Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments

Despite advances in ex vivo expansion of cord blood-derived hematopoietic stem/progenitor cells (CB-HSPC), challenges still remain regarding the ability to obtain, from a single unit, sufficient numbers of cells to treat an adolescent or adult patient. We and others have shown that CB-HSPC can be expanded ex vivo in two-dimensional (2D) cultures, but the absolute percentage of the more primitive stem cells decreases with time. During development, the fetal liver is the main site of HSPC expansion. Therefore, here we investigated, in vitro, the outcome of interactions of primitive HSPC with surrogate fetal liver environments. We compared bioengineered liver constructs made from a natural three-dimensional-liver-extracellular-matrix (3D-ECM) seeded with hepatoblasts, fetal liver-derived (LvSt), or bone marrow-derived stromal cells, to their respective 2D culture counterparts. We showed that the inclusion of cellular components within the 3D-ECM scaffolds was necessary for maintenance of HSPC viability in culture, and that irrespective of the microenvironment used, the 3D-ECM structures led to the maintenance of a more primitive subpopulation of HSPC, as determined by flow cytometry and colony forming assays. In addition, we showed that the timing and extent of expansion depends upon the biological component used, with LvSt providing the optimal balance between preservation of primitive CB HSPC and cellular differentiation. Stem Cells Translational Medicine 2018;7:271–282

Responsible agriculture must adapt to the wetland character of mid‐latitude peatlands

Drained, lowland agricultural peatlands are greenhouse gas (GHG) emission hotspots and a large but vulnerable store of irrecoverable carbon. They exhibit soil loss rates of ~2.0 cm yr−1 and are estimated to account for 32% of global cropland emissions while producing only 1.1% of crop kilocalories. Carbon dioxide emissions account for >80% of their terrestrial GHG emissions and are largely controlled by water table depth. Reducing drainage depths is, therefore, essential for responsible peatland management. Peatland restoration can substantially reduce emissions. However, this may conflict with societal needs to maintain productive use, to protect food security and livelihoods. Wetland agriculture strategies will, therefore, be required to adapt agriculture to the wetland character of peatlands, and balance GHG mitigation against productivity, where halting emissions is not immediately possible. Paludiculture may substantially reduce GHG emissions but will not always be viable in the current economic landscape. Reduced drainage intensity systems may deliver partial reductions in the rate of emissions, with smaller modifications to existing systems. These compromise systems may face fewer hurdles to adoption and minimize environmental harm until societal conditions favour strategies that can halt emissions. Wetland agriculture will face agronomic, socio-economic and water management challenges, and careful implementation will be required. Diversity of values and priorities among stakeholders creates the potential for conflict. Successful implementation will require participatory research approaches and co-creation of workable solutions. Policymakers, private sector funders and researchers have key roles to play but adoption risks would fall predominantly on land managers. Development of a robust wetland agriculture paradigm is essential to deliver resilient production systems and wider environmental benefits. The challenge of responsible use presents an opportunity to rethink peatland management and create thriving, innovative and green wetland landscapes for everyone's future benefit, while making a vital contribution to global climate change mitigation

Influence of treating facility, provider volume, and patient-sharing on survival of patients with multiple myeloma

Background: Population-based studies suggest that patients with multiple myeloma (MM) have better outcomes when treated at high-volume facilities, but the relative contribution of provider expertise and hospital resources to improved outcomes is unknown. This study explored how treating facility, individual provider volume, and patient-sharing between MM specialists and community providers influenced outcomes for patients with MM. Patients and Methods: A state cancer registry linked to public and private insurance claims was used to identify a cohort of patients diagnosed with MM in 2006 through 2012. Three multivariable Cox models were used to examine how the following factors impacted overall survival: (1) evaluation at an NCI-designated Comprehensive Cancer Center (NCICCC), (2) the primary oncologist's volume of patients with MM, and (3) patient-sharing between MM specialists and community oncologists. Results: A total of 1,029 patients diagnosed with MM in 2006 through 2012 were identified. Patients who were not evaluated at an NCICCC had an increased risk of mortality compared with those evaluated at an NCICCC (hazard ratio [HR], 1.50; 95% CI, 1.21-1.86; P,.001). Compared with patients treated by NCICCC MM specialists, those treated by both low-volume community providers (HR, 1.47; 95% CI, 1.14-1.90; P,.01) and high-volume community providers (HR, 1.29; 95% CI, 1.04-1.61; P,.05) had a higher risk of mortality. No difference in mortality was seen between patients treated by NCICCC MM specialists and those treated by the highest-volume community oncologists in the ninth and tenth deciles (HR, 1.08; 95% CI, 0.84-1.37; P 5.5591). Patients treated by community oncologists had a higher risk of mortality regardless of patient-sharing compared with patients treated by MM specialists (eg, community oncologist with a history of sharing vs NCICCC MM specialist: HR, 1.49; 95% CI, 1.10-2.02; P,.05). Conclusions: Findings of this study add to the accumulating evidence showing that patients with MM benefit from care at high-volume facilities, and suggest that similar outcomes can be achieved by the highest-volume providers in the community

The Milky Way Bulge: Observed properties and a comparison to external galaxies

The Milky Way bulge offers a unique opportunity to investigate in detail the role that different processes such as dynamical instabilities, hierarchical merging, and dissipational collapse may have played in the history of the Galaxy formation and evolution based on its resolved stellar population properties. Large observation programmes and surveys of the bulge are providing for the first time a look into the global view of the Milky Way bulge that can be compared with the bulges of other galaxies, and be used as a template for detailed comparison with models. The Milky Way has been shown to have a box/peanut (B/P) bulge and recent evidence seems to suggest the presence of an additional spheroidal component. In this review we summarise the global chemical abundances, kinematics and structural properties that allow us to disentangle these multiple components and provide constraints to understand their origin. The investigation of both detailed and global properties of the bulge now provide us with the opportunity to characterise the bulge as observed in models, and to place the mixed component bulge scenario in the general context of external galaxies. When writing this review, we considered the perspectives of researchers working with the Milky Way and researchers working with external galaxies. It is an attempt to approach both communities for a fruitful exchange of ideas.Comment: Review article to appear in "Galactic Bulges", Editors: Laurikainen E., Peletier R., Gadotti D., Springer Publishing. 36 pages, 10 figure

Modelling impacts of atmospheric deposition and temperature on long-term DOC trends

It is increasingly recognised that widespread and substantial increases in Dissolved organic carbon (DOC) concentrations in remote surface, and soil, waters in recent decades are linked to declining acid deposition. Effects of rising pH and declining ionic strength on DOC solubility have been proposed as potential dominant mechanisms. However, since DOC in these systems is derived mainly from recently-fixed carbon, and since organic matter decomposition rates are considered sensitive to temperature, uncertainty persists over the extent to which other drivers that could influence DOC production. Such potential drivers include fertilization by nitrogen (N) and global warming. We therefore ran the dynamic soil chemistry model MADOC for a range of UK soils, for which time series data are available, to consider the likely relative importance of decreased deposition of sulphate and chloride, accumulation of reactive N, and higher temperatures, on soil DOC production in different soils. Modelled patterns of DOC change generally agreed favourably with measurements collated over 10-20 years, but differed markedly between sites. While the acidifying effect of sulphur deposition appeared to be the predominant control on the observed soil water DOC trends in all the soils considered other than a blanket peat, the model suggested that over the long term, the effects of nitrogen deposition on N-limited soils may have been sufficient to raise the “acid recovery DOC baseline” significantly. In contrast, reductions in non-marine chloride deposition and effects of long term warming appeared to have been relatively unimportant. The suggestion that future DOC concentrations might exceed preindustrial levels as a consequence of nitrogen pollution has important implications for drinking water catchment management and the setting and pursuit of appropriate restoration targets, but findings still require validation from reliable centennial-scale proxy records, such as those being developed using palaeolimnological techniques

Exploring water, sanitation, and hygiene coverage targets for reaching and sustaining trachoma elimination: G-computation analysis

BACKGROUND: Trachoma is the leading infectious cause of blindness. To reduce transmission, water, sanitation, and hygiene (WaSH) improvements are promoted through a comprehensive public health strategy. Evidence supporting the role of WaSH in trachoma elimination is mixed and it remains unknown what WaSH coverages are needed to effectively reduce transmission. METHODS/FINDINGS: We used g-computation to estimate the impact on the prevalence of trachomatous inflammation-follicular among children aged 1-9 years (TF1-9) when hypothetical WaSH interventions raised the minimum coverages from 5% to 100% for "nearby" face-washing water (<30 minutes roundtrip collection time) and adult latrine use in an evaluation unit (EU). For each scenario, we estimated the generalized prevalence difference as the TF1-9 prevalence under the intervention scenarios minus the observed prevalence. Data from 574 cross-sectional surveys conducted in 16 African and Eastern Mediterranean countries were included. Surveys were conducted from 2015-2019 with support from the Global Trachoma Mapping Project and Tropical Data. When modeling interventions among EUs that had not yet met the TF1-9 elimination target, increasing nearby face-washing water and latrine use coverages above 30% was generally associated with consistent decreases in TF1-9. For nearby face-washing water, we estimated a ≥25% decrease in TF1-9 at 65% coverage, with a plateau upon reaching 85% coverage. For latrine use, the estimated decrease in TF1-9 accelerated from 80% coverage upward, with a ≥25% decrease in TF1-9 by 85% coverage. Among EUs that had previously met the elimination target, results were inconclusive. CONCLUSIONS: Our results support Sustainable Development Goal 6 and provide insight into potential WaSH-related coverage targets for trachoma elimination. Targets can be tested in future trials to improve evidence-based WaSH guidance for trachoma

Star clusters near and far; tracing star formation across cosmic time

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00690-x.Star clusters are fundamental units of stellar feedback and unique tracers of their host galactic properties. In this review, we will first focus on their constituents, i.e.\ detailed insight into their stellar populations and their surrounding ionised, warm, neutral, and molecular gas. We, then, move beyond the Local Group to review star cluster populations at various evolutionary stages, and in diverse galactic environmental conditions accessible in the local Universe. At high redshift, where conditions for cluster formation and evolution are more extreme, we are only able to observe the integrated light of a handful of objects that we believe will become globular clusters. We therefore discuss how numerical and analytical methods, informed by the observed properties of cluster populations in the local Universe, are used to develop sophisticated simulations potentially capable of disentangling the genetic map of galaxy formation and assembly that is carried by globular cluster populations.Peer reviewedFinal Accepted Versio

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe