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Abstract Background The importance of parental diet in relation to eventual offspring health is increasing in prominence due to the increased frequency of parents of reproductive age consuming poor diets. Whilst maternal health and offspring outcome have been studied in some detail, the paternal impacts are not as well understood. A father’s poor nutritional status has been shown to have negative consequences on foetal growth and development and ultimately impact the long-term adult health of the offspring. In this study, we examined sperm- and seminal vesicle fluid-mediated mechanisms of preimplantation embryo development alterations in response to sub-optimal paternal diets. Results Male mice were fed a diet to model either under (low-protein diet (LPD)) or over (high-fat/sugar ‘Western’ diet (WD)) nutrition, LPD or WD supplemented with methyl donors or a control diet (CD) before mating with age-matched females. Male metabolic health was influenced by WD and MD-WD, with significant changes in multiple serum lipid classes and hepatic 1-carbon metabolites. Sperm RNA sequencing revealed significant changes to mRNA profiles in all groups when compared to CD (LPD: 32, MD-LPD: 17, WD: 53, MD-WD: 35 transcripts). Separate analysis of the seminal vesicle fluid proteome revealed a significant number of differentially expressed proteins in all groups (LPD: 13, MD-LPD: 27, WD: 24, MD-WD: 19) when compared to control. Following mating, in vitro time-lapse imaging of preimplantation embryos revealed a significant increase in the timing of development in all experimental groups when compared to CD embryos. Finally, qPCR analysis of uterine tissue at the time of implantation identified perturbed expression of Cd14 and Ptgs1 following mating with WD-fed males. Conclusions Our current study shows that paternal nutritional status has the potential to influence male metabolic and reproductive health, impacting on embryonic development and the maternal reproductive tract. This study highlights potential direct (sperm-mediated) and indirect (seminal vesicle fluid-mediated) pathways in which a father’s poor diet could shape the long-term health of his offspring.

Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis. Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 μg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 μg/L/h, n = 58) (mean difference, 13.2 μg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.

Abstract Background In this study, we evaluated the lipidome alterations caused by type 1 diabetes (T1D) and type 2 diabetes (T2D), by determining lipids significantly associated with diabetes overall and in both sexes, and lipids associated with the glycaemic state. Methods An untargeted lipidomic analysis was performed to measure the lipid profiles of 360 subjects (91 T1D, 91 T2D, 74 with prediabetes and 104 controls (CT)) without cardiovascular and/or chronic kidney disease. Ultra-high performance liquid chromatography-electrospray ionization mass spectrometry (UHPLC-ESI-MS) was conducted in two ion modes (positive and negative). We used multiple linear regression models to (1) assess the association between each lipid feature and each condition, (2) determine sex-specific differences related to diabetes, and (3) identify lipids associated with the glycaemic state by considering the prediabetes stage. The models were adjusted by sex, age, hypertension, dyslipidaemia, body mass index, glucose, smoking, systolic blood pressure, triglycerides, HDL cholesterol, LDL cholesterol, alternate Mediterranean diet score (aMED) and estimated glomerular filtration rate (eGFR); diabetes duration and glycated haemoglobin (HbA1c) were also included in the comparison between T1D and T2D. Results A total of 54 unique lipid subspecies from 15 unique lipid classes were annotated. Lysophosphatidylcholines (LPC) and ceramides (Cer) showed opposite effects in subjects with T1D and subjects with T2D, LPCs being mainly up-regulated in T1D and down-regulated in T2D, and Cer being up-regulated in T2D and down-regulated in T1D. Also, Phosphatidylcholines were clearly down-regulated in subjects with T1D. Regarding sex-specific differences, ceramides and phosphatidylcholines exhibited important diabetes-associated differences due to sex. Concerning the glycaemic state, we found a gradual increase of a panel of 1-deoxyceramides from normoglycemia to prediabetes to T2D. Conclusions Our findings revealed an extensive disruption of lipid metabolism in both T1D and T2D. Additionally, we found sex-specific lipidome changes associated with diabetes, and lipids associated with the glycaemic state that can be linked to previously described molecular mechanisms in diabetes.

Abstract Despite groundbreaking advances in the additive manufacturing of polymers, metals, and ceramics, scaled and accurate production of structured carbons remains largely underdeveloped. This work reports a simple method to produce complex carbon materials with very low dimensional shrinkage from printed to carbonized state (less than 4%), using commercially available polypropylene precursors and a fused filament fabrication-based process. The control of macrostructural retention is enabled by the inclusion of fiber fillers regardless of the crosslinking degree of the polypropylene matrix, providing a significant advantage to directly control the density, porosity, and mechanical properties of 3D printed carbons. Using the same printed plastic precursors, different mechanical responses of derived carbons can be obtained, notably from stiff to highly compressible. This report harnesses the power of additive manufacturing for producing carbons with accurately controlled structure and properties, while enabling great opportunities for various applications.

Wastewater surveillance of SARS-CoV-2 has been used around the world to supplement clinical testing data for situational awareness of COVID-19 disease trends. Many regions of the world lack centralized wastewater collection and treatment infrastructure, which presents additional considerations for wastewater surveillance of SARS-CoV-2, including environmental decay of the RT-qPCR gene targets used for quantification of SARS-CoV-2 virions. Given the role of sunlight in the environmental decay of RNA, we evaluated sunlight photolysis kinetics of the N1 gene target in heat-inactivated SARS-CoV-2 with a solar simulator under laboratory conditions. Insignificant photolysis of the N1 target was observed in a photosensitizer-free matrix. Conversely, significant decay of the N1 target was observed in wastewater at a shallow depth (

Lipid functions can be influenced by genetics, age, disease states, and lifestyle factors, particularly dietary patterns, which are crucial in diabetes management. Lipidomics is an expanding field involving the comprehensive exploration of lipids from biological samples. In this cross-sectional study, 396 participants from a Mediterranean region, including individuals with type 1 diabetes (T1D), type 2 diabetes (T2D), and non-diabetic individuals, underwent lipidomic profiling and dietary assessment. Participants completed validated food frequency questionnaires, and lipid analysis was conducted using ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC/MS). Multiple linear regression models were used to determine the association between lipid features and dietary patterns. Across all subjects, acylcarnitines (AcCa) and triglycerides (TG) displayed negative associations with the alternate Healthy Eating Index (aHEI), indicating a link between lipidomic profiles and dietary habits. Various lipid species (LS) showed positive and negative associations with dietary carbohydrates, fats, and proteins. Notably, in the interaction analysis between diabetes and the aHEI, we found some lysophosphatidylcholines (LPC) that showed a similar direction with respect to aHEI in non-diabetic individuals and T2D subjects, while an opposite direction was observed in T1D subjects. The study highlights the significant association between lipidomic profiles and dietary habits in people with and without diabetes, particularly emphasizing the role of healthy dietary choices, as reflected by the aHEI, in modulating lipid concentrations. These findings underscore the importance of dietary interventions to improve metabolic health outcomes, especially in the context of diabetes management.

The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.

Abstract Background Pregnancy-related mortality in the United States is the greatest among all high-income countries, and Georgia has one of the highest maternal mortality rates—almost twice the national rate. Furthermore, inequities exist in rates of pregnancy-related deaths. In Georgia, non-Hispanic Black women are nearly 3 times more likely to die from pregnancy-related complications than non-Hispanic White women. Unlike health equity, a clear definition of maternal health equity is lacking, overall and in Georgia specifically, but is needed to reach consensus and align stakeholders for action. Therefore, we used a modified Delphi method to define maternal health equity in Georgia and to determine research priorities based on gaps in understanding of maternal health in Georgia. Methods Thirteen expert members of the Georgia Maternal Health Research for Action Steering Committee (GMHRA-SC) participated in an iterative, consensus-driven, modified Delphi study comprised of 3 rounds of anonymous surveys. In round 1 (web-based survey), experts generated open-ended concepts of maternal health equity and listed research priorities. In rounds 2 (web-based meeting) and 3 (web-based survey), the definition and research priorities suggested during round 1 were categorized into concepts for ranking based on relevance, importance, and feasibility. Final concepts were subjected to a conventional content analysis to identify general themes. Results The consensus definition of maternal health equity created after undergoing the Delphi method is: maternal health equity is the ultimate goal and ongoing process of ensuring optimal perinatal experiences and outcomes for everyone as the result of practices and policies free of interpersonal or structural bias that tackle current and historical injustices, including social, structural, and political determinants of health impacting the perinatal period and life course. This definition highlights addressing the current and historical injustices manifested in the social determinants of health, and the structural and political structures that impact the perinatal experience. Conclusion The maternal health equity definition and identified research priorities will guide the GMHRA-SC and the broader maternal health community for research, practice, and advocacy in Georgia.

OBJECTIVES/GOALS: Health care accounts for an estimated 10% of U.S. greenhouse gas (GHG) emissions. Concerted efforts to decrease waste are needed including critical appraisal of single use items. The purpose of this study was to conduct life cycle analyses (LCA) of a pediatric single use laryngoscope to inform environmental impact and identify targets to reduce waste. METHODS/STUDY POPULATION: LCA was used to quantify the environmental impact of a single use pediatric laryngoscope. LCA is an industry standard measure of energy consumption, water consumption, and GHG emissions encompassing a “cradle-to-grave” assessment. The GREET model (Greenhouse gases, Regulated Emissions and Energy use in Technologies) and Open LCA model were used as sources for product/raw material data. Separate analysis was completed for the battery powering the light emitting diode (LED) lights. RESULTS/ANTICIPATED RESULTS: The LCA revealed 598.2 g of CO2 equivalents for the 121g single use pediatric laryngoscope. There were an estimated 26,849 cases that used single use laryngoscope last year at our free-standing children’s hospital resulting in 16.1 metric tons of CO2 equivalents. This is equivalent to 41,273 miles driven by an average gasoline powered vehicle. The 1.5 V battery was the highest contributor to the laryngoscope’s GHG emissions. While the battery has an estimated 2,800 hours of life, single use laryngoscopes are reported in the literature as being used for only an average of 30 seconds to 2 minutes. DISCUSSION/SIGNIFICANCE: Single use laryngoscopes are high contributors to GHGs. Specifically, the batteries contained in the laryngoscopes are wasteful and challenging to remove and recycle. Future efforts to decrease waste in the OR should target use of similar items that have reusable battery components to improve environmental sustainability.

Nearly every teacher will experience loss and grief during their years in the classroom. And yet, too often the profession assumes that English language arts (ELA) teachers must hide the emotions that accompany loss. In this article the authors share strategies for supporting English teachers in making sense of their grieving experiences and thinking about how those grieving experiences might interplay with teaching literary texts in ELA classrooms. Based on research analyses, discussions with teachers, and the authors' own experiences in classrooms, they argue that acknowledging competing demands placed on teachers both empowers teachers to recognize the complex work they undertake and helps teachers to work toward healthier ways of teaching and being, especially during grief.

Summary: Strategies targeting methane (CH4) and nitrous oxide (N2O) emissions are critical to meeting global climate targets. Existing literature estimates the emissions of these gases from specific sectors, but this knowledge must be synthesized to prioritize and incentivize CH4 and N2O mitigation. Accordingly, we review emissions sources and mitigation strategies in all key sectors (fuel extraction and combustion, landfilling, agriculture, wastewater treatment, and chemical industry) and the role of carbon markets in reducing emissions. The most accessible reduction opportunities are in the hydrocarbon extraction and waste sectors, where half (>3 Gt-CO2e/year) of the emissions in these sectors could be mitigated at no net cost. In total, 60% of CH4 emissions can be mitigated at less than $50/t-CO2. Expanding the scope of carbon markets to include these emissions could provide cost-effective decarbonization through 2050. We provide recommendations for carbon markets to improve emissions reductions and set prices to appropriately incentivize mitigation.

Biomarker discovery using biobank samples collected from veterinary clinics would deliver insights into the diverse population of pets and accelerate diagnostic development. The acquisition, preparation, processing, and storage of biofluid samples in sufficient volumes and at a quality suitable for later analysis with most suitable discovery methods remain challenging. Metabolomics analysis is a valuable approach to detect health/disease phenotypes. Pre-processing changes during preparation of plasma/serum samples may induce variability that may be overcome using dried blood spots (DBSs). We report a proof of principle study by metabolite fingerprinting applying UHPLC-MS of plasma and DBSs acquired from healthy adult dogs and cats (age range 1–9 years), representing each of 4 dog breeds (Labrador retriever, Beagle, Petit Basset Griffon Vendeen, and Norfolk terrier) and the British domestic shorthair cat (n = 10 per group). Blood samples (20 and 40 μL) for DBSs were loaded onto filter paper, air-dried at room temperature (3 h), and sealed and stored (4°C for ~72 h) prior to storage at −80°C. Plasma from the same blood draw (250 μL) was prepared and stored at −80°C within 1 h of sampling. Metabolite fingerprinting of the DBSs and plasma produced similar numbers of metabolite features that had similar abilities to discriminate between biological classes and correctly assign blinded samples. These provide evidence that DBSs, sampled in a manner amenable to application in in-clinic/in-field processing, are a suitable sample for biomarker discovery using UHPLC-MS metabolomics. Further, given appropriate owner consent, the volumes tested (20–40 μL) make the acquisition of remnant blood from blood samples drawn for other reasons available for biobanking and other research activities. Together, this makes possible large-scale biobanking of veterinary samples, gaining sufficient material sooner and enabling quicker identification of biomarkers of interest.

Abstract Cytoglobin is important in the progression of oral squamous cell carcinoma but the molecular and cellular basis remain to be elucidated. In the current study, we develop a new cell model to study the function of cytoglobin in oral squamous carcinoma and response to cisplatin. Transcriptomic profiling showed cytoglobin mediated changes in expression of genes related to stress response, redox metabolism, mitochondrial function, cell adhesion, and fatty acid metabolism. Cellular and biochemical studies show that cytoglobin expression results in changes to phenotype associated with cancer progression including: increased cellular proliferation, motility and cell cycle progression. Cytoglobin also protects cells from cisplatin-induced apoptosis and oxidative stress with levels of the antioxidant glutathione increased and total and mitochondrial reactive oxygen species levels reduced. The mechanism of cisplatin resistance involved inhibition of caspase 9 activation and cytoglobin protected mitochondria from oxidative stress-induced fission. To understand the mechanism behind these phenotypic changes we employed lipidomic analysis and demonstrate that levels of the redox sensitive and apoptosis regulating cardiolipin are significantly up-regulated in cells expressing cytoglobin. In conclusion, our data shows that cytoglobin expression results in important phenotypic changes that could be exploited by cancer cells in vivo to facilitate disease progression.

Electrification is a key strategy for decarbonizing the industrial sector. Industrial process heating, which still relies heavily on fossil fuel combustion and accounts for the majority of sector wide GHG emissions, is a particularly attractive electrification target. Electrifying industrial boilers represents a cross-cutting opportunity for GHG emissions reductions, given their widespread use in most manufacturing industries. Yet, there are gaps in the understanding of the current population of conventional industrial boilers in the United States that preclude a characterization of boiler electrification's technical potential to reduce fuel consumption and GHG emissions. In this study, we develop an up-to-date dataset of the industrial boiler population in the U.S. and quantify the county-level electricity requirements and net changes in fuel use and GHG emissions under the current electric grid and theoretical future grid scenarios. Our results show an increase of 105 MMmtCO2e and 73 MMmtCO2e in GHG emissions from boiler electrification, with and without the replacement of byproduct fuels, respectively, under the current electric grid, and a reduction of 19 MMmtCO2e and 7 MMmtCO2e in GHG emissions under a future high renewables electric grid. GHG emissions savings are currently possible only in certain regions of the U.S. unless future grids are decarbonized. We also provide discussion that could be useful for policy makers and manufacturing facilities for advancing the electrification of industrial boilers in locations and industries toward fuel savings and GHG emissions reductions.

Objectives: Severe thermal injury (TI) has been associated with increased intestinal permeability and the development of multiple organ dysfunction syndrome. The aim of this case series from a prospective, longitudinal study is to describe the impact of TI on intestinal permeability in critically ill participants with TI versus observations from healthy participants. Methods: Participants with TI ≥ 15% total body surface area and healthy participants were recruited into the study. The co-primary endpoints were lactulose/mannitol [L/M] ratio (a) within 24 h of hospital admission and (b) over time. Exploratory endpoints included fractional excretion of sucralose and changes in blood biomarkers (eg, occludin and soluble CD14 [sCD14]). Clinical severity of injury, demographic and morbidity data were also collected. Results: Fourteen healthy participants and three participants with TI were enrolled. Case histories for two of the three participants with TI showed peak L/M-measured permeability ~10-fold higher than healthy participants, with a clear pattern between degree and timing of injury and increases in permeability. Serum occludin and sCD14 levels were elevated in all three participants with TI versus healthy participants. The study was terminated early with a reduced sample size and duration than planned. Conclusion: Observed changes in L/M-measured permeability of participants with TI support the existing literature of raised intestinal permeability in critically ill individuals, with increases seen in the first few days of hospital admission. Occludin and sCD14 are identified as potential surrogate markers of raised permeability but require validation in larger studies.

Wetlands serve many important ecosystem services, yet the United States lacks up-to-date, high-resolution wetland inventories. New, automated techniques for developing wetland segmentation maps from high-resolution aerial imagery can improve our understanding of the location and amount of wetlands. We assembled training and testing data sets (patch sizes of 28 × 28 m2 and 56 × 56 m2) of high-resolution aerial imagery of wetlands using Illinois Natural History Survey wetland location data and National Agricultural Imagery Project data. Each patch was labeled as wetland or non-wetland. To augment these data sets with additional information, we incorporated digital surface and digital terrain models and topographic wetness index data in the same two patch sizes. Subsequently, we evaluated convolutional neural network (CNN) and Gaussian process-based machine learning methods to produce wetland segmentation maps. We developed the best performing method into a new CNN algorithm, WetSegNet. It exhibited an area under the curve of 98% when used with 56 × 56 m2 patch sizes. WetSegNet developed reliable wetland segmentation maps in test cases in which wetlands would have gone undetected using only the National Land Cover Database. The development of WetSegNet exemplifies the types of data sets and methods that are needed to accelerate the use of high-resolution aerial imagery towards an improved understanding of wetlands. This algorithm could be used by state and federal agencies or other groups to identify wetlands with higher accuracy and at a finer scale than previously possible.

Global energy modeling exercises project significant deployment of CO2 capture and storage (CCS) to bridge the gap between India's pledged climate commitments and the 1. 5°C target. Despite advances in laboratory analyses and process modeling, the information on geologic storage potential in India is limited. Prior studies indicate that the vast majority of storage potential exists in saline aquifers (50–300 Gt-CO2); though, this might be overestimated. These estimates also estimate the theoretical potential in coal seams to be

Multidrug-resistant Gram-negative bacteria pose a global threat to human health. The AcrB efflux pump confers inherent and evolved drug resistance to EnterobacteralesEscherichia coliSalmonella enterica

Objective: To describe demographic and clinical characteristics of Spanish- and English-speaking visitors to a “Healthy Mood” website. Methods: An online study intended to prevent depression by teaching users mood management skills recruited participants globally using primarily Google Ads. Those who consented responded to the Patient Health Questionnaire (PHQ-9) and the MDE Screener (Muñoz, 1998) upon entry into the study. Results: 1423 participants consented, 437 English speakers and 986 Spanish speakers. Of the 1271 participants with sufficient depression symptom data, 65% screened positive for a current major depressive episode, 30% were at high risk for onset of a major depressive episode, and 5% were in the low-risk category. Conclusion: Websites intended to be preventive appear to attract primarily individuals who are currently experiencing enough symptoms to screen positive for a major depressive episode. Only 30% of participants were appropriate for a depression prevention intervention. Therefore, such sites must be ready to encourage those with current depression to obtain professional help as well as ensure that the online self-help interventions are appropriate for participants who could benefit from both preventive and treatment interventions.

Introduction: Kidney transplantation (KT) demands that patients navigate a complex healthcare system and adhere to lifelong therapy and surveillance. Cultural and linguistic discordance between patients and providers has been identified as a barrier to successful KT. We studied KT outcomes and disparities among a native Somali population living in Minnesota. Methods: Between 1995 and 2015, 2,385 patients underwent KT at our institution; 22 were self-designated Somali nationals. Patient and graft survival and time to first rejection were analyzed. Utilization of interpreter services was evaluated. Results: Patient survival for the Somali cohort at 1 year was 100% and 95.5% at 5 years; compared to 97.2% at 1 year and 89.1% at 5 years for the Caucasian cohort (p = 0.40). Graft survival for the Somali cohort at 1 year was 100% and 95.5% at 5 years; for the Caucasian cohort 94.8% and 81.6% (p = 0.35). Rejection-free survival in the Somali cohort was 100% at 1 and 5 years, for the Caucasian cohort 86.2% and 82.1 (p = 0.41). Among 22 adult Somali KT recipients, 15 (68%) patients frequently utilized interpreter services in their KT-related clinical encounters. Conclusion: Immigrant Somali KT recipients, appear to have comparable KT outcomes compared to a contemporaneous Caucasian cohort.

Introduction Myocardial protection against ischaemic-reperfusion injury is a key determinant of heart function and outcome following cardiac surgery in children. However, with current strategies, myocardial injury occurs routinely following aortic cross-clamping, as demonstrated by the ubiquitous rise in circulating troponin. Remote ischaemic preconditioning, the application of brief, non-lethal cycles of ischaemia and reperfusion to a distant organ or tissue, is a simple, low-risk and readily available technique which may improve myocardial protection. The Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial will assess whether remote ischaemic preconditioning, applied to both lower limbs immediately prior to surgery, reduces myocardial injury in cyanotic and acyanotic young children.Methods and analysis The BRICC trial is a two-centre, double-blind, randomised controlled trial recruiting up to 120 young children (age 3 months to 3 years) undergoing primary repair of tetralogy of Fallot or surgical closure of an isolated ventricular septal defect. Participants will be randomised in a 1:1 ratio to either bilateral remote ischaemic preconditioning (3×5 min cycles) or sham immediately prior to surgery, with follow-up until discharge from hospital or 30 days, whichever is sooner. The primary outcome is reduction in area under the time-concentration curve for high-sensitivity (hs) troponin-T release in the first 24 hours after aortic cross-clamp release. Secondary outcome measures include peak hs-troponin-T, vasoactive inotrope score, arterial lactate and central venous oxygen saturations in the first 12 hours, and lengths of stay in the paediatric intensive care unit and the hospital.Ethics and dissemination The trial was approved by the West Midlands-Solihull National Health Service Research Ethics Committee (16/WM/0309) on 5 August 2016. Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Parents will be informed of the results through a newsletter in conjunction with a local charity.Trial registration number ISRCTN12923441.

Observations of the presence or absence of surface water in streams are useful for characterizing streamflow permanence, which includes the frequency, duration, and spatial extent of surface flow in streams and rivers. Such data are particularly valuable for headwater streams, which comprise the vast majority of channel length in stream networks, are often non-perennial, and are frequently the most data deficient. Datasets of surface water presence exist across multiple data collection groups in the United States but are not well aligned for easy integration. Given the value of these data, a unified approach for organizing information on surface water presence and absence collected by diverse surveys would facilitate more effective and broad application of these data and address the gap in streamflow data in headwaters. In this paper, we highlight the numerous existing datasets on surface water presence in headwater streams, including recently developed crowdsourcing approaches. We identify the challenges of integrating multiple surface water presence/absence datasets that include differences in the definitions and categories of streamflow status, data collection method, spatial and temporal resolution, and accuracy of geographic location. Finally, we provide a list of critical and useful components that could be used to integrate different streamflow permanence datasets.

The past decade has seen a large influx of work investigating time of day variation in different human biofluid and tissue metabolomes. The driver of this daily variation can be endogenous circadian rhythms driven by the central and/or peripheral clocks, or exogenous diurnal rhythms driven by behavioural and environmental cycles, which manifest as regular 24 h cycles of metabolite concentrations. This review, of all published studies to date, establishes the extent of daily variation with regard to the number and identity of ‘rhythmic’ metabolites observed in blood, saliva, urine, breath, and skeletal muscle. The probable sources driving such variation, in addition to what metabolite classes are most susceptible in adhering to or uncoupling from such cycles is described in addition to a compiled list of common rhythmic metabolites. The reviewed studies show that the metabolome undergoes significant time of day variation, primarily observed for amino acids and multiple lipid classes. Such 24 h rhythms, driven by various factors discussed herein, are an additional source of intra/inter-individual variation and are thus highly pertinent to all studies applying untargeted and targeted metabolomics platforms, particularly for the construction of biomarker panels. The potential implications are discussed alongside proposed minimum reporting criteria suggested to acknowledge time of day variation as a potential influence of results and to facilitate improved reproducibility.

Obesity is an independent risk factor for stroke, although several clinical studies have reported that obesity improves stroke outcome. Obesity is hypothesised to aid recovery by protecting against post-stroke catabolism. We therefore assessed whether obese mice had an altered metabolic and inflammatory response to stroke. Obese ob/ob mice underwent a 20-min middle cerebral artery occlusion and 24-h reperfusion. Lipid metabolism and expression of inflammatory cytokines were assessed in the plasma, liver and adipose tissue. The obese-specific metabolic response to stroke was assessed in plasma using non-targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) metabolomics coupled with univariate and multivariate analysis. Obesity had no effect on the extent of weight loss 24 h after stroke but affected the metabolic and inflammatory responses to stroke, predominantly affecting lipid metabolism. Specifically, obese mice had increases in plasma free fatty acids and expression of adipose lipolytic enzymes. Metabolomics identified several classes of metabolites affected by stroke in obese mice, including fatty acids and membrane lipids (glycerophospholipids, lysophospholipids and sphingolipids). Obesity also featured increases in inflammatory cytokines in the plasma and adipose tissue. Overall, these results demonstrate that obesity affected the acute metabolic and inflammatory response to stroke and suggest a potential role for adipose tissue in this effect. These findings could have implications for longer-term recovery and also further highlight the importance of considering comorbidities in preclinical stroke research, especially when identifying biomarkers for stroke. However, further work is required to assess whether these changes translate into long-term effects on recovery.