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Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere in a changing climate is critical to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe and synthesize data sets and methodologies to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions (EFOS) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on land use and land-use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly, and its growth rate (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) is estimated with global ocean biogeochemistry models and observation-based data products. The terrestrial CO2 sink (SLAND) is estimated with dynamic global vegetation models. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the year 2021, EFOS increased by 5.1 % relative to 2020, with fossil emissions at 10.1 ± 0.5 GtC yr−1 (9.9 ± 0.5 GtC yr−1 when the cement carbonation sink is included), and ELUC was 1.1 ± 0.7 GtC yr−1, for a total anthropogenic CO2 emission (including the cement carbonation sink) of 10.9 ± 0.8 GtC yr−1 (40.0 ± 2.9 GtCO2). Also, for 2021, GATM was 5.2 ± 0.2 GtC yr−1 (2.5 ± 0.1 ppm yr−1), SOCEAN was 2.9 ± 0.4 GtC yr−1, and SLAND was 3.5 ± 0.9 GtC yr−1, with a BIM of −0.6 GtC yr−1 (i.e. the total estimated sources were too low or sinks were too high). The global atmospheric CO2 concentration averaged over 2021 reached 414.71 ± 0.1 ppm. Preliminary data for 2022 suggest an increase in EFOS relative to 2021 of +1.0 % (0.1 % to 1.9 %) globally and atmospheric CO2 concentration reaching 417.2 ppm, more than 50 % above pre-industrial levels (around 278 ppm). Overall, the mean and trend in the components of the global carbon budget are consistently estimated over the period 1959–2021, but discrepancies of up to 1 GtC yr−1 persist for the representation of annual to semi-decadal variability in CO2 fluxes. Comparison of estimates from multiple approaches and observations shows (1) a persistent large uncertainty in the estimate of land-use change emissions, (2) a low agreement between the different methods on the magnitude of the land CO2 flux in the northern extratropics, and (3) a discrepancy between the different methods on the strength of the ocean sink over the last decade. This living data update documents changes in the methods and data sets used in this new global carbon budget and the progress in understanding of the global carbon cycle compared with previous publications of this data set. The data presented in this work are available at https://doi.org/10.18160/GCP-2022 (Friedlingstein et al., 2022b).

Public health emergencies often affect Poison Control Centre (PCC) operations. We examined possible effects of the coronavirus disease 2019 (COVID-19) pandemic on call volume, call characteristics, and workload in European PCCs. All 65 individual European PCCs were requested to supply data on the number of calls and call characteristics (caller, age groups, reason and specific exposures) from March to June in 2018, 2019, and 2020 (Part 1). Number of calls with specific characteristics was normalised to all calls. Calls (N) and call characteristics (%) were compared between 2020 and 2018/2019 (average), within PCCs/countries and grouped. Correlation between call volume and COVID-19 cases per PCC/country was examined. All PCCs received a survey on workload (Part 2). Parts 1 and 2 were independent. For Part 1, 36 PCCs (21 countries) supplied 26 datasheets. PCCs in the UK and in France merged data and supplied one datasheet each with national data. Summed data showed an increase of 4.5% in call volume from 228.794 in 2018/2019 (average) to 239.170 in 2020 (p < 0.001). Within PCCs/countries, calls significantly increased for 54% of PCCs/countries (N = 14/26) and decreased for 19% (N = 5/26), three of which (N = 3/5) only serve medical professionals. Correlation between call volume and COVID-19 cases was (non-significant) positive (Rho >0.7) in 5/26 PCCs/countries (19%), and negative in 6/26 (23%). Call characteristics (median proportion of grouped data in 2018/2019 vs. 2020) changed: fewer medical professionals called (40 vs. 34%, p < 0.001), calls on intentional exposures decreased (20 vs. 17%, p < 0.012), as did calls on patients between 13 and 17 years (5 vs. 4%, p < 0.05). Calls on specific exposures increased; disinfectants from 1.9 to 5.2%, and cleaning products from 4.4 to 5.7% (p < 0.001). For Part 2, 38 PCCs (24 countries) filled the survey on workload (number/length of shifts and time on PCC duties), which increased in 23/38 PCCs (61%), while 10/38 (26%) worked with fewer employees. Obtaining aggregated European PCC data proved challenging but showed an increase in overall call volume and workload during the first COVID-19 wave. Call characteristics changed including fewer calls from professionals and more calls on specific exposures. Within single PCCs/countries a variety of effects was observed.

With a view to developing a much-needed non-invasive method for monitoring the healthy pluripotent state of human stem cells in culture, we undertook proteomic analysis of the spent medium from cultured embryonic (Man-13) and induced (Rebl.PAT) human pluripotent stem cells (hPSCs). Cells were grown in E8 medium to maintain pluripotency, and then transferred to FGF2 and TGFβ deficient media for 48 hours to replicate an early, undirected dissolution of pluripotency.We identified a distinct proteomic footprint associated with early loss of pluripotency in both hPSC lines, and a strong correlation with changes in the transcriptome. We demonstrate that multiplexing of 4 E8-against 4 E6-enriched biomarkers provides 16 ratio abundances which are each robustly diagnostic for pluripotent state. These biomarkers were further confirmed by Western blotting which demonstrated consistent correlation with the pluripotent state across cell lines, and in response to recovery assays.

BackgroundHeterozygous variants in the cardiac ryanodine receptor gene (RYR2) cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Most pathogenic RYR2 variants are missense variants which result in a gain of function, causing ryanodine receptors to be increasingly sensitive to activation by calcium, have an increased open probability and an increased propensity to develop calcium waves. However, some RYR2 variants can lead to arrhythmias by a loss of function mechanism.ObjectiveTo understand the mechanism by which a novel nonsense variant in RYR2 p.(Arg4790Ter) leads to ventricular arrhythmias.MethodsHuman induced pluripotent stem cells (hiPSCs) harbouring the novel nonsense variant in RYR2 were differentiated into cardiomyocytes (RYR2-hiPSC-CMs) and molecular and calcium handling properties were studied.ResultsRYR2-hiPSC-CMs displayed significant calcium handling abnormalities at baseline and following treatment with isoproterenol. Treatment with carvedilol and nebivolol resulted in a significant reduction in calcium handling abnormalities in the RYR2-hiPSC-CMs. Expression of the mutant RYR2 allele was confirmed at the mRNA level and partial silencing of the mutant allele resulted in a reduction in calcium handling abnormalities at baseline.ConclusionThe nonsense variant behaves similarly to other gain of function variants in RYR2. Carvedilol and nebivolol may be suitable treatments for patients with gain of function RYR2 variants.

Accurate assessment of anthropogenic carbon dioxide (CO$_{2}$) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere in a changing climate – the “global carbon budget” – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe and synthesize data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO$_{2}$ emissions (E$_{FOS}$) are based on energy statistics and cement production data, while emissions from land-use change (E$_{LUC}$), mainly deforestation, are based on land use and land-use change data and bookkeeping models. Atmospheric CO$_{2}$ concentration is measured directly and its growth rate (G$_{ATM}$) is computed from the annual changes in concentration. The ocean CO$_{2}$ sink (S$_{OCEAN}$) and terrestrial CO$_{2}$ sink (S$_{LAND}$) are estimated with global process models constrained by observations. The resulting carbon budget imbalance (B$_{IM}$), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the last decade available (2010–2019), E$_{FOS}$ was 9.6 ± 0.5 GtC yr$^{-1}$ excluding the cement carbonation sink (9.4 ± 0.5 GtC yr−1 when the cement carbonation sink is included), and E$_{LUC}$ was 1.6 ± 0.7 GtC yr$^{-1}$. For the same decade, G$_{ATM}$ was 5.1 ± 0.02 GtC yr$^{-1}$ (2.4 ± 0.01 ppm yr$_{-1}$), S$_{OCEAN}$ 2.5 ± 0.6 GtC yr$^{-1}$, and S$_{LAND}$ 3.4 ± 0.9 GtC yr$^{-1}$, with a budget imbalance B$_{IM}$ of −0.1 GtC yr$^{-1}$ indicating a near balance between estimated sources and sinks over the last decade. For the year 2019 alone, the growth in E$_{FOS}$ was only about 0.1 % with fossil emissions increasing to 9.9 ± 0.5 GtC yr$^{-1}$ excluding the cement carbonation sink (9.7 ± 0.5 GtC yr$^{-1}$ when cement carbonation sink is included), and E$_{LUC}$ was 1.8 ± 0.7 GtC yr$^{-1}$, for total anthropogenic CO$_{2}$ emissions of 11.5 ± 0.9 GtC yr$^{-1}$ (42.2 ± 3.3 GtCO$_{2}$). Also for 2019, G$_{ATM}$ was 5.4 ± 0.2 GtC yr$^{-1}$ (2.5 ± 0.1 ppm yr$^{-1}$), S$_{OCEAN}$ was 2.6 ± 0.6 GtC yr$^{-1}$, and S$_{LAND}$ was 3.1 ± 1.2 GtC yr$^{-1}$, with a B$_{IM}$ of 0.3 GtC. The global atmospheric CO$_{2}$ concentration reached 409.85 ± 0.1 ppm averaged over 2019. Preliminary data for 2020, accounting for the COVID-19-induced changes in emissions, suggest a decrease in E$_{FOS}$ relative to 2019 of about −7 % (median estimate) based on individual estimates from four studies of −6 %, −7 %, −7 % (−3 % to −11 %), and −13 %. Overall, the mean and trend in the components of the global carbon budget are consistently estimated over the period 1959–2019, but discrepancies of up to 1 GtC yr$^{-1}$ persist for the representation of semi-decadal variability in CO$_{2}$ fluxes. Comparison of estimates from diverse approaches and observations shows (1) no consensus in the mean and trend in land-use change emissions over the last decade, (2) a persistent low agreement between the different methods on the magnitude of the land CO$_{2}$ flux in the northern extra-tropics, and (3) an apparent discrepancy between the different methods for the ocean sink outside the tropics, particularly in the Southern Ocean. This living data update documents changes in the methods and data sets used in this new global carbon budget and the progress in understanding of the global carbon cycle compared with previous publications of this data set (Friedlingstein et al., 2019; Le Quéré et al., 2018b, a, 2016, 2015b, a, 2014, 2013). The data presented in this work are available at https://doi.org/10.18160/gcp-2020 (Friedlingstein et al., 2020).

At present, although seasonal sea-ice cover mitigates atmosphere-ocean gas exchange, the Arctic Ocean takes up carbon dioxide (CO2) on the order of −66 to −199 Tg C year−1 (1012 g C), contributing 5–14% to the global balance of CO2 sinks and sources. Because of this, the Arctic Ocean has an important influence on the global carbon cycle, with the marine carbon cycle and atmosphere-ocean CO2 exchanges sensitive to Arctic Ocean and global climate change feedbacks. In the near-term, further sea-ice loss and increases in phytoplankton growth rates are expected to increase the uptake of CO2 by Arctic Ocean surface waters, although mitigated somewhat by surface warming in the Arctic. Thus, the capacity of the Arctic Ocean to uptake CO2 is expected to alter in response to environmental changes driven largely by climate. These changes are likely to continue to modify the physics, biogeochemistry, and ecology of the Arctic Ocean in ways that are not yet fully understood. In surface waters, sea-ice melt, river runoff, cooling and uptake of CO2 through air-sea gas exchange combine to decrease the calcium carbonate (CaCO3) mineral saturation states (Ω) of seawater while seasonal phytoplankton primary production (PP) mitigates this effect. Biological amplification of ocean acidification effects in subsurface waters, due to the remineralization of organic matter, is likely to reduce the ability of many species to produce CaCO3 shells or tests with profound implications for Arctic marine ecosystems

The performance of 36 models (22 ocean color models and 14 biogeochemical ocean circulation models (BOGCMs)) that estimate depth-integrated marine net primary productivity (NPP) was assessed by comparing their output to in situ 14C data at the Bermuda Atlantic Time series Study (BATS) and the Hawaii Ocean Time series (HOT) over nearly two decades. Specifically, skill was assessed based on the models' ability to estimate the observed mean, variability, and trends of NPP. At both sites, more than 90% of the models underestimated mean NPP, with the average bias of the BOGCMs being nearly twice that of the ocean color models. However, the difference in overall skill between the best BOGCM and the best ocean color model at each site was not significant. Between 1989 and 2007, in situ NPP at BATS and HOT increased by an average of nearly 2% per year and was positively correlated to the North Pacific Gyre Oscillation index. The majority of ocean color models produced in situ NPP trends that were closer to the observed trends when chlorophyll-a was derived from high-performance liquid chromatography (HPLC), rather than fluorometric or SeaWiFS data. However, this was a function of time such that average trend magnitude was more accurately estimated over longer time periods. Among BOGCMs, only two individual models successfully produced an increasing NPP trend (one model at each site). We caution against the use of models to assess multiannual changes in NPP over short time periods. Ocean color model estimates of NPP trends could improve if more high quality HPLC chlorophyll-a time series were available. © 2010 by the American Geophysical Union.

There have been few previous studies of surface seawater CO2 partial pressure (pCO2) variability and air-sea CO2 gas exchange rates for the Bering Sea shelf. In 2008, spring and summertime observations were collected in the Bering Sea shelf as part of the Bering Sea Ecological Study (BEST). Our results indicate that the Bering Sea shelf was close to neutral in terms of CO2 sink-source status in springtime due to relatively small air-sea CO2 gradients (i.e., ΔpCO2 and sea-ice cover. However, by summertime, very low seawater pCO2 values were observed and much of the Bering Sea shelf became strongly undersaturated with respect to atmospheric CO2 concentrations. Thus the Bering Sea shelf transitions seasonally from mostly neutral conditions to a strong oceanic sink for atmospheric CO2 particularly in the "green belt" region of the Bering Sea where there are high rates of phytoplankton primary production (PP)and net community production (NCP). Ocean biological processes dominate the seasonal drawdown of seawater pCO2 for large areas of the Bering Sea shelf, with the effect partly countered by seasonal warming. In small areas of the Bering Sea shelf south of the Pribilof Islands and in the SE Bering Sea, seasonal warming is the dominant influence on seawater pCO2, shifting localized areas of the shelf from minor/neutral CO2 sink status to neutral/minor CO2 source status, in contrast to much of the Bering Sea shelf. Overall, we compute that the Bering Sea shelf CO2 sink in 2008 was 157 ± 35 Tg C yr−1 (Tg = 1012 g C) and thus a strong sink for CO2.

The Multi-Spectral Imager (MSI) will be flown on board the EarthCARE spacecraft, under development by the European Space Agency (ESA) and the Japan Aerospace Exploration Agency (JAXA). The fundamental objective of the EarthCARE mission is improving the understanding of the processes involving clouds, aerosols and radiation in the Earth's atmosphere. In addition to the MSI instrument, a Cloud Profiling Radar (CPR), an Atmospheric Lidar (ATLID), and a Broadband Radiometer (BBR) complete the payload of the EarthCARE satellite. By acquiring images of the clouds and aerosol distribution, the MSI instrument will provide important contextual information in support of the radar and lidar geophysical retrievals. The MSI development philosophy is based on the early development of an Engineering Confidence Model (ECM) and the subsequent development of a Proto-flight Model, the model to be launched on-board the EarthCARE satellite. This paper provides an overview of the MSI instrument and its development approach. A description of the ECM and its verification program is also provided. © 2012 SPIE.