A coupling matrix vision for mobile filtering devices with micro-acoustic wave technologies. A systematic approach

Con el espectro radioeléctrico cada vez más saturado, los filtros y duplexores son elementos claves de la tecnología en el mercado de dispositivos discretos para la telefonía móvil. El segmento de usuario de los sistemas de comunicaciones inalámbricas aprovecha las destacadas propiedades de los dispositivos filtrantes basados en resonadores acústicos. Generalmente, el diseño de dispositivos de onda acústica ha sido asumido por técnicas de optimización debido a las restrictivas limitaciones impuestas por la viabilidad tecnológica de los resonadores SAW y BAW, así como las exigentes especificaciones eléctricas. Una respuesta de transmisión muy restrictiva y factores tecnológicos muy limitantes conducen a hacer el diseño más y más complejo y una tarea muy desafiante. El objetivo del trabajo está enfocado en facilitar el diseño de filtros/duplexores y hacerlo más eficiente. En consecuencia, la formulación inicial del problema se ha centrado en la viabilidad tecnológica para implementar filtros de onda acústica. Proporcionar una metodología sistemática es útil para acelerar la curva de aprendizaje de nuevos diseñadores. Los filtros de microondas con elevada selectividad son posibles si sus funciones de transferencia incorporan ceros de transmisión finitos. La introducción de nodos no-resonantes (NRN) da la posibilidad de diseñar filtros con el máximo número de ceros de transmisión finitos sin tener que implementar acoplamientos directos entre la fuente y la carga. Además, las configuraciones en línea con NRN permiten la extracción de los elementos analíticamente. La típica configuración de filtro ladder presenta similitudes características de acuerdo con las redes de prototipo en línea con nodos resonantes y no-resonantes, que son las propiedades de modularidad, para controlar los ceros de transmisión con resonadores independientes, y respuestas completamente canonícas sin acoplamiento fuente-carga directo. Los elementos de la red pasobanda son dados por ecuaciones explícitas en términos de aquellos en los prototipos en línea con NRN que pueden ser sintetizados analíticamente. Como consecuencia, es posible definir una metodología de síntesis directa para obtener los parámetros pasobanda eléctricos de un filtro RF general que está basado en resonadores acústicos. Este trabajo presenta una metodología que proporciona un procedimiento de síntesis sistemático para diseñar filtros y duplexores ladder basados en resonadores de onda micro-acústica. La metodología de diseño utiliza un enfoque nodal basado en NRN y nodos resonantes. La representación de la red mediante una matriz de acoplamiento mixta de nodos resonantes y no resonantes es capaz de gestionar de forma eficiente las restricciones tecnológicas. El procedimiento es eficiente en tiempo, preciso en los resultados y proporciona un profundo entendimiento de las particulares interacciones que se producen entre las restricciones tecnológicas y el funcionamiento del dispositivo. Un completo paquete de software, con un simulador rápido, preciso y de fácil uso, ha sido desarrollado, permitiendo obtener diseños de primera etapa exitosos. Como resultado de la metodología sistemática, hemos desarrollado un método de diseño que combina y sistemáticamente gestiona redes filtrantes compuestas de bloques de polo extraído con bloques de resonadores acoplados, es decir, celdas ladder con secciones CRF. Además, la metodología has sido extendida exitosamente para tener en cuenta el diseño de divisores de potencia con respuesta filtrante por medio de dos topologías diferentes: la configuración ladder y las secciones CRF. La metodología propuesta ofrece una solución que combina el completo cumplimiento de las máscaras de espectro con topologías preparadas para acomodar las restricciones tecnológicas de la tecnología micro-acústica. La metodología ha sido desarrollada orientada nativamente a gestionar la tecnología, como es el ajuste de la limitación en el acoplo electromagnético, y basada en fundamentos de síntesis rigurosos.With a spectrum more and more overcrowded, filters and duplexers are drivers of the technology in the discrete device mobile market. The user segment of wireless communication systems takes profit of the outstanding performance of filtering devices based on acoustic resonators. Usually, the design of acoustic wave devices have been mainly entrusted to optimization techniques because the stringent constraints imposed by the technological feasibility of SAW and BAW resonators and the challenging electrical specifications. A stringent transmission response and very restrictive technological factors lead the design to a more and more complex and challenging task. The aim of the work is focused on easing the filters/duplexers designs and making it more efficient. Consequently, the initial formulation of the problem was focused on the technological feasibility of acoustic wave filters. Providing a systematic methodology is useful to accelerate the learning curve of new entrant designers. Microwave filters with high selectivity are possible if their transfer functions incorporates finite transmission zeros. The inclusion of non-resonant nodes gives the possibility of designing filters with the maximum number of finite transmission zeros without implementing direct couplings between source and load. Furthermore, inline configuration with NRN allows the extraction of the elements analytically. The common ladder filter configuration exhibits characteristic similarities regarding inline prototype networks with resonant and non-resonant nodes, which are the property of modularity, to control transmission zeros by independent resonators, and fully canonical response without a direct source-load coupling. The elements of the lowpass prototype are given by explicit equations in terms of those in in-line prototypes with non-resonating nodes that can be synthesized analytically. As a consequence it is possible to define a direct synthesis methodology to obtain the bandpass electric parameters of a general RF filter that is based on acoustic resonators. This work presents a methodology that provides a systematic synthesis procedure for designing ladder filters and duplexers based on acoustic wave resonators. The methodology uses a nodal approach based on resonating and non-resonating nodes. The coupling matrix representation with a mix of different nature nodes, resonant and non-resonant, is able to efficiently manage the technological restrictions. The procedure is time efficient, precise in the outcomes and provides a deep understanding of the particular interactions between technological constraints and device performance. A complete software package with fast, accurate and easy-to-use simulator has been developed, enabling starting point design success. As a result of the systematic methodology, we have developed a design method that combines and systematically manages a filtering network composed of extracted-pole blocks with coupling resonators blocks, so it is ladder cells with CRF sections. Moreover, the methodology has been successfully extended to take into consideration filtering power dividers by means of two different topologies: ladder configuration and CRF sections. The proposed methodology offers a solution that combines a complete spectrum fulfillment with topologies ready to accommodate technological constraints of micro-acoustics technologies. The methodology has been developed natively oriented to manage with the technology, such as accommodating electromechanical coupling constraints, leveraged in rigorous synthesis foundations

Activation of synovial fibroblasts from patients at revision of their metal-on-metal total hip arthroplasty

BACKGROUND: The toxicity of released metallic particles generated in metal-on-metal (MoM) total hip arthroplasty (THA) using cobalt chromium (CoCr) has raised concerns regarding their safety amongst both surgeons and the public. Soft tissue changes such as pseudotumours and metallosis have been widely observed following the use of these implants, which release metallic by-products due to both wear and corrosion. Although activated fibroblasts, the dominant cell type in soft tissues, have been linked to many diseases, the role of synovial fibroblasts in the adverse reactions caused by CoCr implants remains unknown. To investigate the influence of implants manufactured from CoCr, the periprosthetic synovial tissues and synovial fibroblasts from patients with failed MoM THA, undergoing a revision operation, were analysed and compared with samples from patients undergoing a primary hip replacement, in order to elucidate histological and cellular changes. RESULTS: Periprosthetic tissue from patients with MoM implants was characterized by marked fibrotic changes, notably an increase in collagen content from less than 20% to 45-55%, an increase in α-smooth muscle actin positive cells from 4 to 9% as well as immune cells infiltration. Primary cell culture results demonstrated that MoM synovial fibroblasts have a decreased apoptosis rate from 14 to 6% compared to control synovial fibroblasts. In addition, synovial fibroblasts from MoM patients retained higher contractility and increased responsiveness to chemotaxis in matrix contraction. Their mechanical properties at a single cell level increased as observed by a 60% increase in contraction force and higher cell stiffness (3.3 kPa in MoM vs 2.18 kPa in control), as measured by traction force microscopy and atomic force microscopy. Further, fibroblasts from MoM patients promoted immune cell invasion by secreting monocyte chemoattractant protein 1 (MCP-1, CCL2) and induced monocyte differentiation, which could also be associated with excess accumulation of synovial macrophages. CONCLUSION: Synovial fibroblasts exposed in vivo to MoM THA implants that release CoCr wear debris displayed dramatic phenotypic alteration and functional changes. These findings unravelled an unexpected effect of the CoCr alloy and demonstrated an important role of synovial fibroblasts in the undesired tissue reactions caused by MoM THAs

Amorphous formulations of indomethacin and griseofulvin prepared by electrospinning

Following an array of optimization experiments, two series of electrospun polyvinylpyrrolidone (PVP) fibers were prepared. One set of fibers contained various loadings of indomethacin, known to form stable glasses, and the other griseofulvin (a poor glass former). Drug loadings of up to 33% w/w were achieved. Electron microscopy data showed the fibers largely to comprise smooth and uniform cylinders, with evidence for solvent droplets in some samples. In all cases, the drug was found to exist in the amorphous physical state in the fibers on the basis of X-ray diffraction and differential scanning calorimetry (DSC) measurements. Modulated temperature DSC showed that the relationship between a formulation’s glass transition temperature (<i>T</i>_g) and the drug loading follows the Gordon–Taylor equation, but not the Fox equation. The results of Gordon–Taylor analysis indicated that the drug/polymer interactions were stronger with indomethacin. The interactions between drug and polymer were explored in more detail using molecular modeling simulations and again found to be stronger with indomethacin; the presence of significant intermolecular forces was further confirmed using IR spectroscopy. The amorphous form of both drugs was found to be stable after storage of the fibers for 8 months in a desiccator (relative humidity <25%). Finally, the functional performance of the fibers was studied; in all cases, the drug-loaded fibers released their drug cargo very rapidly, offering accelerated dissolution over the pure drug

Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study

Doc number: 72 Abstract Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model. Methods/design: In a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered. Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period. A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers. Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems. Trial registration: NCT0145089

Increased expression of inducible co-stimulator on CD4+ T-cells in the peripheral blood and synovial fluid of patients with failed hip arthroplasties

OBJECTIVES: T-cells are considered to play an important role in the inflammatory response causing arthroplasty failure. The study objectives were to investigate the composition and distribution of CD4+ T-cell phenotypes in the peripheral blood (PB) and synovial fluid (SF) of patients undergoing revision surgery for failed metal-on-metal (MoM) and metal-on-polyethylene (MoP) hip arthroplasties, and in patients awaiting total hip arthroplasty. METHODS: In this prospective case-control study, PB and SF were obtained from 22 patients (23 hips) undergoing revision of MoM (n = 14) and MoP (n = 9) hip arthroplasties, with eight controls provided from primary hip osteoarthritis cases awaiting arthroplasty. Lymphocyte subtypes in samples were analysed using flow cytometry. RESULTS: The percentages of CD4+ T-cell subtypes in PB were not different between groups. The CD4+ T-cells in the SF of MoM hips showed a completely different distribution of phenotypes compared with that found in the PB in the same patients, including significantly decreased CD4+ T-central memory cells (p < 0.05) and increased T-effector memory cells (p < 0.0001) in the SF. Inducible co-stimulator (ICOS) was the only co-stimulatory molecule with different expression on CD4+ CD28+ cells between groups. In PB, ICOS expression was increased in MoM (p < 0.001) and MoP (p < 0.05) cases compared with the controls. In SF, ICOS expression was increased in MoM hips compared with MoP hips (p < 0.05). CONCLUSIONS: Increased expression of ICOS on CD4+ T-cells in PB and SF of patients with failed arthroplasties suggests that these cells are activated and involved in generating immune responses. Variations in ICOS expression between MoM and MoP hips may indicate different modes of arthroplasty failure. Cite this article: Professor P. A. Revell. Increased expression of inducible co-stimulator on CD4+ T-cells in the peripheral blood and synovial fluid of patients with failed hip arthroplasties. Bone Joint Res 2016;5:52–60. DOI: 10.1302/2046-3758.52.200057

Diagnostic guidelines for the histological particle algorithm in the periprosthetic neo-synovial tissue

Background The identification of implant wear particles and non-implant related particles and the characterization of the inflammatory responses in the periprosthetic neo-synovial membrane, bone, and the synovial-like interface membrane (SLIM) play an important role for the evaluation of clinical outcome, correlation with radiological and implant retrieval studies, and understanding of the biological pathways contributing to implant failures in joint arthroplasty. The purpose of this study is to present a comprehensive histological particle algorithm (HPA) as a practical guide to particle identification at routine light microscopy examination. Methods The cases used for particle analysis were selected retrospectively from the archives of two institutions and were representative of the implant wear and non-implant related particle spectrum. All particle categories were described according to their size, shape, colour and properties observed at light microscopy, under polarized light, and after histochemical stains when necessary. A unified range of particle size, defined as a measure of length only, is proposed for the wear particles with five classes for polyethylene (PE) particles and four classes for conventional and corrosion metallic particles and ceramic particles. Results All implant wear and non-implant related particles were described and illustrated in detail by category. A particle scoring system for the periprosthetic tissue/SLIM is proposed as follows: 1) Wear particle identification at light microscopy with a two-step analysis at low (× 25, × 40, and × 100) and high magnification (× 200 and × 400); 2) Identification of the predominant wear particle type with size determination; 3) The presence of non-implant related endogenous and/or foreign particles. A guide for a comprehensive pathology report is also provided with sections for macroscopic and microscopic description, and diagnosis. Conclusions The HPA should be considered a standard for the histological analysis of periprosthetic neo-synovial membrane, bone, and SLIM. It provides a basic, standardized tool for the identification of implant wear and non-implant related particles at routine light microscopy examination and aims at reducing intra-observer and inter-observer variability to provide a common platform for multicentric implant retrieval/radiological/histological studies and valuable data for the risk assessment of implant performance for regional and national implant registries and government agencies

Sulphate Chelate of CU(II) with p-Toluidine: Addition Reactions with HCI, SCl2, SiCl4, PCl5, SbCI5 & CrO2C12

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Studies on the Adducts of p-Toluidine with Copper(II) & Nickel(II) Sulphates & Their Reactions with Acetylhalides

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