6,771 research outputs found
Jacob and Joseph as Character Names in Modern Literature
The names Jacob and Joseph are of Hebrew origin; they appear often in both the Old and New Testaments and have inspired innumerable names, both actual and literary, throughout the history of Jews and Christians
Outcome following valve surgery in Australia: Development of an enhanced database module
Background: Valvular heart disease, including rheumatic heart disease (RHD), is an important cause of heart disease globally. Management of advanced disease can include surgery and other interventions to repair or replace affected valves. This article summarises the methodology of a study that will incorporate enhanced data collection systems to provide additional insights into treatment choice and outcome for advanced valvular disease including that due to RHD. Methods: An enhanced data collection system will be developed linking an existing Australian cardiac surgery registry to more detailed baseline co-morbidity, medication, echocardiographic and hospital separation data to identify predictors of morbidity and mortality outcome following valve surgery. Discussion: This project aims to collect and incorporate more detailed information regarding pre and postoperative factors and subsequent morbidity. We will use this to provide additional insights into treatment choice and outcome. © 2017 The Author(s)
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Mathematical deconvolution of CAR T-cell proliferation and exhaustion from real-time killing assay data.
Chimeric antigen receptor (CAR) T-cell therapy has shown promise in the treatment of haematological cancers and is currently being investigated for solid tumours, including high-grade glioma brain tumours. There is a desperate need to quantitatively study the factors that contribute to the efficacy of CAR T-cell therapy in solid tumours. In this work, we use a mathematical model of predator-prey dynamics to explore the kinetics of CAR T-cell killing in glioma: the Chimeric Antigen Receptor T-cell treatment Response in GliOma (CARRGO) model. The model includes rates of cancer cell proliferation, CAR T-cell killing, proliferation, exhaustion, and persistence. We use patient-derived and engineered cancer cell lines with an in vitro real-time cell analyser to parametrize the CARRGO model. We observe that CAR T-cell dose correlates inversely with the killing rate and correlates directly with the net rate of proliferation and exhaustion. This suggests that at a lower dose of CAR T-cells, individual T-cells kill more cancer cells but become more exhausted when compared with higher doses. Furthermore, the exhaustion rate was observed to increase significantly with tumour growth rate and was dependent on level of antigen expression. The CARRGO model highlights nonlinear dynamics involved in CAR T-cell therapy and provides novel insights into the kinetics of CAR T-cell killing. The model suggests that CAR T-cell treatment may be tailored to individual tumour characteristics including tumour growth rate and antigen level to maximize therapeutic benefit
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