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Objectives: This study investigated the extent to which immigrant concentration is associated with reductions in neighborhood crime rates in the City of Los Angeles. Methods: A potential outcomes model using two-stage least squares regression was estimated, where immigrant concentration levels in 1990 were used as an instrumental variable to predict immigrant concentration levels in 2000. The instrumental variables design was used to reduce selection bias in estimating the effect of immigrant concentration on changes in official crime rates between 2000 and 2005 for census tracts in the City of Los Angeles, holding constant other demographic variables and area-level fixed effects. Non-parametric smoothers were also employed in a two-stage least squares regression model to control for the potential influence of heterogeneity in immigrant concentration on changes in crime rates. Results: The results indicate that greater predicted concentrations of immigrants in neighborhoods are linked to significant reductions in crime. The results are robust to a number of different model specifications. Conclusions: The findings challenge traditional ecological perspectives that link immigrant settlement to higher rates of crime. Immigration settlement patterns appear to be associated with reducing the social burden of crime. Study conclusions are limited by the potential for omitted variables that may bias the observed relationship between immigrant concentration and neighborhood crime rates, and the use of only official crime data which may under report crimes committed against immigrants. Understanding whether immigrant concentration is an important dynamic of changing neighborhood patterns of crime outside Los Angeles will require replication with data from other U. S. cities. © 2012 Springer Science+Business Media, LLC.

The current research details interviews with 50 victims and 50 defendants who participated in a specialized criminal domestic violence court in Lexington County, South Carolina. These victims and defendants indicated satisfaction with their court experiences, thought the process allowed them to voice their views, felt they were treated with respect, and were generally satisfied with the outcome of their cases. Court observations and interviews with court personnel confirmed that this court has successfully incorporated victims and defendants into the decision-making process while also providing a fair system to address the issue of violence against women. [ABSTRACT FROM AUTHOR]

Twenty-two community nurse practitioners were researched, primarily to establish whether or not they were able to achieve a 'higher level of practice'. Grounded theory, the qualitative research methodology developed by Glaser and Strauss, was used as a framework for the research. Data was gathered using primary observation with some participation (581 consultations being observed in the process), and by interviewing the community nurse practitioners and their clinical managers. From the overall theoretical framework that emerged from the research, a category, the 'combination model of care', was developed as a theoretical model, together with a conceptual framework for the process of nursing, 'HADPIPE'. This model of care/nursing and the HADPIPE framework provide a basis from which nurse practitioners can practice with a holistic nursing focus. The article analyses and discusses the combination model, and provides a detailed example of it in action. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore risk factors and behaviors associated with aggressive and violent behaviors among adolescents. METHODS: A comprehensive review of research literature from various disciplines associated with improving the health and well-being of adolescents. RESULTS: Risk factors and behaviors associated with adolescent aggression and violence are discussed via 6 major factor categories: individual, family, school/academic, peer-related, community and neighborhood, and situational. CONCLUSION: Adolescent aggression and violence develops and manifests within a complex constellation of factors. Prevention intervention efforts should be theory based, multicomponent, and multisystem; they should begin in middle school and continue into high school with a comprehensive evaluation design. [ABSTRACT FROM AUTHOR]

A two-step formal (4 + 1) annulation-dehydration reaction offers a convenient route to C2-arylated indoles and benzofurans. This reaction exploits the bifunctional reactivity of electron-deficient benzyl chlorides with N -sulfonyl-2-aminobenzaldehydes or salicylaldehyde derivatives. The reaction tolerates both electron-withdrawing and donating groups on the substituted aldehydes, as well as variation of electron-withdrawing groups at the para position of the benzyl chloride reagent. This work also identifies interesting byproducts resulting from the self-reaction of these benzyl chlorides under basic conditions.

The coronavirus disease 2019 pandemic highlighted the need for more rapid and routine application of modeling approaches such as quantitative microbial risk assessment (QMRA) for protecting public health. QMRA is a transdisciplinary science dedicated to understanding, predicting, and mitigating infectious disease risks. To better equip QMRA researchers to inform policy and public health management, an Advances in Research for QMRA workshop was held to synthesize a path forward for QMRA research. We summarize insights from 41 QMRA researchers and experts to clarify the role of QMRA in risk analysis by (1) identifying key research needs, (2) highlighting emerging applications of QMRA; and (3) describing data needs and key scientific efforts to improve the science of QMRA. Key identified research priorities included using molecular tools in QMRA, advancing dose-response methodology, addressing needed exposure assessments, harmonizing environmental monitoring for QMRA, unifying a divide between disease transmission and QMRA models, calibrating and/or validating QMRA models, modeling co-exposures and mixtures, and standardizing practices for incorporating variability and uncertainty throughout the source-to-outcome continuum. Cross-cutting needs identified were to: develop a community of research and practice, integrate QMRA with other scientific approaches, increase QMRA translation and impacts, build communication strategies, and encourage sustainable funding mechanisms. Ultimately, a vision for advancing the science of QMRA is outlined for informing national to global health assessments, controls, and policies., (© 2024 The Author(s). Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Iron and steel slags have a long history of both disposal and beneficial use in the coastal zone. Despite the large volumes of slag deposited, comprehensive assessments of potential risks associated with metal(loid) leaching from iron and steel by-products are rare for coastal systems. This study provides a national-scale overview of the 14 known slag deposits in the coastal environment of Great Britain (those within 100 m of the mean high-water mark), comprising geochemical characterisation and leaching test data (using both low and high ionic strength waters) to assess potential leaching risks. The seaward facing length of slag deposits totalled at least 76 km, and are predominantly composed of blast furnace (iron-making) slags from the early to mid-20th Century. Some of these form tidal barriers and formal coastal defence structures, but larger deposits are associated with historical coastal disposal in many former areas of iron and steel production, notably the Cumbrian coast of England. Slag deposits are dominated by melilite phases (e.g. gehlenite), with evidence of secondary mineral formation (e.g. gypsum, calcite) indicative of weathering. Leaching tests typically show lower element (e.g. Ba, V, Cr, Fe) release under seawater leaching scenarios compared to deionised water, largely ascribable to the pH buffering provided by the former. Only Mn and Mo showed elevated leaching concentrations in seawater treatments, though at modest levels (<3 mg/L and 0.01 mg/L, respectively). No significant leaching of potentially ecotoxic elements such as Cr and V (mean leachate concentrations <0.006 mg/L for both) were apparent in seawater, which micro-X-Ray Absorption Near Edge Structure (μXANES) analysis show are both present in slags in low valence (and low toxicity) forms. Although there may be physical hazards posed by extensive erosion of deposits in high-energy coastlines, the data suggest seawater leaching of coastal iron and steel slags in the UK is likely to pose minimal environmental risk., (© 2024. The Author(s).)

Background: Noninvasive neuromonitoring in critically ill children includes multiple modalities that all intend to improve our understanding of acute and ongoing brain injury., Methods: In this article, we review basic methods and devices, applications in clinical care and research, and explore potential future directions for three noninvasive neuromonitoring modalities in the pediatric intensive care unit: automated pupillometry, near-infrared spectroscopy, and transcranial Doppler ultrasonography., Results: All three technologies are noninvasive, portable, and easily repeatable to allow for serial measurements and trending of data over time. However, a paucity of high-quality data supporting the clinical utility of any of these technologies in critically ill children is currently a major limitation to their widespread application in the pediatric intensive care unit., Conclusions: Future prospective multicenter work addressing major knowledge gaps is necessary to advance the field of pediatric noninvasive neuromonitoring., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Multiple recent studies have found elevated lead (Pb) concentrations in tap water in U.S. homes relying on unregulated private wells. The main Pb source is dissolution from household plumbing, fixtures, and well components. Here, we leverage a natural experiment and citizen science approach to evaluate how extending community water service to an environmental justice community relying on private wells affects Pb in household water. We analyzed Pb in 260 first-draw kitchen tap water samples collected by individual homeowners over a 5-month period in residences that did and did not connect to the community system. Before the community water system was extended, 25% of homes had Pb > 15 μg/L (the U.S. regulatory action level for community water systems) in first-draw water samples. Pb was significantly correlated with nickel (ρ = 0.61), zinc (ρ = 0.50), and copper (ρ = 0.40), suggesting that corrosion of brass fittings and fixtures is the main Pb source. Among homes that connected to the community system, Pb decreased rapidly and was sustained at levels well below 15 μg/L over the study period. Overall, connecting to the municipal water supply was associated with a 92.5% decrease in first-draw tap water Pb.

Water pollution arising from abandoned coal mines, is second only to sewage as a source of freshwater pollution and in coalfield catchments mine water can be the dominant pollutant, with oxidised iron smothering the bed of receiving rivers. This study measured greenhouse gases in mine water outflows from sixteen sites across the Midland Valley in Scotland. Radiogenic and stable carbon isotopes measurements (Δ 14 C and δ 13 C) were used to determine the sources of both methane (CH 4 ) and carbon dioxide (CO 2 ) produced within the flooded mine environment. Concentrations of CH 4 -C ranged from 20 to 215 μg l -1 and CO 2 -C from 30 to 120 mg l -1 , with CO 2 accounting for 97 % of the mine water global warming potential. Methane origins included 51 % modern biogenic, 41 % thermogenic and 8 % from hydrogenotrophic methanogenesis of coal. The most significant inverse impact on biogenic CH 4 concentrations was sulphate, most likely due to sulphate reducing bacteria outcompeting methanogens. Carbon dioxide origins included 64 % from the dissolution of limestone, 21 % from terrestrial organic carbon and 15 % from coal. The limestone derived CO 2 was positively correlated with high sulphate concentrations, which resulted in sulphuric acid and caused the dissolution of carbonate from limestone. The mine waters experienced significant carbonate buffering becoming only slightly acidic (pH 6-7), but with significant loss of inorganic carbon. The mine waters had low dissolved oxygen (6-25 %) and high dissolved iron (2 to 65 mg l -1 ) and manganese (0.5 to 5 mg l -1 ) concentrations. Dissolved greenhouse gases from abandoned mines were estimated as 0.27 +0.31-0.18% of Scotland's global warming potential. This novel work has contributed information about the sources and controls of greenhouse gas fluxes in mine waters and identified the need to quantify and report this emissions term., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The plethora of data on PFASs in environmental samples collected in response to growing concern about these chemicals could enable the training of machine-learning models for predicting exposure risks. However, differences in sampling and analysis methods across data sets must be reconciled through data preprocessing, and little information is available about how such manipulations affect the resulting models. This study evaluates how data preprocessing influences machine-learned Bayesian network models of PFOA in groundwater. We link 19 years of PFOA measurements from Minnesota, USA, to publicly available information about potential PFOA sources and factors that may influence their environmental fate. Nine different preprocessing methods were tested, and the resulting data sets were used to train models to predict the probability of PFOA ≥ 35 ppt, the 2017 Minnesota health advisory level. Different preprocessing approaches produced varying model structures with significantly different accuracies. Nonetheless, models showed similar relationships between predictor variables and PFOA exposure risks, and all models were relatively accurate, distinguishing wells at high risk from those at low risk for 82.0% to 89.0% of test data samples. There was a trade-off between data quality and model performance since a stricter data screening strategy decreased the sample size for model training.

CO 2 mineralization in slag has gained significant attention since it occurs with minimal human intervention and energy input. While the amount of theoretical CO 2 that can be captured within slag has been quantified based on slag composition in several studies, the microstructural and mineralogical effects of slag on its ability to capture CO 2 have not been fully addressed. In this work, the CO 2 uptake within legacy slag samples is analyzed through microstructural characterization. Slag samples were collected from the former Ravenscraig steelmaking site in Lanarkshire, Scotland. The collected samples were studied using X-ray Computed Tomography (XCT) to understand the distribution and geometry of pore space, as well as with scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy (EDS) to visualize the distribution of elements within the studied samples. Electron backscatter diffraction (EBSD) was used to study the minerals distribution. The samples were also characterized through X-ray diffraction (XRD) and X-ray fluorescence (XRF), and the amount of captured CO 2 was quantified using thermogravimetric analysis (TGA). Our results demonstrate that CO 2 uptake occurs to the extent of ∼9-30 g CO 2 / kg slag. The studied samples are porous in nature, with pore space occupying up to ∼30% of their volumes, and they are dominated by åkermanite-gehlenite minerals which interact with the atmospheric CO 2 slowly at ambient conditions. EDS and EBSD results illustrate that the precipitated carbonate in slag is calcite, and that the precipitation of calcite is accompanied by the formation of a Si-O-rich layer. The provided analysis concludes that the porous microstructure as well as the minerals distribution in slag should be considered in forecasting and designing large-scale solutions for passive CO 2 mineralization in slag., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The vast majority of residents of high-income countries (≥90%) reportedly have high access to safely managed drinking water. Owing perhaps to the widely held perception of near universal access to high-quality water services in these countries, the burden of waterborne disease in these contexts is understudied. This systematic review aimed to: identify population-scale estimates of waterborne disease in countries with high access to safely managed drinking water, compare methods to quantify disease burden, and identify gaps in available burden estimates. We conducted a systematic review of population-scale disease burden estimates attributed to drinking water in countries where ≥90% of the population has access to safely managed drinking water per official United Nations monitoring. We identified 24 studies reporting estimates for disease burden attributable to microbial contaminants. Across these studies, the median burden of gastrointestinal illness risks attributed to drinking water was ∼2,720 annual cases per 100,000 population. Beyond exposure to infectious agents, we identified 10 studies reporting disease burden-predominantly, cancer risks-associated with chemical contaminants. Across these studies, the median excess cancer cases attributable to drinking water was 1.2 annual cancer cases per 100,000 population. These median estimates slightly exceed WHO-recommended normative targets for disease burden attributable to drinking water and these results highlight that there remains important preventable disease burden in these contexts, particularly among marginalized populations. However, the available literature was scant and limited in geographic scope, disease outcomes, range of microbial and chemical contaminants, and inclusion of subpopulations (rural, low-income communities; Indigenous or Aboriginal peoples; and populations marginalized due to discrimination by race, ethnicity, or socioeconomic status) that could most benefit from water infrastructure investments. Studies quantifying drinking water-associated disease burden in countries with reportedly high access to safe drinking water, focusing on specific subpopulations lacking access to safe water supplies and promoting environmental justice, are needed., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jacqueline MacDonald Gibson reports financial support was provided by National Science Foundation. Heather M. Murphy reports financial support was provided by Canada Research Chairs Program. Jemaneh Habtewold reports financial support was provided by Canada Research Chairs Program. Debbie Lee reports financial support was provided by Pennsylvania Commonwealth Universal Research Enhancement Program and the National Institutes of Health., (Copyright © 2023. Published by Elsevier Ltd.)

Atropisomeric, bench-stable benzoazepine-fused isoindoles were synthesized via oxidation from isoindoline precursors. Using the isoindoles 5d - f as models, the stereochemistry and conformational folding of the systems were examined. Chiral UHPLC was used to analyze the rate of racemization and calculate the Gibbs free energy of enantiomerization (Δ G ‡ Enant ). X-ray crystallography, 1 H NMR spectroscopy, and DFT calculations were used to elucidate the three axes of chirality and clarify the structural factors contributing to Δ G ‡ Enant . Tandem rotation around the axes of chirality precludes the formation of diastereomers, with rotational restriction of the C aryl -N sulfonamide bond determined as the moderator of atropisomeric stability in the system, affected primarily by steric hindrance as well as by π-stacking interactions facilitated by the folded conformation of the sulfonamide over the isoindole moiety.

There is growing global concern that greenhouse gas (GHG) emissions from water bodies are increasing because of interactions between nutrient levels and climate warming. This paper investigates key land-cover, seasonal and hydrological controls of GHGs by comparison of the semi-natural, agricultural and urban environments in a detailed source-to-sea study of the River Clyde, Scotland. Riverine GHG concentrations were consistently oversaturated with respect to the atmosphere. High riverine concentrations of methane (CH 4 ) were primarily associated with point source inflows from urban wastewater treatment, abandoned coal mines and lakes, with CH 4 -C concentrations between 0.1 - 44 µg l -1 . Concentrations of carbon dioxide (CO 2 ) and nitrous oxide (N 2 O) were mainly driven by nitrogen concentrations, dominated by diffuse agricultural inputs in the upper catchment and supplemented by point source inputs from urban wastewater in the lower urban catchment, with CO 2 -C concentrations between 0.1 - 2.6 mg l -1 and N 2 O-N concentrations between 0.3 - 3.4 µg l -1 . A significant and disproportionate increase in all GHGs occurred in the lower urban riverine environment in the summer, compared to the semi-natural environment, where GHG concentrations were higher in winter. This increase and change in GHG seasonal patterns points to anthropogenic impacts on microbial communities. The loss of total dissolved carbon, to the estuary is approximately 48.4 ± 3.6 Gg C yr -1 , with the annual inorganic carbon export approximately double that of organic carbon and four times that of CO 2, with CH 4 accounting for 0.03%, with the anthropogenic impact of disused coal mines accelerating DIC loss. The annual loss of total dissolved nitrogen to the estuary is approximately 4.03 ± 0.38 Gg N yr -1 of which N 2 O represents 0.06%. This study improves our understanding of riverine GHG generation and dynamics which can contribute to our knowledge of their release to the atmosphere. It identifies where action could support reductions in aquatic GHG generation and emission., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Importance: Structural racism has resulted in long-standing disinvestment and dilapidated environmental conditions in Black neighborhoods. Abandoned houses signal neglect and foster stress and fear for residents, weakening social ties and potentially contributing to poor health and safety., Objective: To determine whether abandoned house remediation reduces gun violence and substance-related outcomes and increases perceptions of safety and use of outdoor space., Design, Setting, and Participants: This cluster randomized trial was conducted from January 2017 to August 2020, with interventions occurring between August 2018 and March 2019. The study included abandoned houses across Philadelphia, Pennsylvania, and surveys completed by participants living nearby preintervention and postintervention. Data analysis was performed from March 2021 to September 2022., Interventions: The study consisted of 3 arms: (1) full remediation (installing working windows and doors, cleaning trash, weeding); (2) trash cleanup and weeding only; and (3) a no-intervention control., Main Outcomes and Measures: Difference-in-differences mixed-effects regression models were used to estimate the effect of the interventions on multiple primary outcomes: gun violence (weapons violations, gun assaults, and shootings), illegal substance trafficking and use, public drunkenness, and perceptions of safety and time outside for nearby residents., Results: A master list of 3265 abandoned houses was randomly sorted. From the top of this randomly sorted list, a total of 63 clusters containing 258 abandoned houses were formed and then randomly allocated to 3 study arms. Of the 301 participants interviewed during the preintervention period, 172 (57.1%) were interviewed during the postintervention period and were included in this analysis; participants were predominantly Black, and most were employed. Study neighborhoods were predominantly Black with high percentages of low-income households. Gun violence outcomes increased in all study arms, but increased the least in the full remediation arm. The full housing remediation arm, compared with the control condition, showed reduced weapons violations by -8.43% (95% CI, -14.68% to -1.19%), reduced gun assaults by -13.12% (95% CI, -21.32% to -3.01%), and reduced shootings by a nonsignificant -6.96% (95% CI, -15.32% to 3.03%). The trash cleanup arm was not associated with a significant differential change in any gun violence outcome. Instances of illegal substance trafficking and use and public drunkenness outcomes were not significantly affected by the housing remediation or trash cleanup treatment. Perceptions of neighborhood safety and time spent outside were unaffected by the intervention. The study arms did differ in a baseline characteristic and some preintervention trends, which raises questions regarding other potential nonmeasured differences between study arms that could have influenced estimates. No evidence of displacement of gun violence outcomes was found., Conclusions and Relevance: In this cluster randomized controlled trial among low-income, predominantly Black neighborhoods, inexpensive, straightforward abandoned housing remediation was directly linked to significant relative reductions in weapons violations and gun assaults, and suggestive reductions in shootings., Trial Registration: isrctn.org Identifier: ISRCTN14973997.

Background and Objectives: Few data are available regarding the use of anesthetic infusions for refractory status epilepticus (RSE) in children and neonates, and ketamine use is increasing despite limited data. We aimed to describe the impact of ketamine for RSE in children and neonates., Methods: Retrospective single-center cohort study of consecutive patients admitted to the intensive care units of a quaternary care children's hospital treated with ketamine infusion for RSE., Results: Sixty-nine patients were treated with a ketamine infusion for RSE. The median age at onset of RSE was 0.7 years (interquartile range 0.15-7.2), and the cohort included 13 (19%) neonates. Three patients (4%) had adverse events requiring intervention during or within 12 hours of ketamine administration, including hypertension in 2 patients and delirium in 1 patient. Ketamine infusion was followed by seizure termination in 32 patients (46%), seizure reduction in 19 patients (28%), and no change in 18 patients (26%)., Discussion: Ketamine administration was associated with few adverse events, and seizures often terminated or improved after ketamine administration. Further data are needed comparing first-line and subsequent anesthetic medications for treatment of pediatric and neonatal RSE., Classification of Evidence: This study provides Class IV evidence on the therapeutic utility of ketamine for treatment of RSE in children and neonates., (© 2022 American Academy of Neurology.)

Weathering of silicate-rich industrial wastes such as slag can reduce emissions from the steelmaking industry. During slag weathering, different minerals spontaneously react with atmospheric CO 2 to produce calcite. Here, we evaluate the CO 2 uptake during slag weathering using image-based analysis. The analysis was applied to an X-ray computed tomography (XCT) dataset of a slag sample associated with the former Ravenscraig steelworks in Lanarkshire, Scotland. The element distribution of the sample was studied using scanning electron microscopy (SEM), coupled with energy-dispersive spectroscopy (EDS). Two advanced image segmentation methods, namely trainable WEKA segmentation in the Fiji distribution of ImageJ and watershed segmentation in Avizo ® 9.3.0, were used to segment the XCT images into matrix, pore space, calcite, and other precipitates. Both methods yielded similar volume fractions of the segmented classes. However, WEKA segmentation performed better in segmenting smaller pores, while watershed segmentation was superior in overcoming the partial volume effect presented in the XCT data. We estimate that CO 2 has been captured in the studied sample with an uptake between 20 and 17 kg CO 2 /1,000 kg slag for TWS and WS, respectively, through calcite precipitation.

Alkaline wastes have been the focus of many studies as they act as CO 2 sinks and have the potential to offset emissions from mining and steelmaking industries. Passive carbonation of alkaline wastes mimics natural silicate weathering and provides a promising alternative pathway for CO 2 capture and storage as carbonates, requiring marginal human intervention when compared to ex-situ carbonation. This review summarizes the extant research that has investigated the passive carbonation of alkaline wastes, namely ironmaking and steelmaking slag, mine tailings and demolition wastes, over the past two decades. Here we report different factors that affect passive carbonation to address challenges that this process faces and to identify possible solutions. We identify avenues for future research such as investigating how passive carbonation affects the surrounding environment through interaction with the biosphere and the hydrosphere. Future research should also consider economic analyses to provide investors with an in-depth understanding of passive carbonation techniques. Based on the reviewed materials, we conclude that passive carbonation can be an important contributor to climate change mitigation strategies, and its potential can be intensified by applying simple waste management practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Community-based research inclusive of self-assessment and objective environmental metrics can be enhanced by the collection of biomarker data in unity toward assessing the health impacts of the totality of environmental stress driven by structural racism. Cortisol dynamic range (CDR), a measure of chronic stress burden, may underpin place-based connections to health, but a gap remains in elucidating community-based CDR methodology., Purpose: To 1) assess the feasibility of cortisol collection and CDR measurement in a community-based study with home-based, participant-directed specimen collection, and 2) explore the association between CDR and other individual and environmental measures in a sample of predominantly Black participants. Methods : In this cross-sectional, observational study in predominantly Black urban neighborhoods, participants (n = 73) completed health assessments and in-home, self-collected salivary cortisol. For feasibility, CDR (peak-nadir) was compared to cortisol awakening response (CAR) slope over time. Comparisons of CDR quartile by person and place variables were explored (ANOVA)., Results: The cohort (77% Black, 39.7% <$15 k/year income, high perceived stress) completed 98.6% of cortisol collection timepoints. CDR was calculated in all participants without interruptions to sleep-wake cycle as seen with CAR collection. Participants in the lowest quartile of CDR were the oldest (p = 0.03) with lowest reported mental health (p = 0.048) with no associations seen for CAR., Conclusion: Participant-collected CDR is more feasible than cortisol measures dependent on slopes over time in a community-based, predominately Black cohort with exploratory findings supporting relevance to outcomes of interest to future work. Future community-based studies should integrate CDR with environment and psychosocial measures., Competing Interests: The authors received support in training and completion of the study from the University of Pennsylvania Perelman School of Medicine. The study was funded in part by grant 5R01AA024941 from the National Institutes of Health., (© 2022 The Authors. Published by Elsevier Ltd.)

Aim: Cerebral oxygenation (rSO2) is not routinely measured during pediatric cardiopulmonary resuscitation (CPR). We aimed to determine whether higher intra-arrest rSO2 was associated with return of spontaneous circulation (ROSC) and survival to hospital discharge., Methods: Prospective, single-center observational study of cerebral oximetry using near-infrared spectroscopy (NIRS) during pediatric cardiac arrest from 2016 to 2020. Eligible patients had ≥30 s of rSO2 data recorded during CPR. We compared median rSO2 and percentage of rSO2 measurements above a priori thresholds for the entire event and the final five minutes of the CPR event between patients with and without ROSC and survival to discharge., Results: Twenty-one patients with 23 CPR events were analyzed. ROSC was achieved in 17/23 (73.9%) events and five/21 (23.8%) patients survived to discharge. The median rSO2 was higher for events with ROSC vs. no ROSC for the overall event (62% [56%, 70%] vs. 45% [35%, 51%], p = 0.025) and for the final 5 minutes of the event (66% [55%, 72%] vs. 43% [35%, 44%], p = 0.01). Patients with ROSC had a higher percentage of measurements above 50% during the final five minutes of CPR (100% [100%, 100%] vs. 0% [0%, 29%], p = 0.01). There was no association between rSO2 and survival to discharge., Conclusions: Higher cerebral rSO2 during CPR for pediatric cardiac arrest was associated with higher rates of ROSC but not with survival to discharge., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Nuclear magnetic resonance (NMR) spectroscopy was used to monitor glutathione metabolism in alginate-encapsulated JM-1 hepatoma cells perfused with growth media containing [3,3′-13C2]-cystine. After 20 h of perfusion with labeled medium, the 13C NMR spectrum is dominated by the signal from the 13C-labeled glutathione. Once 13C-labeled, the high intensity of the glutathione resonance allows the acquisition of subsequent spectra in 1.2 min intervals. At this temporal resolution, the detailed kinetics of glutathione metabolism can be monitored as the thiol alkylating agent monobromobimane (mBBr) is added to the perfusate. The addition of a bolus dose of mBBr results in rapid diminution of the resonance for 13C-labeled glutathione due to a loss of this metabolite through alkylation by mBBr. As the glutathione resonance decreases, a new resonance due to the production of intracellular glutathione-bimane conjugate is detectable. After clearance of the mBBr dose from the cells, intracellular glutathione repletion is then observed by a restoration of the 13C-glutathione signal along with wash-out of the conjugate. These data demonstrate that standard NMR techniques can directly monitor intracellular processes such as glutathione depletion with a time resolution of approximately < 2 min.

Early life exposure to environmental lead (Pb) has been linked to decreased IQ, behavior problems, lower lifetime earnings, and increased criminal activity. Beginning in the 1970s, limits on Pb in paint, gasoline, food cans, and regulated water utilities sharply curtailed US environmental Pb exposure. Nonetheless, hundreds of thousands of US children remain at risk. This study reports on how unregulated private well water is an underrecognized Pb exposure source that is associated with an increased risk of teenage juvenile delinquency. We build a longitudinal dataset linking blood Pb measurements for 13,580 children under age 6 to their drinking water source, individual- and neighborhood-level demographics, and reported juvenile delinquency records. We estimate how early life Pb exposure from private well water influences reported delinquency. On average, children in homes with unregulated private wells had 11% higher blood Pb than those with community water service. This higher blood Pb was significantly associated with reported delinquency. Compared to children with community water service, those relying on private wells had a 21% (95% CI: 5 to 40%) higher risk of being reported for any delinquency and a 38% (95% CI: 10 to 73%) increased risk of being reported for serious delinquency after age 14. These results suggest that there could be substantial but as-yet-unrecognized social benefits from intervention programs to prevent children's exposure to Pb from private wells, on which 13% of the US population relies., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

The Environmental Protection Agency's definition of "Green Chemistry" is "the design of chemical products and processes that reduces or eliminates the use or generation of hazardous substances. Green chemistry applies across the life cycle of a chemical product, including its design, manufacture, use, and ultimate disposal." Conventional omic tissue extraction procedures use solvents that are toxic and carcinogenic, such as chloroform and methyl-tert-butyl ether for lipidomics, or caustic chaotropic solutions for genomics and transcriptomics, such as guanidine or urea. A common preservation solution for pathology is formaldehyde, which is a carcinogen. Use of acetonitrile as a universal biospecimen preservation and extraction solvent will reduce these hazardous wastes, because it is less toxic and more environmentally friendly than the conventional solvents used in biorepository and biospecimen research. A new extraction method never applied to multi-omic, system biology research, called cold-induced phase separation (CIPS), uses freezing point temperatures to induce a phase separation of acetonitrile-water mixtures. Also, the CO 2 exposure during CIPS will acidify the water precipitating DNA out of aqueous phase. The resulting phase separation brings hydrophobic lipids to the top acetonitrile fraction that is easily decanted from the bottom aqueous fraction, especially when the water is frozen. This CIPS acetonitrile extract contains the lipidome (lipids), the bottom aqueous fraction is sampled to obtain the transcriptome (RNA) fraction, and the remaining water and pellet is extracted with 60% acetonitrile to isolate the metabolome (<1 kD polar molecules). Finally, steps 4 and 5 use a TRIzol™ liquid-liquid extraction SOP of the pellet to isolate the genome (DNA) and proteome (proteins). This chapter details the multi-omic sequential extraction SOP and potential problems associated with each of the 5 steps, with steps 2, 4, and 5 still requiring validation. The metabolomic and lipidomic extraction efficiencies using the CIPS SOP is compared to conventional solvent extraction SOPs and is analyzed by nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS), respectively. Acetonitrile biospecimen preservation combined with the CIPS multi-omic extraction SOP is green chemistry technology that will eliminate the generation of the hazardous substances associated with biospecimen processing and permits separation and safe disposal of acetonitrile avoiding environmental contamination., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Supplementation of glucogenic precursors in roughage diets may increase production responses due to improved efficiencies of nutrient utilization. Therefore, the objective of this study was to determine the effect of source of supplemental glucogenic potential (GP) on forage digestibility, serum metabolites, energy utilization, and rumen parameters of growing wethers consuming a roughage diet (8.8% crude protein, 71.4% ash-free neutral detergent fiber). Crossbred wethers (49.1 ± 4.7 kg initial BW; n = 16) were utilized in a 4 × 4 replicated Latin Square design with four periods of 21 d. Supplements were designed to supplement increasing amount of GP: 1) no supplementation (CON; 0 g), 2) 40 g of calcium propionate (CAP; 30 g of GP), 3) 70 g of blood meal + 100 g of feather meal (BF; 40 g of GP), or 4) combination of CAP and BF (COMBO; 70 g of GP). Total fecal and urine collection was conducted from days 13-17 to calculate digestibility estimates and urinary losses. An acetate tolerance test was administered on day 17 to determine the effect of GP on acetate clearance. Blood samples were collected on day 19 and were analyzed for serum concentrations of glucose, urea N (SUN), non-esterified fatty acids, and amino acids. Rumen fluid was collected on day 21 to determine supplementation effects on ruminal volatile fatty acid (VFA) and ammonia concentrations. Wethers receiving BF and COMBO supplementation had greatest ( P ≤ 0.01) DM and OM total tract digestibility. Supplementation did not affect ( P ≥ 0.37) NDF digestibility or digestible energy. Urinary nitrogen excretion was greatest ( P = 0.02) for BF and COMBO. Circulating serum essential amino acid concentration was increased ( P < 0.01) in BF and COMBO compared to CAP and CON. In addition, BF and COMBO had increased ( P < 0.01) SUN concentrations compared to CAP and CON. Acetate half-life was not affected ( P = 0.39) by supplementation strategy. However, area under the curve (AUC) for acetate was decreased ( P = 0.04) with supplementation of BF and COMBO compared to CON-fed wethers. Ruminal propionate concentration was increased ( P ≤ 0.01) for wethers fed CAP and COMBO supplementation, which resulted in decreased ( P ≤ 0.01) A:P ratio. Overall, these results indicate that the increased propionate supply by providing propionate salts did not result in a protein sparing impact or increased N retention., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

On-site sewage treatment systems can be an important source of antibiotic resistant bacteria and organic micropollutants into adjacent groundwater. Due to the frequent proximity of private wells to septic systems, this contamination is a concern to communities that do not have access to public municipal services. In both rural and urban environments, low-income communities, indigenous communities and those of color are disproportionately affected by well contamination. The objective of this study was to assess well water quality in an underserved North Carolina community by performing a comprehensive evaluation of microbial and organic micropollutant occurrence and determining possible sources of contamination. Well water, septic tanks, and adjacent municipal water were sampled. Culture- and molecular biology-based microbial analysis and non-targeted, high resolution mass spectrometry chemical analysis were conducted to assess water quality in comparison to nearby municipal water. Three of thirteen homes had between 1 and 6.3 CFUs/100 mL of E. coli and two homes had fecal bacteria resistant to antibiotics in their well water. The water of four homes showed concentrations of the artificial sweetener sucralose, a wastewater tracer, higher than the municipal water (range ~ 60-1500 ng L -1 ). The human-specific HF183 fecal marker was detected in 79% of the wells tested. The presence of pharmaceuticals and personal care products in four home wells, along with the presence of pesticides and insecticides in two homes, suggest possible contamination from septic tanks and lawn care runoff. The implications of this work highlight the necessity of wider scale contaminant evaluation of well water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Medium-ring (7-9-membered) benzo-fused N-heterocycles - a core structure in several important pharmaceuticals - have a diverse range of interesting conformational and stereochemical properties which arise from restricted bond rotation in the non-aromatic ring. The atropisomers of these pharmaceutically relevant N-heterocycles typically exhibit different biological activities, warranting the need to deeply understand the factors controlling the conformation and stereochemistry of the systems. Beginning with a brief introduction to atropisomer classification, this review will detail a number of medium-ring benzo-fused N-heterocycle systems from the recent literature to provide an overview of structural factors which can affect the atropisomeric nature of the systems by altering the overall conformation and rate of stereo-inversion. As well as general factors such as ring-size and sterics, the impact of additional stereocentres in these systems will be addressed. This includes the differences between sulfur, nitrogen and carbon stereocentres, and the consequences of stereocentre placement around the N-heterocycle ring. Further, conformational stabilisation via non-covalent intramolecular bonds will be explored. As such, this review represents a significant resource for aiding in the design, synthesis and study of new and potentially bioactive medium-ring benzo-fused N-heterocycles.

Objective: To determine the variability in pediatric death by neurologic criteria (DNC) protocols between US pediatric institutions and compared to the 2011 DNC guidelines., Methods: In this cross-sectional study of DNC protocols obtained from pediatric institutions in the United States via regional organ procurement organizations, protocols were evaluated across 5 domains: general DNC procedures, prerequisites, neurologic examination, apnea testing, and ancillary testing. Descriptive statistics compared protocols to each other and the 2011 guidelines., Results: A total of 130 protocols were analyzed with 118 dated after publication of the 2011 guidelines. Of those 118 protocols, identification of a mechanism of irreversible brain injury was required in 97%, while 67% required an observation period after acute brain injury before DNC evaluation. Most protocols required guideline-based prerequisites such as exclusion of hypotension (94%), hypothermia (97%), and metabolic derangements (92%). On neurologic examination, 91% required a lack of responsiveness, 93% no response to noxious stimuli, and 99% loss of brainstem reflexes. A total of 84% of protocols required the guideline-recommended 2 apnea tests. CO 2 targets were consistent with guidelines in 64%. Contrary to guidelines, 15% required ancillary testing for all patients and 15% permitted ancillary studies that are not validated in pediatrics., Conclusion: Variability exists between pediatric institutional DNC protocols in all domains of DNC determination, especially with respect to apnea and ancillary testing. Better alignment of DNC protocols with national guidelines may improve the consistency and accuracy of DNC determination., (© 2021 American Academy of Neurology.)

Per- and polyfluoroalkyl substances (PFAS) are emerging contaminants that pose significant challenges in mechanistic fate and transport modeling due to their diverse and complex chemical characteristics. Machine learning provides a novel approach for predicting the spatial distribution of PFAS in the environment. We used spatial location information to link PFAS measurements from 1207 private drinking water wells around a fluorochemical manufacturing facility to a mechanistic model of PFAS air deposition and to publicly available data on soil, land use, topography, weather, and proximity to multiple PFAS sources. We used the resulting linked data set to train a Bayesian network model to predict the risk that GenX, a member of the PFAS class, would exceed a state provisional health goal (140 ng/L) in private well water. The model had high accuracy (ROC curve index for five-fold cross-validation of 0.85, 90% CI 0.84-0.87). Among factors significantly associated with GenX risk in private wells, the most important was the historic rate of atmospheric deposition of GenX from the fluorochemical manufacturing facility. The model output was used to generate spatial risk predictions for the study area to aid in risk assessment, environmental investigations, and targeted public health interventions., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

This study characterizes potential soil lead (Pb) exposure risk at the household scale in Greensboro, North Carolina, using an innovative combination of field sampling, statistical analysis, and machine-learning techniques. Soil samples were collected at the dripline, yard, and street side at 462 households (total sample size = 2310). Samples were analyzed for Pb and then combined with publicly available data on potential historic Pb sources, soil properties, and household and neighborhood demographic characteristics. This curated data set was then analyzed with statistical and machine-learning techniques to identify the drivers of potential soil Pb exposure risks and to build predictive models. Among all samples, 43% exceeded current guidelines for Pb in residential gardens. There were significant racial disparities in potential soil Pb exposure risk; soil Pb at the dripline increased by 19% for every 25% increase in the neighborhood population identifying as Black. A machine-learned Bayesian network model was able to classify residential parcels by risk of exceeding residential gardening standards with excellent reproducibility in cross validation. These findings underscore the need for targeted outreach programs to prevent Pb exposure in residential areas and demonstrate an approach for prioritizing outreach locations.

The World Health Organization has declared antibiotic resistance "one of the biggest threats to global health." Mounting evidence suggests that antibiotic use in industrial-scale hog farming is contributing to the spread of antibiotic-resistant Staphylococcus aureus. To capture available evidence on these risks, we searched peer-reviewed studies published before June 2017 and conducted a meta-analysis of these studies' estimates of the prevalence of swine-associated, antibiotic-resistant S. aureus in animals, humans, and the environment. The 166 relevant studies revealed consistent evidence of livestock-associated methicillin-resistant S. aureus (MRSA) in hog herds (55.3%) raised with antibiotics. MRSA prevalence was also substantial in slaughterhouse pigs (30.4%), industrial hog operation workers (24.4%), and veterinarians (16.8%). The prevalence of swine-associated, multidrug-resistant S. aureus (MDRSA)-with resistance to three or more antibiotics-is not as well documented. Nonetheless, sufficient studies were available to estimate MDRSA pooled prevalence in conventional hog operation workers (15.0%), workers' household members (13.0%), and community members (5.37%). Evidence also suggests that antibiotic-resistant S. aureus can be present in air, soil, water, and household surface samples gathered in or near high-intensity hog operations. An important caveat is that prevalence estimates for humans reflect colonization, not active infection, and the health risks of colonization remain poorly understood. In addition, these pooled results may not represent risks in specific locations, due to wide geographic variation. Nonetheless, these results underscore the need for additional preventive action to stem the spread of antibiotic-resistant pathogens from livestock operations and a streamlined reporting system to track this risk., (© 2020 Society for Risk Analysis.)

Although the Flint, Michigan, water crisis renewed concerns about lead (Pb) in city drinking water, little attention has been paid to Pb in private wells, which provide drinking water for 13% of the US population. This study evaluates the risk of Pb exposure in children in households relying on private wells. It is based on a curated dataset of blood Pb records from 59,483 North Carolina children matched with household water source information. We analyze the dataset for statistical associations between children's blood Pb and household drinking water source. The analysis shows that children in homes relying on private wells have 25% increased odds (95% CI 6.2 to 48%, P < 0.01) of elevated blood Pb, compared with children in houses served by a community water system that is regulated under the Safe Drinking Water Act. This increased Pb exposure is likely a result of corrosion of household plumbing and well components, because homes relying on private wells rarely treat their water to prevent corrosion. In contrast, corrosion control is required in regulated community water systems. These findings highlight the need for targeted outreach to prevent Pb exposure for the 42.5 million Americans depending on private wells for their drinking water., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions., Methods: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437., Findings: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts., Interpretation: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer., Funding: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac., (© 2020 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Eighteenth-century events, replete with Dickensian dualities, brought two Enlightenment families to America. Pierre-Samuel du Pont and Joseph Priestley contemplated relocating their families decades before immigrating. After arriving, they discovered deficiencies in education and chemistry. Their experiences were indicative of the challenges in transmitting transatlantic chemistry. The Priestleys were primed to found an American chemical legacy. Science connected Priestley to British manufacturers, Continental chemists, and American statesmen. Priestley's marriage into the Wilkinson ironmaster dynasty, and Lunar Society membership, helped his sons apprentice, and befriend manufacturer-chemist Thomas Cooper. However, ideological persecution forced them from England. Priestley's plans for his sons to inherit Wilkinson's ironworks evaporated; in America, efforts to establish manufactories, colonies, farms, and a college miscarried. Cooper taught college chemistry, but his materialism provoked dismissals. The Du Ponts were unlikely founders of an industrial-chemistry empire. Du Pont's philosophy promulgated that agriculture, not industry, produced wealth. Eleuthère-Irénée apprenticed in France's gunpowder administration, however, plans for his succession died and director Antoine Lavoisier, a family friend, was executed. E.-I. and Du Pont's arrest precipitated relocation to America. Du Pont's utopian colony and schemes proved unrealistic. Nevertheless, E.-I.'s gunpowder manufactory-utilizing transatlantic contacts and privileged knowledge of advanced French chemistry-succeeded through practical application.

The 2013-2016 Ebola epidemic revived concerns about infection risks to wastewater workers. Prior research has shown that wastewater can contain a variety of known and emerging pathogens and that wastewater workers are at increased risk of infectious illnesses. However, guidelines on using personal protective equipment (PPE) to decrease these risks are lacking. We engaged 34 wastewater utility personnel and public health experts to conduct a job safety analysis identifying tasks in which workers could be exposed to pathogens and to develop a PPE selection matrix for preventing those exposures. We identified 43 relevant job tasks. Recommended PPE ranges from durable gloves (all tasks) to safety glasses (24 tasks), Tyvek suits or coveralls (4 tasks), and respiratory protection (N95 mask or face mask, depending on the activity, 10 tasks). The PPE selection matrix can serve as a guide for protecting the 120,000 wastewater workers in the United States from known and emerging pathogens. PRACTITIONER POINTS: Wastewater workers are at increased risk of infectious illnesses. Policies to protect wastewater workers from these illnesses are lacking. We developed guidelines for use of personal protective equipment by wastewater workers to prevent exposure to infectious agents., (© 2019 Water Environment Federation.)

Background: Imatinib mesylate (imatinib) is the first-line treatment for newly diagnosed chronic myeloid leukemia (CML) due to its remarkable hematologic and cytogenetic responses. We previously demonstrated that the imatinib-resistant CML cells (Myl-R) contained elevated Lyn activity and intracellular creatine pools compared to imatinib-sensitive Myl cells., Methods: Stable isotope metabolic labeling, media creatine depletion, and Na + /K + -ATPase inhibitor experiments were performed to investigate the origin of creatine pools in Myl-R cells. Inhibition and shRNA knockdown were performed to investigate the specific role of Lyn in regulating the Na + /K + -ATPase and creatine uptake., Results: Inhibition of the Na + /K + -ATPase pump (ouabain, digitoxin), depletion of extracellular creatine or inhibition of Lyn kinase (ponatinib, dasatinib), demonstrated that enhanced creatine accumulation in Myl-R cells was dependent on uptake from the growth media. Creatine uptake was independent of the Na + /creatine symporter (SLC6A8) expression or de novo synthesis. Western blot analyses showed that phosphorylation of the Na + /K + -ATPase on Tyr 10 (Y10), a known regulatory phosphorylation site, correlated with Lyn activity. Overexpression of Lyn in HEK293 cells increased Y10 phosphorylation (pY10) of the Na + /K + -ATPase, whereas Lyn inhibition or shRNA knockdown reduced Na + /K + -ATPase pY10 and decreased creatine accumulation in Myl-R cells. Consistent with enhanced uptake in Myl-R cells, cyclocreatine (Ccr), a cytotoxic creatine analog, caused significant loss of viability in Myl-R compared to Myl cells., Conclusions: These data suggest that Lyn can affect creatine uptake through Lyn-dependent phosphorylation and regulation of the Na + /K + -ATPase pump activity., General Significance: These studies identify kinase regulation of the Na + /K + -ATPase as pivotal in regulating creatine uptake and energy metabolism in cells., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Drinking water is a lingering hazard in the effort to eliminate childhood exposure to lead (Pb), a neurotoxin that affects cognitive and behavioral development. This study characterized Pb in municipal drinking water at North Carolina, US, childcare centers. The study also demonstrates a scalable, citizen science-based drinking water testing strategy for Pb at childcare centers., Methods: Licensed childcare centers in four North Carolina counties were recruited. One administrator per center completed a survey and was trained to collect first-draw drinking water samples in their center. Samples were shipped with pre-paid labels for laboratory analysis using inductively coupled plasma mass spectrometry. Multilevel logistic regression and Bayesian network analysis were used to identify factors associated with a risk of exceeding the 1 μg/L American Academy of Pediatrics reference level and the US Environmental Protection Agency (US EPA) 15 μg/L treatment-based action level. Results were provided to centers along with risk mitigation recommendations., Results: Of 103 enrolled centers, 86 completed the study, submitting 1,266 drinking water samples in total. Approximately 77% of drinking water samples contained detectable Pb (≥0.1 μg/L), and 97% of centers had at least one drinking water sample with detectable Pb. More than 63% of centers had at least one drinking water sample with >1 μg/L Pb, and 17% of centers had at least one drinking water sample with Pb above 15 μg/L. There was high variability in Pb concentrations at water points within the same center., Discussion: This study demonstrated a high prevalence and variability of Pb in first-draw samples of drinking water at childcare centers in North Carolina, US. Results underscore the importance of testing for Pb at every tap used for drinking and cooking in childcare centers. The use of employees as citizen scientists is a feasible strategy to identify Pb in specific drinking water taps., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)