For minimally displaced RHFs, non-operative management with immediate mobilisation was reported by 90.2% (n = 92) as opposed to 9.8% (n = 10) for initial immobilisation in plaster or brace. The most cited indication for radial head arthroplasty as opposed to fixation was increased patient age or low functional demand in 69.9% of responses (n = 71). In total, 41.2% (n = 42) indicated the need for a future randomised controlled trial (RCT) concerning the management of RHF. Only five RCTs were returned by the literature review. Discussion There is considerable variability in the management of RHF among an experienced cohort of surgeons. With the interest declared by the participating surgeons, there is a call for a well-designed sufficiently powered RCT.

Alzheimer’s disease (AD) is the leading cause of dementia in individuals over 65 in the U.S. Prevalence is projected to double by 2050, but current treatments cannot stop the progression of AD. Treatments administered before severe cognitive decline may be effective; identification of biomarkers for preclinical and prodromal stages of AD is therefore imperative. Cerebral blood flow (CBF) is a potential early biomarker for AD; generally, older adults with AD have decreased CBF compared to normally aging peers. Characterization should include the relationships between CBF and AD risk factors and pathologies. We assessed the relationships between CBF quantified by arterial spin labeled MRI, hypertension,APOEε4, and tau and amyloid PET in 77 older adults: cognitively normal, subjective cognitive decline, and mild cognitive impairment. Tau and amyloid aggregation were related to altered CBF, and some of these relationships were dependent on hypertension orAPOEε4 status. Our findings suggest a complex relationship between risk factors, AD pathologies, and CBF that warrants future studies of CBF as a potential early biomarker for AD.

For well over a millennium after his death in the fifth century, Attila the Hun was victim to calumnious artistic and verbal representations as the quintessential barbarian and Other. Some historians defamed him a half-human. Others slandered his name by adapting a brief corporeal catalog compiled by Jordanes in the Getica (c. 551), a history of the Goths. Jordanes’ pejorative assessment of Attila’s supposed physical characteristics (arrogant gait and gaze, snub nose, alleged offensive skin pigmentation) served later chroniclers as an explanation for the failures and successes of Attila, helping to influence reader perception. Medieval and early modern representations of Attila call to mind the campaign against Tamerlane in art and print. Here are gathered for the first time several early German versions of the physical features of Attila, as transmitted by Jordanes.

Purpose: Expert selected landmark points on clinical image pairs to provide a basis for rigid registration validation. Using combinatorial rigid registration optimization (CORRO) provide a statistically characterized reference data set for image registration of the pelvis by estimating optimal registration. Materials ad Methods: Landmarks for each CT/CBCT image pair for 58 cases were identified. From the landmark pairs, combination subsets of k-number of landmark pairs were generated without repeat, forming k-set for k=4, 8, and 12. A rigid registration between the image pairs was computed for each k-combination set (2,000-8,000,000). The mean and standard deviation of the registration were used as final registration for each image pair. Joint entropy was used to validate the output results. Results: An average of 154 (range: 91-212) landmark pairs were selected for each CT/CBCT image pair. The mean standard deviation of the registration output decreased as the k-size increased for all cases. In general, the joint entropy evaluated was found to be lower than results from commercially available software. Of all 58 cases 58.3% of the k=4, 15% of k=8 and 18.3% of k=12 resulted in the better registration using CORRO as compared to 8.3% from a commercial registration software. The minimum joint entropy was determined for one case and found to exist at the estimated registration mean in agreement with the CORRO algorithm. Conclusion: The results demonstrate that CORRO works even in the extreme case of the pelvic anatomy where the CBCT suffers from reduced quality due to increased noise levels. The estimated optimal registration using CORRO was found to be better than commercially available software for all k-sets tested. Additionally, the k-set of 4 resulted in overall best outcomes when compared to k=8 and 12, which is anticipated because k=8 and 12 are more likely to have combinations that affected the accuracy of the registration.

Amid increasing calls for universities to transition to online learning, there is a need to explore how platforms and technology can provide positive student experiences and support learning. In this paper, we discuss the implementation of an online peer learning and recommender platform in a large, multi-campus, first-year health subject (n = 2095). The Recommendation in Personalised Peer Learning Environments (RiPPLE) platform supports student’s co-creation of learning resources and allows for students to provide feedback and rate their peers’ submissions. Our results indicated that both student engagement and academic performance were positively impacted for users by the introduction of the RiPPLE platform, but that academic preparedness, in the form of students’ ATAR scores, strongly influenced their engagement and the benefits received. Implications for practice or policy: We explored if students were willing to co-create learning resources online. Our study piloted an online platform known as Recommendation in Personalised Peer Learning Environments (RiPPLE). Critical analysis provides insights into fostering online engagement and peer learning. We further offer recommendations for future practice on how to embed online student co-creation of curriculum.

We present an updated fuel-based oil and gas (FOG) inventory with estimates of nitrogen oxide (NOx) emissions from oil and natural gas production in the contiguous US (CONUS). We compare the FOG inventory with aircraft-derived ("top-down") emissions for NOx over footprints that account for ∼25% of US oil and natural gas production. Across CONUS, we find that the bottom-up FOG inventory combined with other anthropogenic emissions is on average within ∼10% of top-down aircraft-derived NOx emissions. We also find good agreement in the trends of NOx from drilling- and production-phase activities, as inferred by satellites and in the bottom-up inventory. Leveraging tracer-tracer relationships derived from aircraft observations, methane (CH4) and non-methane volatile organic compound (NMVOC) emissions have been added to the inventory. Our total CONUS emission estimates for 2015 of oil and natural gas are 0.45 ± 0.14 Tg NOx/yr, 15.2 ± 3.0 Tg CH4/yr, and 5.7 ± 1.7 Tg NMVOC/yr. Compared to the US National Emissions Inventory and Greenhouse Gas Inventory, FOG NOx emissions are ∼40% lower, while inferred CH4 and NMVOC emissions are up to a factor of ∼2 higher. This suggests that NMVOC/NOx emissions from oil and gas basins are ∼3 times higher than current estimates and will likely affect how air quality models represent ozone formation downwind of oil and gas fields.

Objective To determine the relationship between patient characteristics and performance on the visio-vestibular examination (VVE) in a cohort of healthy youth athletes and explore the potential association between the VVE and other standardized concussion batteries. Design Cross-sectional. Setting Suburban middle and high school. Patients One hundred ninety subjects age 11 to 18 enrolled before their respective scholastic sport season between August 2017 and March 2020. Assessment of independent variables Patient age, sex, concussion history, comorbidities, hours of weekly exercise, Sport Concussion Assessment Tool, 5th edition (SCAT-5), King-Devick (K-D), Postconcussion Symptom Inventory (PCSI). Main outcome measures Visio-vestibular examination abnormalities (smooth pursuit, horizontal and vertical saccades, horizontal and vertical gaze stability, convergence, right and left monocular accommodation, complex tandem gait). Results Overall, 29.5% of subjects had at least one of 9 VVE elements abnormal, 7.9% at least 2, and 3.2% at least 3. None of 72 comparisons of the VVE elements, when stratified by age, sex, concussion history, history of headaches, attention deficit hyperactivity disorder, learning issues, psychiatric problems, motion sickness, or weekly hours of exercise, reached significance using the Benjamini-Hochberg procedure at a false discovery rate of 5%. There were no significant associations between VVE elements and the SCAT-5, K-D, or PCSI. Conclusions The VVE is robust across multiple patient characteristics. Although healthy subjects may have one abnormal element, multiple abnormal elements are a less common feature, making multiple abnormal elements more indicative of concussion, highlighting the use of this assessment in the setting of injury. The VVE tests unique domains when compared with the PCSI, SCAT-5, and K-D.

Background The coronavirus disease 2019 (COVID‐19) pandemic has had wide‐ranging health effects and increased isolation. Older with cancer patients might be especially vulnerable to loneliness and poor mental health during the pandemic. Methods The authors included active participants enrolled in the longitudinal Thinking and Living With Cancer study of nonmetastatic breast cancer survivors aged 60 to 89 years (n = 262) and matched controls (n = 165) from 5 US regions. Participants completed questionnaires at parent study enrollment and then annually, including a web‐based or telephone COVID‐19 survey, between May 27 and September 11, 2020. Mixed‐effects models were used to examine changes in loneliness (a single item on the Center for Epidemiologic Studies–Depression [CES‐D] scale) from before to during the pandemic in survivors versus controls and to test survivor‐control differences in the associations between changes in loneliness and changes in mental health, including depression (CES‐D, excluding the loneliness item), anxiety (the State‐Trait Anxiety Inventory), and perceived stress (the Perceived Stress Scale). Models were adjusted for age, race, county COVID‐19 death rates, and time between assessments. Results Loneliness increased from before to during the pandemic (0.211; P = .001), with no survivor‐control differences. Increased loneliness was associated with worsening depression (3.958; P < .001) and anxiety (3.242; P < .001) symptoms and higher stress (1.172; P < .001) during the pandemic, also with no survivor‐control differences. Conclusions Cancer survivors reported changes in loneliness and mental health similar to those reported by women without cancer. However, both groups reported increased loneliness from before to during the pandemic that was related to worsening mental health, suggesting that screening for loneliness during medical care interactions will be important for identifying all older women at risk for adverse mental health effects of the pandemic., Older breast cancer survivors and matched noncancer controls experienced similar increases in loneliness from before to during the COVID‐19 pandemic. Women who reported increased loneliness also experienced worsening depression and anxiety symptoms and higher stress during the pandemic.

Background The adenoma detection rate (ADR) is one of the main quality indicators of a colonoscopy but requires combining endoscopic and histologic data. However, the polyp detection rate (PDR) requires only endoscopic assessment and has been proposed as a proxy measure for the ADR. Aims To calculate a conversion factor for PDR to ADR, for use as a future surrogate of ADR when only PDR is available. Methods The Southwest Ontario Colonoscopy cohort consists of all outpatient colonoscopies performed across 20 hospitals in Southwestern Ontario between April 2017 and February 2018. Data was collected prospectively through a mandatory quality assurance form that was completed after each procedure and pathology reports were manually reviewed. Endoscopies with associated histologic findings were included. The PDR and true ADR were calculated for each physician. A weighted polyp to adenoma detection rate quotient (APDRQ) was calculated, weighting each physician’s APDRQ by the number of procedures performed. The APDRQ was determined for all outpatient procedures and specifically for screening/surveillance indications. Results During the study period, 57 endoscopists performed 31,721 colonoscopies. The overall PDR was 41.1% and the ADR was 26.5%. The weighted ADPDRQ was 0.638 (95% CI: 0.600, 0.675). When limited to screening/surveillance colonoscopies, the weighted ADPDR was 0.616 (95% CI: 0.564, 0.669). To better understand the influence of endoscopists with low ADR: PDR, we excluded those with ratio below ( Conclusions In this large, population-based, cohort study, we calculated the ADR; PDR ratio. We propose this may be used in future studies to infer ADR when only PDR is available. Scatter plot of correlation between ADR and PDR, by physician. The dashed line indicates the line for which ADR=PDR, the maximum value the ADR can take for a given PDR. The marker size is proportional to the number of colonoscopies performed. Funding Agencies None

Human activity impacts the evolutionary trajectories of many species worldwide. Global trade of agricultural goods contributes to the dispersal of pathogens reshaping their genetic makeup and providing opportunities for virulence gains. Understanding how pathogens surmount control strategies and cope with new climates is crucial to predicting the future impact of crop pathogens. Here, we address this by assembling a global thousand-genome panel of Zymoseptoria tritici, a major fungal pathogen of wheat reported in all production areas worldwide. We identify the global invasion routes and ongoing genetic exchange of the pathogen among wheat-growing regions. We find that the global expansion was accompanied by increased activity of transposable elements and weakened genomic defenses. Finally, we find significant standing variation for adaptation to new climates encountered during the global spread. Our work shows how large population genomic panels enable deep insights into the evolutionary trajectory of a major crop pathogen.

Frogeye leaf spot, caused by the fungus Cercospora sojina, is a threat to soybeans in the southeastern and midwestern United States that can be controlled by crop genetic resistance. Limited genetic resistance to the disease has been reported, and only three sources of resistance have been used in modern soybean breeding. To discover novel sources and identify the genomic locations of resistance that could be used in soybean breeding, a GWAS was conducted using a panel of 329 soybean accessions selected to maximize genetic diversity. Accessions were phenotyped using a 1-5 visual rating and by using image analysis to count lesion number and measure the percent of leaf area diseased. Eight novel loci on eight chromosomes were identified for three traits utilizing the FarmCPU or BLINK models, of which a locus on chromosome 11 was highly significant across all model-trait combinations. KASP markers were designed using the SoySNP50K Beadchip and variant information from 65 of the accessions that have been sequenced to target SNPs in the gene model Glyma.11g230400, a LEUCINE-RICH REPEAT RECEPTOR-LIKE PROTEIN KINASE. The association of a KASP marker, GSM990, designed to detect a missense mutation in the gene was the most significant with all three traits in a genome-wide association, and the marker may be useful to select for resistance to frogeye leaf spot in soybean breeding.

Background: Few studies have examined psychiatric symptoms during the acute phase following a concussion in adolescents. Thus, this study compares anxiety and depression in acutely concussed and nonconcussed adolescents. Hypothesis: Acutely concussed adolescents will report greater anxiety and depressive symptoms compared with nonconcussed adolescents. Study Design: Prospective cohort study. Level of Evidence: Level 3. Methods: Data were collected from 282 adolescents (111 concussed within 28 days of injury, 171 nonconcussed), 13 to 18 years of age, who completed Patient-Reported Outcome Measurement Information System (PROMIS) Anxiety and Depressive Symptoms measures. We calculated average T-scores for anxiety and depression across both groups and compared the proportion of those who scored above normal limits. Finally, we calculated risk ratios for anxiety and depression scores above normal limits. Results: Average T-scores for anxiety did not differ in concussed versus nonconcussed adolescents (mean: 45.9 [SD 10.84] vs 45.2 [8.1], respectively, P = 0.54), whereas average T-scores for depression were significantly higher in concussed versus nonconcussed adolescents (46.0 [10.88] vs 42.8 [8.48], respectively, P < 0.01). The proportion of concussed adolescents above normal limits for depression was greater than nonconcussed adolescents (32.4% vs 20.5%, respectively, P = 0.02). Post hoc sensitivity analyses excluding those with a history of anxiety or depression demonstrated a 1.45 (95% CI, 0.97, 2.01) and 1.56 (95% CI, 0.95, 2.56) increased risk of an above-normal anxiety and depression score for concussed compared with nonconcussed adolescents, respectively, although both were nonsignificant. Conclusion: Although we found few significant differences between the 2 groups, the results highlight that many concussed adolescents met the threshold for above-average symptoms on the depression and anxiety PROMIS measures. Clinical Relevance: In adolescents, there is increased risk for psychiatric sequalae in the acute period after a concussion. As such, we suggest that clinicians consider incorporating depression screening when caring for adolescents after a concussion.

This longitudinal study compared children’s health behaviors before the COVID-19 pandemic versus during the pandemic. This analysis examined the association between individual-level characteristics and health behavior change. Four prospective cohort studies in the Environmental influences on Child Health Outcomes (ECHO) Program contributed data. Children aged 4–12 years and their caregivers were recruited in California, Colorado, North Dakota, and New Hampshire. Dietary intake, physical activity, screen time, and sleep duration were assessed with questionnaires pre-pandemic and during the pandemic. The final sample included 347 children: 47% female and 62% non-Hispanic White. Compared with pre-pandemic, weekday screen time duration was higher during the pandemic (3.0 vs. 4.5 h, p < 0.001). Unadjusted increases in screen time duration differed by race and ethnicity: 1.3 h/day for non-Hispanic White children, 2.3 h/day for Hispanic children, and 5.3 h/day for non-Hispanic Black children. Overall, no changes occurred in sugar-sweetened beverage (SSB) intake (p = 0.26), discretionary food intake (p = 0.93), and physical activity (p = 0.15). Sleep duration increased by 30 min among children who did not meet sleep recommendations pre-pandemic. Child sex and maternal education level were not associated with health behavior change. The pandemic may have exacerbated disparities in some health behaviors. Families may need support to re-establish healthy routines.