The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

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European Position Paper on Rhinosinusitis and Nasal Polyps 2020

Co-stimulatory and co-inhibitory receptors have a pivotal role in T cell biology, as they determine the functional outcome of T cell receptor (TCR) signalling. The classic definition of T cell co-stimulation continues to evolve through the identification of new co-stimulatory and co-inhibitory receptors, the biochemical characterization of their downstream signalling events and the delineation of their immunological functions. Notably, it has been recently appreciated that co-stimulatory and co-inhibitory receptors display great diversity in expression, structure and function, and that their functions are largely context dependent. Here, we focus on some of these emerging concepts and review the mechanisms through which T cell activation, differentiation and function is controlled by co-stimulatory and co-inhibitory receptors.

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Molecular mechanisms of T cell co-stimulation and co-inhibition

羟氨苄青霉素引起大疱性类天疱疮样疹

Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fillers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specific degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fibers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specific biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed.

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Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review.

Voice disorders affect patients profoundly, and acoustic tools can potentially measure voice function objectively. Disordered sustained vowels exhibit wide-ranging phenomena, from nearly periodic to highly complex, aperiodic vibrations, and increased "breathiness". Modelling and surrogate data studies have shown significant nonlinear and non-Gaussian random properties in these sounds. Nonetheless, existing tools are limited to analysing voices displaying near periodicity, and do not account for this inherent biophysical nonlinearity and non-Gaussian randomness, often using linear signal processing methods insensitive to these properties. They do not directly measure the two main biophysical symptoms of disorder: complex nonlinear aperiodicity, and turbulent, aeroacoustic, non-Gaussian randomness. Often these tools cannot be applied to more severe disordered voices, limiting their clinical usefulness. This paper introduces two new tools to speech analysis: recurrence and fractal scaling, which overcome the range limitations of existing tools by addressing directly these two symptoms of disorder, together reproducing a "hoarseness" diagram. A simple bootstrapped classifier then uses these two features to distinguish normal from disordered voices. On a large database of subjects with a wide variety of voice disorders, these new techniques can distinguish normal from disordered cases, using quadratic discriminant analysis, to overall correct classification performance of 91.8 ± 2.0%. The true positive classification performance is 95.4 ± 3.2%, and the true negative performance is 91.5 ± 2.3% (95% confidence). This is shown to outperform all combinations of the most popular classical tools. Given the very large number of arbitrary parameters and computational complexity of existing techniques, these new techniques are far simpler and yet achieve clinically useful classification performance using only a basic classification technique. They do so by exploiting the inherent nonlinearity and turbulent randomness in disordered voice signals. They are widely applicable to the whole range of disordered voice phenomena by design. These new measures could therefore be used for a variety of practical clinical purposes.

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Exploiting Nonlinear Recurrence and Fractal Scaling Properties for Voice Disorder Detection

The aerodynamic transfer of energy from glottal airflow to vocal fold tissue during phonation was explored using complementary synthetic and numerical vocal fold models. The synthetic model was fabricated using a flexible polyurethane rubber compound. The model size, shape, and material properties were generally similar to corresponding human vocal fold characteristics. Regular, self-sustained oscillations were achieved at a frequency of approximately 120 Hz. The onset pressure was approximately 1.2 kPa. A corresponding two-dimensional finite element model was developed using geometry definitions and material properties based on the synthetic model. The finite element model upstream and downstream pressure boundary conditions were based on experimental values acquired using the synthetic model. An analysis of the fully coupled fluid and solid numerical domains included flow separation and unsteady effects. The numerical results provided detailed flow data that was used to investigate aerodynamic energy transfer mechanisms. The results support the hypothesis that a cyclic variation of the orifice profile from a convergent to a divergent shape leads to a temporal asymmetry in the average wall pressure, which is the key factor for the achievement of self-sustained vocal fold oscillations. me rica.

Aerodynamic transfer of energy to the vocal folds

Acoustic analogy methods are used as post-processing tools to predict aerodynamically generated sound from numerical solutions of unsteady flow. The Ffowcs Williams–Hawkings (FW–H) equation and related formulations, such as Farassat’s Formulations 1 and 1A, are among the commonly used analogies because of their relative low computation cost and their robustness. These formulations assume the propagation of sound waves in a medium at rest. The present paper describes a surface integral formulation based on the convective wave equation, which takes into account the presence of a mean flow. The formulation was derived to be easy to implement as a numerical post-processing tool for computational fluid dynamics codes. The new formulation constitutes one possible extension of Farassat’s Formulation 1 and 1A based on the convective form of the FW–H equation.

An acoustic analogy formulation for moving sources in uniformly moving media

Adaptive-passive noise control with self-tuning helmholtz resonators

The aerodynamic generation of sound during phonation was studied using direct numerical simulations of the airflow and the sound field in a rigid pipe with a modulated orifice. Forced oscillations with an imposed wall motion were considered, neglecting fluid–structure interactions. The compressible, two-dimensional, axisymmetric form of the Navier–Stokes equations were numerically integrated using highly accurate finite difference methods. A moving grid was used to model the effects of the moving walls. The geometry and flow conditions were selected to approximate the flow within an idealized human glottis and vocal tract during phonation. Direct simulations of the flow and farfield sound were performed for several wall motion programs, and flow conditions. An acoustic analogy based on the Ffowcs Williams–Hawkings equation was then used to decompose the acoustic source into its monopole, dipole, and quadrupole contributions for analysis. The predictions of the farfield acoustic pressure using the acoustic...

Computational aeroacoustics of phonation, part I: Computational methods and sound generation mechanisms.

The results are described of the second part of an ongoing study aimed at performing direct numerical simulations of translaryngeal flows during phonation. The use of accurate numerical schemes allows the radiated sound to be calculated directly, without the need for acoustic analogy models. The goal is to develop a better understanding of this class of flow, and of the basic sound generation mechanisms involved in phonation. In the present study, the effects of subglottal pressure and of glottal oscillation frequency on the near-field flow and farfield sound were investigated. The effects of the presence of the ventricular folds downstream of the oscillating glottal region were also examined. The results highlighted the effects of subglottal pressure and oscillation frequency on the jet vortical structure, wall pressure and shear stress, and sound radiation. Jet impingement on the ventricular folds introduced additional dipole sources similar to those observed in problems involving grazing flows over cavities.

Luc Mongeau

Papers

Aerodynamic transfer of energy to the vocal folds

An acoustic analogy formulation for moving sources in uniformly moving media

Adaptive-passive noise control with self-tuning helmholtz resonators

Computational aeroacoustics of phonation, part I: Computational methods and sound generation mechanisms.

Computational aeroacoustics of phonation, part II: Effects of flow parameters and ventricular folds.