Outcome of relapsed/refractory acute promyelocytic leukaemia in children, adolescents and young adult patients — a 25‐year Italian experience

n/

TransCom model simulations of methane: Comparison of vertical profiles with aircraft measurements

To assess horizontal and vertical transports of methane (CH4) concentrations at different heights within the troposphere, we analyzed simulations by 12 chemistry transport models (CTMs) that participated in the TransCom-CH4 intercomparison experiment. Model results are compared with aircraft measurements at 13 sites in Amazon/Brazil, Mongolia, Pacific Ocean, Siberia/Russia, and United States during the period of 2001-2007. The simulations generally show good agreement with observations for seasonal cycles and vertical gradients. The correlation coefficients of the daily averaged model and observed CH4 time series for the analyzed years are generally larger than 0.5, and the observed seasonal cycle amplitudes are simulated well at most sites, considering the between-model variances. However, larger deviations show up below 2 km for the model-observation differences in vertical profiles at some locations, e.g., at Santarem, Brazil, and in the upper troposphere, e.g., at Surgut, Russia. Vertical gradients and concentrations are underestimated at Southern Great Planes, United States, and Santarem and overestimated at Surgut. Systematic overestimation and underestimation of vertical gradients are mainly attributed to inaccurate emission and only partly to the transport uncertainties. However, large differences in model simulations are found over the regions/seasons of strong convection, which is poorly represented in the models. Overall, the zonal and latitudinal variations in CH4 are controlled by surface emissions below 2.5 kmand transport patterns in the middle and upper troposphere. We show that the models with larger vertical gradients, coupled with slower horizontal transport, exhibit greater CH4 interhemispheric gradients in the lower troposphere. These findings have significant implications for the future development of more accurate CTMs with the possibility of reducing biases in estimated surface fluxes by inverse modelling

Simulating CH_4 and CO_2 over South and East Asia using the zoomed chemistry transport model LMDz-INCA

The increasing availability of atmospheric measurements of greenhouse gases (GHGs) from surface stations can improve the retrieval of their fluxes at higher spatial and temporal resolutions by inversions, provided that transport models are able to properly represent the variability of concentrations observed at different stations. South and East Asia (SEA; the study area in this paper including the regions of South Asia and East Asia) is a region with large and very uncertain emissions of carbon dioxide (CO_2) and methane (CH_4), the most potent anthropogenic GHGs. Monitoring networks have expanded greatly during the past decade in this region, which should contribute to reducing uncertainties in estimates of regional GHG budgets. In this study, we simulate concentrations of CH_4 and CO_2 using zoomed versions (abbreviated as ZAs) of the global chemistry transport model LMDz-INCA, which have fine horizontal resolutions of  ∼ 0.66° in longitude and  ∼ 0.51° in latitude over SEA and coarser resolutions elsewhere. The concentrations of CH_4 and CO_2 simulated from ZAs are compared to those from the same model but with standard model grids of 2.50° in longitude and 1.27° in latitude (abbreviated as STs), both prescribed with the same natural and anthropogenic fluxes. Model performance is evaluated for each model version at multi-annual, seasonal, synoptic and diurnal scales, against a unique observation dataset including 39 global and regional stations over SEA and around the world. Results show that ZAs improve the overall representation of CH_4 annual gradients between stations in SEA, with reduction of RMSE by 16–20% compared to STs. The model improvement mainly results from reduction in representation error at finer horizontal resolutions and thus better characterization of the CH_4 concentration gradients related to scattered distributed emission sources. However, the performance of ZAs at a specific station as compared to STs is more sensitive to errors in meteorological forcings and surface fluxes, especially when short-term variabilities or stations close to source regions are examined. This highlights the importance of accurate a priori CH_4 surface fluxes in high-resolution transport modeling and inverse studies, particularly regarding locations and magnitudes of emission hotspots. Model performance for CO_2 suggests that the CO_2 surface fluxes have not been prescribed with sufficient accuracy and resolution, especially the spatiotemporally varying carbon exchange between land surface and atmosphere. In addition, the representation of the CH_4 and CO_2 short-term variabilities is also limited by model's ability to simulate boundary layer mixing and mesoscale transport in complex terrains, emphasizing the need to improve sub-grid physical parameterizations in addition to refinement of model resolutions

Simulating CH_4 and CO_2 over South and East Asia using the zoomed chemistry transport model LMDz-INCA

The increasing availability of atmospheric measurements of greenhouse gases (GHGs) from surface stations can improve the retrieval of their fluxes at higher spatial and temporal resolutions by inversions, provided that transport models are able to properly represent the variability of concentrations observed at different stations. South and East Asia (SEA; the study area in this paper including the regions of South Asia and East Asia) is a region with large and very uncertain emissions of carbon dioxide (CO_2) and methane (CH_4), the most potent anthropogenic GHGs. Monitoring networks have expanded greatly during the past decade in this region, which should contribute to reducing uncertainties in estimates of regional GHG budgets. In this study, we simulate concentrations of CH_4 and CO_2 using zoomed versions (abbreviated as ZAs) of the global chemistry transport model LMDz-INCA, which have fine horizontal resolutions of  ∼ 0.66° in longitude and  ∼ 0.51° in latitude over SEA and coarser resolutions elsewhere. The concentrations of CH_4 and CO_2 simulated from ZAs are compared to those from the same model but with standard model grids of 2.50° in longitude and 1.27° in latitude (abbreviated as STs), both prescribed with the same natural and anthropogenic fluxes. Model performance is evaluated for each model version at multi-annual, seasonal, synoptic and diurnal scales, against a unique observation dataset including 39 global and regional stations over SEA and around the world. Results show that ZAs improve the overall representation of CH_4 annual gradients between stations in SEA, with reduction of RMSE by 16–20% compared to STs. The model improvement mainly results from reduction in representation error at finer horizontal resolutions and thus better characterization of the CH_4 concentration gradients related to scattered distributed emission sources. However, the performance of ZAs at a specific station as compared to STs is more sensitive to errors in meteorological forcings and surface fluxes, especially when short-term variabilities or stations close to source regions are examined. This highlights the importance of accurate a priori CH_4 surface fluxes in high-resolution transport modeling and inverse studies, particularly regarding locations and magnitudes of emission hotspots. Model performance for CO_2 suggests that the CO_2 surface fluxes have not been prescribed with sufficient accuracy and resolution, especially the spatiotemporally varying carbon exchange between land surface and atmosphere. In addition, the representation of the CH_4 and CO_2 short-term variabilities is also limited by model's ability to simulate boundary layer mixing and mesoscale transport in complex terrains, emphasizing the need to improve sub-grid physical parameterizations in addition to refinement of model resolutions

The origins and persistence of Homo floresiensis on Flores: biogeographical and ecological perspectives

The finding of archaeological evidence predating 1 Ma and a small hominin species (Homo floresiensis) on Flores, Indonesia, has stimulated much research on its origins and ancestry. Here we take a different approach and examine two key questions – 1) how did the ancestors of H. floresiensis reach Flores and 2) what are the prospects and difficulties of estimating the likelihood of hominin persistence for over 1 million years on a small island? With regard to the first question, on the basis of the biogeography we conclude that the mammalian, avian, and reptilian fauna on Flores arrived from a number of sources including Java, Sulawesi and Sahul. Many of the terrestrial taxa were able to float or swim (e.g. stegodons, giant tortoises and the Komodo dragon), while the rodents and hominins probably accidentally rafted from Sulawesi, following the prevailing currents. The precise route by which hominins arrived on Flores cannot at present be determined, although a route from South Asia through Indochina, Sulawesi and hence Flores is tentatively supported on the basis of zoogeography. With regards to the second question, we find the archaeological record equivocal. A basic energetics model shows that a greater number of small-bodied hominins could persist on Flores than larger-bodied hominins (whether H. floresiensis is a dwarfed species or a descendent of an early small-bodied ancestor is immaterial here), which may in part explain their apparent long-term success. Yet the frequent tsunamis and volcanic eruptions in the region would certainly have affected all the taxa on the island, and at least one turnover event is recorded, when Stegodon sondaari became extinct. The question of the likelihood of persistence may be unanswerable until we know much more about the biology of H. floresiensis

Variability and quasi-decadal changes in the methane budget overthe period 2000–2012

Following the recent Global Carbon Project (GCP) synthesis of the decadal methane (CH4/ budget over 2000– 2012 (Saunois et al., 2016), we analyse here the same dataset with a focus on quasi-decadal and inter-annual variability in CH4 emissions. The GCP dataset integrates results from topdown studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models (including process-based models for estimating land surface emissions and atmospheric chemistry), inventories of anthropogenic emissions, and data-driven approaches.The annual global methane emissions from top-down studies, which by construction match the observed methane growth rate within their uncertainties, all show an increase in total methane emissions over the period 2000–2012, but this increase is not linear over the 13 years. Despite differences between individual studies, the mean emission anomaly of the top-down ensemble shows no significant trend in total methane emissions over the period 2000–2006, during the plateau of atmospheric methane mole fractions, and also over the period 2008–2012, during the renewed atmospheric methane increase. However, the top-down ensemble mean produces an emission shift between 2006 and 2008, leading to 22 [16–32] Tg CH4 yr1 higher methane emissions over the period 2008–2012 compared to 2002–2006. This emission increase mostly originated from the tropics, with a smaller contribution from mid-latitudes and no significant change from boreal regions. The regional contributions remain uncertain in top-down studies. Tropical South America and South and East Asia seem to contribute the most to the emission increase in the tropics. However, these two regions have only limited atmospheric measurements and remain therefore poorly constrained. The sectorial partitioning of this emission increase between the periods 2002–2006 and 2008–2012 differs from one atmospheric inversion study to another. However, all topdown studies suggest smaller changes in fossil fuel emissions (from oil, gas, and coal industries) compared to the mean of the bottom-up inventories included in this study. This difference is partly driven by a smaller emission change in China from the top-down studies compared to the estimate in the Emission Database for Global Atmospheric Research (EDGARv4.2) inventory, which should be revised to smaller values in a near future. We apply isotopic signatures to the emission changes estimated for individual studies based on five emission sectors and find that for six individual top-down studies (out of eight) the average isotopic signature of the emission changes is not consistent with the observed change in atmospheric 13CH4. However, the partitioning in emission change derived from the ensemble mean is consistent with this isotopic constraint. At the global scale, the top-down ensemble mean suggests that the dominant contribution to the resumed atmospheric CH4 growth after 2006 comes from microbial sources (more from agriculture and waste sectors than from natural wetlands), with an uncertain but smaller contribution from fossil CH4 emissions. In addition, a decrease in biomass burning emissions (in agreement with the biomass burning emission databases) makes the balance of sources consistent with atmospheric 13CH4 observations. In most of the top-down studies included here, OH concentrations are considered constant over the years (seasonal variations but without any inter-annual variability). As a result, the methane loss (in particular through OH oxidation) varies mainly through the change in methane concentrations and not its oxidants. For these reasons, changes in the methane loss could not be properly investigated in this study, although it may play a significant role in the recent atmospheric methane changes as briefly discussed at the end of the paper.Published11135–111616A. Geochimica per l'ambienteJCR Journa

Massively Parallel Sequencing and Analysis of the Necator americanus Transcriptome

The blood-feeding hookworm Necator americanus infects hundreds of millions of people. To elucidate fundamental molecular biological aspects of this hookworm, the transcriptome of adult Necator americanus was studied using next-generation sequencing and in silico analyses. Contigs (n = 19,997) were assembled from the sequence data; 6,771 of them had known orthologues in the free-living nematode Caenorhabditis elegans, and most encoded proteins with WD40 repeats (10.6%), proteinase inhibitors (7.8%) or calcium-binding EF-hand proteins (6.7%). Bioinformatic analyses inferred that C. elegans homologues are involved mainly in biological pathways linked to ribosome biogenesis (70%), oxidative phosphorylation (63%) and/or proteases (60%). Comparative analyses of the transcriptomes of N. americanus and the canine hookworm, Ancylostoma caninum, revealed qualitative and quantitative differences. Essential molecules were predicted using a combination of orthology mapping and functional data available for C. elegans. Further analyses allowed the prioritization of 18 predicted drug targets which did not have human homologues. These candidate targets were inferred to be linked to mitochondrial metabolism or amino acid synthesis. This investigation provides detailed insights into the transcriptome of the adult stage of N. americanus

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD