The effects of CO2, climate and land-use on terrestrial carbon balance, 1920-1992: An analysis with four process-based ecosystem models

The concurrent effects of increasing atmospheric CO2 concentration, climate variability, and cropland establishment and abandonment on terrestrial carbon storage between 1920 and 1992 were assessed using a standard simulation protocol with four process-based terrestrial biosphere models. Over the long-term(1920–1992), the simulations yielded a time history of terrestrial uptake that is consistent (within the uncertainty) with a long-term analysis based on ice core and atmospheric CO2 data. Up to 1958, three of four analyses indicated a net release of carbon from terrestrial ecosystems to the atmosphere caused by cropland establishment. After 1958, all analyses indicate a net uptake of carbon by terrestrial ecosystems, primarily because of the physiological effects of rapidly rising atmospheric CO2. During the 1980s the simulations indicate that terrestrial ecosystems stored between 0.3 and 1.5 Pg C yr−1, which is within the uncertainty of analysis based on CO2 and O2 budgets. Three of the four models indicated (in accordance with O2 evidence) that the tropics were approximately neutral while a net sink existed in ecosystems north of the tropics. Although all of the models agree that the long-term effect of climate on carbon storage has been small relative to the effects of increasing atmospheric CO2 and land use, the models disagree as to whether climate variability and change in the twentieth century has promoted carbon storage or release. Simulated interannual variability from 1958 generally reproduced the El Niño/Southern Oscillation (ENSO)-scale variability in the atmospheric CO2 increase, but there were substantial differences in the magnitude of interannual variability simulated by the models. The analysis of the ability of the models to simulate the changing amplitude of the seasonal cycle of atmospheric CO2 suggested that the observed trend may be a consequence of CO2 effects, climate variability, land use changes, or a combination of these effects. The next steps for improving the process-based simulation of historical terrestrial carbon include (1) the transfer of insight gained from stand-level process studies to improve the sensitivity of simulated carbon storage responses to changes in CO2 and climate, (2) improvements in the data sets used to drive the models so that they incorporate the timing, extent, and types of major disturbances, (3) the enhancement of the models so that they consider major crop types and management schemes, (4) development of data sets that identify the spatial extent of major crop types and management schemes through time, and (5) the consideration of the effects of anthropogenic nitrogen deposition. The evaluation of the performance of the models in the context of a more complete consideration of the factors influencing historical terrestrial carbon dynamics is important for reducing uncertainties in representing the role of terrestrial ecosystems in future projections of the Earth system

Emergency medical services utilisation among febrile children attending emergency departments across Europe: an observational multicentre study

Children constitute 6-10% of all patients attending the emergency department (ED) by emergency medical services (EMS). However, discordant EMS use in children occurs in 37-61% with fever as an important risk factor. We aimed to describe EMS utilisation among febrile children attending European EDs. This study is part of an observational multicentre study assessing management and outcome in febrile children up to 18 years (MOFICHE) attending twelve EDs in eight European countries. Discordant EMS use was defined as the absence of markers of urgency including intermediate/high triage urgency, advanced diagnostics, treatment, and admission in children transferred by EMS. Multivariable logistic regression analyses were performed for the association between (1) EMS use and markers of urgency, and (2) patient characteristics and discordant EMS use after adjusting all analyses for the covariates age, gender, visiting hours, presenting symptoms, and ED setting. A total of 5464 (15%, range 0.1-42%) children attended the ED by EMS. Markers of urgency were more frequently present in the EMS group compared with the non-EMS group. Discordant EMS use occurred in 1601 children (29%, range 1-59%). Age and gender were not associated with discordant EMS use, whereas neurological symptoms were associated with less discordant EMS use (aOR 0.2, 95%CI 0.1-0.2), and attendance out of office hours was associated with more discordant EMS use (aOR 1.6, 95%CI 1.4-1.9). Settings with higher percentage of self-referrals to the ED had more discordant EMS use (p < 0.05).  Conclusion: There is large practice variation in EMS use in febrile children attending European EDs. Markers of urgency were more frequently present in children in the EMS group. However, discordant EMS use occurred in 29%. Further research is needed on non-medical factors influencing discordant EMS use in febrile children across Europe, so that pre-emptive strategies can be implemented. What is Known: •Children constitute around 6-10% of all patients attending the emergency department by emergency medical services. •Discordant EMS use occurs in 37-61% of all children, with fever as most common presenting symptom for discordant EMS use in children. What is New: •There is large practice variation in EMS use among febrile children across Europe with discordance EMS use occurring in 29% (range 1-59%), which was associated with attendance during out of office hours and with settings with higher percentage of self-referrals to the ED. •Future research is needed focusing on non-medical factors (socioeconomic status, parental preferences and past experience, healthcare systems, referral pathways, out of hours services provision) that influence discordant EMS use in febrile children across Europe

Variation in hospital admission in febrile children evaluated at the Emergency Department (ED) in Europe : PERFORM, a multicentre prospective observational study

Funding Information: This project was funded by the European Union?s Horizon 2020 research and innovation programme to ML (Grant No. 668303), the NIHR Newcastle Biomedical Research Centre at Newcastle Hospitals NHS foundation trust to ME, and the National Institute for Health Research to RGN (CL-2018-21-007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021 Borensztajn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.OBJECTIVES: Hospitalisation is frequently used as a marker of disease severity in observational Emergency Department (ED) studies. The comparison of ED admission rates is complex in potentially being influenced by the characteristics of the region, ED, physician and patient. We aimed to study variation in ED admission rates of febrile children, to assess whether variation could be explained by disease severity and to identify patient groups with large variation, in order to use this to reduce unnecessary health care utilization that is often due to practice variation. DESIGN: MOFICHE (Management and Outcome of Fever in children in Europe, part of the PERFORM study, www.perform2020.org), is a prospective cohort study using routinely collected data on febrile children regarding patient characteristics (age, referral, vital signs and clinical alarming signs), diagnostic tests, therapy, diagnosis and hospital admission. SETTING AND PARTICIPANTS: Data were collected on febrile children aged 0-18 years presenting to 12 European EDs (2017-2018). MAIN OUTCOME MEASURES: We compared admission rates between EDs by using standardised admission rates after adjusting for patient characteristics and initiated tests at the ED, where standardised rates >1 demonstrate higher admission rates than expected and rates <1 indicate lower rates than expected based on the ED patient population. RESULTS: We included 38,120 children. Of those, 9.695 (25.4%) were admitted to a general ward (range EDs 5.1-54.5%). Adjusted standardised admission rates ranged between 0.6 and 1.5. The largest variation was seen in short admission rates (0.1-5.0), PICU admission rates (0.2-2.2), upper respiratory tract infections (0.4-1.7) and fever without focus (0.5-2.7). Variation was small in sepsis/meningitis (0.9-1.1). CONCLUSIONS: Large variation exists in admission rates of febrile children evaluated at European EDs, however, this variation is largely reduced after correcting for patient characteristics and therefore overall admission rates seem to adequately reflect disease severity or a potential for a severe disease course. However, for certain patient groups variation remains high even after adjusting for patient characteristics.publishersversionPeer reviewe

Early Loss of Xist RNA Expression and Inactive X Chromosome Associated Chromatin Modification in Developing Primordial Germ Cells

The inactive X chromosome characteristic of female somatic lineages is reactivated during development of the female germ cell lineage. In mouse, analysis of protein products of X-linked genes and/or transgenes located on the X chromosome has indicated that reactivation occurs after primordial germ cells reach the genital ridges.We present evidence that the epigenetic reprogramming of the inactive X-chromosome is initiated earlier than was previously thought, around the time that primordial germ cells (PGCs) migrate through the hindgut. Specifically, we find that Xist RNA expression, the primary signal for establishment of chromosome silencing, is extinguished in migrating PGCs. This is accompanied by displacement of Polycomb-group repressor proteins Eed and Suz(12), and loss of the inactive X associated histone modification, methylation of histone H3 lysine 27.We conclude that X reactivation in primordial germ cells occurs progressively, initiated by extinction of Xist RNA around the time that germ cells migrate through the hindgut to the genital ridges. The events that we observe are reminiscent of X reactivation of the paternal X chromosome in inner cell mass cells of mouse pre-implantation embryos and suggest a unified model in which execution of the pluripotency program represses Xist RNA thereby triggering progressive reversal of epigenetic silencing of the X chromosome

Reproducibility of Standing Posture for X-Ray Radiography: A Feasibility Study of the BalancAid with Healthy Young Subjects

Unreliable spinal X-ray radiography measurement due to standing postural variability can be minimized by using positional supports. In this study, we introduce a balancing device, named BalancAid, to position the patients in a reproducible position during spinal X-ray radiography. This study aimed to investigate the performance of healthy young subjects’ standing posture on the BalancAid compared to standing on the ground mimicking the standard X-rays posture in producing a reproducible posture for the spinal X-ray radiography. A study on the posture reproducibility measurement was performed by taking photographs of 20 healthy young subjects with good balance control standing on the BalancAid and the ground repeatedly within two consecutive days. We analyzed nine posterior–anterior (PA) and three lateral (LA) angles between lines through body marks placed in the positions of T3, T7, T12, L4 of the spine to confirm any translocations and movements between the first and second day measurements. No body marks repositioning was performed to avoid any error. Lin’s CCC test on all angles comparing both standing postures demonstrated that seven out of nine angles in PA view, and two out of three angles in LA view gave better reproducibility for standing on the BalancAid compared to standing on the ground. The PA angles concordance is on average better than that of the LA angles

Active Chromatin Marks Are Retained on X Chromosomes Lacking Gene or Repeat Silencing Despite XIST/Xist Expression in Somatic Cell Hybrids

X-chromosome inactivation occurs early in mammalian development and results in the inactive X chromosome acquiring numerous hallmarks of heterochromatin. While XIST is a key player in the inactivation process, the method of action of this ncRNA is yet to be determined.To assess which features of heterochromatin may be directly recruited by the expression and localization of the XIST RNA we have analyzed a mouse/human somatic cell hybrid in which expression of human and mouse XIST/Xist has been induced from the active X by demethylation. Such hybrids had previously been demonstrated to disconnect XIST/Xist expression from gene silencing and we confirm maintenance of X-linked gene expression, even close to the Xist locus, despite the localized expression of mouse Xist.Loss of the active chromatin marks H3 acetylation and H3 lysine 4 methylation was not observed upon XIST/Xist expression, nor was there a gain of DNA methylation; thus these marks of facultative heterochromatin are not solely dependent upon Xist expression. Cot-1 holes, regions of depleted RNA hybridization with a Cot-1 probe, were observed upon Xist expression; however, these were at reduced frequency and intensity in these somatic cells. Domains of human Cot-1 transcription were observed corresponding to the human chromosomes in the somatic cell hybrids. The Cot-1 domain of the X was not reduced with the expression of XIST, which fails to localize to the human X chromosome in a mouse somatic cell background. The human inactive X in a mouse/human hybrid cell also shows delocalized XIST expression and an ongoing Cot-1 domain, despite X-linked gene silencing. These results are consistent with recent reports separating Cot-1 silencing from genic silencing, but also demonstrate repetitive element expression from an otherwise silent X chromosome in these hybrid cells

Rapid Viral Testing and Antibiotic Prescription in Febrile Children with Respiratory Symptoms Visiting Emergency Departments in Europe

Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 668303 and No. 848196. The Research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. For the remaining authors no sources of funding were declared. Publisher Copyright: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.Background. Inappropriate antibiotic prescribing often occurs in children with self-limiting respiratory tract infections, contributing to antimicrobial resistance. It has been suggested that rapid viral testing can reduce inappropriate antibiotic prescribing. We aimed to assess the association between rapid viral testing at the Emergency Department (ED) and antibiotic prescription in febrile children. Methods. This study is part of the MOFICHE study, which is an observational multicenter study including routine data of febrile children (0-18 years) attending 12 European EDs. In children with respiratory symptoms visiting 6 EDs equipped with rapid viral testing, we performed multivariable logistic regression analysis regarding rapid viral testing and antibiotic prescription adjusted for patient characteristics, disease severity, diagnostic tests, focus of infection, admission, and ED. Results. A rapid viral test was performed in 1061 children (8%) and not performed in 11,463 children. Rapid viral test usage was not associated with antibiotic prescription (aOR 0.9, 95% CI: 0.8-1.1). A positive rapid viral test was associated with less antibiotic prescription compared with children without test performed (aOR 0.6, 95% CI: 0.5-0.8), which remained significant after adjustment for CRP and chest radiograph result. Twenty percent of the positively tested children received antibiotics. A negative rapid viral test was not associated with antibiotic prescription (aOR 1.2, 95% CI: 1.0-1.4). Conclusions. Rapid viral test usage did not reduce overall antibiotic prescription, whereas a positive rapid viral test did reduce antibiotic prescription at the ED. Implementation of rapid viral testing in routine emergency care and compliance to the rapid viral test outcome will reduce inappropriate antibiotic prescribing at the ED.publishersversionPeer reviewe

A NICE combination for predicting hospitalisation at the Emergency Department : a European multicentre observational study of febrile children

Funding Information: DB, UB, EC, JD, ME, MF, NH, BK, FMT, HM, EL, ML, MP, IRC, FS, MT, CV, SY, DZ and WZ report grants from the European Union. Horizon 2020 research and innovation programme during the study conduct. FS reports a grant from the Slovenian Research Agency outside the submitted work. Funding Information: MP reports a grant from Pfizer and financial support from Pfizer and Sanofi outside the submitted work. MF reports a grant from CSL Behring outside the submitted work. RN reports a grant from the National Institute for Health Research during the study conduct. ME reports financial support from the National Institute for Health Research Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust and Newcastle University ng the study conduct. MT is a member of the Advisory Board of MSD and Pfizer, a member of the National Committee on Immunization Practices and a member of the national Scientific Advisory Group for the management of the pandemic. Publisher Copyright: © 2021 The Author(s)Background: Prolonged Emergency Department (ED) stay causes crowding and negatively impacts quality of care. We developed and validated a prediction model for early identification of febrile children with a high risk of hospitalisation in order to improve ED flow. Methods: The MOFICHE study prospectively collected data on febrile children (0–18 years) presenting to 12 European EDs. A prediction models was constructed using multivariable logistic regression and included patient characteristics available at triage. We determined the discriminative values of the model by calculating the area under the receiver operating curve (AUC). Findings: Of 38,424 paediatric encounters, 9,735 children were admitted to the ward and 157 to the PICU. The prediction model, combining patient characteristics and NICE alarming, yielded an AUC of 0.84 (95%CI 0.83-0.84). The model performed well for a rule-in threshold of 75% (specificity 99.0% (95%CI 98.9-99.1%, positive likelihood ratio 15.1 (95%CI 13.4-17.1), positive predictive value 0.84 (95%CI 0.82-0.86)) and a rule-out threshold of 7.5% (sensitivity 95.4% (95%CI 95.0-95.8), negative likelihood ratio 0.15 (95%CI 0.14-0.16), negative predictive value 0.95 (95%CI 0.95-9.96)). Validation in a separate dataset showed an excellent AUC of 0.91 (95%CI 0.90- 0.93). The model performed well for identifying children needing PICU admission (AUC 0.95, 95%CI 0.93-0.97). A digital calculator was developed to facilitate clinical use. Interpretation: Patient characteristics and NICE alarming signs available at triage can be used to identify febrile children at high risk for hospitalisation and can be used to improve ED flow. Funding: European Union, NIHR, NHS.publishersversionPeer reviewe

Emergency medical services utilisation among febrile children attending emergency departments across Europe:an observational multicentre study

Children constitute 6–10% of all patients attending the emergency department (ED) by emergency medical services (EMS). However, discordant EMS use in children occurs in 37–61% with fever as an important risk factor. We aimed to describe EMS utilisation among febrile children attending European EDs. This study is part of an observational multicentre study assessing management and outcome in febrile children up to 18 years (MOFICHE) attending twelve EDs in eight European countries. Discordant EMS use was defined as the absence of markers of urgency including intermediate/high triage urgency, advanced diagnostics, treatment, and admission in children transferred by EMS. Multivariable logistic regression analyses were performed for the association between (1) EMS use and markers of urgency, and (2) patient characteristics and discordant EMS use after adjusting all analyses for the covariates age, gender, visiting hours, presenting symptoms, and ED setting. A total of 5464 (15%, range 0.1–42%) children attended the ED by EMS. Markers of urgency were more frequently present in the EMS group compared with the non-EMS group. Discordant EMS use occurred in 1601 children (29%, range 1–59%). Age and gender were not associated with discordant EMS use, whereas neurological symptoms were associated with less discordant EMS use (aOR 0.2, 95%CI 0.1–0.2), and attendance out of office hours was associated with more discordant EMS use (aOR 1.6, 95%CI 1.4–1.9). Settings with higher percentage of self-referrals to the ED had more discordant EMS use (p &lt; 0.05). Conclusion: There is large practice variation in EMS use in febrile children attending European EDs. Markers of urgency were more frequently present in children in the EMS group. However, discordant EMS use occurred in 29%. Further research is needed on non-medical factors influencing discordant EMS use in febrile children across Europe, so that pre-emptive strategies can be implemented. What is Known: •Children constitute around 6–10% of all patients attending the emergency department by emergency medical services. •Discordant EMS use occurs in 37–61% of all children, with fever as most common presenting symptom for discordant EMS use in children. What is New: •There is large practice variation in EMS use among febrile children across Europe with discordance EMS use occurring in 29% (range 1–59%), which was associated with attendance during out of office hours and with settings with higher percentage of self-referrals to the ED. •Future research is needed focusing on non-medical factors (socioeconomic status, parental preferences and past experience, healthcare systems, referral pathways, out of hours services provision) that influence discordant EMS use in febrile children across Europe.</p