Accuracy of the new rapid test for monitoring adalimumab levels

The loss of response to adalimumab (ADL) has been related to low serum concentrations at trough. Currently, most methods commercially available for the quantification of ADL are enzyme-linked immunosorbent assay (ELISA) based, with a turnaround time of approximately 8 h, delaying the target dosage adjustment to the subsequent infusion. In this study, we aimed to evaluate the performance of the newly available rapid-test ADL quantification assay by comparing it with three established ELISA methods, using spiked samples and a set of clinical samples.info:eu-repo/semantics/publishedVersio

Comparison of Human Memory CD8 T Cell Responses to Adenoviral Early and Late Proteins in Peripheral Blood and Lymphoid Tissue

Treatment of invasive adenovirus (Ad) disease in hematopoietic stem cell transplant (SCT) recipients with capsid protein hexon-specific donor T cells is under investigation. We propose that cytotoxic T cells (CTLs) targeted to the late protein hexon may be inefficient in vivo because the early Ad protein E3-19K downregulates HLA class I antigens in infected cells. In this study, CD8+ T cells targeted to highly conserved HLA A2-restricted epitopes from the early regulatory protein DNA polymerase (P-977) and late protein hexon (H-892) were compared in peripheral blood (PB) and tonsils of naturally infected adults. In tonsils, epitope-specific pentamers detected a significantly higher frequency of P-977+CD8+ T cells compared to H-892+CD8+ T cells; this trend was reversed in PB. Tonsil epitope-specific CD8+ T cells expressed IFN-γ and IL-2 but not perforin or TNF-α, whereas PB T cells were positive for IFN-γ, TNF-α, and perforin. Tonsil epitope-specific T cells expressed lymphoid homing marker CCR7 and exhibited lower levels of the activation marker CD25 but higher proliferative potential than PB T cells. Finally, in parallel with the kinetics of mRNA expression, P-977-specific CTLs lysed targets as early as 8 hrs post infection. In contrast, H-892-specific CTLs did not kill unless infected fibroblasts were pretreated with IFN-γ to up regulate HLA class I antigens, and cytotoxicity was delayed until 16–24 hours. These data show that, in contrast to hexon CTLs, central memory type DNA polymerase CTLs dominate the lymphoid compartment and kill fibroblasts earlier after infection without requiring exogenous IFN-γ. Thus, use of CTLs targeted to both early and late Ad proteins may improve the efficacy of immunotherapy for life-threatening Ad disease in SCT recipients

Marginal increase of sunitinib exposure by grapefruit juice

Clinical Oncolog

Model-reduced gradient-based history matching

Gradient-based history matching algorithms can be used to adapt the uncertain parameters in a reservoir model using production data. They require, however, the implementation of an adjoint model to compute the gradients, which is usually an enormous programming effort. We propose a new approach to gradient-based history matching which is based on model reduction, where the original (nonlinear and high-order) forward model is replaced by a linear reduced-order forward model and, consequently, the adjoint of the tangent linear approximation of the original forward model is replaced by the adjoint of a linear reduced-order forward model. The reducedorder model is constructed with the aid of the proper orthogonal decomposition method. Due to the linear character of the reduced model, the corresponding adjoint model is easily obtained. The gradient of the objective function is approximated, and the minimization problem is solved in the reduced space; the procedure is iterated with the updated estimate of the parameters if necessary. The proposed approach is adjointfree and can be used with any reservoir simulator. The method was evaluated for a waterflood reservoir with channelized permeability field. A comparison with an adjoint-based history matching procedure shows that the model-reduced approach gives a comparable quality of history matches and predictions. The computational efficiency of the model-reduced approach is lower than of an adjoint-based approach, but higher than of an approach where the gradients are obtained with simple finite differences.Delft Institute of Applied MathematicsElectrical Engineering, Mathematics and Computer Scienc