Microprojection arrays applied to skin generate mechanical stress, induce an inflammatory transcriptome and cell death, and improve vaccine-induced immune responses

Abstract: Chemical adjuvants are typically used to improve immune responses induced by immunisation with protein antigens. Here we demonstrate an approach to enhance immune responses that does not require chemical adjuvants. We applied microprojection arrays to the skin, producing a range of controlled mechanical energy to invoke localised inflammation, while administering influenza split virus protein antigen. We used validated computational modelling methods to identify links between mechanical stress and energy generated within the skin strata and resultant cell death. We compared induced immune responses to those induced by needle-based intradermal antigen delivery and used a systems biology approach to examine the nature of the induced inflammatory response, and correlated this with markers of cell stress and death. Increasing the microprojection array application energy and the addition of QS-21 adjuvant were each associated with enhanced antibody response to delivered antigen and with induction of gene transcriptions associated with TNF and NF-κB signalling pathways. We concluded that microprojection intradermal antigen delivery inducing controlled local cell death could potentially replace chemical adjuvants to enhance the immune response to protein antigen

Coronary plaque composition as assessed by greyscale intravascular ultrasound and radiofrequency spectral data analysis

Objectives: (i) To explore the relation between greyscale intravascular ultrasound (IVUS) plaque qualitative classification and IVUS radiofrequency data (RFD) analysis tissue types; (ii) to evaluate if plaque composition as assessed by RFD analysis can be predicted by visual assessment of greyscale IVUS images. Methods: In 120 IVUS-RFD cross-sections, a sector of the plaque with homogenous tissue composition (e.g., fibrous, fibrofatty, necrotic core, and dense calcium) was selected. Two experienced observers analyzed twice the corresponding greyscale IVUS images to: (1) classify the selected sectors according to greyscale IVUS plaque type classification and (2) predict the tissue type expected in the sector by RFD analysis. Results: In the greyscale IVUS plaque type classification, the observers agreed in 90/120 sectors (κ = 0.64). Calcified, soft and mixed plaques by greyscale IVUS classification were mainly composed of dense calcium, fibrofatty, and necrotic core, respectively, in the RFD analysis. The plaques classified in greyscale IVUS as fibrous were actually fibrous tissue by IVUS RFD in only 30% of the cases. Overall, high interobserver variability in the prediction of RFD results by visual assessment of greyscale IVUS images (κ = 0.23 for observer 1 and 0.55 for observer 2) was found. Sens

Prevalence, predictors, and outcomes of patient prosthesis mismatch in women undergoing TAVI for severe aortic stenosis: Insights from the WIN-TAVI registry

Objective: To evaluate the incidence, predictors and outcomes of female patients with patient-prosthesis mismatch (PPM) following transcatheter aortic valve intervention (TAVI) for severe aortic stenosis (AS). Background: Female AS TAVI recipients have a significantly lower mortality than surgical aortic valve replacement (SAVR) recipients, which could be attributed to the potentially lower PPM rates. TAVI has been associated with lower rates of PPM compared to SAVR. PPM in females post TAVI has not been investigated to date. Methods: The WIN-TAVI (Women's INternational Transcatheter Aortic Valve Implantation) registry i

isolation and characterization of vessel associated stem progenitor cells from skeletal muscle

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Global instability of helical vortex breakdown

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An asymptotic framework to alleviate hysteresis induced by axisymmetric vortex breakdown in a contracting pipe

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Sensitivity of vortex-shedding in unsteady wake based on a self-consistent model

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Self-consistent triple decomposition of the turbulent flow over a backward-facing step under finite amplitude harmonic forcing

International audienceWe investigate the saturation of harmonically forced disturbances in the turbulent flow over a backward-facing step subjected to a finite amplitude forcing. The analysis relies on a triple decomposition of the unsteady flow into mean, coherent and incoherent components. The coherent-incoherent interaction is lumped into a Reynolds averaged Navier-Stokes (RANS) eddy viscosity model, and the mean-coherent interaction is analysed via a semi-linear resolvent analysis building on the laminar approach by Mantic-Lugo & Gallaire (2016 J. Fluid Mech. 793, 777-797. (doi:10.1017/jfm.2016.109)). This provides a self-consistent modelling of the interaction between all three components, in the sense that the coherent perturbation structures selected by the resolvent analysis are those whose Reynolds stresses force the mean flow in such a way that the mean flow generates exactly the aforementioned perturbations, while also accounting for the effect of the incoherent scale. The model does not require any input from numerical or experimental data, and accurately predicts the saturation of the forced coherent disturbances, as established from comparison to time-averages of unsteady RANS simulation data

A weakly nonlinear mechanism for mode selection in swirling jets, 23rd International Congress of Theoretical and Applied Mechanics

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