Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival

[EN] Purpose: To determine if preoperative vascular heterogeneity of glioblastoma is predictive of overall survival of patients undergoing standard-of-care treatment by using an unsupervised multiparametric perfusion-based habitat-discovery algorithm. Materials and Methods: Preoperative magnetic resonance (MR) imaging including dynamic susceptibility-weighted contrast material-enhanced perfusion studies in 50 consecutive patients with glioblastoma were retrieved. Perfusion parameters of glioblastoma were analyzed and used to automatically draw four reproducible habitats that describe the tumor vascular heterogeneity: high-angiogenic and low-angiogenic regions of the enhancing tumor, potentially tumor-infiltrated peripheral edema, and vasogenic edema. Kaplan-Meier and Cox proportional hazard analyses were conducted to assess the prognostic potential of the hemodynamic tissue signature to predict patient survival. Results: Cox regression analysis yielded a significant correlation between patients' survival and maximum relative cerebral blood volume (rCBV(max)) and maximum relative cerebral blood flow (rCBF(max)) in high-angiogenic and low-angiogenic habitats (P < .01, false discovery rate-corrected P < .05). Moreover, rCBF(max) in the potentially tumor-infiltrated peripheral edema habitat was also significantly correlated (P < .05, false discovery rate-corrected P < .05). Kaplan-Meier analysis demonstrated significant differences between the observed survival of populations divided according to the median of the rCBV(max) or rCBF(max) at the high-angiogenic and low-angiogenic habitats (log-rank test P < .05, false discovery rate-corrected P < .05), with an average survival increase of 230 days. Conclusion: Preoperative perfusion heterogeneity contains relevant information about overall survival in patients who undergo standard-of-care treatment. The hemodynamic tissue signature method automatically describes this heterogeneity, providing a set of vascular habitats with high prognostic capabilities.Study supported by H2020 European Institute of Innovation and Technology (POC-2016.SPAIN-07) and Universitat Politecnica de Valencia (PAID-10-14). J.J.A., E.F.G., and J.M.G.G. supported by Secretaria de Estado de Investigacion, Desarrollo e Innovacion (DPI2016-80054-R, TIN2013-43457-R). E.F.G. supported by CaixaImpulse program from Fundacio Bancaria "la Caixa" (LCF/TR/CI16/10010016). E.F.G and A.A.B. supported by the Universitat Politecnica de Valencia Instituto Investigacion Sanitaria de La Fe (C05).Juan -Albarracín, J.; Fuster García, E.; Pérez-Girbés, A.; Aparici-Robles, F.; Alberich Bayarri, A.; Revert Ventura, AJ.; Martí Bonmatí, L.... (2018). Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival. Radiology. 287(3):944-954. https://doi.org/10.1148/radiol.2017170845S944954287

Evaluation of a novel continuous glucose monitoring-based method for mealtime insulin dosing - the iBolus - in subjects with type 1 diabetes using continuous subcutaneous insulin infusion therapy: a randomized controlled trial

This is a copy of an article published in the Diabetes Technology and Therapeutics © 2012 [copyright Mary Ann Liebert, Inc.]; Diabetes Technology and Therapeutics is available online at: http://online.liebertpub.com.[EN] Objective: Prandial insulin dosing is an empirical practice associated frequently with poor reproducibility in postprandial glucose response. Based on continuous glucose monitoring (CGM), a method for prandial insulin administration (iBolus) is presented and evaluated for people with type 1 diabetes using CSII therapy. Subjects and Methods: An individual patient¿s model for a 5-h postprandial period was obtained from 6-day ambulatory CGM and used for iBolus calculation in 12 patients with type 1 diabetes. In a double-blind, crossover study each patient underwent four meal tests with 40 g or 100 g of carbohydrates (CHOs), both on two occasions. For each meal, the iBolus or the traditional bolus (tBolus) was given before mealtime (t 0) in a randomized order. We measured the postprandial glycemic response as the area under the curve of plasma glucose (AUC-PG0¿5h) and variability as the individual coef¿cient of variation (CV) of AUC-PG0¿5h. The contribution of the insulin-to-CHO ratio, CHO, plasma glucose at t 0 (PGt0), and insulin dose to AUC-PG0¿5h and its CV was also investigated. Results: AUC-PG0¿5h was similar with either bolus for 40-g (iBolus vs. tBolus, 585.5¿127.5 vs. 689.2¿180.7 mg/dL$h) or 100-g (752.1¿237.7 vs. 760.0¿263.2 mg/dL$h) CHO meals. A multiple regression analysis revealed a signi¿cant model only for the tBolus, with PGt0 being the best predictor of AUC-PG0¿5h explaining approximately 50% of the glycemic response. Observed variability was greater with the iBolus (CV, 16.7¿15.3% vs. 10.1¿12.5%) but independent of the factors studied. Conclusions: A CGM-based algorithm for calculation of prandial insulin is feasible, although it does not reduce unpredictability of individual glycemic responses. Causes of variability need to be identi¿ed and analyzed for further optimization of postprandial glycemic control.We are grateful to Mrs. Sara Correa, Fundacion INCLIVA-Hospital Clinico Universitario de Valencia, and Mrs. Geles Viguer, Hospital Clinico Universitario de Valencia, for their invaluable help in conducting the study. We also thanks Dr. Carmine Fanelli, University of Perugia, Dr. Howard Zisser, Sansum Diabetes Research Institute, and Prof. Alberto Ferrer, Universitat Politecnica de Valencia, for their suggestions on study design and data analysis. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007/2013) under grant agreement 252085 and from the Spanish Ministry of Science under grants DPI2010-20764-C02-01 and DPI2011-28112-C04-01.Rossetti, P.; Ampudia Blasco, FJ.; Laguna Sanz, AJ.; Revert Tomás, A.; Vehí Casellas, J.; Ascaso, JF.; Bondía Company, J. (2012). Evaluation of a novel continuous glucose monitoring-based method for mealtime insulin dosing - the iBolus - in subjects with type 1 diabetes using continuous subcutaneous insulin infusion therapy: a randomized controlled trial. Diabetes Technology & Therapeutics. 14(11):1043-1052. https://doi.org/10.1089/dia.2012.0145S10431052141

Sealing Performance of a Turbine Rim Chute Seal Under Rotationally-Induced Ingestion

This study focuses on the sealing capability of a turbine rim seal subject to hot gas ingestion driven purely by the rotor disc pumping effect rather than that induced by mainstream features such as vane and rotor blade passing. The aim is to provide useful data for conditions in which rotation dominates, and to clarify the flow physics involved in rim sealing. Experimental measurements of sealing effectiveness for a chute seal are presented for the first time without and with an axial, axisymmetric mainstream flow external to the seal. The test matrix covers a range of rotational Reynolds number, Re , from 1.5x106 to 3x106, and nondimensional flow rate, C , from 0 to 4x104 with the mainstream flow (when present) scaled to match engine representative conditions of axial Reynolds number, Re . Results from steady pressure and gas concentration measurements within the rotor-stator disc cavity and the rim seal gap are presented and compared to published data for other seal designs. Sealing performance of the chute seal is somewhat similar to that of axial clearance seals with the same minimum clearance

Sealing Performance of a Turbine Rim Chute Seal Under Rotationally-Induced Ingestion

This study focuses on the sealing capability of a turbine rim seal subject to hot gas ingestion driven purely by the rotor disc pumping effect rather than that induced by mainstream features such as vane and rotor blade passing. The aim is to provide useful data for conditions in which rotation dominates, and to clarify the flow physics involved in rim sealing. Experimental measurements of sealing effectiveness for a chute seal are presented for the first time without and with an axial, axisymmetric mainstream flow external to the seal. The test matrix covers a range of rotational Reynolds number, Re , from 1.5x106 to 3x106, and nondimensional flow rate, C , from 0 to 4x104 with the mainstream flow (when present) scaled to match engine representative conditions of axial Reynolds number, Re . Results from steady pressure and gas concentration measurements within the rotor-stator disc cavity and the rim seal gap are presented and compared to published data for other seal designs. Sealing performance of the chute seal is somewhat similar to that of axial clearance seals with the same minimum clearance

Wall-modeled large eddy simulations of axial turbine rim sealing

This paper presents wall-modeled large-eddy simulations (WMLES) of a chute-type turbine rim seal. Configurations with an axisymmetric annulus flow and with nozzle guide vanes fitted (but without rotor blades) are considered. The passive scalar concentration solution and WMLES are validated against available data in the literature for uniform convection and a rotor-stator cavity flow. The WMLES approach is shown to be effective, giving significant improvements over an eddy viscosity turbulence model, in prediction of rim seal effectiveness compared to research rig measurements. WMLES requires considerably less computational time than wall-resolved LES, and has the potential for extension to engine conditions. All WMLES solutions show rotating inertial waves in the chute seal. Good agreement between WMLES and measurements for sealing effectiveness in the configuration without vanes is found. For cases with vanes fitted, the WMLES simulation shows less ingestion than the measurements, and possible reasons are discussed