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  • Terzidis, Emmanouil, 1994, et al. (författare)
  • Tumor volume definitions in head and neck squamous cell carcinoma - Comparing PET/MRI and histopathology
  • 2023
  • Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 180
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: In cancer treatment precise definition of the tumor volume is essential, but despite development in imaging modalities, this remains a challenge. Here, pathological tumor volumes from the surgical specimens were obtained and compared to tumor volumes defined from modern PET/ MRI hybrid imaging. The purpose is to evaluate mismatch between the volumes defined from imaging and pathology was estimated and potential clinical impact.Methods and Materials: Twenty-five patients with head and neck squamous cell carcinoma were scanned on an integrated PET/MRI system prior to surgery. Three gross tumor volumes (GTVs) from the primary tumor site were delineated defined from MRI (GTVMRI), PET (GTVPET) and one by utilizing both anatomical images and clinical information (GTVONCO). Twenty-five primary tumor specimens were extracted en bloc, scanned with PET/MRI and co-registered to the patient images. Each specimen was sectioned in blocks, sliced and stained with haematoxylin and eosin. All slices were digitalized and tumor delineated by a head and neck pathologist. The pathological tumor areas in all slices were interpolated yielding a pathological 3D tumor volume (GTVPATO). GTVPATO was compared with the imaging GTV's and potential mismatch was estimated.Results: Thirteen patients were included. The mean volume of GTVONCO was larger than the GTV's defined from PET or MRI. The mean mismatch of the GTVPATO compared to the GTVPET, GTVMRI and GTVONCO was 31.9 %, 54.5 % and 27.9 % respectively, and the entire GTVPATO was only fully encompassed in GTVONCO in 1 of 13 patients. However, after the addition of a clinical 5 mm margin the GTVPATO was fully encompassed in GTVONCO in 11 out of 13 patients.Conclusions: Despite modern hybrid imaging modalities, a mismatch between imaging and pathological defined tumor volumes was observed in all patients. A 5 mm clinical margin was sufficient to ensure inclusion of the entire pathological volume in 11 out of 13 patients.(c) 2023 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 180 (2023) 1-8 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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  • Laursen, K. R., et al. (författare)
  • An RCT of acute health effects in COPD-patients after passive vape exposure from e-cigarettes
  • 2021
  • Ingår i: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: E-cigarette use has been shown to have short-term acute effects among active users but less is known of the acute passive effects, particularly among individuals with existing respiratory diseases. Objective: To investigate local and systemic effects of short-term passive vape exposure among patients with mild or moderate chronic obstructive pulmonary disease (COPD). Methods: In a double-blinded crossover study 16 non-smoking COPD-patients (mean age 68) were randomly exposed for 4 h to passive vape (median PM2.5: 18 mu g/m(3) (range: 8-333)) and clean air (PM2.5 < 6 mu g/m(3)) separated by 14 days. Particles were measured using an ultrafine particle counter (P-TRAK) and a scanning mobility particle sizer (SMPS). Health effects including Surfactant Protein-A (SP-A) and albumin in exhaled air, spirometry, FeNO, and plasma proteins were evaluated before, right after, and 24 hours after exposure. Participants reported symptoms throughout exposure sessions. Data were analyzed using mixed models. Results: SP-A in exhaled air was negatively affected by exposure to vape and several plasma proteins increased significantly. Throat irritation was more pronounced during passive vape exposure, while FVC and FEV1 decreased, however, not significantly. Conclusions: SP-A in exhaled air and some plasma proteins were affected by passive vape in patients with COPD indicating inflammation, showing that passive vape exposure is potentially harmful.
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  • Barnes, H., et al. (författare)
  • Occupation versus environmental factors in hypersensitivity pneumonitis: population attributable fraction
  • 2020
  • Ingår i: Erj Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 6:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Despite well-documented case series of hypersensitivity pneumonitis (HP), epidemiological data delineating relative contributions of risk factors are sparse. To address this, we estimated HP risk in a case-referent study of occupational and nonoccupational exposures. Methods: We recruited cases of HP by ICD-9 codes from an integrated healthcare delivery system (IHCDS) and a tertiary medical care centre. We drew referents, matched for age and sex, from the IHCDS. Participants underwent comprehensive, structured telephone interviews eliciting details of occupational and home environmental exposures. We employed a hierarchical analytic approach for data reduction based on the false discovery rate method within clusters of exposures. We measured lung function and selected biomarkers in a subset of participants. We used multivariate logistic regression to estimate exposure-associated odds ratios (ORs) and population attributable fractions (PAFs) for HP. Results: We analysed data for 192 HP cases (148 IHCDS; 44 tertiary care) and 229 referents. Occupational exposures combined more than doubled the odds of developing HP (OR 2.67; 95% CI 1.73-4.14) with a PAF of 34% (95% CI 21-46%); nonoccupational bird exposure also doubled the HP odds (OR 2.02; 95% CI 1.13-3.60), with a PAF of 12% (3-21%). Lung function and selected biomarkers did not substantively modify the risk estimates on the basis of questionnaire data alone. Discussion: In a case-referent approach evaluating HP risk, identifiable exposures accounted, on an epidemiological basis, for approximately two in three cases of disease; conversely, for one in three, the risk factors for disease remained elusive.
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  • Ghaderi, A, et al. (författare)
  • A ROR1 Small Molecule Inhibitor (KAN0441571C) Induced Significant Apoptosis of Mantle Cell Lymphoma (MCL) Cells
  • 2022
  • Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 14:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The receptor tyrosine kinase orphan receptor 1 (ROR1) is absent in most normal adult tissues but overexpressed in various malignancies and is of importance for tumor cell survival, proliferation, and metastasis. In this study, we evaluated the apoptotic effects of a novel small molecule inhibitor of ROR1 (KAN0441571C) as well as venetoclax (BCL-2 inhibitor), bendamustine, idelalisib (PI3Kδ inhibitor), everolimus (mTOR inhibitor), and ibrutinib (BTK inhibitor) alone or in combination in human MCL primary cells and cell lines. ROR1 expression was evaluated by flow cytometry and Western blot (WB). Cytotoxicity was analyzed by MTT and apoptosis by Annexin V/PI staining as well as signaling and apoptotic proteins (WB). ROR1 was expressed both in patient-derived MCL cells and human MCL cell lines. KAN0441571C alone induced significant time- and dose-dependent apoptosis of MCL cells. Apoptosis was accompanied by decreased expression of MCL-1 and BCL-2 and cleavage of PARP and caspase 3. ROR1 was dephosphorylated as well as ROR1-associated signaling pathway molecules, including the non-canonical WNT signaling pathway (PI3Kδ/AKT/mTOR). The combination of KAN0441571C and ibrutinib, venetoclax, idelalisib, everolimus, or bendamustine had a synergistic apoptotic effect and significantly prevented phosphorylation of ROR1-associated signaling molecules as compared to KAN0441571C alone. Our results suggest that targeting ROR1 by a small molecule inhibitor, KAN0441571C, should be further evaluated particularly in combination with other targeting drugs as a new therapeutic approach for MCL.
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  • Ghaderi, A, et al. (författare)
  • ROR1 Is Expressed in Diffuse Large B-Cell Lymphoma (DLBCL) and a Small Molecule Inhibitor of ROR1 (KAN0441571C) Induced Apoptosis of Lymphoma Cells
  • 2020
  • Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The receptor tyrosine kinase ROR1 is absent in most normal adult tissues, but overexpressed in several malignancies. In this study, we explored clinical and functional inhibitory aspects of ROR1 in diffuse large B-cell lymphoma (DLBCL). ROR1 expression in tumor cells was more often observed in primary refractory DLBCL, Richter’s syndrome and transformed follicular lymphoma than in relapsed and non-relapsed DLBCL patients (p < 0.001). A survival effect of ROR1 expression was preliminarily observed in relapsed/refractory patients independent of gender and stage but not of age, cell of origin and international prognostic index. A second generation small molecule ROR1 inhibitor (KAN0441571C) induced apoptosis of ROR1+ DLBCL cell lines, similar to venetoclax (BCL-2 inhibitor) but superior to ibrutinib (BTK inhibitor). The combination of KAN0441571C and venetoclax at EC50 concentrations induced almost complete killing of DLBCL cell lines. Apoptosis was accompanied by the downregulation of BCL-2 and MCL-1 and confirmed by the cleavage of PARP and caspases 3, 8, 9. PI3Kδ/AKT/mTOR (non-canonical Wnt pathway) as well as β-catenin and CK1δ (canonical pathway) were inactivated. In zebra fishes transplanted with a ROR1+ DLBCL cell line, KAN0441571C induced a significant tumor reduction. New drugs with mechanisms of action other than those available for DLBCL are warranted. ROR1 inhibitors might represent a novel promising approach.
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  • Hallgren, C., et al. (författare)
  • Validating a Simplified Lung Ultrasound Protocol for Detection and Quantification of Pulmonary Edema in Patients With Chronic Kidney Disease Receiving Maintenance Hemodialysis
  • 2023
  • Ingår i: Journal of Ultrasound in Medicine. - : Wiley. - 0278-4297 .- 1550-9613. ; 42:9, s. 2013-2021
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Pulmonary edema is a common clinical problem and lung ultrasound (LUS) presents an efficient method for evaluating this pathology. This study aims to investigate if a clinically efficient LUS protocol can quantify the level of extravascular lung fluid in patients receiving hemodialysis, and to develop a simplified B-line scoring system based on this protocol.Methods A simple 8-area LUS approach was used for the assessment of the extravascular fluid status in patients before, during, and after receiving hemodialysis. The LUS assessments were compared to the amount of removed fluid over time. To determine the best B-line score system, different scorings for each zone were tested in a linear mixed model with pseudo R-square model fit against removed fluid. The B-line score was further validated through correlations with changes in oxygen saturation, grade of dyspnea, and body weight over time.Results A total of 53 patients were included and examined on 108 hemodialysis occasions. Median fluid removal was 2.3 L. The B-line score model with best fit was a score of 0 points in a zone with 0 or 1 B-lines, 1 point with 2 or 3 B-lines, 2 points with 3 or more B-lines, and 3 points with any interstitial confluence. Using this B-line score, we found a significant association with amount of removed fluid, oxygen saturation, grade of dyspnea, and change in body weight.Conclusion A straightforward protocol for LUS and B-line score system was shown valid for quantification of pulmonary edema and fluid removal in hemodialysis patients. The scoring system developed here can be useful also in other patient groups, but this requires further validation.
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  • Jansen, Willemijn J, et al. (författare)
  • Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
  • 2022
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
  • Tidskriftsartikel (refereegranskat)abstract
    • One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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  • Laursen, K. R., et al. (författare)
  • Airway and systemic biomarkers of health effects after short-term exposure to indoor ultrafine particles from cooking and candles - A randomized controlled double-blind crossover study among mild asthmatic subjects
  • 2023
  • Ingår i: Particle and Fibre Toxicology. - 1743-8977. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThere is insufficient knowledge about the systemic health effects of exposure to fine (PM2.5) and ultrafine particles emitted from typical indoor sources, including cooking and candlelight burning. We examined whether short-term exposure to emissions from cooking and burning candles cause inflammatory changes in young individuals with mild asthma. Thirty-six non-smoking asthmatics participated in a randomized controlled double-blind crossover study attending three exposure sessions (mean PM2.5 & mu;g/m(;)(3) polycyclic aromatic hydrocarbons ng/m(3)): (a) air mixed with emissions from cooking (96.1; 1.1), (b) air mixed with emissions from candles (89.8; 10), and (c) clean filtered air (5.8; 1.0). Emissions were generated in an adjacent chamber and let into a full-scale exposure chamber where participants were exposed for five hours. Several biomarkers were assessed in relation to airway and systemic inflammatory changes; the primary outcomes of interest were surfactant Protein-A (SP-A) and albumin in droplets in exhaled air - novel biomarkers for changes in the surfactant composition of small airways. Secondary outcomes included cytokines in nasal lavage, cytokines, C-reactive protein (CRP), epithelial progenitor cells (EPCs), genotoxicity, gene expression related to DNA-repair, oxidative stress, and inflammation, as well as metabolites in blood. Samples were collected before exposure start, right after exposure and the next morning.ResultsSP-A in droplets in exhaled air showed stable concentrations following candle exposure, while concentrations decreased following cooking and clean air exposure. Albumin in droplets in exhaled air increased following exposure to cooking and candles compared to clean air exposure, although not significant. Oxidatively damaged DNA and concentrations of some lipids and lipoproteins in the blood increased significantly following exposure to cooking. We found no or weak associations between cooking and candle exposure and systemic inflammation biomarkers including cytokines, CRP, and EPCs.ConclusionsCooking and candle emissions induced effects on some of the examined health-related biomarkers, while no effect was observed in others; Oxidatively damaged DNA and concentrations of lipids and lipoproteins were increased in blood after exposure to cooking, while both cooking and candle emissions slightly affected the small airways including the primary outcomes SP-A and albumin. We found only weak associations between the exposures and systemic inflammatory biomarkers. Together, the results show the existence of mild inflammation following cooking and candle exposure.
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  • Lõhmus, Mare, et al. (författare)
  • What makes children learn how to swim? – health, lifestyle and environmental factors associated with swimming ability among children in the city of Malmö, Sweden
  • 2022
  • Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Swimming ability among children in the city of Malmö, Sweden is strongly affected by socioeconomic differences. We investigated to what extent mediating health and lifestyle factors, such as children’s eating, sleeping and physical activity habits, as well as the characteristics of the social and working environment at both school and home, could explain the socioeconomic gradient in swimming ability. Methods: Our study population included children who started their first-grade school-year in 2012 or 2013 at any of the public primary schools of Malmö, Sweden. Cross-sectional, self-reported questionnaire-based data about health status and swimming ability in the fourth grade (age 10) were included from the Pupil Health Database (ELSA) for 3468 children. Results: Children’s self-reported swimming ability was strongly associated with both individual- and school-based sociodemographic variables. Nine health, lifestyle and environmental variables were identified as potential mediators and included in the final model. Four of these variables, “Activity”, “Outdoor time”, “Social relationships at home and on the free time”, and “Positivity about future”, were significantly and positively associated with children’s ability to swim. Conclusions: Social support, optimism for the future and an active lifestyle were positively associated with children’s swimming skills; however, compared to the socioeconomic factors, these health- and lifestyle factors contributed very little. It is possible, that interventions concerning children’s swimming ability in lower socioeconomic neighbourhoods, should in addition to children’s swimming lessons, target the whole families with the goal of increasing their possibilities for socialising and engaging in different kinds of recreational activities.
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  • Munshi, Pashna N., et al. (författare)
  • Age no bar : A CIBMTR analysis of elderly patients undergoing autologous hematopoietic cell transplantation for multiple myeloma
  • 2020
  • Ingår i: Cancer. - : WILEY. - 0008-543X .- 1097-0142. ; 126:23, s. 5077-5087
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. Methods The authors investigated the outcomes of AHCT in patients with MM who were aged >= 70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged >= 70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, aPvalue <.01 was considered to be statistically significant a priori. Results An increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged >= 70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m(2)overall, 58% of the patients aged >= 70 years received Mel at a dose of 140 mg/m(2). On multivariate analysis, patients aged >= 70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1-1.7 [P = .06]), REL (HR, 1.03; 99% CI, 0.9-1.1 [P = 0.6]), PFS (HR, 1.06; 99% CI, 1-1.2 [P = 0.2]), and OS (HR, 1.2; 99% CI, 1-1.4 [P = .02]) compared with the reference group (those aged 60-69 years). In patients aged >= 70 years, Mel administered at a dose of 140 mg/m(2)was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m(2), including day 100 NRM (1% [95% CI, 1%-2%] vs 0% [95% CI, 0%-1%];P = .003]), 2-year PFS (64% [95% CI, 60%-67%] vs 69% [95% CI, 66%-73%];P = .003), and 2-year OS (85% [95% CI, 82%-87%] vs 89% [95% CI, 86%-91%];P = .01]), likely representing frailty. Conclusions The results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups.
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  • Pilgaard, Frida I.H., et al. (författare)
  • Socioeconomic differences in swimming ability among children in Malmö, southern Sweden : Initial results from a community-level intervention
  • 2020
  • Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 48:5, s. 495-501
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To investigate to what extent socioeconomic differences in swimming abilities persist among children in the city of Malmö, Sweden, after a community-level swimming intervention programme in public primary schools. Methods: A compulsory swimming education programme was launched in 2014 in second grade (at age 8) in all public primary schools in Malmö, Sweden. Data for the present study on sociodemographic conditions and self-reported swimming ability in fourth grade (age 10) were used for the last birth cohort unexposed (n = 1695) and the first birth cohort exposed (n = 1773) to the intervention. Results: The swimming ability was 78 and 77%, respectively, in the pre- and post-intervention cohorts. Significantly lower self-reported swimming ability was found both pre- and post-intervention among children with support activities in school, with parents born outside Europe, North America and Australia, with manual working, unemployed or studying parents and in children enrolled in schools with socioeconomic index below median. Conclusions: The findings do not suggest that sociodemographic differences in swimming ability have decreased in the first birth cohort exposed to the community-level intervention in Malmö. Striking differences in self-reported swimming ability were noted when the children reached the fourth grade both pre- and post-intervention with marked lower abilities in socially disadvantaged groups. Monitoring of swimming abilities should continue for the present, and similar interventions aimed at reducing inequalities among children. Efforts to increase water comfort at preschool age ought to be considered.
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  • Tian, H., et al. (författare)
  • A comprehensive quantification of global nitrous oxide sources and sinks
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 586:7828, s. 248-256
  • Tidskriftsartikel (refereegranskat)abstract
    • Nitrous oxide (N2O), like carbon dioxide, is a long-lived greenhouse gas that accumulates in the atmosphere. Over the past 150 years, increasing atmospheric N2O concentrations have contributed to stratospheric ozone depletion1 and climate change2, with the current rate of increase estimated at 2 per cent per decade. Existing national inventories do not provide a full picture of N2O emissions, owing to their omission of natural sources and limitations in methodology for attributing anthropogenic sources. Here we present a global N2O inventory that incorporates both natural and anthropogenic sources and accounts for the interaction between nitrogen additions and the biochemical processes that control N2O emissions. We use bottom-up (inventory, statistical extrapolation of flux measurements, process-based land and ocean modelling) and top-down (atmospheric inversion) approaches to provide a comprehensive quantification of global N2O sources and sinks resulting from 21 natural and human sectors between 1980 and 2016. Global N2O emissions were 17.0 (minimum–maximum estimates: 12.2–23.5) teragrams of nitrogen per year (bottom-up) and 16.9 (15.9–17.7) teragrams of nitrogen per year (top-down) between 2007 and 2016. Global human-induced emissions, which are dominated by nitrogen additions to croplands, increased by 30% over the past four decades to 7.3 (4.2–11.4) teragrams of nitrogen per year. This increase was mainly responsible for the growth in the atmospheric burden. Our findings point to growing N2O emissions in emerging economies—particularly Brazil, China and India. Analysis of process-based model estimates reveals an emerging N2O–climate feedback resulting from interactions between nitrogen additions and climate change. The recent growth in N2O emissions exceeds some of the highest projected emission scenarios3,4, underscoring the urgency to mitigate N2O emissions. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
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