Persistent Variation in Medicare Payment Authorization for Home Hemodialysis Treatments

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142984/1/hesr12650-sup-0001-AppendixSA1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142984/2/hesr12650.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142984/3/hesr12650_am.pd

In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosis

Contrast-induced nephropathy accounts for >10% of all causes of hospital-acquired renal failure, causes a prolonged in-hospital stay and represents a powerful predictor of poor early and late outcome. Mechanisms of contrast-induced nephropathy are not completely understood. In vitro data suggests that contrast media (CM) induces a direct toxic effect on renal tubular cells through the activation of the intrinsic apoptotic pathway. It is unclear whether this effect has a role in the clinical setting. In this work, we evaluated the effects of CM both in vivo and in vitro. By analyzing urine samples obtained from patients who experienced contrast-induced acute kidney injury (CI-AKI), we verified, by western blot and immunohistochemistry, that CM induces tubular renal cells apoptosis. Furthermore, in cultured cells, CM caused a dose–response increase in reactive oxygen species (ROS) production, which triggered Jun N-terminal kinases (JNK1/2) and p38 stress kinases marked activation and thus apoptosis. Inhibition of JNK1/2 and p38 by different approaches (i.e. pharmacological antagonists and transfection of kinase-death mutants of the upstream p38 and JNK kinases) prevented CM-induced apoptosis. Interestingly, N-acetylcysteine inhibited ROS production, and thus stress kinases and apoptosis activation. Therefore, we conclude that CM-induced tubular renal cells apoptosis represents a key mechanism of CI-AKI

Prediction of enteric methane production, yield and intensity of beef cattle using an intercontinental database

Enteric methane (CH4) production attributable to beef cattle contributes to global greenhouse gas emissions. Reliably estimating this contribution requires extensive CH4 emission data from beef cattle under different management conditions worldwide. The objectives were to: 1) predict CH4 production (g d¬-1 animal-1), yield [g (kg dry matter intake; DMI)-1] and intensity [g (kg average daily gain)-1] using an intercontinental database (data from Europe, North America, Brazil, Australia and South Korea); 2) assess the impact of geographic region, and of higher- and lower-forage diets. Linear models were developed by incrementally adding covariates. A K-fold cross-validation indicated that a CH4 production equation using only DMI that was fitted to all available data had a root mean square prediction error (RMSPE; % of observed mean) of 31.2%. Subsets containing data with ≥ 25% and ≤ 18% dietary forage contents had an RMSPE of 30.8 and 34.2%, with the all-data CH4 production equation, whereas these errors decreased to 29.3 and 28.4%, respectively, when using CH4 prediction equations fitted to these subsets. The RMSPE of the ≥ 25% forage subset further decreased to 24.7% when using multiple regression. Europe- and North America-specific subsets predicted by the best performing ≥ 25% forage multiple regression equation had RMSPE of 24.5 and 20.4%, whereas these errors were 24.5 and 20.0% with region-specific equations, respectively. The developed equations had less RMSPE than extant equations evaluated for all data (22.5 vs. 23.2%), for higher-forage (21.2 vs. 23.1%), but not for the lower-forage subsets (28.4 vs. 27.9%). Splitting the dataset by forage content did not improve CH4 yield or intensity predictions. Predicting beef cattle CH4 production using energy conversion factors, as applied by the Intergovernmental Panel on Climate Change, indicated that adequate forage content-based and region-specific energy conversion factors improve prediction accuracy and are preferred in national or global inventories

A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.

Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies