Priorities, opportunities, and challenges for integrating microorganisms into Earth system models for climate change prediction.

Climate change jeopardizes human health, global biodiversity, and sustainability of the biosphere. To make reliable predictions about climate change, scientists use Earth system models (ESMs) that integrate physical, chemical, and biological processes occurring on land, the oceans, and the atmosphere. Although critical for catalyzing coupled biogeochemical processes, microorganisms have traditionally been left out of ESMs. Here, we generate a "top 10" list of priorities, opportunities, and challenges for the explicit integration of microorganisms into ESMs. We discuss the need for coarse-graining microbial information into functionally relevant categories, as well as the capacity for microorganisms to rapidly evolve in response to climate-change drivers. Microbiologists are uniquely positioned to collect novel and valuable information necessary for next-generation ESMs, but this requires data harmonization and transdisciplinary collaboration to effectively guide adaptation strategies and mitigation policy.

Bystander cardiopulmonary resuscitation for paediatric out-of-hospital cardiac arrest in England: An observational registry cohort study.

INTRODUCTION: Bystander cardiopulmonary resuscitation (BCPR) is strongly advocated by resuscitation councils for paediatric out-of-hospital cardiac arrests (OHCAs). However, there are limited reports on rates of BCPR in children and its relationship with return of spontaneous circulation (ROSC) or survival outcomes. OBJECTIVE: We describe the rate of BCPR and its association with any ROSC and survival- to- hospital-discharge. METHODS: We conducted retrospective analysis of prospectively collected paediatric (<18 years of age) OHCA cases in England; we included specialist registry patients treated by emergency medical services (EMS) with known BCPR status and outcome between January 2014 and November 2018. Data included patient demographics, aetiology, witness status, initial rhythm, EMS, season, time of day and bystander status. Associations between BCPR, and any ROSC and survival-to-hospital-discharge outcomes were explored using multivariable logistic regression. RESULTS: There were 2363 paediatric OHCAs treated across 11 EMS regions. BCPR was performed in 69.6% (1646/2363) of the cases overall (range 57.7% (206/367) to 83.7% (139/166) across EMS regions). Only 34.9% (550/1572) of BCPR cases were witnessed. Overall, any ROSC was achieved in 22.8% (523/2289) and survival to hospital discharge in 10.8% (225/2066). Adjusted odds ratio (aOR) for any ROSC was significantly improved following BCPR compared to no BCPR (aOR 1.37, 95% CI 1.03-1.81), but adjusted odds ratio for survival-to-hospital-discharge were similar (aOR 1.01, 95% CI 0.66-1.55). CONCLUSIONS: BCPR was associated with improved rates of any ROSC but not survival-to-hospital-discharge. Variations in EMS BCPR rates may indicate opportunities for regional targeted increase in public BCPR education.

Characteristics of Restart a Heart 2019 event locations in the UK.

INTRODUCTION: Restart a Heart (RSAH) is an annual CPR mass training initiative delivered predominantly by ambulance services in the UK. The aim of this study was to identify to what extent voluntary participation in the 2019 initiative delivered training to the population with the highest need. METHODS: A cross-sectional observational study of location characteristics for RSAH training events conducted by UK ambulance services. Descriptive statistics were used to analyse event and area characteristics. National cardiac arrest registry data were used to establish proportions of training coverage in "hot spot" areas with above national median incidence of cardiac arrest and below median bystander CPR rates. The significance of observed differences were tested using chi-square for proportions and t-test for means. RESULTS: Twelve of 14 UK ambulance services participated, training 236,318 people. Most of the events (82%) were held in schools, and schoolchildren comprised most participants (81%). RSAH events were held in areas that were less densely populated (p < 0.001), were more common in affluent areas (p < 0.001), and had a significantly lower proportion of black residents (p < 0.05) and higher proportion of white residents (p < 0.05). Events were held in 28% of known "hot spot" areas in England. CONCLUSION: With mandatory CPR training for school children in England, Scotland and Wales there is an opportunity to re-focus RSAH resources to deliver training for all age groups in OHCA "hot spots", communities with higher proportions of black residents, and areas of deprivation. In Northern Ireland, we recommend targeting schools in areas with similar characteristics.

Knockout of apolipoprotein A-I decreases parenchymal and vascular ß-amyloid pathology in the Tg2576 mouse model of Alzheimer's disease.

AIMS: Apolipoprotein A-I (apoA-I), the principal apolipoprotein associated with high-density lipoproteins in the periphery, is also found at high concentrations in the cerebrospinal fluid. Previous studies have reported either no impact or vascular-specific effects of apoA-I knockout (KO) on ß-amyloid (Aß) pathology. However, the putative mechanism(s) by which apoA-I may influence Aß deposition is unknown. METHODS: We evaluated the effect of apoA-I deletion on Aß pathology, Aß production and clearance from the brain in the Tg2576 mouse model of Alzheimer's disease (AD). RESULTS: Contrary to previous reports, deletion of the APOA1 gene significantly reduced concentrations of insoluble Aß40 and Aß42 and reduced plaque load in both the parenchyma and blood vessels of apoA-I KO × Tg2576 mice compared to Tg2576 animals. This was not due to decreased Aß production or alterations in Aß species. Levels of soluble clusterin/apoJ were significantly higher in neurons of apoA-I KO mice compared to both wildtype (WT) and apoA-I KO × Tg2576 mice. In addition, clearance of Aß along intramural periarterial drainage pathways was significantly higher in apoA-I KO mice compared to WT animals. CONCLUSION: These data suggest that deletion of apoA-I is associated with increased clearance of Aß and reduced parenchymal and vascular Aß pathology in the Tg2576 model. These results suggest that peripheral dyslipidaemia can modulate the expression of apolipoproteins in the brain and may influence Aß clearance and aggregation in AD.

Fat-bone interaction within the bone marrow milieu: Impact on hematopoiesis and systemic energy metabolism.

The relationship between fat, bone and systemic metabolism is a growing area of scientific interest. Marrow adipose tissue is a well-recognized component of the bone marrow milieu and is metabolically distinct from current established subtypes of adipose tissue. Despite recent advances, the functional significance of marrow adipose tissue is still not clearly delineated. Bone and fat cells share a common mesenchymal stem cell (MSC) within the bone marrow, and hormones and transcription factors such as growth hormone, leptin, and peroxisomal proliferator-activated receptor γ influence MSC differentiation into osteoblasts or adipocytes. MSC osteogenic potential is more vulnerable than adipogenic potential to radiation and chemotherapy, and this confers a risk for an abnormal fat-bone axis in survivors following cancer therapy and bone marrow transplantation. This review provides a summary of data from animal and human studies describing the relationship between marrow adipose tissue and hematopoiesis, bone mineral density, bone strength, and metabolic function. The significance of marrow adiposity in other metabolic disorders such as osteoporosis, diabetes mellitus, and estrogen and growth hormone deficiency are also discussed. We conclude that marrow adipose tissue is an active endocrine organ with important metabolic functions contributing to bone energy maintenance, osteogenesis, bone remodeling, and hematopoiesis. Future studies on the metabolic role of marrow adipose tissue may provide the critical insight necessary for selecting targeted therapeutic interventions to improve altered hematopoiesis and augment skeletal remodeling in cancer survivors.

Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12-14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.

Higgs physics at the CLIC electron-positron linear collider.

The Compact Linear Collider (CLIC) is an option for a future [Formula: see text] collider operating at centre-of-mass energies up to [Formula: see text], providing sensitivity to a wide range of new physics phenomena and precision physics measurements at the energy frontier. This paper is the first comprehensive presentation of the Higgs physics reach of CLIC operating at three energy stages: [Formula: see text], 1.4 and [Formula: see text]. The initial stage of operation allows the study of Higgs boson production in Higgsstrahlung ([Formula: see text]) and [Formula: see text]-fusion ([Formula: see text]), resulting in precise measurements of the production cross sections, the Higgs total decay width [Formula: see text], and model-independent determinations of the Higgs couplings. Operation at [Formula: see text] provides high-statistics samples of Higgs bosons produced through [Formula: see text]-fusion, enabling tight constraints on the Higgs boson couplings. Studies of the rarer processes [Formula: see text] and [Formula: see text] allow measurements of the top Yukawa coupling and the Higgs boson self-coupling. This paper presents detailed studies of the precision achievable with Higgs measurements at CLIC and describes the interpretation of these measurements in a global fit.

A National Survey on the Diagnosis and Treatment of Paediatric Growth Hormone Deficiency.

Many countries have established regulations regarding growth hormone (GH) treatment in children, to standardise care and reduce cost. In this study, we describe current practice in Ireland surrounding child measurement and the approach to diagnosis of GH deficiency. A questionnaire was sent to 139 paediatricians in Ireland and 35 (9 paediatric endocrinologists) responded. Only 13 (37.1%) use the recommended 2-person technique for measuring children under 2. Amongst GH prescribers, there were a variety of GH Stimulation Tests used, sex steroid priming was used by 8 (80%) and the general cut off for a passed test was consistent (7ng/ml). Brand rotation (n=5, 50%) and cost (n=3, 30%) were the most common criteria for deciding the formulation of GH prescribed. We recommend that departments review their child measurement technique and equipment. We also advise the establishment of national guidelines for the use of GH, and a prospective registry for GH treated children.

Auscultate, palpate and tap: time to re-evaluate.

AIM: To determine the accuracy of current methods of heart rate (HR) assessment. METHODS: All participants palpated a simulated pulsating umbilicus (UMB), listened to a tapping rate (TAP) and auscultated a simulated HR (AUSC). A simulated HR of 54, 88 and 128 beats per minute (bpm) was randomised for all methods. RESULTS: Twenty-nine healthcare staff participated in this study. Correct assessment of HR of 54 bpm as being within the 0-59 range occurred in 17.2% UMB, 17.2% TAP and 31% AUSC and was obtained in <10 seconds by 48.3%, 65.5% and 62.1%, respectively. A rate of 88 bpm was correctly assessed as within the 60-100 range in 82.8% UMB, 79.3% TAP and 79.3% AUSC and was obtained in <10 seconds by 55.2%, 58.6% and 55.2%, respectively. A rate of 128 bpm was identified as >100 bpm by 96.6% UMB, 93.1% TAP, and 93.1% AUSC and was obtained in <10 seconds by 51.7%, 55.2% and 62.1%, respectively. CONCLUSION: Current methods in assessing rates below 60 bpm are inaccurate and may overestimate HR. We recommend that these methods alone should not be relied upon in neonatal resuscitation and objective assessment of heart rate should be readily available at all newborn resuscitations.

Serial GH Measurement After Intravenous Catheter Placement Alone Can Detect Levels Above Stimulation Test Thresholds in Children.

CONTEXT: GH stimulation testing is limited by poor specificity and reproducibility in identifying GH deficiency. Intravenous line placement (IVP) in pediatrics may be a stimulus for GH secretion. OBJECTIVE: The objective of the study was to determine whether the measurement of GH at baseline as well as 15 and 30 minutes after IVP detects additional patients with sufficient peak GH concentrations who are not identified by a subsequent insulin tolerance test (ITT). METHODS: The ITT protocol was modified to include GH measurement at the time of IVP (t = 0) and 15 (t = 15) and 30 (t = 30) minutes later. Insulin was administered at t = 30, and an ITT was performed as per standard protocols. Children were grouped according to the indication for ITT: initial evaluation of GH deficiency (group 1); and GH deficiency at transition to adulthood (group 2). RESULTS: Ninety-seven patients were included (76 in group 1, 21 in group 2). Of these, 27 (28%) had a peak GH concentration of 7 ng/mL or greater (19 in group 1, eight in group 2) either after IVP or ITT. Thirteen subjects (11 in group 1, two in group 2) had GH concentrations of 7 ng/mL or greater after IVP, without exceeding this on a subsequent ITT. Among the 11 group 1 patients, three of these GH peaks of 7 ng/mL or greater occurred at t = 0, 5 at t = 15, and 5 at t = 30, including one patient who had a peak GH of 7 ng/mL or greater at all three time points. CONCLUSION: Some children will not have a sufficient GH response to pharmacological stimuli but will have a robust response to IVP. We recommend GH measurement after IVP in children undergoing GH stimulation testing, particularly when there is a delay between IVP and the administration of the pharmacological stimulus.