Lambert McCall (mousediving58)

In recent years, metabolomic analyses have been increasingly performed in studies with an epidemiological design. Since 2012, the National Cancer Institute has recognized the importance of supporting these efforts by strategically building resources and infrastructure to move this area forward. This review outlines those efforts, including building infrastructure, leveraging existing resources, establishing the COnsortium of METabolomics Studies (COMETS), and improving rigor and reproducibility.Quantitative modeling of the subcutaneous absorption processes of protein therapeutics is challenging. Here we have proposed a "two-pore" PBPK model that is able to simultaneously characterize plasma PK of different-size protein therapeutics in mice. The skin compartment is evolved to mechanistically account for the absorption pathways through lymph and blood capillaries, as well as local degradation at the SC injection site. The model is developed using in-house plasma PK data generated following subcutaneous administration of 6 different-size protein therapeutics (13-150 kDa) in mice. The model was able to capture plasma PK of all molecules following intravenous and subcutaneous administration relatively well. From the observed plasma PK profiles, as well as from the model simulation result, several important PK descriptors were found to be dependent on protein size for FcRn nonbinding molecules. A positive correlation was found between Tmax and protein size. A "U" shape relationship was found between Cmax and protein size. Negative correlations were observed between bioavailability (F) and local degradation rate (kdeg,SC), and F and protein size. Pathway analysis of the model was conducted for the subcutaneous absorption process, and continuous relationships were established between the percentage of absorption through lymphatic and vascular pathways and protein size. selleck screening library This PBPK model could serve as a platform for the development of different-size protein therapeutics and will be scaled up to humans for translational studies in the future.A rational water quality assessment program directly affects a success of a national socio-economic development strategy. This study was aimed to evaluate and classify surface water quality in Dong Thap province, Vietnam, using set pair analysis (SPA) and national water quality index (WQI_VN) methods. The water quality data was collected at 58 locations in 2019 by the Department of Natural Resources and Environment of Dong Thap province. Sixteen variables including temperature (°C), pH, turbidity (NTU), dissolved oxygen (DO, mg/L), biological oxygen demand (BOD, mg/L), chemical oxygen demand (COD, mg/L), total suspended solids (TSS, mg/L), ammonia (N-NH4+, mg/L), nitrite (N-NO2-), nitrate (N-NO3-, mg/L), total nitrogen (TN, mg/L), orthophosphate (P-PO43-, mg/L), chloride (Cl-, mg/L), sulfate (SO42-, mg/L), coliform (MPN/100 mL), and Escherichia coli (MPN/100 mL) were monitored four times a year (58 water samples × 16 parameters × 4 monitoring times). The findings presented that TSS, BOD, COD, N-NH4+, N-NO2-, P-PO43-, coliform, and E. coli were the main constraints on water quality. The results of the entropy weight calculation indicated that deteriorated water quality was in the order of microbiological > nutrients > organic matters. Surface water quality was evaluated at medium (level III) and poor (level IV) by SPA and WQI_VN, respectively; however, the combination of SPA and entropy weight was considered more efficient in this classification and a positive spatial autocorrelation was also found through Moran's I. The spatial distribution of water quality based on SPA classification revealed that better water quality was found in the inner parts of the study area. Due to its ease and effectiveness, set pair analysis should be considered for inclusion in the water quality assessment program of Vietnam. Malignant peritoneal mesothelioma is a rare and often fa