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We report the magnitude of the induced magnetic moment in CVD-grown epitaxial and rotated-domain graphene in proximity with a ferromagnetic Ni film, using polarized neutron reflectivity (PNR) and X-ray magnetic circular dichroism (XMCD). The XMCD spectra at the C K-edge confirms the presence of a magnetic signal in the graphene layer and the sum rules give a magnetic moment of up to $\sim\,0.47\,\mu$_B/C atom induced in the graphene layer. For a more precise estimation, we conducted PNR measurements. The PNR results indicate an induced magnetic moment of $\sim$ 0.53 $\mu$_B/C atom at 10 K for rotated graphene and $\sim$ 0.38 $\mu$_B/C atom at 10 K for epitaxial graphene. Additional PNR measurements on graphene grown on a non-magnetic Ni_9Mo_1 substrate, where no magnetic moment in graphene is measured, suggest that the origin of the induced magnetic moment is due to the opening of the graphene's Dirac cone as a result of the strong C pz-3d hybridization., Comment: 21 pages, 7 figures

The kidney has an extraordinary ability to maintain glomerular filtration despite natural fluctuations in blood pressure and nephron loss. This is partly due to local coordination between single-nephron filtration and vascular perfusion. An improved understanding of the three-dimensional (3-D) functional coordination between nephrons and the vasculature may provide a new perspective of the heterogeneity of kidney function and could inform targeted therapies and timed interventions to slow or prevent the progression of kidney disease. Here, we developed magnetic resonance imaging (MRI) tools to visualize single-nephron function in 3-D throughout the isolated perfused rat kidney. We used an intravenous slow perfusion of a glomerulus-targeted imaging tracer [cationized ferritin (CF)] to map macromolecular dynamics and to identify glomeruli in 3-D, followed by a bolus of a freely filtered tracer (gadolinium diethylenetriamine penta-acetic acid) to map filtration kinetics. There was a wide intrakidney distribution of CF binding rates and estimated single-nephron glomerular filtration rate (eSNGFR) between nephrons. eSNGFR and CF uptake rates did not vary significantly by distance from the kidney surface. eSNGFR varied from ∼10 to ∼100 nL/min throughout the kidney. Whole single-kidney GFR was similar across all kidneys, despite differences in the distributions eSNGFR of and glomerular number, indicating a robust adaptive regulation of individual nephrons to maintain constant single-kidney GFR in the presence of a natural variation in nephron number. This work provides a framework for future studies of single-nephron function in the whole isolated perfused kidney and experiments of single-nephron function in vivo using MRI.

BACKGROUND AND OBJECTIVES: The current threshold used for oliguria in the definition of neonatal AKI has been empirically defined as 1 ml/kg per hour. Urine output criteria are generally poorly documented, resulting in uncertainty in the most accurate threshold to identify AKI in very preterm infants with known tubular immaturity. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a bicentric study including 473 very preterm infants (24(0/7)–29(6/7) weeks of gestation) born between January 2014 and December 2018 with urine output measurements every 3 hours during the first 7 days of life and two serum creatinine measurements during the first 10 days of life. AKI was defined using the neonatal Kidney Disease Improving Global Outcomes (KDIGO) definition. We tested whether higher urine output thresholds (1.5 or 2 ml/kg per hour) in modified AKI definitions may better discriminate neonatal mortality compared with the current definition. RESULTS: Early-onset AKI was developed by 101 of 473 (21%) very preterm infants. AKI was diagnosed on the basis of urine output criteria alone (no rise in creatinine) for 27 of 101 (27%) participants. Early-onset AKI was associated with higher risk of death before discharge (adjusted odds ratio, 3.9; 95% confidence interval, 1.9 to 7.8), and the AKI neonatal KDIGO score showed good discriminative performance for neonatal mortality, with an area under the receiver operating characteristic (ROC) curve of 0.68 (95% confidence interval, 0.61 to 0.75). Modified AKI definitions that included higher urine output thresholds showed significantly improved discriminative performance, with areas under the ROC curve of 0.73 (95% confidence interval, 0.66 to 0.80) for the 1.5-ml/kg per hour threshold and 0.75 (95% confidence interval, 0.68 to 0.81) for the 2-ml/kg per hour threshold. CONCLUSIONS: Early-onset AKI was diagnosed on the basis of urine output exclusively for a quarter of the cases. Furthermore, modified AKI definitions that included higher urine output improved the discriminative performance for predicting mortality.

Acute kidney injury (AKI), particularly of greater severity and longer duration, is associated with increased morbidity and mortality in the pediatric population. AKI frequently occurs during sepsis, yet the knowledge of risk factors for sepsis-associated AKI in the PICU is limited. We aimed to identify risk factors for AKI that develops or persists after 72 hours from sepsis recognition in pediatric patients with severe sepsis.Retrospective cohort study.PICU at an academic, tertiary-care center.Children greater than 1 month and less than or equal to 18 years with severe sepsis in the combined cardiac and medical/surgical PICU between December 1, 2013, and December 31, 2020, at the University of Virginia Children's Hospital.None.The cohort included 124 patients with severe sepsis with 33 patients (27%) who were postcardiac surgery with cardiopulmonary bypass. AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The primary outcome was severe AKI, defined as KDIGO stage 2 or 3 AKI present at any point between days 3 and 7 after sepsis recognition. Severe AKI was present in 25 patients (20%). Factors independently associated with severe AKI were maximum vasoactive-inotropic score (VIS) within 48 hours after sepsis recognition and fluid overload. The presence of severe AKI was associated with increased inhospital mortality.In children with severe sepsis, the degree of hemodynamic support as measured by the VIS and the presence of fluid overload may identify patients at increased risk of developing severe AKI.

Progression of chronic liver diseases is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections, impact gut microbiome composition and metabolite production. Using a multi-omics approach on 850 fecal samples from 263 patients with acute or chronic liver disease, we demonstrate that patients hospitalized for liver disease have reduced microbiome diversity and a paucity of bioactive metabolites. We find that patients treated with the orally administered but non-absorbable disaccharide lactulose have increased densities of intestinalBifidobacteriaand reduced incidence of systemic infections and mortality.Bifidobacteriametabolize lactulose, produce high concentrations of acetate and acidify the gut lumen, which, in combination, can reduce the growth of antibiotic-resistant pathobionts such as Vancomycin-resistantEnterococcus faecium. Our studies suggest that lactulose andBifidobacteriaserve as a synbiotic to reduce rates of infection in patients with severe liver disease.

SummaryNonalcoholic fatty liver disease (NAFLD) is multifactorial in nature, affecting over a billion people worldwide. The gut microbiome has emerged as an associative factor in NAFLD, yet mechanistic contributions are unclear. Here, we show fast food (FF) diets containing high fat, added cholesterol, and fructose/glucose drinking water differentially impact short- vs. long-term NAFLD severity and progression in conventionally-raised, but not germ-free mice. Correlation and machine learning analyses independently demonstrate FF diets induce early and specific gut microbiota changes that are predictive of NAFLD indicators, with corresponding microbial community instability relative to control-fed mice. Shotgun metagenomics showed FF diets containing high cholesterol elevate fecal pro-inflammatory effectors over time, relating to a reshaping of host hepatic metabolic and inflammatory transcriptomes. FF diet-induced gut dysbiosis precedes onset and is highly predictive of NAFLD outcomes, providing potential insights into microbially-based pathogenesis and therapeutics.HighlightsGerm-free mice are protected from fast-food diet-induced NAFLD.Fast-food diets rapidly shift gut microbiota composition and function.Increasing dietary cholesterol exacerbates hepatic inflammation only in SPF mice.Fast-food diet-induced gut dysbiosis precedes and predicts late-stage NAFLD severity.

The Quite Intense Kinetics Reflectometer (QIKR) will be a general-purpose, horizontal-sample-surface neutron reflectometer. Reflectometers measure the proportion of an incident probe beam reflected from a surface as a function of wavevector (momentum) transfer to infer the distribution and composition of matter near an interface. The unique scattering properties of neutrons make this technique especially useful in the study of soft matter, biomaterials, and materials used in energy storage. Exploiting the increased brilliance of the Spallation Neutron Source Second Target Station, QIKR will collect specular and off-specular reflectivity data faster than the best existing such machines. It will often be possible to collect complete specular reflectivity curves using a single instrument setting, enabling "cinematic " operation, wherein the user turns on the instrument and "films " the sample. Samples in time-dependent environments (e.g., temperature, electrochemical, or undergoing chemical alteration) will be observed in real time, in favorable cases with frame rates as fast as 1 Hz. Cinematic data acquisition promises to make time-dependent measurements routine, with time resolution specified during post-experiment data analysis. This capability will be deployed to observe such processes as in situ polymer diffusion, battery electrode charge-discharge cycles, hysteresis loops, and membrane protein insertion into lipid layers. (c) 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). U.S. Department of Energy [DE-AC05-00OR22725]; U.S. Department of Energy's Office of Basic Energy Sciences, Division of Materials Science and Engineering Published version This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan). G.M.V. was supported by the U.S. Department of Energy's Office of Basic Energy Sciences, Division of Materials Science and Engineering.

Objective To determine the association of dysnatremia in the first postnatal week and risk of acute kidney injury (AKI) and mortality. Study design A secondary analysis of 1979 neonates in the AWAKEN cohort evaluated the association of dysnatremia with (1) AKI in the first postnatal week and (2) mortality, utilizing time-varying Cox proportional hazard models. Result Dysnatremia developed in 50.2% of the cohort and was not associated with AKI. Mortality was associated with hyponatremia (HR 2.15, 95% CI 1.07-4.31), hypernatremia (HR 4.23, 95% CI 2.07-8.65), and combined hypo/hypernatremia (HR 6.39, 95% CI 2.01-14.01). In stratified models by AKI-status, hypernatremia and hypo/hypernatremia increased risk of mortality in neonates without AKI. Conclusion Dysnatremia within the first postnatal week was associated with increased risk of mortality. Hypernatremia and combined hypo/hypernatremia remained significantly associated with mortality in neonates without AKI. This may reflect fluid strategies kidney injury independent of creatinine and urine-output defined AKI, and/or systemic inflammation.

Kidney pathologies are often highly heterogeneous. To comprehensively understand kidney structure and pathology, it is critical to develop tools to map tissue microstructure in the context of the whole, intact organ. Magnetic resonance imaging (MRI) can provide a unique, three-dimensional view of the kidney and allows for measurements of multiple pathological features. Here, we developed a platform to systematically render and map gross and microstructural features of the human kidney based on three-dimensional MRI. These features include pyramid number and morphology as well as the associated medulla and cortex. In a subset of these kidneys, we also mapped individual glomeruli and glomerular volumes using cationic ferritin-enhanced MRI to report intrarenal heterogeneity in glomerular density and size. Finally, we rendered and measured regions of nephron loss due to pathology and individual glomerular volumes in each pyramidal unit. This work provides new tools to comprehensively evaluate the kidney across scales, with potential applications in anatomic and physiological research, transplant allograft evaluation, biomarker development, biopsy guidance, and therapeutic monitoring. These image rendering and analysis tools could eventually impact the field of transplantation medicine to improve longevity matching of donor allografts and recipients and reduce discard rates through the direct assessment of donor kidneys. NEW & NOTEWORTHY We report the application of cutting-edge image analysis approaches to characterize the pyramidal geometry, glomerular microstructure, and heterogeneity of the whole human kidney imaged using MRI. This work establishes a framework to improve the detection of microstructural pathology to potentially facilitate disease monitoring or transplant evaluation in the individual kidney.

ImportanceIncreasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge.ObjectiveTo develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy.Evidence ReviewAt the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations.FindingsThe meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy.Conclusions and RelevanceExisting evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.

BACKGROUND: Increased understanding of characteristics of urinary tract infection (UTI) among very low birthweight infants (VLBW) might lead to improvement in detection and treatment. Continuous monitoring for abnormal heart rate characteristics (HRC) could provide early warning of UTIs. OBJECTIVE: Describe the characteristics of UTI, including HRC, in VLBW infants. METHODS: We reviewed records of VLBW infants admitted from 2005–2010 at two academic centers participating in a randomized clinical trial of HRC monitoring. Results of all urine cultures, renal ultrasounds (RUS), and voiding cystourethrograms (VCUG) were assessed. Change in the HRC index was analyzed before and after UTI. RESULTS: Of 823 VLBW infants (27.7±2.9 weeks GA, 53% male), 378 had > / = 1 urine culture obtained. A UTI (≥10,000 CFU and >five days of antibiotics) was diagnosed in 80 infants, (10% prevalence, mean GA 25.8±2.0 weeks, 76% male). Prophylactic antibiotics were administered to 29 (36%) infants after UTI, of whom four (14%) had another UTI. Recurrent UTI also occurred in 7/51 (14%) of infants not on uroprophylaxis after their first UTI. RUS was performed after UTI in 78%, and hydronephrosis and other major anomalies were found in 19%. A VCUG was performed in 48% of infants and 18% demonstrated vesicoureteral reflux (VUR). The mean HRC rose and fell significantly in the two days before and after diagnosis of UTI. CONCLUSIONS: UTI was diagnosed in 10% of VLBW infants, and the HRC index increased prior to diagnosis, suggesting that continuous HRC monitoring in the NICU might allow earlier diagnosis and treatment of UTI.

Living with type 1 diabetes and using continuous subcutaneous insulin infusion (CSII), the authors travelled together for four months through 11 countries. Travelling with type 1 diabetes presents various added challenges. Personal experience of the challenges faced by the authors in relation to their diabetes are discussed along with the ways they were able to overcome these challenges. A review of general aspects one may encounter when travelling with type 1 diabetes and CSII follows. This provides an insightful overview for individuals living with type 1 diabetes intending to travel as well as healthcare professionals involved in providing care to those with type 1 diabetes intending to travel.

Acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD). However, there are few tools to detect microstructural changes after AKI. Here, cationic ferritin-enhanced magnetic resonance imaging (CFE-MRI) was applied to examine the heterogeneity of kidney pathology in the transition from AKI to CKD. Adult male mice received folic acid followed by cationic ferritin and were euthanized at four days (AKI), four weeks (CKD-4) or 12 weeks (CKD-12). Kidneys were examined by histologic methods and CFE-MRI. In the CKD-4 and CKD-12 groups, glomerular number was reduced and atubular cortical lesions were observed. Apparent glomerular volume was larger in the AKI, CKD-4 and CKD-12 groups compared to controls. Glomerular hypertrophy occurred with ageing. Interglomerular distance and glomerular density were combined with other MRI metrics to distinguish the AKI and CKD groups from controls. Despite significant heterogeneity, the noninvasive (MRI-based) metrics were as accurate as invasive (histological) metrics at distinguishing AKI and CKD from controls. To assess the toxicity of cationic ferritin in a CKD model, CKD-4 mice received cationic ferritin and were examined one week later. The CKD-4 groups with and without cationic ferritin were similar, except the iron content of the kidney, liver, and spleen was greater in the CKD-4 plus cationic ferritin group. Thus, our study demonstrates the accuracy and safety of CFE-MRI to detect whole kidney pathology allowing for the development of novel biomarkers of kidney disease and providing a foundation for future in vivo longitudinal studies in mouse models of AKI and CKD to track nephron fate.

Working in academia for women of color is a labor of love. This essay chronicles five women who have been challenged by their roles as purveyors of social justice, equity and access for children, y...

Acute kidney injury (AKI) in premature neonates is common due to the administration of life-saving therapies. The impact of AKI on renal morphology and susceptibility to further renal damage is poorly understood. Recent advances in radiological imaging have allowed integration of soft tissue morphology in the intact organ, facilitating a more complete understanding of changes in tissue microstructure associated with pathology. Here, we applied magnetic resonance imaging (MRI) to detect both glomerular and vascular changes in a rabbit model of neonatal AKI, induced by indomethacin and gentamicin. Using combined spin-echo MRI and cationic ferritin enhanced gradient-echo MRI (CFE-MRI), we observed (a) an increased cortical arterial diameter in the AKI cohort compared to healthy controls, and (b) focal loss of vascular density and glomerular loss in a circumferential band ~1 mm from the cortical surface. This combined use of vascular and glomerular imaging may give insight into the etiology of AKI and its impact on renal health later in life.

As a result of preterm birth, immature kidneys are exposed to interventions in the NICU that promote survival, but are nephrotoxic. Furthermore, the duration of renal development may be truncated in these vulnerable neonates. Immaturity and nephrotoxic exposures predispose preterm newborns to acute kidney injury (AKI), particularly in the low birth weight and extremely preterm gestational age groups. Several studies have associated preterm birth as a risk factor for future chronic kidney disease (CKD). However, only a few publications have investigated the impact of neonatal AKI on CKD development. Here, we will review the evidence linking preterm birth and AKI in the NICU to CKD and highlight the knowledge gaps and opportunities for future research. For neonatal intensive care studies, we propose the inclusion of AKI as an important short-term morbidity outcome and CKD findings such as a reduced glomerular filtration rate in the assessment of long-term outcomes.