19 research outputs found

    Heat Transfer Through Plasma-Sprayed Thermal Barrier Coatings in Gas Turbines: A Review of Recent Work

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    A review is presented of how heat transfer takes place in plasma-sprayed (zirconia-based) thermal barrier coatings (TBCs) during operation of gas turbines. These characteristics of TBCs are naturally of central importance to their function. Current state-of-the-art TBCs have relatively high levels of porosity (~15%) and the pore architecture (i.e., its morphology, connectivity, and scale) has a strong influence on the heat flow. Contributions from convective, conductive, and radiative heat transfer are considered, under a range of operating conditions, and the characteristics are illustrated with experimental data and modeling predictions. In fact, convective heat flow within TBCs usually makes a negligible contribution to the overall heat transfer through the coating, although what might be described as convection can be important if there are gross through-thickness defects such as segmentation cracks. Radiative heat transfer, on the other hand, can be significant within TBCs, depending on temperature and radiation scattering lengths, which in turn are sensitive to the grain structure and the pore architecture. Under most conditions of current interest, conductive heat transfer is largely predominant. However, it is not only conduction through solid ceramic that is important. Depending on the pore architecture, conduction through gas in the pores can play a significant role, particularly at the high gas pressures typically acting in gas turbines (although rarely applied in laboratory measurements of conductivity). The durability of the pore structure under service conditions is also of importance, and this review covers some recent work on how the pore architecture, and hence the conductivity, is affected by sintering phenomena. Some information is presented concerning the areas in which research and development work needs to be focussed if improvements in coating performance are to be achieved

    Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer

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    PURPOSE The population pharmacokinetic/pharmacodynamic (PK/PD) approach was prospectively integrated in the clinical development of docetaxel to assess the PK profile in a large population of patients and investigate systemic exposure as a prognostic factor for clinical outcome. PATIENTS AND METHODS PK analysis was performed at first course in 24 phase II studies of docetaxel monotherapy using four randomized limited-sampling schedules. Bayesian estimates of clearance (CL), area under the concentration-time curve (AUC), and peak and duration of plasma levels greater than threshold levels were used as measures of exposure. PD data included for efficacy, response rate, time to first response, and time to progression (TTP) in breast cancer and non-small-cell lung cancer (NSCLC), and for toxicity, grade 4 neutropenia, and febrile neutropenia at first course and time to onset of fluid retention. PK/PD analysis was conducted using logistic and Cox multivariate regression models. RESULTS PK protocol implementation was successful. Most of the patients registered (721 of 936, 77%) were sampled and 68% were assessable for PK (640 patients). First-course docetaxel AUC was a significant predictor (P = .0232) of TTP in NSCLC (n = 151). Docetaxel CL was a strong independent predictor (P &lt; .0001) of both grade 4 neutropenia and febrile neutropenia (n = 582). Cumulative dose was the strongest predictor (P &lt; .0001) of the time to onset of fluid retention (n = 631). However, the duration of exposure over 0.20 micromol/L (0.16 microg/mL) at first course was an independent predictor (P = .0029). Few patients (n = 25, 4%) received the recommended dexamethasone premedication. CONCLUSION First-course docetaxel PK is a predictor of first-course hematologic toxicity, but also of fluid retention, which is cumulative in nature. Patients with elevated hepatic enzymes have a 27% reduction in docetaxel CL and are at a higher risk of toxicity. A starting dose of 75 mg/m2 is currently being evaluated in this population. Prospective implementation of large-scale population PK/PD evaluation is feasible in early drug development and this approach generates clinically relevant findings. </jats:sec
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