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Abstract Single crystal paleointensity (SCP) reveals that the Moon lacked a long-lived core dynamo, though mysteries remain. An episodic dynamo, seemingly recorded by some Apollo basalts, is temporally and energetically problematic. We evaluate this enigma through study of ~3.7 billion-year-old (Ga) Apollo basalts 70035 and 75035. Whole rock analyses show unrealistically high nominal magnetizations, whereas SCP indicate null fields, illustrating that the former do not record an episodic dynamo. However, deep crustal magnetic anomalies might record an early lunar dynamo. SCP studies of 3.97 Ga Apollo breccia 61016 and 4.36 Ga ferroan anorthosite 60025 also yield null values, constraining any core dynamo to the Moon’s first 140 million years. These findings suggest that traces of Earth’s Hadean atmosphere, transferred to the Moon lacking a magnetosphere, could be trapped in the buried lunar regolith, presenting an exceptional target for future exploration.

Abstract The time from conception through the first year of life is the most dynamic period in human development. This time period is particularly important for infants born very preterm (

Abstract Background Childhood traumatic experiences may result in post-traumatic stress disorder. Although pediatricians are encouraged to address these traumas in clinical encounters, measures of childhood traumatic stress have not been adopted by primary care clinicians. In this study, we describe the feasibility and potential utility of the UCLA Brief Screen, a validated screener for childhood traumatic stress symptoms, in pediatric primary care clinics. Methods Children 6–17 years of age presenting for routine well-child care in community-based pediatric clinics were eligible for traumatic stress screening. We described the feasibility and acceptability of screening based on screener adoption by eligible pediatric clinicians. We assessed the potential utility of screening based on prevalence and distribution of potentially traumatic events and traumatic stress symptoms in this general pediatric population. Finally, we compared results of the UCLA Brief Screen with those of the Patient Health Questionnaire-A to evaluate associations between symptoms of traumatic stress, depression, and suicidality among adolescents in this community setting. Results 14/18 (77.8%) pediatric clinicians in two clinics offered an adapted UCLA Brief Screen during 2359/4959 (47.6%) eligible well-child checks over 14 months. 1472/2359 (62.4%) of offered screeners were completed, returned, and scored. One-third (32.5%) of completed screeners captured a potentially traumatic event experience described by either children or caregivers. Moderate to severe traumatic stress symptoms were identified in 10.7% and 5.2% of patients, respectively. Concurrent depression screening revealed that 68.3% of adolescents with depressive symptoms reported a potentially traumatic event (PTE) and 80.5% had concurrent traumatic stress symptoms. Adolescents reporting a PTE were 3.5 times more likely to report thoughts of suicide or self-harm than those without this history. Conclusions Results from this pilot study suggest that traumatic stress screening in the pediatric primary care setting may be feasible and may identify and classify mental health symptoms missed with current screening practices for depression. The prevalence of PTEs and traumatic stress symptoms associated with PTEs support the potential utility of a standardized screening in early identification of and response to children with clinically important symptoms of childhood traumatic stress. Future research should evaluate meaningful clinical outcomes associated with traumatic stress screening.

Abstract Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age. DNA methylation was measured from buccal swabs collected at NICU discharge using the Illumina MethylationEPIC Bead Array. Attention problems were assessed at 2 years of adjusted age using the attention problems subscale of the Child Behavior Checklist (CBCL). After adjustment for multiple testing, DNA methylation at 33 CpG sites was associated with child attention problems. Differentially methylated CpG sites were located in genes previously linked to physical and mental health, including several genes associated with ADHD in prior epigenome-wide and genome-wide association studies. Several CpG sites were located in genes previously linked to exposure to prenatal risk factors in the NOVI sample. Neonatal epigenetics measured at NICU discharge could be useful in identifying preterm children at risk for long-term attention problems and related psychiatric disorders, who could benefit from early prevention and intervention efforts.

Abstract Platelets, small hemostatic blood cells, are derived from megakaryocytes. Both bone marrow and lung are principal sites of thrombopoiesis although underlying mechanisms remain unclear. Outside the body, however, our ability to generate large number of functional platelets is poor. Here we show that perfusion of megakaryocytes ex vivo through the mouse lung vasculature generates substantial platelet numbers, up to 3000 per megakaryocyte. Despite their large size, megakaryocytes are able repeatedly to passage through the lung vasculature, leading to enucleation and subsequent platelet generation intravascularly. Using ex vivo lung and an in vitro microfluidic chamber we determine how oxygenation, ventilation, healthy pulmonary endothelium and the microvascular structure support thrombopoiesis. We also show a critical role for the actin regulator Tropomyosin 4 in the final steps of platelet formation in lung vasculature. This work reveals the mechanisms of thrombopoiesis in lung vasculature and informs approaches to large-scale generation of platelets.

ABSTRACTEpigenetic age acceleration is a risk factor for chronic diseases of ageing and may reflect aspects of biological ageing. However, few studies have examined epigenetic ageing during the early neonatal period in preterm infants, who are at heightened risk of developmental problems. We examined relationships between neonatal age acceleration, neonatal morbidities, and neurobehavioral domains among very preterm (

This perspective paper seeks to lay out an efficient approach for health care providers, researchers, and other stakeholders involved in interventions aimed at improving care coordination to partner in locating and using applicable care coordination theory. The objective is to learn from relevant theory-based literature about fit between intervention options and coordination needs, thereby bringing insights from theory to enhance intervention design, implementation, and troubleshooting. To take this idea from an abstract notion to tangible application, our workgroup on models and measures from the Veterans Health Administration (VA) State of the Art (SOTA) conference on care coordination first summarizes our distillation of care coordination theoretical frameworks (models) into three common conceptual domains-context of an intervention, locus in which an intervention is applied, and specific design features of the intervention. Then we apply these three conceptual domains to four cases of care coordination interventions ("use cases") chosen to represent various scopes and stages of interventions to improve care coordination for veterans. Taken together, these examples make theory more accessible and practical by demonstrating how it can be applied to specific cases. Drawing from theory offers one method to anticipate which intervention options match a particular coordination situation.

Objective: To examine changes in hospitalization trends and healthcare utilization among Veterans following Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act implementation. Data Sources and Study Setting: VA Corporate Data Warehouse and Centers for Medicare and Medicaid Services datasets. Study Design: Retrospective cohort study to compare 7‐ and 30‐day rates for unplanned readmission and emergency department visits following index hospital stays based on payor type (VHA facility stay, VA‐funded stay in community facility [CC], or Medicare‐funded community stay [CMS]). Segmented regression models were used to compare payors and estimate changes in outcome levels and slopes following MISSION Act implementation. Data Collection/Extraction Methods: Veterans with active VA primary care utilization and ≥1 acute hospitalization between January 1, 2016 and December 31, 2021. Principal Findings: Monthly index stays increased for all payors until MISSION Act implementation, when VHA and CMS admissions declined while CC admissions accelerated and overtook VHA admissions. In December 2021, CC admissions accounted for 54% of index admissions, up from 25% in January 2016. From adjusted models, just prior to implementation (May 2019), Veterans with CC admissions had 47% greater risk of 7‐day readmission (risk ratio [RR]: 1.47, 95% confidence interval [CI]: 1.43, 1.51) and 20% greater risk of 30‐day readmission (RR: 1.20, 95% CI: 1.19, 1.22) compared with those with VHA admissions; both effects persisted post‐implementation. Pre‐implementation CC admissions were also associated with higher 7‐ and 30‐day ED visits, but both risks were substantially lower by study termination (RR: 0.90, 95% CI: 0.88, 0.91) and (RR: 0.89, 95% CI: 0.87, 0.90), respectively. Conclusions: MISSION Act implementation was associated with substantial shifts in treatment site and federal payor for Veteran hospitalizations. Post‐implementation readmission risk was estimated to be higher for those with CC and CMS index admissions, while post‐implementation risk of ED utilization following CC admissions was estimated to be lower compared with VHA index admissions. Reasons for this divergence require further investigation. [ABSTRACT FROM AUTHOR]

Background Non-invasive biomarkers of immune checkpoint inhibitor-associated acute tubulointerstitial nephritis (ICI-nephritis) are urgently needed. Because ICIs block immune checkpoint pathways that include cytotoxic T lymphocyte antigen 4 (CTLA4), we hypothesized that biomarkers of immune dysregulationpreviously defined in patients with congenital CTLA4 deficiency, including elevated soluble interleukin-2 receptor alpha (sIL-2R) and flow cytometric cell-based markers of B and T cell dysregulation in peripheral blood may aid the diagnosis of ICI-nephritis.Methods A retrospective cohort of patients diagnosed with ICI-nephritis was compared with three prospectively enrolled control cohorts: ICI-treated controls without immune-related adverse events, patients not on ICIs with hemodynamic acute kidney injury (hemodynamic AKI), and patients not on ICIs with biopsy proven acute interstitial nephritis from other causes (non-ICI-nephritis). sIL-2R level and flow cytometric parameters were compared between groups using Wilcoxon rank sum test or Kruskal-Wallis test. Receiver operating characteristic curves were generated to define the accuracy of sIL-2R and flow cytometric biomarkers in diagnosing ICI-nephritis. The downstream impact of T cell activation in the affected kidney was investigated using archived biopsy samples to evaluate the gene expression of IL2RA, IL-2 signaling, and T cell receptor signaling in patients with ICI-nephritis compared with other causes of drug-induced nephritis, acute tubular injury, and histologically normal controls.Results sIL-2R level in peripheral blood was significantly higher in patients with ICI-nephritis (N=24) (median 2.5-fold upper limit of normal (ULN), IQR 1.9–3.3), compared with ICI-treated controls (N=10) (median 0.8-fold ULN, IQR 0.5–0.9, p96%) when compared with either ICI-treated or hemodynamic AKI controls. By peripheral blood flow cytometry analysis, lower absolute CD8+T cells, CD45RA+CD8+ T cells, memory CD27+B cells, and expansion of plasmablasts were prominent features of ICI-nephritis compared with ICI-treated controls. Gene expressions for IL2RA, IL-2 signaling, and T cell receptor signaling in the kidney tissue with ICI-nephritis were significantly higher compared with controls.Conclusion Elevated sIL-2R level and flow cytometric markers of both B and T cell dysregulation may aid the diagnosis of ICI-nephritis.

Reliable estimates of population density and size are crucial to wildlife conservation, particularly in the context of the Endangered Species Act. In the United States, ocelots (Leopardus pardalis pardalis) were listed as endangered in 1982, and to date, only one population density estimate has been reported in Texas. In this study, we integrated vegetation metrics derived from LiDAR and spatial capture-recapture models to discern factors of ocelot encounter rates and estimated localized population estimates on private ranchlands in coastal southern Texas. From September 2020 to May 2021, we conducted a camera trap study across 42 camera stations on the East Foundation’s El Sauz Ranch, which was positioned within a larger region of highly suitable woody and herbaceous cover for ocelots. We observed a high density of ocelots (17.6 ocelots/100 km2) and a population size of 36.3 ocelots (95% CI: 26.1–58.6) with the 206.25 km2 state space area of habitat. The encounter probability of ocelots increased with greater canopy cover at 1-2 m height and decreasing proximity to woody cover. These results suggest that the incorporation of LiDAR-derived vegetative canopy metrics allowed us to understand where ocelots are likely to be detected, which may aid in current and future population monitoring efforts. These population estimates reflect the first spatially explicit and most recent estimates in a portion of the northernmost population of ocelots in southern Texas. This study further demonstrates the importance of private working lands for the recovery of ocelots in Texas.

Abstract Background Cardiovascular (CV) disease is the leading cause of death among United States women. Rural residence and ethnic-minority status are individually associated with increased CV mortality. Managing dyslipidemia is important in the prevention of CV mortality. However, the impact of race/ethnicity and location of residence on sex differences in dyslipidemia management is not well understood. Therefore, we sought to understand the joint effects of race/ethnicity and location of residence on lipid management differences between veteran men and women with type 2 diabetes (T2D). Methods Veterans Health Administration and Centers for Medicare and Medicaid Services data were used to perform a longitudinal cohort study of veterans with T2D (2007–2016). Mixed effects logistic regression with a random intercept was used to model the association between sex and low-density lipoprotein (LDL) > 100 mg/dL and its interaction with race/ethnicity and location of residence after adjusting for all measured covariates. Results When female sex and rural location of residence were both present, they were associated with an antagonistic harmful effect on LDL. Similar antagonistic harmful effects on LDL were observed when the joint effect of female sex and several minority race/ethnicity groups were evaluated. After adjusting for measured covariates, the odds of LDL > 100 mg/dL were higher for urban women (OR = 2.66, 95%CI 2.48–2.85) and rural women (OR = 3.26, 95%CI 2.94–3.62), compared to urban men. The odds of LDL > 100 mg/dL was the highest among non-Hispanic Black (NHB) women (OR = 5.38, 95%CI 4.45–6.51) followed by non-Hispanic White (NHW) women (OR = 2.59, 95%CI 2.44–2.77), and Hispanic women (OR = 2.56, 95%CI 1.79–3.66). Conclusion Antagonistic harmful effects on LDL were observed when both female sex and rural location of residence were present. These antagonistic effects on LDL were also present when evaluating the joint effect of female sex and several minority race/ethnicity groups. Disparities were most pronounced in NHB and rural women, who had 5.4 and 3.3 times the odds of elevated LDL versus NHW and urban men after adjusting for important covariates. These striking effect sizes in a population at high cardiovascular risk (i.e., older with T2D) suggest interventions aimed at improving lipid management are needed for individuals falling into one or more groups known to face health disparities.

Dynamical model skill in forecasting extratropical precipitation is limited beyond the medium-range (around 15 d), but such models are often more skilful at predicting atmospheric variables. We explore the potential benefits of using weather pattern (WP) predictions as an intermediary step in forecasting UK precipitation and meteorological drought on sub-seasonal timescales. Mean sea-level pressure forecasts from the European Centre for Medium-Range Weather Forecasts ensemble prediction system (ECMWF-EPS) are post-processed into probabilistic WP predictions. Then we derive precipitation estimates and dichotomous drought event probabilities by sampling from the conditional distributions of precipitation given the WPs. We compare this model to the direct precipitation and drought forecasts from the ECMWF-EPS and to a baseline Markov chain WP method. A perfect-prognosis model is also tested to illustrate the potential of WPs in forecasting. Using a range of skill diagnostics, we find that the Markov model is the least skilful, while the dynamical WP model and direct precipitation forecasts have similar accuracy independent of lead time and season. However, drought forecasts are more reliable for the dynamical WP model. Forecast skill scores are generally modest (rarely above 0.4), although those for the perfect-prognosis model highlight the potential predictability of precipitation and drought using WPs, with certain situations yielding skill scores of almost 0.8 and drought event hit and false alarm rates of 70 % and 30 %, respectively.

Neonatal encephalopathy (NE) accounts for ~23% of the 2.4 million annual global neonatal deaths. Approximately 99% of global neonatal deaths occur in low-resource settings, however, accurate data from these low-resource settings are scarce. We reviewed risk factors of neonatal mortality in neonates admitted with neonatal encephalopathy from a tertiary neonatal unit in Zimbabwe. A retrospective review of risk factors of short-term neonatal encephalopathy mortality was conducted at Sally Mugabe Central Hospital (SMCH) (November 2018 -October 2019). Data were gathered using a tablet-based data capture and quality improvement newborn care application (Neotree). Analyses were performed on data from all admitted neonates with a diagnosis of neonatal encephalopathy, incorporating maternal, intrapartum, and neonatal risk predictors of the primary outcome: mortality. 494/2894 neonates had neonatal encephalopathy on admission and were included. Of these, 94 died giving a neonatal encephalopathy-case fatality rate (CFR) of 190 per 1000 admitted neonates. Caesarean section (odds ratio (OR) 2.95(95% confidence interval (CI) 1.39-6.25), convulsions (OR 7.13 (1.41-36.1)), lethargy (OR 3.13 (1.24-7.91)), Thompson score "11-14" (OR 2.98 (1.08-8.22)) or "15-22" (OR 17.61 (1.74-178.0)) were significantly associated with neonatal death. No maternal risk factors were associated with mortality. Nearly 1 in 5 neonates diagnosed with neonatal encephalopathy died before discharge, similar to other low-resource settings but more than in typical high-resource centres. The Thompson score, a validated, sensitive and specific tool for diagnosing neonates with neonatal encephalopathy was an appropriate predictive clinical scoring system to identify at risk neonates in this setting. On univariable analysis time-period, specifically a period of staff shortages due to industrial action, had a significant impact on neonatal encephalopathy mortality. Emergency caesarean section was associated with increased mortality, suggesting perinatal care is likely to be a key moment for future interventions.

The purpose of this study was to investigate the perceptions of both industry professionals and faculty members of technology-based programs concerning the preparedness of recent graduates as they began a quality related position. To gain this information, surveys were administered among managers and technical leaders in industry and compared with surveys of faculty members from four-year industrial technology and engineering technology programs. Recent graduates were evaluated with regard to both theoretical knowledge and applied skills. By analyzing survey results, recent literature, and in-depth conversations with industry professionals, recommendations are made for improving quality control curricula and better serving industry needs. (Contains 3 figures and 1 table.)

In low-lying coastal regions, flooding arises from oceanographic (storm surges plus tides and/or waves), fluvial (increased river discharge), and/or pluvial (direct surface run-off) sources. The adverse consequences of a flood can be disproportionately large when these different sources occur concurrently or in close succession, a phenomenon that is known as “compound flooding”. In this paper, we assess the potential for compound flooding arising from the joint occurrence of high storm surge and high river discharge around the coast of the UK. We hypothesise that there will be spatial variation in compound flood frequency, with some coastal regions experiencing a greater dependency between the two flooding sources than others. We map the dependence between high skew surges and high river discharge, considering 326 river stations linked to 33 tide gauge sites. We find that the joint occurrence of high skew surges and high river discharge occurs more frequently during the study period (15–50 years) at sites on the south-western and western coasts of the UK (between three and six joint events per decade) compared to sites along the eastern coast (between zero and one joint events per decade). Second, we investigate the meteorological conditions that drive compound and non-compound events across the UK. We show, for the first time, that spatial variability in the dependence and number of joint occurrences of high skew surges and high river discharge is driven by meteorological differences in storm characteristics. On the western coast of the UK, the storms that generate high skew surges and high river discharge are typically similar in characteristics and track across the UK on comparable pathways. In contrast, on the eastern coast, the storms that typically generate high skew surges are mostly distinct from the types of storms that tend to generate high river discharge. Third, we briefly examine how the phase and strength of dependence between high skew surge and high river discharge is influenced by the characteristics (i.e. flashiness, size, and elevation gradient) of the corresponding river catchments. We find that high skew surges tend to occur more frequently with high river discharge at catchments with a lower base flow index, smaller catchment area, and steeper elevation gradient. In catchments with a high base flow index, large catchment area, and shallow elevation gradient, the peak river flow tends to occur several days after the high skew surge. The previous lack of consideration of compound flooding means that flood risk has likely been underestimated around UK coasts, particularly along the south-western and western coasts. It is crucial that this be addressed in future assessments of flood risk and flood management approaches.

A unified model for the formation of martian rock types is required to understand Mars’s formation and evolution. Here the authors show that nakhlite and chassignite meteorites originate from melting of metasomatized depleted mantle lithosphere, whereas shergottite melts originate from deep plume sources.

There are 2. 4 million annual neonatal deaths worldwide. Simple, evidence-based interventions such as temperature control could prevent approximately two-thirds of these deaths. However, key problems in implementing these interventions are a lack of newborn-trained healthcare workers and a lack of data collection systems. NeoTree is a digital platform aiming to improve newborn care in low-resource settings through real-time data capture and feedback alongside education and data linkage. This project demonstrates proof of concept of the NeoTree as a real-time data capture tool replacing handwritten clinical paper notes over a 9-month period in a tertiary neonatal unit at Harare Central Hospital, Zimbabwe. We aimed to deliver robust data for monthly mortality and morbidity meetings and to improve turnaround time for blood culture results among other quality improvement indicators. There were 3222 admissions and discharges entered using the NeoTree software with 41 junior doctors and 9 laboratory staff trained over the 9-month period. The NeoTree app was fully integrated into the department for all admission and discharge documentation and the monthly presentations became routine, informing local practice. An essential factor for this success was local buy-in and ownership at each stage of the project development, as was monthly data analysis and presentations allowing us to rapidly troubleshoot emerging issues. However, the laboratory arm of the project was negatively affected by nationwide economic upheaval. Our successes and challenges piloting this digital tool have provided key insights for effective future roll-out in Zimbabwe and other low-income healthcare settings.