Esophageal tracheobronchoplasty for diseases of the central airway

AbstractThree infants with congenital tracheal stenosis and three adults with various diseases of the central airway underwent esophageal tracheobronchoplasty to repair long-segment stenoses and defects. The primary operative goal was enlargement of the stenosis ( n = 4), repair of the defect ( n = 1), or both ( n = 1). Cardiopulmonary support was required in two cases. All three infants were operated on for generalized congenital tracheal stenoses. There was one postoperative death on the fifth day. Another infant died of pneumonia 3 months after operation. Tracheal patency was excellent in two infants. One infant is well without symptoms 6 years after the operation, although balloon dilation was required three times during the first postoperative year. In the three adult patients, the primary diseases were congenital tracheal stenosis, iatrogenic injury associated with relapsing polychondritis, and malignant mediastinal tumor involving the trachea. All lesions involved both the trachea and main stem bronchi. Postoperative airway patency was excellent in all three adults, although expandable metallic stents had to be inserted in one patient. Postoperative pulmonary function was improved, particularly forced expiratory volume in 1 second and peak expiratory flow rate. Although the postoperative mortality rate was still high, especially among the infants, and prolonged postoperative ventilatory support was required for five of the six patients, long-term patency and postoperative pulmonary functional improvement are encouraging. (J Thorac Cardiovasc Surg 1996;112:124-9

The antiretroviral potency of APOBEC1 deaminase from small animal species

Although the role of the APOBEC3-dependent retroelement restriction system as an intrinsic immune defense against human immunodeficiency virus type1 (HIV-1) infection is becoming clear, only the rat ortholog of mammalian APOBEC1s (A1) thus far has been shown to possess antiviral activity. Here, we cloned A1 cDNAs from small animal species, and showed that similar to rat A1, both wild-type and Δvif HIV-1 infection was inhibited by mouse and hamster A1 (4- to 10-fold), whereas human A1 had negligible effects. Moreover, rabbit A1 significantly reduced the infectivity of both HIV-1 virions (>300-fold), as well as that of SIVmac, SIVagm, FIV and murine leukemia virus. Immunoblot analysis showed that A1s were efficiently incorporated into the HIV-1 virion, and their packaging is mediated through an interaction with the nucleocapsid Gag domain. Interestingly, there was a clear accumulation of particular C-T changes in the genomic RNAs of HIV-1 produced in their presence, with few G-A changes in the proviral DNA. Together, these data reveal that A1 may function as a defense mechanism, regulating retroelements in a wide range of mammalian species

Intercomparison of atmospheric Carbonyl Sulfide (TransCom-COS; Part one): Evaluating the impact of transport and emissions on tropospheric variability using ground-based and aircraft data

We present a comparison of atmospheric transport model simulations for carbonyl sulfide (COS), within the framework of the ongoing atmospheric tracer transport model intercomparison project “TransCom”. Seven atmospheric transport models participated in the inter-comparison experiment and provided simulations of COS mixing ratios in the troposphere over a 9-year period (2010–2018), using prescribed state-of-the-art surface fluxes for various components of the atmospheric COS budget: biospheric sink, oceanic source, sources from fire and industry. Since the biosphere is the largest sink of COS, we tested sink estimates produced by two different biosphere models. The main goals of TransCom-COS are (a) to investigate the impact of the transport uncertainty and emission distribution in simulating the spatio-temporal variability of COS mixing ratios in the troposphere, and (b) to assess the sensitivity of simulated tropospheric COS mixing ratios to the seasonal and diurnal variability of the COS biosphere fluxes. To this end, a control case with state-of-the-art seasonal fluxes of COS was constructed. Models were run with the same fluxes and without chemistry to isolate transport differences. Further, two COS flux scenarios were compared: one using a biosphere flux with a monthly time resolution and the other using a biosphere flux with a three-hourly time resolution. In addition, we investigated the sensitivity of the simulated concentrations to different biosphere fluxes and to indirect oceanic emissions through dimethylsulfide (DMS) and carbon disulfide (CS2). The modelled COS mixing ratios were assessed against in-situ observations from surface stations and aircraft

Global Carbon Budget 2022

Accurate assessment of anthropogenic carbon dioxide (CO$_2$) 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 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$_{OCEAN}$) is estimated with global ocean biogeochemistry models and observation-based data products. The terrestrial CO$_2$ sink (S$_{LAND}$) is estimated with dynamic global vegetation models. 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 year 2021, E$_{FOS}$ 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 E$_{LUC}$ was 1.1 ± 0.7 GtC yr$^{−1}$, for a total anthropogenic CO$_2$ emission (including the cement carbonation sink) of 10.9 ± 0.8 GtC yr$^{−1}$ (40.0 ± 2.9 GtCO$_2$). Also, for 2021, G$_{ATM}$ was 5.2 ± 0.2 GtC yr$^{−1}$ (2.5 ± 0.1 ppm yr$^{−1}$), S$_{OCEAN}$ was 2.9  ± 0.4 GtC yr$^{−1}$, and S$_{LAND}$ was 3.5 ± 0.9 GtC yr$^{−1}$, with a B$_{IM}$ of −0.6 GtC yr$^{−1}$ (i.e. the total estimated sources were too low or sinks were too high). The global atmospheric CO$_2$ concentration averaged over 2021 reached 414.71 ± 0.1 ppm. Preliminary data for 2022 suggest an increase in E$_{FOS}$ relative to 2021 of +1.0 % (0.1 % to 1.9 %) globally and atmospheric CO$_2$ 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 CO$_2$ 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 CO$_2$ 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)

Resolving early mesoderm diversification through single-cell expression profiling.

In mammals, specification of the three major germ layers occurs during gastrulation, when cells ingressing through the primitive streak differentiate into the precursor cells of major organ systems. However, the molecular mechanisms underlying this process remain unclear, as numbers of gastrulating cells are very limited. In the mouse embryo at embryonic day 6.5, cells located at the junction between the extra-embryonic region and the epiblast on the posterior side of the embryo undergo an epithelial-to-mesenchymal transition and ingress through the primitive streak. Subsequently, cells migrate, either surrounding the prospective ectoderm contributing to the embryo proper, or into the extra-embryonic region to form the yolk sac, umbilical cord and placenta. Fate mapping has shown that mature tissues such as blood and heart originate from specific regions of the pre-gastrula epiblast, but the plasticity of cells within the embryo and the function of key cell-type-specific transcription factors remain unclear. Here we analyse 1,205 cells from the epiblast and nascent Flk1(+) mesoderm of gastrulating mouse embryos using single-cell RNA sequencing, representing the first transcriptome-wide in vivo view of early mesoderm formation during mammalian gastrulation. Additionally, using knockout mice, we study the function of Tal1, a key haematopoietic transcription factor, and demonstrate, contrary to previous studies performed using retrospective assays, that Tal1 knockout does not immediately bias precursor cells towards a cardiac fate.We thank M. de Bruijn, A. Martinez-Arias, J. Nichols and C. Mulas for discussion, the Cambridge Institute for Medical Research Flow Cytometry facility for their expertise in single-cell index sorting, and S. Lorenz from the Sanger Single Cell Genomics Core for supervising purification of Tal1−/− sequencing libraries. ChIP-seq reads were processed by R. Hannah. Research in the authors’ laboratories is supported by the Medical Research Council, Cancer Research UK, the Biotechnology and Biological Sciences Research Council, Bloodwise, the Leukemia and Lymphoma Society, and the Sanger-EBI Single Cell Centre, and by core support grants from the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust - MRC Cambridge Stem Cell Institute and by core funding from Cancer Research UK and the European Molecular Biology Laboratory. Y.T. was supported by a fellowship from the Japan Society for the Promotion of Science. W.J. is a Wellcome Trust Clinical Research Fellow. A.S. is supported by the Sanger-EBI Single Cell Centre. This work was funded as part of Wellcome Trust Strategic Award 105031/D/14/Z ‘Tracing early mammalian lineage decisions by single-cell genomics’ awarded to W. Reik, S. Teichmann, J. Nichols, B. Simons, T. Voet, S. Srinivas, L. Vallier, B. Göttgens and J. Marioni.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature1863

Incidence of orthostatic hypotension and cardiovascular response to postoperative early mobilization in patients undergoing cardiothoracic and abdominal surgery

Background: In cardiothoracic and abdominal surgery, postoperative complications remain major clinical problems. Early mobilization has been widely practiced and is an important component in preventing complications, including orthostatic hypotension (OH) during postoperative management. We investigated cardiovascular response during early mobilization and the incidence of OH after cardiothoracic and abdominal surgery. Methods: In this prospective observational study, we consecutively analyzed data from 495 patients who underwent elective cardiothoracic and abdominal surgery. We examined the incidence of OH, and the independent risk factors associated with OH during early mobilization after major surgery. Multivariate logistic regression was performed using various characteristics of patients to identify OH-related independent factors. Results: OH was observed in 191 (39%) of 495 patients. The incidence of OH in cardiac, thoracic, and abdominal groups was 39 (33%) of 119, 95 (46%) of 208, and 57 (34%) of 168 patients, respectively. Male sex (OR 1.538; p = 0.03) and epidural anesthesia (OR 2.906; p < 0.001) were independently associated with OH on multivariate analysis. Conclusions: These results demonstrate that approximately 40% patients experience OH during early mobilization aftercardiothoracic and abdominal surgery. Sex was identified as an independent factor for OH during early mobilization after all three types of surgeries, while epidural anesthesia was only identified after thoracic surgery. Therefore, the frequent occurrence of OH during postoperative early mobilization should be recognized

The global methane budget 2000–2017

Understanding and quantifying the global methane (CH4) budget is important for assessing realistic pathways to mitigate climate change. Atmospheric emissions and concentrations of CH4 continue to increase, making CH4 the second most important human-influenced greenhouse gas in terms of climate forcing, after carbon dioxide (CO2). The relative importance of CH4 compared to CO2 depends on its shorter atmospheric lifetime, stronger warming potential, and variations in atmospheric growth rate over the past decade, the causes of which are still debated. Two major challenges in reducing uncertainties in the atmospheric growth rate arise from the variety of geographically overlapping CH4 sources and from the destruction of CH4 by short-lived hydroxyl radicals (OH). To address these challenges, we have established a consortium of multidisciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate new research aimed at improving and regularly updating the global methane budget. Following Saunois et al. (2016), we present here the second version of the living review paper dedicated to the decadal methane budget, integrating results of top-down studies (atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up estimates (including process-based models for estimating land surface emissions and atmospheric chemistry, inventories of anthropogenic emissions, and data-driven extrapolations). For the 2008–2017 decade, global methane emissions are estimated by atmospheric inversions (a top-down approach) to be 576 Tg CH4 yr−1 (range 550–594, corresponding to the minimum and maximum estimates of the model ensemble). Of this total, 359 Tg CH4 yr−1 or ∼ 60 % is attributed to anthropogenic sources, that is emissions caused by direct human activity (i.e. anthropogenic emissions; range 336–376 Tg CH4 yr−1 or 50 %–65 %). The mean annual total emission for the new decade (2008–2017) is 29 Tg CH4 yr−1 larger than our estimate for the previous decade (2000–2009), and 24 Tg CH4 yr−1 larger than the one reported in the previous budget for 2003–2012 (Saunois et al., 2016). Since 2012, global CH4 emissions have been tracking the warmest scenarios assessed by the Intergovernmental Panel on Climate Change. Bottom-up methods suggest almost 30 % larger global emissions (737 Tg CH4 yr−1, range 594–881) than top-down inversion methods. Indeed, bottom-up estimates for natural sources such as natural wetlands, other inland water systems, and geological sources are higher than top-down estimates. The atmospheric constraints on the top-down budget suggest that at least some of these bottom-up emissions are overestimated. The latitudinal distribution of atmospheric observation-based emissions indicates a predominance of tropical emissions (∼ 65 % of the global budget, < 30∘ N) compared to mid-latitudes (∼ 30 %, 30–60∘ N) and high northern latitudes (∼ 4 %, 60–90∘ N). The most important source of uncertainty in the methane budget is attributable to natural emissions, especially those from wetlands and other inland waters. Some of our global source estimates are smaller than those in previously published budgets (Saunois et al., 2016; Kirschke et al., 2013). In particular wetland emissions are about 35 Tg CH4 yr−1 lower due to improved partition wetlands and other inland waters. Emissions from geological sources and wild animals are also found to be smaller by 7 Tg CH4 yr−1 by 8 Tg CH4 yr−1, respectively. However, the overall discrepancy between bottom-up and top-down estimates has been reduced by only 5 % compared to Saunois et al. (2016), due to a higher estimate of emissions from inland waters, highlighting the need for more detailed research on emissions factors. Priorities for improving the methane budget include (i) a global, high-resolution map of water-saturated soils and inundated areas emitting methane based on a robust classification of different types of emitting habitats; (ii) further development of process-based models for inland-water emissions; (iii) intensification of methane observations at local scales (e.g., FLUXNET-CH4 measurements) and urban-scale monitoring to constrain bottom-up land surface models, and at regional scales (surface networks and satellites) to constrain atmospheric inversions; (iv) improvements of transport models and the representation of photochemical sinks in top-down inversions; and (v) development of a 3D variational inversion system using isotopic and/or co-emitted species such as ethane to improve source partitioning

Modelling of greenhouse gases and related species in the Arctic environment

Numerical modelling of greenhouse gases (GHGs) has become an integral part for understanding amplitude and variability in their concentrations and sources/sinks, atmospheric transport and climate implication. Carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) are the three major species studied in the Arctic Green Network of Excellence (GRENE), a programme funded by the Ministry of Education, Culture, Sports, Science and Technology-Japan (MEXT). In addition some of the ozone depleting substances, e.g., methyl chloroform (CH3CCl3), have provided strong constrain on the global mean abundance of hydroxyl (OH) radical and its relative abundance in the northern and southern hemispheres (NH/SH OH ratio; Patra et al., 2014). Being the main destroyer of many of the GHGs (e.g., CH4, hydrofluorocarbons), accurate quantification of OH was needed for estimation of CH4 sink in the troposphere, and thus the sources on the Earth’s surface by inverse modelling (Patra et al., 2016). OH is also contributes to chemical production of CO2, up to ~50% of land/ocean sink. The modellers are also required to verify the accuracy of model transport using tracers of short (e.g., 222Rn with 3.8 days) and long (SF6 with 3200 yrs) lifetimes. For understanding of the carbon cycle science, analyses of oxygen (O2/N2) variability are also conducted. List of chemistry-transport models (CTMs) participating in the Arctic GRENE programme are given Table 1.O08-05, Final Symposium on GRENE-Arctic Climate Change Research Project = GRENE北極気候変動研究事業研究成果報告会 (3-4 March, 2016, National Institute for Japanese Language and Linguistics, Tachikawa, Japan