Flanagan Collins (whaleelbow0)

Extramedullary disease (EMD) represents a high-risk state of multiple myeloma (MM) associated with poor prognosis. While most anti-myeloma therapeutics demonstrate limited efficacy in this setting, some studies exploring the utility of chimeric antigen receptor (CAR)-modified T cells reported promising results. We have recently designed SLAMF7-directed CAR T cells for the treatment of MM. SLAMF7 is a transmembrane receptor expressed on myeloma cells that plays a role in myeloma cell homing to the bone marrow. Currently, the only approved anti-SLAMF7 therapeutic is the monoclonal antibody elotuzumab, but its efficacy in EMD has not been investigated thoroughly. Thus, we retrospectively analyzed the efficacy of elotuzumab-based combination therapy in a cohort of 15 patients with EMD. Moreover, since the presence of the target antigen is an indispensable prerequisite for effective targeted therapy, we investigated the SLAMF7 expression on extramedullary located tumor cells before and after treatment. We observed limited efficacy of elotuzumab-based combination therapies, with an overall response rate of 40% and a progression-free and overall survival of 3.8 and 12.9 months, respectively. Before treatment initiation, all available EMD tissue specimens (n = 3) demonstrated a strong and consistent SLAMF7 surface expression by immunohistochemistry. Furthermore, to investigate a potential antigen reduction under therapeutic selection pressure, we analyzed samples of de novo EMD (n = 3) outgrown during elotuzumab treatment. Again, immunohistochemistry documented strong and consistent SLAMF7 expression in all samples. In aggregate, our data point towards a retained expression of SLAMF7 in EMD and encourage the development of more potent SLAMF7-directed immunotherapies, such as CAR T cells.A multi-year dataset of measurements of CO2 concentrations, eddy covariance fluxes, and meteorological parameters over the city centre of Florence (Italy) has been analysed to assess the role of anthropogenic emissions and meteorology in controlling urban CO2 concentrations. The latter exhibited a negative correlation with air temperature, wind speed, solar radiation, and sensible heat flux and a positive one with relative humidity and emissions. A linear and an artificial neural network (ANN) model have been developed and validated for short-term modelling of 3-h CO2 concentrations. The ANN model performed better, with mean bias of 0.58 ppm, root mean square error within 30 ppm, and r2=0.49. Data clustering through the self-organized maps allowed to disentangle the role played by emissions and meteorological parameters in influencing CO2 concentrations. Sensitivity analysis of CO2 concentrations revealed a primary role played by the meteorological parameters, particularly wind speed. These results highlighted that (i) emission reduction actions at local urban scale should be better tied to actual and expected meteorological conditions and (ii) those actions alone have limited effects (e.g. a 20% emission reduction would result in a 3% CO2 concentrations reduction). For all these reasons, large-scale policies would be needed.Given that compensation for ecological and economic benefits is an effective way to address the imbalance between the coordinated development of regional ecological environment and economic growth, this study aims to explore the horizontal ecological compensation mechanism under the differentiated responsibilities of different regions in China. In this paper, the ecological deficit and surplus zones are divided by ecological footprint analysis, and the evolution of the ecological deficit and surplus zones and their per capita coal consumption in 30 provinces (municipalities and autonomous regions) from 2004 to 2018 are analyzed. Afterwards, the panel threshold model is used to validate the conclusion. The results show that there is an inverted U-shaped feature between ecological environment and economic growth in each region, whi