The NASA Goddard Earth Observing System (GEOS) Composition Forecast (GEOS-29CF) provides recent estimates and five-day forecasts of atmospheric composition to the public in near-real time. To do ...this, the GEOS Earth system model is coupled with the GEOS-Chem tropospheric-stratospheric unified chemistry extension (UCX) to represent composition from the surface to the top of the GEOS atmosphere (0.01 hPa). The GEOS-CF system is described, including updates made to the GEOS-Chem UCX mechanism within GEOS-CF for improved representation of stratospheric chemistry. Comparisons are made against balloon, lidar and satellite observations for stratospheric composition, including measurements of ozone (O3) and important nitrogen and chlorine species related to stratospheric O3recovery. The GEOS-CF nudges the stratospheric O3towards the GEOS Forward Processing (GEOS FP) assimilated O3product; as a result the stratospheric O3in the GEOS-CF historical estimate agrees well with observations. During abnormal dynamical and chemical environments such as the 2020 polar vortexes, the GEOS-CF O3forecasts are more realistic than GEOS FP O3forecasts because of the inclusion of the complex GEOS-Chem UCX stratospheric chemistry. Overall, the spatial patterns of the GEOS-CF simulated concentrations of stratospheric composition agree well with satellite observations. However, there are notable biases – such as low NOx and HNO3 in the polar regions and generally low HCl throughout the stratosphere – and future improvements to the chemistry mechanism and emissions are discussed. GEOS-CF is a new tool for the research community and instrument teams observing trace gases in the stratosphere and troposphere, providing near-real-time three-dimensional gridded information on atmospheric composition.
The characteristics of the extratropical transition (ET) of tropical cyclones and its impact on the midlatitude flow are examined in the THORPEX Interactive Grand Global Ensemble (TIGGE) multimodel ...ensemble prediction system (EPS). Ten ensemble forecasts initialized prior to ET for five tropical cyclones in 2008 are investigated using an empirical orthogonal function analysis and fuzzy clustering methodology. Each forecast contains 231 members from eight different global EPS. The EPS contributing to TIGGE differ in their spread and their contributions to the different scenarios. Some of the individual EPS are generally confined to only a few scenarios, whereas others contribute regularly to almost all. TIGGE contains more development scenarios than European Centre for Medium Range Weather Forecast (ECMWF) EPS but the full range of development scenarios is only found with the ECMWF included in the multimodel EPS.
Key Points
Investigation of ET in the new TIGGE dataset, based on EOF‐/cluster analysis
Individual TIGGE ensembles contribute differently to development scenarios
TIGGE offers new development scenarios, full range only if ECMWF EPS is included
Soil compaction impacts growing conditions for plants: it increases the mechanical resistance to root growth and modifies the soil pore system and consequently the supply of water and oxygen to the ...roots. The least limiting water range (LLWR) defines a range of soil water contents within which root growth is minimally limited with regard to water supply, aeration and penetration resistance. The LLWR is a function of soil bulk density (BD), and hence directly affected by soil compaction. In this paper, we present a new model, ‘SoilFlex‐LLWR’, which combines a soil compaction model with the LLWR concept. We simulated the changes in LLWR due to wheeling with a self‐propelled forage harvester on a Swiss clay loam soil (Gleyic Cambisol) using the new SoilFlex‐LLWR model, and compared measurements of the LLWR components as a function of BD with model estimations. SoilFlex‐LLWR allows for predictions of changes in LLWR due to compaction caused by agricultural field traffic and therefore provides a quantitative link between impact of soil loading and soil physical conditions for root growth.
...while the general statement that the length of time between submission and publication in biomedical journals is shorter than in other fields is true, there is great variation across journals. ......making biomedical preprints widely accessible before and during peer review and the other important contributions of publishers serves to alert colleagues and other readers to one's findings in advance of publication, though certainly the final version of an article would be the one most people in the field would regard as definitive. ...preprints help scientists receive additional feedback from the community, which may add to the effectiveness of journal-organized peer review. ...preprints facilitate innovative peer-review models, such as overlay journals, which collect and curate content that is hosted in other archives (for example, the mathematics journal Discrete Analysis).
The β-3 sympathomimetic agonist BRL37344 restored nestin-positive cells within the stem cell niche, and thereby normalized blood counts and improved myelofibrosis in a mouse model of
-V617F-positive ...myeloproliferative neoplasms. We therefore tested the effectiveness of mirabegron, a β-3 sympathomimetic agonist, in a phase II trial including 39
-V617F-positive patients with myeloproliferative neoplasms and a mutant allele burden more than 20%. Treatment consisted of mirabegron 50 mg daily for 24 weeks. The primary end point was reduction of
-V617F allele burden of 50% or over, but this was not reached in any of the patients. One patient achieved a 25% reduction in
-V617F allele burden by 24 weeks. A small subgroup of patients showed hematologic improvement. As a side study, bone marrow biopsies were evaluated in 20 patients. We found an increase in the nestin
cells from a median of 1.09 (interquartile range 0.38-3.27)/mm
to 3.95 (interquartile range 1.98-8.79)/mm
(
<0.0001) and a slight decrease of reticulin fibrosis from a median grade of 1.0 (interquartile range 0-3) to 0.5 (interquartile range 0-2) (
=0.01) between start and end of mirabegron treatment. Despite the fact that the primary end point of reducing
-V617F allele burden was not reached, the observed effects on nestin
mesenchymal stem cells and reticulin fibrosis is encouraging, and shows that mirabegron can modify the microenvironment where the
-mutant stem cells are maintained. (Registered at
).
On March 25 and 26, 2015, the National Heart, Lung, and Blood Institute sponsored a meeting on the State of the Science in Transfusion Medicine on the National Institutes of Health (NIH) campus in ...Bethesda, Maryland, which was attended by a diverse group of 330 registrants. The meeting's goal was to identify important research questions that could be answered in the next 5 to 10 years and which would have the potential to transform the clinical practice of transfusion medicine. These questions could be addressed by basic, translational, and/or clinical research studies and were focused on four areas: the three “classical” transfusion products (i.e., red blood cells, platelets, and plasma) and blood donor issues. Before the meeting, four working groups, one for each area, prepared five major questions for discussion along with a list of five to 10 additional questions for consideration. At the meeting itself, all of these questions, and others, were discussed in keynote lectures, small‐group breakout sessions, and large‐group sessions with open discourse involving all meeting attendees. In addition to the final lists of questions, provided herein, the meeting attendees identified multiple overarching, cross‐cutting themes that addressed issues common to all four areas; the latter are also provided. It is anticipated that addressing these scientific priorities, with careful attention to the overarching themes, will inform funding priorities developed by the NIH and provide a solid research platform for transforming the future practice of transfusion medicine.
Background
Surgical care is an important, yet often neglected component of child health in low- and middle-income countries (LMICs). This study examines the potential impact of scaling up surgical ...care at first-level hospitals in LMICs within the first 20 years of life.
Methods
Epidemiological data from the global burden of disease 2019 Study and a counterfactual method developed for the disease control priorities; 3rd Edition were used to estimate the number of treatable deaths in the under 20 year age group if surgical care could be scaled up at first-level hospitals. Our model included three digestive diseases, four maternal and neonatal conditions, and seven common traumatic injuries.
Results
An estimated 314,609 (95% UI, 239,619–402,005) deaths per year in the under 20 year age group could be averted if surgical care were scaled up at first-level hospitals in LMICs. Most of the treatable deaths are in the under-5 year age group (80.9%) and relates to improved obstetrical care and its effect on reducing neonatal encephalopathy due to birth asphyxia and trauma. Injuries are the leading cause of treatable deaths after age 5 years. Sixty-one percent of the treatable deaths occur in lower middle-income countries. Overall, scaling up surgical care at first-level hospitals could avert 5·1% of the total deaths in children and adolescents under 20 years of age in LMICs per year.
Conclusions
Improving the capacity of surgical services at first-level hospitals in LMICs has the potential to avert many deaths within the first 20 years of life.
Severely‐debilitating or life‐threatening (SDLT) diseases include conditions in which life expectancy is short or quality of life is greatly diminished despite available therapies. As such, the ...medical context for SDLT diseases is comparable to advanced cancer and the benefit vs. risk assessment and development of SDLT disease therapeutics should be similar to that of advanced cancer therapeutics. A streamlined development approach would allow patients with SDLT conditions earlier access to therapeutics and increase the speed of progression through development. In addition, this will likely increase the SDLT disease therapeutic pipeline, directly benefiting patients and reducing the economic and societal burden of SDLT conditions. Using advanced‐stage heart failure (HF) as an example that illustrates the concepts applicable to other SDLT indications, this article proposes a streamlined development paradigm for SDLT disease therapeutics and recommends development of aligned global regulatory guidance.
Earth- and space-based observations provide synergistic information for space mission encounters by providing data over longer timescales, at different wavelengths and using techniques that are ...impossible with an in situ flyby. We report here such observations in support of the EPOXI spacecraft flyby of comet 103P/Hartley 2. The nucleus is small and dark, and exhibited a very rapidly changing rotation period. Prior to the onset of activity, the period was ~16.4 hr. Starting in 2010 August the period changed from 16.6 hr to near 19 hr in December. With respect to dust composition, most volatiles and carbon and nitrogen isotope ratios, the comet is similar to other Jupiter-family comets. What is unusual is the dominance of CO2-driven activity near perihelion, which likely persists out to aphelion. Near perihelion the comet nucleus was surrounded by a large halo of water-ice grains that contributed significantly to the total water production.
Several transfer RNAs (tRNAs) contain inosine (I) at the first position of their anticodon (position 34); this modification is thought to enlarge the codon recognition capacity during protein ...synthesis. The tRNA-specific adenosine deaminase of Saccharomyces cerevisiae that forms I$_{34}$ in tRNAs is described. The heterodimeric enzyme consists of two sequence-related subunits (Tad2p/ADAT2 and Tad3p/ADAT3), both of which contain cytidine deaminase (CDA) motifs. Each subunit is encoded by an essential gene (TAD2 and TAD3), indicating that I$_{34}$ is an indispensable base modification in elongating tRNAs. These results provide an evolutionary link between the CDA superfamily and RNA-dependent adenosine deaminases (ADARs/ADATs).
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