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Climate change is leading to a disproportionately large warming in the high northern latitudes, but the magnitude and sign of the future carbon balance of the Arctic are highly uncertain. Using 40 terrestrial biosphere models for the Alaskan Arctic from four recent model intercomparison projects – NACP (North American Carbon Program) site and regional syntheses, TRENDY (Trends in net land atmosphere carbon exchanges), and WETCHIMP (Wetland and Wetland CH4 Inter-comparison of Models Project) – we provide a baseline of terrestrial carbon cycle uncertainty, defined as the multi-model standard deviation (σ) for each quantity that follows. Mean annual absolute uncertainty was largest for soil carbon (14.0 ± 9.2 kg C m−2), then gross primary production (GPP) (0.22 ± 0.50 kg C m−2 yr−1), ecosystem respiration (Re) (0.23 ± 0.38 kg C m−2 yr−1), net primary production (NPP) (0.14 ± 0.33 kg C m−2 yr−1), autotrophic respiration (Ra) (0.09 ± 0.20 kg C m−2 yr−1), heterotrophic respiration (Rh) (0.14 ± 0.20 kg C m−2 yr−1), net ecosystem exchange (NEE) (−0.01 ± 0.19 kg C m−2 yr−1), and CH4 flux (2.52 ± 4.02 g CH4 m−2 yr−1). There were no consistent spatial patterns in the larger Alaskan Arctic and boreal regional carbon stocks and fluxes, with some models showing NEE for Alaska as a strong carbon sink, others as a strong carbon source, while still others as carbon neutral. Finally, AmeriFlux data are used at two sites in the Alaskan Arctic to evaluate the regional patterns; observed seasonal NEE was captured within multi-model uncertainty. This assessment of carbon cycle uncertainties may be used as a baseline for the improvement of experimental and modeling activities, as well as a reference for future trajectories in carbon cycling with climate change in the Alaskan Arctic and larger boreal region.

Elevated atmospheric CO₂ concentration (eCO₂) has the potential to increase vegetation carbon storage if increased net primary production causes increased long‐lived biomass. Model predictions of eCO₂ effects on vegetation carbon storage depend on how allocation and turnover processes are represented. We used data from two temperate forest free‐air CO₂ enrichment (FACE) experiments to evaluate representations of allocation and turnover in 11 ecosystem models. Observed eCO₂ effects on allocation were dynamic. Allocation schemes based on functional relationships among biomass fractions that vary with resource availability were best able to capture the general features of the observations. Allocation schemes based on constant fractions or resource limitations performed less well, with some models having unintended outcomes. Few models represent turnover processes mechanistically and there was wide variation in predictions of tissue lifespan. Consequently, models did not perform well at predicting eCO₂ effects on vegetation carbon storage. Our recommendations to reduce uncertainty include: use of allocation schemes constrained by biomass fractions; careful testing of allocation schemes; and synthesis of allocation and turnover data in terms of model parameters. Data from intensively studied ecosystem manipulation experiments are invaluable for constraining models and we recommend that such experiments should attempt to fully quantify carbon, water and nutrient budgets.

The mounting evidence for effective delivery of psychological interventions by non-specialists in low- and middle-income settings has led to a rapid expansion of mental health and psychosocial support trainings globally. As such, there is a demand for strategies on how to train and implement these services to attain adequate quality. This study aims to evaluate the added value of a competency-driven approach to training of facilitators for a group intervention for children with severe emotional distress in Lebanon. In a controlled before and after study, 24 trainees were randomly allocated to participate in either a competency-driven training (CDT) or training-as-usual (TAU) (1 : 1) for a psychological intervention for children with severe emotional distress. We assessed the change in demonstrated competencies, using standardised role-plays, before and after the training. Measures included the 13-item Working with children-Assessment of Competencies Tool (WeACT), the 15-item ENhancing Assessment of Common Therapeutic factors (ENACT) and the 6-item Group facilitation: Assessment of Competencies Tool (GroupACT). The trainer in the experimental arm used pre-training and during training competency assessment scores to make real-time adjustment to training delivery. Due to COVID-19 pandemic restrictions, all activities were done remotely. CDT resulted in significantly better outcomes on increasing competencies on the WeACT (repeated measures analysis of variance; = 6.49, < 0.018) and on the GroupACT (Mann-Whitney = 22, < 0.003), though not statistically significant on the ENACT. There is no significant between-group difference on the reduction of harmful behaviours, mainly because both forms of training appear equally successful in eliminating such behaviours. This proof-of-concept study demonstrates the potential of CDT, using standardised assessment of trainee competencies, to contribute to better training outcomes without extending the duration of training. CDT can result in up to 18% greater increase in adequate competency, when compared to TAU. The study also yields recommendations for further enhancing the benefits of competency-driven strategies. A fully powered trial is needed to confirm these findings.

Terrestrial ecosystems carbon and water cycles are tightly coupled through photosynthesis and evapotranspiration processes. The ratios of carbon stored to carbon uptake and water loss to carbon gain are key ecophysiological indicators essential to assess the magnitude and response of the terrestrial plant to the changing climate. Here, we use estimates from 10 terrestrial ecosystem models to quantify the impacts of climate, atmospheric CO 2 concentration, and nitrogen (N) deposition on water use efficiency (WUE), and carbon use efficiency (CUE). We find that across models, WUE increases over the 20 th Century particularly due to CO 2 fertilization and N deposition and compares favorably to experimental studies. Also, the results show a decrease in WUE with climate for the last 3 decades, in contrasts with up-scaled flux observations that demonstrate a constant WUE. Modeled WUE responds minimally to climate with modeled CUE exhibiting no clear trend across space and time. The divergence between simulated and observationally-constrained WUE and CUE is driven by modeled NPP and autotrophic respiration, nitrogen cycle, carbon allocation, and soil moisture dynamics in current ecosystem models. We suggest that carbon-modeling community needs to reexamine stomatal conductance schemes and the soil-vegetation interactions for more robust modeling of carbon and water cycles.

Denosumab is a monoclonal anti-RANKL antibody that inhibits bone resorption, increases bone mass, and reduces fracture risk. Denosumab discontinuation causes an extensive wave of rebound resorption, but the cellular mechanisms remain poorly characterized. We utilized in situ hybridization (ISH) as a direct approach to identify the cells that activate osteoclastogenesis through the RANKL/OPG pathway. ISH was performed across species, skeletal sites, and following recombinant OPG (OPG:Fc) and parathyroid hormone 1–34 (PTH) treatment of mice. OPG:Fc treatment in mice induced an increased expression of RANKL mRNA mainly in trabecular, but not endocortical bone surface cells. Additionally, a decreased expression of OPG mRNA was detected in bone surface cells and osteocytes of both compartments. A similar but more pronounced effect on RANKL and OPG expression was seen one hour after PTH treatment. These findings suggest that bone surface cells and osteocytes conjointly regulate the activation of osteoclastogenesis, and that OPG:Fc treatment induces a local accumulation of osteoclastogenic activation sites, ready to recruit and activate osteoclasts upon treatment discontinuation. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data from murine bone marrow stromal cells revealed that Tnfsf11+ cells expressed high levels of Mmp13, Limch1, and Wif1, confirming their osteoprogenitor status. ISH confirmed co-expression of Mmp13 and Tnfsf11 in bone surface cells of both vehicle- and OPG:Fc-treated mice. Under physiological conditions of human/mouse bone, RANKL is expressed mainly by osteoprogenitors proximate to the osteoclasts, while OPG is expressed mainly by osteocytes and bone-forming osteoblasts.

Cow's milk allergy (CMA) is treated in formula-fed infants with an extensive protein hydrolysate. This study aimed to evaluate the nutritional safety of a non-thickened and thickened extensively casein hydrolyzed protein formula (NT- and T-eCHF) in infants with CMA. Infants younger than 6 mo old with a positive cow milk challenge test, positive IgE, or skin prick test for cow milk were selected. Weight and length were followed during the 6 mo intervention with the NT-eCHF and T-eCHF. A challenge was performed in 50/71 infants with suspected CMA and was positive in 34/50. All children with confirmed CMA tolerated the eCHF. The T-eCHF leads to a significant improvement of the stool consistency in the whole population and in the subpopulation of infants with proven CMA. Height and weight evolution was satisfactory throughout the 6 mo study. The eCHF fulfills the criteria of a hypoallergenic formula and the NT- and T-eCHF reduced CMA symptoms. Growth was within normal range. •The evolution of anthropometric parameters with extensive hydrolysate is excellent.•This extensive casein hydrolysate fulfils the required criteria for a hypo-allergenic formula•The thickened extensive hydrolysate alleviates regurgitation in non-allergic infants.

The capacity of terrestrial ecosystems to sequester carbon dioxide (CO2) from the atmosphere is expected to be altered by climate change and CO2 fertilization, but this projection is limited by our understanding of how the soil system interacts with plants. Understanding the soil–vegetation interactions is essential to assess the magnitude and response of terrestrial ecosystems to the changing climate. Here, we used soil profile and satellite data to explore the role that soil properties play in regulating water and carbon use by plants. Data obtained for 19 terrestrial ecosystem sites in a warm temperate and humid climate were used to investigate the relationship between remotely sensed data and soil physical and chemical properties. Classification and regression tree results showed that in situ soil carbon isotope (δ13C), and soil order were significant predictors (r2 = 0.39, mean absolute error (MAE) = 0 of 0.175 gC/KgH2O) of remotely sensed water use efficiency (WUE) based on the Moderate Resolution Imaging Spectroradiometer (MODIS). Soil extractable calcium (Ca), and land cover type were significant predictors of remotely sensed carbon use efficiency (CUE) based on MODIS and Landsat data-(r2 = 0.64–0.78, MAE = 0.04–0.06). We used gross primary productivity (GPP) derived from solar-induced fluorescence (SIF) data, based on the Orbiting Carbon Observatory-2 (OCO-2), to calculate WUE and CUE (referred to as WUESIF and CUESIF, respectively) for our study sites. The regression tree analysis revealed that soil organic matter and soil extractable magnesium (Mg), δ13C, and soil silt content were the important predictors of both WUESIF (r2 = 0.19, MAE = 0.64 gC/KgH2O) and CUESIF (r2 = 0.45, MAE = 0.1), respectively. Our results revealed the importance of soil extractable Ca, soil carbon (S13C is a facet of soil carbon content), and soil organic matter predicting CUE and WUE. Insights gained from this study highlighted the importance of biotic and abiotic factors regulating plant and soil interactions. These types of data are timely and critical for accurate predictions of how terrestrial ecosystems respond to climate change.

Medullary carcinoma of the breast (MedBC) is a rare histological type that accounts for less than 5% of all invasive breast cancers. Here, we performed an exploratory study aimed to determine whether imaging mass cytometry (IMC) can be used to characterize the immune infiltration and the spatial distribution heterogeneity in the rare subtype of MedBC compared to atypical MedBC and TNBC-TILS+ tumors. In both MedBC and TNBC-TILs+, there was a notable enrichment of immune cells in the peripheral regions of the tumors, whereas in atypical MedBC, the immune cells exhibited a central enrichment pattern. This distribution of infiltrated cells reflects an active immune recruitment correlated to more favorable prognosis. In MedBC, spatial analysis shows that immune cells are localized at a greater distance from the tumor cells. IMC highlights the heterogeneity of immune microenvironment across three main subtypes of breast tumors and could help to define distinct immune patterns.

BackgroundAlumina particles from the grit blasting of Ti-alloy stems are suspected to contribute to aseptic loosening. An alumina-reduced stem surface was hypothesized to improve osseointegration and show comparable short-term outcomes to those of a standard stem.MethodsIn this prospective, double-blind, randomized trial, 26 standard (STD) and 27 experimental new technology (NT) stems were implanted. The latter were additionally treated by acid etching and ice blasting to remove alumina particles from the grit-blasting process. Follow-up occurred at 12 and 24 months. Bone mineral density (BMD) around the stem was measured by a dual-energy x-ray absorptiometry device (DEXA). Radiographs were reviewed for alterations. Clinical scoring comprised the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Harris Hip Score (HHS). Survival rates were calculated up to 50 months.ResultsLower mean BMD and more severe cortical hypertrophies were found in the NT group. At 12 months, radiolucent lines were observed mostly in the metaphyseal zone for both groups, with a progression tendency in the NT group at 24 months. At 12 months, pain scores and the WOMAC total and physical activity scores were significantly lower in the NT group, without any differences thereafter. The number of NT stem revisions amounted to 6 (24%) and 11 (41%) at 24 and 50 months, respectively.ConclusionIn the NT group, unexpected catastrophic failure rates of 41% caused by early aseptic loosening were noted within 50 months. Compared with the STD stems, NT stems lead to poor clinical and radiographic results.Level of evidence: II.Trial Registration: NCT05053048.