Improved winter data coverage of the Southern Ocean CO2 sink from extrapolation of summertime observations

The Southern Ocean is an important sink of anthropogenic CO2, but it is among the least well-observed ocean basins, and consequentially substantial uncertainties in the CO2 flux reconstruction exist. A recent attempt to address historically sparse wintertime sampling produced ‘pseudo’ wintertime observations of surface pCO2 using subsurface summertime observations south of the Antarctic Polar Front. Here, we present an estimate of the Southern Ocean CO2 sink that combines a machine learning-based mapping method with an updated set of pseudo observations that increases regional wintertime data coverage by 68 compared with the historical dataset. Our results confirm the suggestion that improved winter coverage has a modest impact on the reconstruction, slightly strengthening the uptake trend in the 2000s. After also adjusting for surface boundary layer temperature effects, we find a 2004-2018 mean sink of −0.16 ± 0.07 PgC yr−1 south of the Polar Front and −1.27 ± 0.23 PgC yr−1 south of 35°S, consistent with independent estimates from atmospheric data. © 2022, The Author(s)

Towards understanding the variability in biospheric CO2 fluxes:Using FTIR spectrometry and a chemical transport model to investigate the sources and sinks of carbonyl sulfide and its link to CO2

Understanding carbon dioxide (CO2) biospheric processes is of great importance because the terrestrial exchange drives the seasonal and interannual variability of CO2 in the atmosphere. Atmospheric inversions based on CO2 concentration measurements alone can only determine net biosphere fluxes, but not differentiate between photosynthesis (uptake) and respiration (production). Carbonyl sulfide (OCS) could provide an important additional constraint: it is also taken up by plants during photosynthesis but not emitted during respiration, and therefore is a potential means to differentiate between these processes. Solar absorption Fourier Transform InfraRed (FTIR) spectrometry allows for the retrievals of the atmospheric concentrations of both CO2 and OCS from measured solar absorption spectra. Here, we investigate co-located and quasi-simultaneous FTIR measurements of OCS and CO2 performed at five selected sites located in the Northern Hemisphere. These measurements are compared to simulations of OCS and CO2 using a chemical transport model (GEOS-Chem). The coupled biospheric fluxes of OCS and CO2 from the simple biosphere model (SiB) are used in the study. The CO2 simulation with SiB fluxes agrees with the measurements well, while the OCS simulation reproduced a weaker drawdown than FTIR measurements at selected sites, and a smaller latitudinal gradient in the Northern Hemisphere during growing season when comparing with HIPPO (HIAPER Pole-to-Pole Observations) data spanning both hemispheres. An offset in the timing of the seasonal cycle minimum between SiB simulation and measurements is also seen. Using OCS as a photosynthesis proxy can help to understand how the biospheric processes are reproduced in models and to further understand the carbon cycle in the real world

COVID-19: UK frontline intensivists' emerging learning.

The Intensive Care Society held a webinar on 3 April 2020 at which representatives from 11 of the most COVID-19 experienced hospital trusts in England and Wales shared learning around five specific topic areas in an open forum. This paper summarises the emerging learning and practice shared by those frontline clinicians

Variability of North Atlantic CO2 fluxes for the 2000-2017 period estimated from atmospheric inverse analyses

This is the final version. Available on open access from the European Geosciences Union via the DOI in this recordData availability: The data sources are the following: (i) Atmospheric CO2 measurements were taken from obspack_co2_1_GLOBALVIEWplus_v4.2_2019-03-19 (https://gml.noaa.gov/ccgg/obspack/data.php?id=obspack_co2_1_GLOBALVIEWplus_v4.2_2019-03-19, (ObsPack, Cooperative Global Atmospheric Data Integration Project, 2018, last access: 14 October 2020); (ii) Prior ocean flux oc_v1.7 from Rödenbeck et al. (2013) were taken from http://www.bgc-jena.mpg.de/CarboScope/ (last access: 5 June 2020). Prior ocean flux from Landschützer et al. (2016) were taken from https://www.ncei.noaa.gov/access/ocean-carbon-data-system/oceans/SPCO2_1982_present_ETH_SOM_FFN.html (last access: 6 May 2020). Prior ocean flux from Takahashi et al. (2009) were taken from ftp://ftp.as.harvard.edu/gcgrid/geos-chem (last access: 9 July 2018). (iii) CarbonTracker CT2019 results were provided by NOAA ESRL, Boulder, Colorado, USA, from the website at http://carbontracker.noaa.gov (Jacobson et al., 2020, last access: 15 May 2020). CTE flux estimates were downloaded from ftp://ftp.wur.nl/carbontracker/data/fluxes/data_flux1x1_monthly/ (van der Laan-Luijkx et al., 2017, last access: 24 November 2020). The flux estimates from CAMS (v18r2) were taken from https://apps.ecmwf.int/datasets/data/cams-ghg-inversions/ (Chevallier et al., 2019, last access: 6 December 2019). (iv) The model CO2 fluxes for JULES (land) and GOBMs (ocean) were taken from Le Quéré et al. (2018). Time series of reconstructed surface ocean pCO2 and CO2 fluxes (LSCE-FFNN) from Denvil-Sommer et al. (2019) are the first version of CMEMS, downloaded from https://resources.marine.copernicus.eu/?option=com_csw&task=results (last access: 14 January 2021). The products from Iida et al. (2015) were downloaded from http://www.data.jma.go.jp/gmd/kaiyou/english/co2_flux/co2_flux_data_en.html (last access: 14 January 2021). The products from Zeng et al. (2015) were downloaded from https://db.cger.nies.go.jp/DL/10.17595/20201020.001.html.en (last access: 14 January 2021). The products from CMEMS, CSIR, and Watson were taken from Friedlingstein et al. (2020).We present new estimates of the regional North Atlantic (15–80∘ N) CO2 flux for the 2000–2017 period using atmospheric CO2 measurements from the NOAA long-term surface site network in combination with an atmospheric carbon cycle data assimilation system (GEOS-Chem–LETKF, Local Ensemble Transform Kalman Filter). We assess the sensitivity of flux estimates to alternative ocean CO2 prior flux distributions and to the specification of uncertainties associated with ocean fluxes. We present a new scheme to characterize uncertainty in ocean prior fluxes, derived from a set of eight surface pCO2-based ocean flux products, and which reflects uncertainties associated with measurement density and pCO2-interpolation methods. This scheme provides improved model performance in comparison to fixed prior uncertainty schemes, based on metrics of model–observation differences at the network of surface sites. Long-term average posterior flux estimates for the 2000–2017 period from our GEOS-Chem–LETKF analyses are −0.255 ± 0.037 PgC yr−1 for the subtropical basin (15–50∘ N) and −0.203 ± 0.037 PgC yr−1 for the subpolar region (50–80∘ N, eastern boundary at 20∘ E). Our basin-scale estimates of interannual variability (IAV) are 0.036 ± 0.006 and 0.034 ± 0.009 PgC yr−1 for subtropical and subpolar regions, respectively. We find statistically significant trends in carbon uptake for the subtropical and subpolar North Atlantic of −0.064 ± 0.007 and −0.063 ± 0.008 PgC yr−1 decade−1; these trends are of comparable magnitude to estimates from surface ocean pCO2-based flux products, but they are larger, by a factor of 3–4, than trends estimated from global ocean biogeochemistry models.Natural Environment Research Council (NERC

CD28 between tolerance and autoimmunity: The side effects of animal models [version 1; referees: 2 approved]

Regulation of immune responses is critical for ensuring pathogen clearance and for preventing reaction against self-antigens. Failure or breakdown of immunological tolerance results in autoimmunity. CD28 is an important co-stimulatory receptor expressed on T cells that, upon specific ligand binding, delivers signals essential for full T-cell activation and for the development and homeostasis of suppressive regulatory T cells. Many in vivo mouse models have been used for understanding the role of CD28 in the maintenance of immune homeostasis, thus leading to the development of CD28 signaling modulators that have been approved for the treatment of some autoimmune diseases. Despite all of this progress, a deeper understanding of the differences between the mouse and human receptor is required to allow a safe translation of pre-clinical studies in efficient therapies. In this review, we discuss the role of CD28 in tolerance and autoimmunity and the clinical efficacy of drugs that block or enhance CD28 signaling, by highlighting the success and failure of pre-clinical studies, when translated to humans

Characterization of a New Mouse Model for Peripheral T Cell Lymphoma in Humans

Peripheral T cell lymphomas (PTCLs) are associated with a poor prognosis due to often advanced disease at the time of diagnosis and due to a lack of efficient therapeutic options. Therefore, appropriate animal models of PTCL are vital to improve clinical management of this disease. Here, we describe a monoclonal CD8+ CD4− αβ T cell receptor Vβ2+ CD28+ T cell lymphoma line, termed T8-28. T8-28 cells were isolated from an un-manipulated adult BALB/c mouse housed under standard pathogen-free conditions. T8-28 cells induced terminal malignancy upon adoptive transfer into syngeneic BALB/c mice. Despite intracellular expression of the cytotoxic T cell differentiation marker granzyme B, T8-28 cells appeared to be defective with respect to cytotoxic activity as read-out in vitro. Among the protocols tested, only addition of interleukin 2 in vitro could partially compensate for the in vivo micro-milieu in promoting growth of the T8-28 lymphoma cells

Chronic Thromboembolic Pulmonary Hypertension

The pulmonary hypertension (PH) and right heart dysfunction that results from chronic thromboembolic involvement of the pulmonary vascular bed is potentially curable with surgical endarterectomy. Over the past several decades, growing clinical experience has brought about increased recognition of this treatable form of PH. Moreover, advances in cardiothoracic surgical techniques have given an increasing number of patients with chronic thromboembolic PH (CTEPH) a surgical remedy with decreasing perioperative morbidity and mortality risks. The availability of pulmonary hypertensive—specific medical therapy for CTEPH patients with surgically inaccessible disease also has been a positive therapeutic advance over the past several years. However, despite this progress, chronic thromboembolic disease as a sequela of acute pulmonary emboli continues to be underappreciated. Furthermore, even if CTEPH has been appropriately diagnosed, misinterpretation of diagnostic information may lead to the inappropriate exclusion of patients from surgical consideration. This may result in the prescription of pulmonary hypertensive medical therapy in CTEPH patients with potentially surgically correctable disease. This difficulty arises from a lack of objective criteria as to what constitutes surgical chronic thromboembolic disease, which primarily is a result of the variability in surgical experience in specialty centers in the United States. Consequently, clinicians must be wary about using pulmonary hypertensive medications in CTEPH patients. Before prescription, it is important to exclude patients from surgical consideration by consulting a specialized center with expertise in this discipline

CpG site degeneration triggered by the loss of functional constraint created a highly polymorphic macaque drug-metabolizing gene, CYP1A2

<p>Abstract</p> <p>Background</p> <p>Elucidating the pattern of evolutionary changes in drug-metabolizing genes is an important subject not only for evolutionary but for biomedical research. We investigated the pattern of divergence and polymorphisms of macaque <it>CYP1A1 </it>and <it>CYP1A2 </it>genes, which are major drug-metabolizing genes in humans. In humans, <it>CYP1A2 </it>is specifically expressed in livers while <it>CYP1A1 </it>has a wider gene expression pattern in extrahepatic tissues. In contrast, macaque <it>CYP1A2 </it>is expressed at a much lower level than <it>CYP1A1 </it>in livers. Interestingly, a previous study has shown that <it>Macaca fascicularis CYP1A2 </it>harbored unusually high genetic diversity within species. Genomic regions showing high genetic diversity within species is occasionally interpreted as a result of balancing selection, where natural selection maintains highly diverged alleles with different functions. Nevertheless many other forces could create such signatures.</p> <p>Results</p> <p>We found that the <it>CYP1A1/2 </it>gene copy number and orientation has been highly conserved among mammalian genomes. The signature of gene conversion between <it>CYP1A1 </it>and <it>CYP1A2 </it>was detected, but the last gene conversion event in the simian primate lineage occurred before the <it>Catarrhini-Platyrrhini </it>divergence. The high genetic diversity of macaque <it>CYP1A2 </it>therefore cannot be explained by gene conversion between <it>CYP1A1 </it>and <it>CYP1A2</it>. By surveying <it>CYP1A2 </it>polymorphisms in total 91 <it>M. fascicularis </it>and <it>M. mulatta</it>, we found several null alleles segregating in these species, indicating functional constraint on <it>CYP1A2 </it>in macaques may have weakened after the divergence between humans and macaques. We propose that the high genetic diversity in macaque <it>CYP1A2 </it>is partly due to the degeneration of CpG sites, which had been maintained at a high level by purifying selection, and the rapid degeneration process was initiated by the loss of functional constraint on macaque <it>CYP1A2</it>.</p> <p>Conclusions</p> <p>Our findings show that the highly polymorphic <it>CYP1A2 </it>gene in macaques has not been created by balancing selection but by the burst of CpG site degeneration after loss of functional constraint. Because the functional importance of <it>CYP1A1/2 </it>genes is different between humans and macaques, we have to be cautious in extrapolating a drug-testing data using substrates metabolized by <it>CYP1A </it>genes from macaques to humans, despite of their somewhat overlapping substrate specificity.</p

Introducing a new ICRU report: Prescribing, recording and reporting electron beam therapy

The ICRU published several Reports about volumes and doses specifications for radiotherapy, such as the Report 29 (1978), devoted to photon and electron beam therapy. This report 29 becoming absolete, a new Report was published in 1993 for external photon beam radiotherapy, the Report 50, recommending new definitions and more accurate specifications. With electran beams specific problems are raised, and the ICRU considered suitable to prepare a special Report for them, to be published in the near future.The main features of the present draft are as follows:1.Volumes specifications in agreement with the ICRU Report 50,•Volumes to be determined before treatment planning: gross tumour volume (GTV), c1inical target volume (CTV), organs at risk volumes (OR).•Volume to be determined during treatment planning: Planning target volume (PTV).•Volumes resulting fram the treatment plan chosen: treatment volume (TV), irradiated volume (IV).In the future Report on electron beams, an additional volume is defined, the internal target volume (ITV) geometrical concept representing the volume en-compassing the c1inical target volume, taking into consideration margins due to the variations of the clinical target volume in position, shape an size. A similar concept has been extended to organs at risk, the planning organ at risk volume.2.Dose specificationThe general statements for photon beams apply:•dose at a reference point (ICRU point) situated at or near the center of the planning target volume and, when possible, near or on the central axis of the electron beam at the depth of the peak dose.•Minimal and maximal doses in the planning target volume•Dose delivered to the organs at risk•Additional information is recommended, when possible (e.g. DVH).With electron beams, the dose homogeneity expected within the PTV (± 5 to ± 10 %) requires an adaptation of the terapeutic range concept, such that the value of the isodose surface encompassing the PTV be situated between 85 % and 95 % of the reference dose. The peak absorbed dose on the beam axis should always been specified, even if it is different fram the reference dose.At last, as in Report 50, three levels of dose evaluation for reporting are considered, depending on the aim of the treatment and the data available