Mapping the dielectric properties of cells with nanoscale spatial resolution can be an important tool in nanomedicine and nanotoxicity analysis, which can complement structural and mechanical nanoscale measurements. Recently we have shown that dielectric constant maps can be obtained on dried fixed cells in air environment by means of scanning dielectric force volume microscopy. Here, we demonstrate that such measurements can also be performed in the much more challenging case of fixed cells in liquid environment. Performing the measurements in liquid media contributes to preserve better the structure of the fixed cells, while also enabling accessing the local dielectric properties under fully hydrated conditions. The results shown in this work pave the way to address the nanoscale dielectric imaging of living cells, for which still further developments are required, as discussed here. The dielectric properties of cells have been the subject of intense research over the years due to its relevance in many fundamental and applied biological problems. At the whole cell level, changes in the dielectric properties of cells have been studied as possible cancer markers  or cell The measurement of the dielectric properties at the whole cell level can be done through electrokinetic techniques, such as dielectrophoresis , electroImpedance-based measurements can provide also local dielectric information by reducing the measuring electrode size via patterned microelectrode array planar devices (MEAs) ,12, in lD) or by applying a high frequency electric potential, higher than the dielectric relaxation frequency of the electrolyte. Nevertheless, to the best of our knowledge, such modes have not yet been applied to the challenging case of the nanoscale dielectric imaging of cells in liquid environment.Electric force-based scanning probe microscopy  in force detection mode , offer aIn this paper we will show how in-liquid SDM, which has already been successfully applied to study the capacitive properties of self-assembled monolayers (SAMs) , lipid b2 and 37 ℃, the cells were observed and seemed completely attached and spread on the gold substrate. Then, cells were fixed. The medium was washed with PBS, and the cells were incubated with 2.5% glutaraldehyde in PBS for 10 min. After fixation, the cells were washed consecutively with different solutions: 75%, 50% and 25% PBS, ultrapure MilliQ water, and 10 mM 3-(N-morpholino)propanesulfonic acid (MOPS ) buffer. Prior to the Atomic Force Microscopy (AFM) experiments, the cells and substrate were moved from the petri dish to the AFM sample holder and a drop of 10 mM MOPS buffer was placed onto the sample to perform the experiments in fully hydrated conditions.HeLa cells from a lab cell line seeded on top of gold-coated silicon substrates were used in the present study. The protocol to prepare the sample was optimized from the different options shown in , and it mod = 5 kHz and fel = 5 MHz, was applied between a conductive tip  and the metallic substrate. The value of k was determined by means of the thermal noise method. The relatively large uncertainties in the determination of k (up to a 20%) can affect the extracted geometric parameters of the tip but they do not affect remarkably the extracted homogeneous dielectric constants. The choice of fel was done prior to the experiments by selecting a frequency above the critical relaxation frequency of the solution [ωmod are acquired. In-liquid SDFVM measurements were done following the methods of in-liquid SDM ,36,38,39solution , and belThe deflection of the cantilever is used to determine the contact point with the sample and hence determine the sample’s topography, while the oscillation amplitude is used to measure the derivative of the capacitance of the system, dC/dz, referred to as the capacitance gradient, through the following relationship see Ref. ).The operation of in-liquid SDM in the fast force-volumetric scan mode prevents the application of lateral forces to the sample, crucial in the case of weekly adhered samples like cells. Nevertheless, for the case of extremely soft samples (like living cells), this mode can add an extra complication to the data processing, since the determination of the tip-sample contact point is not straightforward, thus the unperturbed sample’s topography can be difficult to reconstruct  enables building up the so-called Data Cubes from the ensemble of acquired electrical deflection and oscillation curves, from where, all the different classical electrostatic force microscopy (EFM) images can be retrieved  .cell, equal to the local thickness of the cell, and dielectric constant, εcell, to be determined (see sol. Ionic conductivity effects are not included since the frequency of the applied voltage (fel = 5 MHz) is larger than the dielectric relaxation frequency of the electrolyte solution (fRC = 0.5 MHz), that can be calculated via conductivity (σsol) measurements as: tip = 2.7 µF/cm2 and csubs are added to the tip and bare substrate parts to model interfacial effects in electrolytes, as described elsewhere [We determined the local equivalent homogeneous dielectric constant of the cells in electrolyte media by using a local thick-film dielectric model . This moined see a. The enus works  by a conlsewhere . The miclsewhere . With thlsewhere .ω). cell, is lower than the dielectric constant of the electrolyte solution, εsol. Therefore, despite the cell being basically filled with electrolyte solution, still the dielectric images can sense the dielectric contribution of the cell components. Nevertheless, dC/dz constant plane images are not yet dielectric constant maps. To derive them, one needs to consider the local geometrical features of the cell, such as the thickness, shape, and internal structure.cell, span a wide range of values from ≈20 in the cell extended parts to ≈80 in the central part. As advanced before, most of these values are smaller than the dielectric constant of the solution εsol = 80, from where the negative contrast in the constant plane dielectric images. In the Discussion section, we explain the origin of the wide range of values obtained and the information that can be obtained from them concerning the cell dielectric properties.To generate the dielectric constant map, we used here a local thick-dielectric model with calibrated tip geometrical parameters . We derived effective local dielectric constant maps of fixed HeLa cells in an electrolyte solution, by means of the cutting-edge advances of in-liquid SDFVM, based here, on a simple thick-film model for their quantification. The dielectric constants obtained with this approach represent the equivalent homogeneous dielectric constant of a small volume located below the tip at each sample position. Therefore, a combination of both, the local dielectric constant of the cell biomolecular components  and the water content of the cell, is simultaneously mapped. The equivalent homogeneous dielectric constant obtained is used to identify the presence of internal heterogenous dielectric properties.cell values as a function of the height of the cell. There is an obvious correlation between the dielectric constant values and the height (thickness) of the cell, which automatically implies that some internal dielectric heterogeneity should be present. For a cell, the main internal dielectric heterogeneity is given by the presence of the cell membrane, the cytoplasmic region (containing the organelles and other sub-cellular structures) and water. Due to the high dielectric constant of water, the contribution of the cytoplasmic structures in the volume probed by the tip, in a first approximation, can be taken as a small correction to the dielectric response of water.m = ε0·εm/hm, where hm and εm are the thickness and dielectric constant of the layer, respectively, which represent the cell membrane and an internal thick layer of thickness hcyto and dielectric constant εcyto representing the cytoplasmatic region  follow nicely the trend of the experimental values. The values obtained for both parameters are within the range of values reported in the literature for eukaryotic cells, what is quite remarkable. This result indicates that the dielectric constant maps can provide information on both the dielectric properties of the cell content and of the cell membrane. We note that the cell content is expected to be composed of electrolyte solution, but due to the crowded nature of the cell cytoplasm it may happen that its actual dielectric constant differs from that supposed for water and would resemble more to the dielectric constant of a biological solution with proteins, lipids, DNA, etc., at the frequency of the measurements. The effect of the variations of εcyto predicted by the model is shown in the inset of To support this interpretation, we considered a “core-shell” thick dielectric model, with two thin layers of specific capacitance cgion see b. FigureThe previous analysis explains why, in solution ≈ 80. Namely, if the dielectric response of a region is smaller than the one of the solutions, that means that the detection of some low polarizable biocomponent of the cell is affecting the local polarizability. Likewise, if the dielectric response of a region is higher than the one of the solutions, it implies some higher polarizability of the region. The main sources of change in the dielectric response can be identified as either different local dielectric response of the different biochemical compounds or as different amount of solution volume in the region the tip is sensitive to. Other sources of changes in the dielectric response could also be assigned to local conductivity changes that can arise mixed resistive/capacitive response or different local adsorbates present in the cell surface as stated above. For the measurements reported here on fixed cells, for which the internal and external solution should have a similar ionic composition, we expect conductivity effects to be neglectable (if any), since the measurements are made at frequencies larger than the dielectric relaxation frequency of the electrolyte.Contrary to what happens in the case of the dielectric mapping of fixed cells in dry conditions , where tcell considered in the model, inducing an overestimation or underestimation of the dielectric constant value depending on whether the true topography is higher or lower than the measured one).In addition to what is said above, we must consider at least three potential sources of error in the dielectric constant determination in the present work: The non-realistic geometrical model used , the small conductivity effects if the intracellular media remains with a higher molarity than the extracellular solution (which would turn into an overestimation of the dielectric constant) and the error in the contact point determination . Cell media for living cells experiments are normally rich in ions to avoid an osmotic shock and also in nutrients necessary to maintain cell functions. However, the presence of large amounts of mobile charges in the electrolyte may hinder the operation of in-liquid SDM, limited by its operation at frequencies larger than the electrolyte relaxation frequency, which escalates quickly with solute molarity. Thus, a balance must be achieved for the realization of the experiments between preserving cell structure and being able to measure its dielectric properties with in-liquid SDM. Typically, using the experimental setup we implemented for this work, allows to reach the 10–100 MHz frequency range of applied electric voltage, and considering other similar implementations one can even reach the GHz range if a refinement of the electric shielding circuitry is carried out [The extension of the proposed approach to the case of living cells still needs further investigation. Living cells are delicate samples and need to be maintained in specific electrolyte media to keep its structure and function, and with controlled temperature (37 ℃) and COried out . This exThe extension of the proposed method to the dielectric imaging of living cells comes with other additional adversities, such as the complication of the determination of the “true-topography” of the cell or the presence of active cell movements during the scan times. If such struggles are overcome, we envision in-liquid SDM to be an excellent tool to map both static and slow-dynamic biological processes happening at the cellular and subcellular scale, challenging to access by means of any other state-of-the-art electrochemical, optical or impedance-based methods, which show overwhelmingly large parasitic capacitive contributions when implemented with sub-micrometric electrodes.We applied the recent developments of in-liquid scanning dielectric microscopy in force-volume mode to the challenging case of imaging the dielectric properties of fixed eukaryotic cells in electrolyte solutions. We derived local equivalent homogeneous dielectric constant maps of the cells with nanometric spatial resolution and showed that they provide information on both the water content of the cell and the dielectric properties of the cell membrane and cytoplasmatic content. The results presented here pave the way for the more interesting case of dielectric imaging of living cells at the nanoscale, where dielectric changes during biological functional processes could be potentially studied.


Hand pose estimation from RGB images has always been a difficult task, owing to the incompleteness of the depth information. Moon et al. improved the accuracy of hand pose estimation by using a new network, InterNet, through their unique design. Still, the network still has potential for improvement. Based on the architecture of MobileNet v3 and MoGA, we redesigned a feature extractor that introduced the latest achievements in the field of computer vision, such as the ACON activation function and the new attention mechanism module, etc. Using these modules effectively with our network, architecture can better extract global features from an RGB image of the hand, leading to a greater performance improvement compared to InterNet and other similar networks. Considering the continuous development of information techniques, various electronic devices equipped with artificial intelligence systems have been integrated into our lives ,2, and tUsing deep learning methods to estimate hand pose based on a RGB image, one of the possible methods is InterNet, which was introduced by . InterNeWe redesigned a feature extractor based on deep neural networks to replace the simpler ResNet-50  backboneWe introduced the multi-spectral attention mechanism named FcaNet  to proceWe tried to improve the overall training procedure of the network to obtain more information from the available data.Still, as the single structure of the feature extraction network in the original InterNet, it has huge potential for improvement. In the years after the publication of the original InterNet network, tremendous progress has been made in the field of machine learning and deep neural networks . For theSubsequently, we will introduce the related methods of hand pose estimation based on deep learning in In this section, we will briefly introduce the related work on hand pose estimation based on deep learning. There are several preliminary studies on hand pose estimation. We refer to ,3 as welConsidering a previous study, depth map was mainly used for depth information extraction and position information inference for hand pose estimation . DeepPri2 HAND, a self-supervised 3D hand reconstruction network, which can jointly estimate pose, shape, texture, and the camera viewpoint.In 2017, Zimmermann et al.  used CNNFor hand-object pose estimation, Bardia et al.  proposedIn this section, we will briefly review the original InterNet architecture and its related data processing procedure to contrast with our modifications to the network in The InterNet aims to estimate 3D hand key-points position from a single RGB image. The whole network pipeline is shown in hL, which constrains the network to infer the attribution and quantity of the hands appearing in the image; (2) the L2 loss function handL, which is used to constrain the 2.5D hand posture and estimate the accuracy of the position of the joint points; (3) L1 loss function relL, which constrains the estimation of the Euclidean distance between the root point of the right and left hands. The three loss functions are additively combined with the same weight, and they work together for end-to-end model training.The author designed a combination of three loss functions, defining: (1) the binary cross-entropy function To annotate the key-points of the hand, Moon et al.  directlyIn this section, we will describe in detail the modifications we made to the original enhanced InterNet method with our initial motivation, including the improved and redesigned feature extraction network, feature map processing, and new network model training methods.In recent research, the MobileNet family shows greater efficiency and computational performance ratio in computer vision tasks with a small or medium amount of data than classic network backbone, such as ResNet . To extrWe refer to the design of MobileNet v2  and use Hou et al. proposed a coordinate attention mechanism , which hMa et al. proposed the ACON activation function. They obtained motivation from the function Among the commonly used activation functions, the structure is basically as The author constructed the approximate fitting smooth differentiable function function . The autBased on the above operations, the author believed that other maximum-based activation functions in the ReLU family can be transformed into the ACON family. The author used the same method to deal with the PReLU function , where This activation function learns the linearity and non-linearity gate of the entire activation function area of a specific network location by setting hyperparameters to switch between active and inactive states. In this study, we use the ACON-C function. We added this activation function to the end of the separable convolution before the inverted residual block of the feature extractor and achieved good results.Considering the latest achievements in the above deep learning field, we designed a feature extraction network with superior performance using a combination of architectures similar to MobileNet v3 and MoGA networks . The structure is shown in The hand pose estimation tasks commonly face a problem of insufficient information, whether from the local pixel aspect or from the global spectrum aspect ,3. To soUpon obtaining the feature map through the feature extraction network, we did not directly send it to the subsequent fully connected layer and linear structure to determine whether there are left and right hands, the number of hands in the image, or to fit the location heatmap of the key-points. The feature map is a three-dimensional tensor with a number of channels much larger than the size of length and height. In our network, its size is 2048 × 8 × 8; therefore, we use a new attention mechanism to process it to preserve as much information in the frequency domain as possible before the subsequent processing.We process the feature maps obtained from the feature extraction network through the FcaNet layer  proposed by Qin et al. . The autIn previous hand pose estimation tasks, attention mechanism modules were rarely used. On the one hand, studies on the attention mechanism are still progressing. Many current attention mechanisms in spatial or frequency domain could not improve the performance of the network in hand pose estimation tasks. On the other hand, the attention mechanism can play a better role in promoting network performance in some datasets; nevertheless, the effect is not obvious in the other datasets and may even have the opposite effect. Considering the analysis of the principle and the continuous attempts of its correct application to the network structure, we can add multiple types of attention mechanism modules to the whole network to improve its performance on different datasets. The ablation analysis in subsequent experiments can prove the effectiveness of the functional modules in our method.Compared to the original InterNet, using the widely used Adam  as the oWe evaluated our InterNet+ network on RGB datasets used for hand pose estimation, including the STB and RHD datasets, and the feasibility test conducted on the incomplete InterHand2.6M dataset (5 fps version) . We compWe conducted experiments mainly on the STB and RHD datasets based on the proposed InterNet+ network, with both of them having achieved considerable accuracy improvements compared to the original model, and achieved state-of-the-art results. At the same time, in order to prove the effectiveness of the method, we also conducted a small number of experiments on InterHand2.6M dataset (5 fps version). Referring to reference , we hereThe stereo hand pose tracking benchmark (STB)  is one oThe Rendered Handpose Dataset (RHD)  is also The dataset uses 20 characters to perform 39 actions, totaling 43,986 frames . The resolution is 320 × 320, providing depth segmentation mask and 2D and 3D position annotation information of 21 key-points.Compensating for the insufficiencies in the previous datasets for the identification of interactive gestures and multi-hand targets,  proposedOur network model is trained in the following environment:System: ubuntu 16.04 with 64G RAMCPU: Intel Xeon E5-2620 × 32 GPU: NVIDIA GeForce RTX 2080Ti × 2.N represents the number of the hand key-points in single image.We use widely used mean end point error , and the RHD training result is taken from 189 epochs.The comparison of our hand pose estimation results with the original InterNet and other methods is shown in The comparison and analysis reveal that our method has a greater improvement in the accuracy of hand pose estimation compared to other similar methods. Moreover, compared to the original InterNet, our network has a smaller data volume, lighter weight, and faster speed under the same conditions in the experiment as shown in To better demonstrate the convergence of our method, we compared the convergence process that achieved the best results on the STB dataset within 50 epochs to the original method, and the results are shown in Considering the InterHand2.6M dataset, we use mean per joint position error (MPJPE, which is defined as a Euclidean distance between predicted and ground-truth 3D joint locations after root joint alignment [This experiment verifies the usability of our method on multi-target hands and interactive gestures and its ability to equivalently replace the original network. The comparative analysis also demonstrates that our method can still achieve better results in accurate single-handed target recognition than the original method using less data.Regarding the design and layout of the functional modules we used in the network, we conducted ablation analysis experiments on the STB and RHD datasets to verify the effectiveness of the functional modules we used.Compared to the background, the hand target often occupies a smaller proportion of the pixels, and there are many problems, such as insufficient resolution and incomplete information. The introduction of the attention mechanism can theoretically promote the network’s focused cognition and feature extraction of the target area.We evaluated the feasibility of introducing the newly proposed coordinate attention mechanism in the feature extraction process of the hand pose estimation network. We carried out experimental comparisons on the STB and RHD datasets, respectively. Thereafter, we verified the effectiveness of the coordinate attention mechanism module in the network of the feature extractor. We compared it to the previous SE attention mechanism module, and we observed that the coordinate attention mechanism is better for improving network performance. The experimental results are shown in In the previous study, the attention mechanism module was seldom used in the tasks of hand pose estimation. We perceive such vacancies in network design. Owing to the particularity of the hand pose estimation task, we introduced a new attention mechanism into the network to improve the performance of the network. Based on the better results of the module based on the coordinate attention mechanism, we performed preliminary processing on the extracted feature maps to facilitate the subsequent operations.We also evaluated the feasibility of using a new frequency-domain attention mechanism in the processing of the feature map of the hand pose estimation network. Similarly, we conducted experiments on the STB and RHD datasets, respectively. This verified the effectiveness of the multi-spectral attention mechanism module in the hand pose estimation network feature extractor. The experimental results are shown in The development of feature extraction backbone. Recently, scholars have re-examined the widely used convolutional neural network backbones such as ResNet, made new improvements, and targeted adjustments to training strategies . These iThe rise of Transformer in the field of computer vision . PreviouConsidering the data acquisition for hand posture estimation, scholars are gradually replacing manual labeling with automatic or semi-automatic methods. Using neural networks and other learning models for more accurate labeling can help reduce the workload caused by manual labeling.Since the publication of the InterNet network and the InterHand2.6M dataset, studies on the interactive and multi-objective hand pose estimation have continued to advance. Based on the original infrastructure of the InterNet, we redesigned its feature extraction part to make a better use of the input information to achieve a greater improvement in performance. Considering the continuous development in the field of deep learning as well as computer vision, we can expect the following developments to positively impact studies in the field:Still, there are some limitations in our research. To begin with, due to the need to ensure the hand pose estimation function of the whole network, we did not make innovative changes to the feature processing network, “PoseNet”. Secondly, due to equipment reasons, we have not yet been able to make inferences on the full version of the InterHand2.6M dataset. In addition, we have not yet verified the versatility of our feature extraction network for other human pose estimation tasks.In our future research, we will verify our network’s effectiveness and accuracy performance on the full version of InterHand2.6M dataset. Furthermore, we will start with the loss function to reduce the parameters amount in the whole network. In the current thinking, we plan to use a supervised loss to define different hand joints in different scenarios to calculate the total geometric deviation. To appropriately exclude unnecessary hand joints from the loss calculation to reduce the amount of calculation.From the other aspect, on the basis of improving network effectiveness performance and accuracy, we will try to improve functionality, such as the interaction scenarios between hands and objects. In addition, we will apply our feature extraction network to other human pose estimation tasks to verify versatility.


The article focuses on a high-resolution ultrasound sensor for real-time monitoring of liquid analytes in cylindrical pipes, tubes, or capillaries. The development of such a sensor faces the challenges of acoustic energy losses, including dissipation at liquid/solid interface and acoustic wave radiation along the pipe. Furthermore, we consider acoustic resonant mode coupling and mode conversion. We show how the concept of phononic crystals can be applied to solve these problems and achieve the maximum theoretically possible Q-factor for resonant ultrasonic sensors. We propose an approach for excitation and measurement of an isolated radial resonant mode with minimal internal losses. The acoustic energy is effectively localized in a narrow probing area due to the introduction of periodically arranged sectioned rings around the tube. We present a sensor design concept, which optimizes the coupling between the tubular resonator and external piezoelectric transducers. We introduce a 2D-phononic crystal in the probing region for this purpose. The Q-factor of the proposed structures show the high prospects for phononic crystal pipe sensors. Ultrasonic sensors are well-developed instruments and hold a long tradition. They are used for non-destructive, non-invasive and accurate measurements of technical and bio-liquids with a broad variety of chemical/biological compositions  as well A typical method for measuring the bulk properties of liquids is using the resonances of acoustic waves in liquid-filled cavities. Resonators can be of rectangular or cylindrical shape, made of stiff solid materials (such as stainless steel or glass). The shift of the resonance frequencies of standing waves in a liquid-filled cavity is strongly related to a change in the speed of sound of the liquid (mixture). The loss factor  is associated with the attenuation of acoustic waves in the liquid volume. However, various types of other loss, specifically at the solid liquid interface, acoustic wave radiation into the liquid volume outside the resonator cavity, acoustic mode coupling and mode conversion must be taken into account. Without special measures, these mechanisms can become dominant, larger than the intrinsic liquid damping in the resonator chamber.This paper focuses on a high-resolution ultrasonic sensor for real-time monitoring of liquid analytes in cylindrical pipelines. The cylindrical shape  is the most natural shape when working with liquids. The development of sensors which are adapted to tubes is a current demand in medicine and biology , in the food and chemical industries (online monitoring of the composition of liquid in pipes and microreactors at different stages of the process), or in mechanical engineering . As known, various acoustic resonance modes can be excited in a cylindrical resonator. Longitudinal, azimuthal, and radial modes are the most important ones . Our stu-Excitation of the radial mode turns out to be the optimal one in comparison with other modes, hence, how can the radial mode in a long channel be excited and readout?;-How can this mode be sufficiently isolated to avoid disturbances by other modes?;-Acoustic (resonance) energy can be radiated along the pipe axis, hence, how can acoustic energy be localized in a small resonant liquid region within a pipeline?;-The piezoelectric transducers such as PZT have usually a broad resonance, hence, how can the optimal coupling between the high-Q liquid resonator and piezoelectric elements be achieved?The development of a highly sensitive tubular sensor faces a number of questions:In this work, we present a solution to the aforementioned problems by using the concept of phononic crystals. Phononic crystals (PnC)s are periodic composite materials with spatial modulation of elasticity, mass density, and longitudinal and transverse velocities of elastic waves. The typical structure consists of scattering centres with elastic properties which differ from the homogeneous matrix surrounding the scatters ,24. PnCsTubular phononic crystals are a fundamentally new sensor design concept for in-line monitoring of liquids in cylindrical structures such as vessels, pipes, tubes or capillaries. This type of phononic crystal is created by a radical change in lattice geometry from 2D planar or 3D Cartesian, with translational symmetry to 3D cylindrical with both translational and rotational symmetries. This novel concept exploits a new way of controlling acoustic fields in liquids and elastic fields in solids in order to realize the most optimal sensing field in the liquid. Acoustic waves are tailored so that they perturb sub-volumes of the liquid in the pipe, revealing their physical properties. We have introduced the idea of using tubular phononic crystals in  and furtAnother beneficial engineering consequence should be mentioned: the sensor measures across the pipe, not along the pipe. The design neither requires any mechanical obstacle inside the pipe nor transducer elements at one or both ends of the pipe. In terms of a (micro)fluidic system, all elements of the 1D- and the 2D-PnC, as well as the piezoelectric transducers, are mounted at the outer rim of the pipe; thus, i.e., the fluid can freely flow through the pipe.Resonant acoustic sensors achieve high sensitivity by optimal selection and successful excitation and detection of the resonant mode as well as its isolation from other vibration modes of the structure. The Q-factor of the sensor increases by minimizing all kinds of loss mechanisms. The realization of a high-Q tubular acoustic sound velocity sensor involves several challenges. Technical tubes are long and open systems. A liquid-filled tube has many different resonance modes; their characteristics are determined not only by the conditions of the propagation of acoustic waves in the solid and liquid parts, but also by liquid/solid interactions. Challenges arise from finding a way to excite the optimal high-Q mode and its isolation and effective readout, and also from the necessity to suppress acoustic loss mechanisms caused by radiation, mode conversion and coupling as well as losses at the solid/liquid interface.In this study, we propose an approach that aims to improve the performance of a tubular resonant sensor using phononic crystal concepts. Periodically modulated acoustic properties in space result in real and virtual reflective boundaries for sound waves. They control the acoustic wave interference conditions and propagation of sound at specified frequencies. With this approach, the geometry becomes the key to tune the basic characteristics of the sensor system.-the type of resonant mode of liquid pressure in the channel should provide minimal shear viscous losses;-the acoustic wave energy should be focused in a narrow section of the pipe channel, in which resonance measurements are carried out;-losses due to the radiation of acoustic energy into the passive parts of the sensor and (micro)fluidic structure should be eliminated;-acoustic measurements in flow systems should be realized without creating additional local hydraulic resistances.It implies the fulfillment of the following requirements:A theoretical analysis of the sensor structure and its components was carried out on the basis of numerical simulation using COMSOL Multiphysics software.The key element of the acoustic sensor is the liquid cavity resonator. In this article, we have explored tubular resonators and how they must be designed in order to reach the maximum Q-factor. At the same time, the inner cavity has a cylindrical shape, is filled with a liquid, has a considerable length with a constant inner diameter, is without any obstacles, and does not contain any technological holes or any other elements. This corresponds to the requirement that the investigated liquid can flow freely through the tube without encountering any additional hydraulic resistances.1). The pipe material (2) is coloured in gray. It can be glass or stainless steel or another solid material with low acoustic losses. Such a simple tube is characterized by two geometrical parameters: the inner and outer diameter (din and dout). The total length of the tube is much larger than its diameter. In dr and length lr, arranged in the direction of the tube axis to realize a 1D-phononic crystal with lattice period az. The purpose of the 1D-PnC is to control the propagation of acoustic waves along the pipe. The number of rings nr can be different. ns equal-equidistant sectors one gets the structures in ns is equal to 3 and 4, respectively. Sectioned rings significantly expand the possibilities of tubular photonic crystal properties tuning. All sectioned rings can be of same size (apc) and their diameter (dpc). The design of a three-dimensional phononic crystal around the tube is not limited to the to the intention of ame size c,d, or tame size e,f. The ame size g. This 2v is the speed of sound in a liquid; p is the pressure; r =  is the coordinate vector; t is the time.The acoustic pressure time fluctuation in liquid is governed by the wave equation :(1) in the cylindrical coordinates is:d and length L:l, m and n are integers ≥ 0; P is the pressure magnitude, J is the Bessel function; the parameter values l, m and n in Equations (4) and (5) number radial, azimuthal and longitudinal eigenmodes.Applying the boundary conditions to Equation (2) for the cylindrical cavity of diameter obtained :(4)pl,m,iu are the components of the elastic displacement field; ijT are the stress tensor components; i and j are indices running from 1 to 3.In practise, the pressure distribution in liquids and the resonance eigenfrequencies in a cylindrical resonator differ from the analytical solution in Equation (4), since elastic waves in the solid body of the resonator were not considered there. To take into account a solid-liquid interaction, the Equation (1) must be self-consistently solved with the equation of propagation of acoustic waves through solid media:ns is the normal vector directed away from the solid part; F is the force per unit area representing the load on the cylinder walls; nf is the normal vector directed away from the liquid volume; u is the mechanical displacement vector in the solid; q is the acceleration vector reported by the liquid.Conditions at the boundaries of the solid-liquid section are as follows:Until now, we have not taken into account the problem of dissipation of the energy of acoustic waves. In order to simulate a real situation, we must introduce these losses into physical and mathematical models.A:A(r) is a complex-valued magnitude as a function of the position vector; ω = 2πf. Dissipation can be modelled by a complex speed of sound for liquids and a complex acoustic impedance for solids. The ratio between the total stored and the total lost energy in a device depends not only on the individual loss terms but also on the energy distribution within the device [Wst is the energy stored in the system; fres is the resonance frequency; jQ is the jth loss mechanism.Mathematically, damping can be taken into account using an approach that involves a complex representation of time harmonic fields e device . This ex-Bulk losses in liquids due to viscosity. The bulk viscosity plays an important role for ultrasonic wave propagation in most liquids and is associated with damping of longitudinal waves. The dynamic viscosity also contributes to volumetric losses;-Thermal damping in the bulk of liquid. Any acoustic field induces a fluctuating temperature field due to thermoacoustic coupling. In the bulk, this fluctuating temperature field is proportional to the acoustic pressure. Thermal conduction in the liquid bulk leads to a loss factor, which causes the so-called thermoelastic damping. It depends on the ratio of specific heats, the heat conductivity and the specific heat at constant pressure;-Viscosity loss at the walls of resonator cavity, i.e., at liquid/solid interfaces. A viscous boundary layer on the walls of a liquid-filled cavity is the main source of dissipation. Due to the no-slip boundary condition at the interface between the solid and the liquid, the viscous boundary layer is a transition layer in which the tangential component of the liquid velocity adapts to the velocity of the solid boundary. During each cycle, the viscous shear in this layer dissipates a fraction of the acoustic energy. In terms of the sensor, the amount depends on both the resonance mode and the shape of the cavity;-Thermal damping at the liquid/solid interface. A thermal boundary interaction creates a thermal boundary layer and contributes to dissipation of acoustic resonance energy;-Radiation losses. A pipe that the sensor is intended for has a much larger length than the length of the sensor. Attempts to excite acoustic resonance in some part of the pipe inevitably leads to the fact that part of the resonance energy will spread out along the axis of the pipe. Part of the ultrasonic energy will radiate into passive volumes of the system and into the environment;-Losses due to particles suspended in the liquid. They depend on particle size (compared to the ultrasonic wavelength) and their mechanical properties. Consideration should be given to scattering and thermo-viscous dissipation at the particle-liquid interface. We do not consider damping due to suspended particles, since we are studying homogeneous liquids. Nevertheless, a good Q-factor of the tubular acoustic sensor extends the possibilities of characterizing the presence of particles in the analyte by the width of the resonance peaks and to estimate their concentration, particle size distribution, etc., see e.g., ;-Losses in solid materials. They depend on the constitutive behaviour of the solid material; viscoelasticity and thermoelasticity are the sources of acoustic wave energy dissipation. Furthermore, piezoelectric elements introduce dielectric and piezoelectric dissipation, leading to a complex dependence on the conditions of motion and vibration mode. Material behaviour, including damping, can vary significantly with temperature and frequency. In addition to volume scattering, energy is also lost from the surfaces of the device.The damping mechanisms important for acoustic tubular liquid sensor structures are (a detailed description of the damping mechanisms can be found in the review ):-Bulk lUsing materials such as stainless steel or glass to build the resonator, losses in a solid part of a system can be safely neglected since the viscosity of these materials is extremely low. It should be noted that solid materials must satisfy the condition of homogeneity, where internal structural inhomogeneities are much smaller than the acoustic wavelength. From this point of view, 3D printing technologies may currently not be useful.-Scaling. One of the advantages of resonant (sensor) principles is the tight correlation between resonance frequency and resonator dimension. Therefore, many  papers apply reduced values, e.g., a normalized frequency scale. However, this concept fails if frequency-dependent effects such as relaxation phenomena (volumetric) or size-to-wavelength dependent effects, such as stick-slip or wetting phenomena  or surface roughness (fabrication) issues, become significant;-Excitation and readout electronics. Our high-Q resonant sensor requires a circuitry able to measure the resonance frequency and the respective half-bandwidth with high accuracy. During development and in lab environment a  impedance analyser is an appropriate solution. We have developed miniaturized solutions specifically designed for resonant sensors , both neIn addition, several aspects should be noted:When comparing all of the possible sources of acoustic energy loss, viscosity of the liquid and radiation of acoustic energy along the pipe are the most important loss mechanisms and the most important challenge to enhance the sensor’s resolution.v is the velocity vector of the liquid; T is the temperature; γ is the coefficient of specific heat, κth is the thermal conductivity; ρ is the density; Cp is the specific heat at constant pressure; β is the volumetric compressibility; η is the shear viscosity; ηB is the bulk viscosity; v is the speed of sound. The volumetric and shear viscosity as the dissipation coefficients for the compressive motion of the fluid are associated with friction. Bulk liquid losses are the most fundamental natural limitation of the sensitivity of acoustic liquid sensors.To consider the losses in the liquid bulk, a general description of the propagation of sound in a compressible fluid can be conducted using the Navier-Stokes and continuity equations . In addith are the viscous and thermal penetration depths, respectively.Viscosity and thermal damping at the liquid/solid interface can be considered by the self-consistent solution of the Equations (6), (11) and (12). These losses occur in the near-surface layers of the liquid of the following depths:To minimize damping at the liquid/solid interface, we have searched for the most optimal mode in a tubular resonator, i.e., one which does not show shear displacement at this interface.To minimize radiation losses, along with losses at interfaces, we propose a sensor resonator structure based on To sum up, we cannot neglect acoustic energy losses in the liquid and at the solid/liquid interface. They are significant and determine the Q-factor of the resonance. However, besides the sound velocity of the liquid, liquid viscosity provides additional independent and hence important information about the liquid in the pipe. Still, liquid bulk viscosity contains already this information, hence shear viscosity at the solid/liquid interface is redundant and should be avoided, Task 1. We propose the radial mode realizing a sharp sensor resonance.Acoustic energy radiation should be avoided by an appropriate 1D-phononic crystal design along the pipe, Task 2. We propose the structure shown in Since the Q-factor is the most important parameter for the resolution of the resonant sensor, the following questions are of great interest: how does the Q-factor of liquid resonances in a pipe depend on the type of acoustic eigenmode, frequency and pipe diameter? How can the corresponding resonant modes be excited and what is their sensitivity to changes in the speed of sound? How do solid/liquid interfaces affect the Q-factor of resonances?The infinitely long liquid-filled cylindrical resonator, as shown in −3. The numerical calculation was carried out by the finite element method based on the self-consistent solution of the Navier-Stokes equations for a liquid and the equation of propagation of elastic waves in a solid. The mesh size for the finite element method was considered as the viscous and thermal damping at the liquid-solid interface, which is significantly less than the penetration depth of shear waves into the liquid (see Equation (13)). To excite a longitudinal mode ), a vector of displacement (u) was applied to the liquid-filled cylindrical pipe parallel to its axis (um) was kept constant throughout the infinitely long pipe and acted in harmonic law at resonance frequency. To excite the first azimuthal mode ), the mechanical displacement vector was applied perpendicular to the pipe , the mechanical displacement vector was applied normal to the pipe surface , azimuthal (AM) and radial (RM) liquid pressure modes. All of the other modes are either higher harmonics or a superposition of these fundamental modes. Therefore, by understanding the behaviour of these basic modes, we can extrapolate this knowledge to other cases. We are specifically interested in what are the theoretical limits of the Q-factor of these resonant modes and how the Q-factor changes depending on frequency. The temperature was taken equally at 20 °C. Water was taken as a liquid ) of the modes depend on their resonance frequency. The dependence of the Q-factor of each of the main eigenmodes on the frequency are shown in In We propose to use the periodic arrangement of rings to create virtual boundaries realizing the Bragg-type reflection of acoustic waves propagating along the pipe. We apply the ability of phononic crystals to control and tailor elastic and acoustic wave propagation.r; k is the wave vector.Given that the tubular phononic crystal is a periodic structure in z-direction, the Bloch theorem can be used to determine the eigen solutions. According to this theorem, the displacement vector can be represented as a product of a propagating wave and a periodic function describing the phononic crystal:As previous results show , a phonoE is the Young’s modulus; In din, dout, dr, lr, az, ns, φ). The number of ring sectors (ns) can theoretically vary from 3 to infinity. An increase in ns improves the pressure distribution in the pipe towards an ideal displacement distribution of the radial mode  and (12)). Simulations show that the Q-factor of a given dip . In terms of structural mechanics , the strAs simulations show, the radial mode has the highest resolution of the speed of sound measurement. In addition to a slightly higher direct dependence on sound velocity, the Q-factor of the radial mode is by orders of magnitude higher, hence the Figure of Merit, FoMIs higher by orders of magnitude as well. The differences in the characteristics between the modes are determined by the acoustic losses at the solid/liquid interface of the tubular resonator. Our analyses have shown that shear viscous losses, associated with friction at the solid/liquid interface, are the most significant ones. For the radial resonance mode, the pressure distribution in the liquid is such that the maximum pressure is equidistant from its interface to the pipe and is close to the axis of the cylindrical pipe. Surfaces of equal phase are equidistant from solid/liquid interfaces, too. Therefore, the pressure gradient tangential to the solid wall is zero and shear viscous losses thus vanish. This makes the radial mode the most preferable for sensor applications.Besides a  high-Q pipe resonator, acoustic energy radiation out of the resonator volume along the pipe axis must also be avoided. In this study, we propose the application of a periodic arrangement of sectioned rings for realizing a Bragg-type reflection of acoustic waves in the liquid and in the solid propagating along the pipe axis. The key point is the fact that real reflective boundaries of the liquid inside the pipe must be avoided not to disturb a free flow of the liquid. All of the required structural elements are therefore located on the outer rim of the pipe. The inner surface of the pipe keeps absolutely smooth and even.A tubular phononic crystal based on ring segments has proven its adaptability not only regarding the tuning of an acoustic bandgap, but it also turned out to be convenient in realizing the radial mode excitation and detection in a specific unit cell. A striking result is the fact that two periods to the left and right of the central cell are already sufficient in significantly improving the resonance characteristics. This corresponds to In contrast to the traditional approach in phononic crystal sensor literature, we propose a different, more effective approach, which consists in the excitation and readout of the radial resonant mode by directly addressing the acoustic field to the central unit cell of a tubular phononic crystal. The current state of this approach surrounds the center of a 1D-tubular phononic crystal by a 2D-phononic crystal. Furthermore, this approach allows optimization of the coupling of only one piezoelectric transducer with the acoustic field in the liquid-filled pipe resonator. This approach minimizes all the considered loss mechanisms and achieves an extremely high Q-factor.The article critically analyses the idea and the physical principles of a novel acoustic liquid sensor concept. We present arguments supporting the proposed approach that combines ultrasonic measurement, resonant sensor and phononic crystal capabilities. Our alternative design of a tubular resonant acoustofluidic sensor uniquely combines the known properties of 1D- and 2D-phononic crystals for the benefit of concentrated acoustic energy in the measurement space.As consequence of our analyses of the dominant mechanisms of losses in tubular liquid-filled resonators, the influence of acoustic mode regimes, solid-liquid interactions, geometric aspects and frequency dependencies, we have been able to propose an approach for excitation and measurement of an isolated radial resonant mode with minimal internal losses in a liquid-filled pipe. We could effectively localize the acoustic energy in a narrow probing area by the introduction of periodically arranged ring segments around the tube. The additional 2D-phononic surrounding probing region optimizes the coupling between the tubular resonator and an external piezoelectric transducer. Only one transducer is required, which should minimize the design of an electrical oscillator. The estimates of the theoretical Q-factor of the proposed sensor shows the high prospects for the pipe-based phononic crystal sensor.-The radial resonance mode, the pressure distribution in the liquid, the maximum pressure equidistant from the solid/liquid interface and close to the axis of the cylindrical pipe avoids shear viscous losses, usually most significant in acoustofluidic devices and associated with the friction at the liquid/solid interface. Surfaces of equal phase are equidistant from liquid/solid interfaces too. Therefore, the pressure gradient, tangential to the solid wall, is zero and shear viscous losses vanish;-Our work extends the field of phononic crystal liquid sensors by a novel combination of 1D and 2D designs;-A 2D-phononic crystal realizes the coupling with a single piezoelectric transducer;-A 1D-phononic crystal composed of ring segments is suited to focusing on an isolated radial mode in a cylindrical tube, preventing radiation losses along the tube axis and providing access to a Q-factor of the acoustic resonances improved by orders of magnitude. The PnC requires elements on the outer surface of a cylindrical pipe only and does not introduce additional local hydraulic resistances;-The sensor has a high potential in the field of liquid properties evaluation in microfluidic channels or macroscopic tubes or pipes e.g., in chemical industry.The results of numerical studies show the following:Future research concentrates on two aspects of the error analysis: firstly, deviations from the ideal geometry, including surface roughness as well as diameter and layer thickness deviations along the pipe, and secondly, the influence of non-acoustic parameters, specifically temperature and pressure . The act


A large number of clinical concepts are categorized under standardized formats that ease the manipulation, understanding, analysis, and exchange of information. One of the most extended codifications is the International Classification of Diseases (ICD) used for characterizing diagnoses and clinical procedures. With formatted ICD concepts, a patient profile can be described through a set of standardized and sorted attributes according to the relevance or chronology of events. This structured data is fundamental to quantify the similarity between patients and detect relevant clinical characteristics. Data visualization tools allow the representation and comprehension of data patterns, usually of a high dimensional nature, where only a partial picture can be projected. In this paper, we provide a visual analytics approach for the identification of homogeneous patient cohorts by combining custom distance metrics with a flexible dimensionality reduction technique. First we define a new metric to measure the similarity between diagnosis profiles through the concordance and relevance of events. Second we describe a variation of the Simplified Topological Abstraction of Data (STAD) dimensionality reduction technique to enhance the projection of signals preserving the global structure of data. The MIMIC-III clinical database is used for implementing the analysis into an interactive dashboard, providing a highly expressive environment for the exploration and comparison of patients groups with at least one identical diagnostic ICD code. The combination of the distance metric and STAD not only allows the identification of patterns but also provides a new layer of information to establish additional relationships between patient cohorts. The method and tool presented here add a valuable new approach for exploring heterogeneous patient populations. In addition, the distance metric described can be applied in other domains that employ ordered lists of categorical data. Patient profiling and selection are a crucial step in the setup of clinical trials. The process involves analytical methods to handle the increasing amount of healthcare data but is still extremely labor-intensive . NeverthTo support the expert in the selection of suitable patients, visual analytics solutions can enable the exploration of a patient population, make recruitment consistent across studies, enhance selection accuracy, increase the number of selected participants, and significantly reduce the overall cost of the selection process . Visual Many types of information about the patient profile such as diagnosis, procedures, and prescriptions are available under standardized categories contained in taxonomies or dictionaries, e.g., the International Classification of Diseases (ICD), Medical Dictionary for Regulatory Activities (MedDRA) and the Anatomical Therapeutic Chemical (ATC) Classification System. Each patient is for example linked to an ordered list of diagnoses, which are semantic concepts that are (in the case of MIMIC ) orderedIn this paper, a novel approach for exploring clinical patient data is introduced. In particular, we focus on patient profiles represented by a set of diagnosis ICD codes sorted by relevance. The distance metric considers the sorted concepts as input, and the resulting pairwise values are used to create a graph where similar patients are connected.The remaining part of this paper is organized as follows. In the section “Background”, we give an overview of related work in categorical events and graphical projections of patient similarity. The section “Materials and Methods” describes the proposed distance metric and modifications applied on the base algorithms STAD for visualizing patient population. In “Results”, we demonstrate the effectiveness of the approach in a real-world dataset. The section “Discussion” compares other methods and alternative metrics for similar data. Finally, the section “Conclusion” presents conclusions and possible directions for future work.The exploration and analysis of patients through similarity measures has been presented in different areas of bioinformatics and biomedicine, and also data mining and information visualization. In this section, we review the related literature on these areas below, and we focus on the notion of similarity measures for categorical events and graphical representation of patient similarity.Different distance metrics exist for unordered lists of categorical data, including the overlap coefficient , the Jacn where n corresponded to its level in the hierarchy.In the context of medical diagnoses, the International Classification of Diseases (ICD) codes have been widely used for describing patient similarity. However, these typically consider the hierarchical structure of the ICD codes. In our work, however, we will not leverage the hierarchical structure of the ICD codes, but employ the ICD grouping as described by Alternative approaches such as those by Visually representing pairwise distance matrices remains a challenge. Most often, dimensionality reduction techniques are used to bring the number of dimensions down to two so that the data can be represented in a scatterplot . Such scIn addition to scatterplot representations, alternative visual solutions are also possible, for example heatmaps , treemapThe International Classification of Diseases (ICD) is a diagnosis and procedure coding system used by hospitals to bill for care provided. They are further used by health researchers in the study of electronic medical records (EMR) due to the ease of eliciting clinical information regarding patient status. Although these administrative databases were not designed for research purposes, their efficiency compared to the manual review of records and demonstrated reliability of information extracted have democratized the analysis of health data in this way . Even thIn the MIMIC dataset which was used for this work , each pacA and cB, which contributes to the similarity according to the following formula:The similarity between two patients (diagnosis profiles) A and B is based on which diagnoses  are present in both, as well as the position of these elements in the list. Consider a match M between two concepts S = MSepsis + MUrinarytractinfection + MHypertension = ln 1.25 + ln 1.20 + ln 1.17 ≃ 0.56.The position mentioned in the formula corresponds to the positional index in the list. As an example, the individual contribution of the concept “Sepsis” for patients A and B in S needs to be converted into a distance measure D = 1 − Snormalized where Snormalized = S/max(S).To perform the patient analysis in STAD , the similarity measure Distance measures in categorical variables are built based on a binary statement of zero or one. Unlike other data types, categorical data generate a bimodal distribution, which can be considered as a normal when the element contains multiple dimensions . The simDX into a graph U. This method converts datapoints in multi-dimensional space into an unweighted graph in which nearby points in input space are mapped to neighboring vertices in graph space. This is achieved by maximizing the Pearson correlation between the original distance matrix and a distance matrix based on the shortest paths between any two nodes in the graph (which is the objective function to be optimized). STAD projections of multi-dimensional data allow the extraction of complex patterns. The input for a STAD transformation consists of a distance matrix of the original data, which in this case is based on the metric as defined in the previous section.Simplified Topological Abstraction of Data (STAD)  is a dimAs mentioned above, high dissimilarity between datapoints  results in a left-skewed distance distribution. Unfortunately, this skew poses a problem for STAD analysis. As mentioned above, the STAD method visualizes the distances between elements by means of the path length between nodes. Hence, to represent a big distance between two elements, STAD needs to use a set of intermediate connections that help to describe a long path. In case no intermediate nodes can be found, the algorithm forces a direct connection between the two nodes. As a result, in a left-skewed distribution, STAD tends to generate networks with an excessively high number of links, even when high correlation can be achieved as shown in dnetworkedge refers to the sum of distances of edges included in the network , which avoids the problem on datasets of dissimilar items through the use of a modified objective function. To reduce the number of links between dissimilar datapoints we alter the STAD method to incorporate the ratio work see . Note thR is added to the objective function of the algorithm, which maximizes the correlation ρ between the distance matrices DX (of the input dataset) and DU (based on shortest path distances in the graph). When including the ratio R, the objective function in STAD-R is not only a maximization problem based on the Pearson correlation but also a maximization of ratio R. This ratio R is the sum of those distances of datapoints in DX that are directly connected in network U. The ratio The result of STAD-R over STAD is presented in The STAD-R algorithm generates networks with considerably lower number of links compared to the correlation-based version. The ratio R restricts the inclusion of dissimilarities and therefore, the number of edges in the network. This new constraint also alters the number of edges in networks generated from other distributions types, e.g., right-skewed or normal. Nevertheless, the general “shape” of the resulting network remains the same. An example is presented in http://vda-lab.be/mimic.html.We applied this approach to the MIMIC-III database , which iThe interface is composed of two main parts: an overview node-link network visualization including all patients , and a mThe output of Louvain community detection  is addedThe definition of a custom similarity metric together with a flexible dimensionality reduction technique constitute the key elements of our approach. In this section, we evaluate the benefits of STAD to detect patterns in diagnostic data compared to other popular methods and further discuss the application of the presented distance metric in a different but similar context.The projection of distances in STAD-R aims to enhance the representation of similarities using networks. Similar groups of patients tend to be inter-connected and perceived as a homogeneous cohort. The outputs of three popular algorithms  are compared with STAD-R in In the four plots of In Sp). It compares the distances for every pair of points between the original data space and the two-dimensional projection (nn).Although the interpretation of these visualizations is difficult to assess, quality metrics may help quantify the previous intuitions. ojection . Local dojection . We evalThe richness of the node-link diagram representation of STAD-R cannot be captured using node position in the 2D plane alone. Therefore, STAD-R is analyzed from two perspectives. First, as the abstract graph generated by STAD-R (STAD-R graph) and, second, the two-dimensional projection after graph drawing (STAD-R layout). The abstract graph only considers the connections between nodes to determine the distances between them, whereas the graph drawing results only consider the node placement in the 2D plane.Based on the values from The diagnosis similarity described in section “Diagnosis similarity and distances” is designed for assessing distance between diagnosis profiles, but the principles presented here can be generalized to other terminologies. For example, the procedures which patients receive during a hospital stay are also recorded and also follow an ICD codification: they also contain a list of categories similar to diagnosis. Unlike ICD diagnoses lists, which encodes priority, the order of procedure code lists indicate the sequence in which encode procedures were performed. Thus the weight distribution in the similarity that was used for the diagnosis metric must be adapted to the nature of the procedure data. We can alter the formula to include the relative distance between positions of matched elements instead of the top position in the diagnosis case. Formally, the similarity between two procedure concepts can be then described as follows:As with diagnosis similarity, the metric is estimated as the sum of individual contributions of matched concepts, In this paper, we introduced a custom distance metric for lists of diagnoses and procedures, as well as an extension to STAD to improve its effectiveness for dissimilar datapoints. The diagnosis similarity measure can be applied to any ordered list of categories in a manner that is not possible with the measures available in the literature so far. The metric is designed to identify differences between patients through standardized concepts (diagnosis and procedures) where the weights of matching concepts are adapted to highlight the most relevant terms. As mentioned in Moreover, as discussed previously, STAD-R can reveal equivalent data signals at multiple levels to other dimensionality reduction methods. Quantitative and qualitative (user) evaluation of the method can be further extended with other datasets to assess both the information captured by the graph and the benefits of node-links diagrams to represent the similarity between datapoints. In future work, we plan to further explore STAD-R in collaboration with domain experts in diverse case studies. We also plan to build a more robust interface that allows the computation and exploration of STAD-R networks in a tailored environment.


The use of unmanned aerial vehicle (UAV) applications has grown rapidly over the past decade with the introduction of low-cost microelectromechanical system (MEMS)-based sensors that measure angular velocity, gravity, and magnetic field, which are important for an object orientation determination. However, the use of low-cost sensors has also been limited because their readings are easily distorted by unwanted internal and/or external noise signals such as environmental magnetic disturbance, which lead to errors in attitude and heading estimation results. In an extended Kalman filter (EKF) process, this study proposes a method for mitigating the effect of magnetic disturbance on attitude determination by using a double quaternion parameters for representation of orientation states, which decouples the magnetometer from attitude computation. Additionally, an online measurement error covariance matrix tuning system was implemented to reject the impact of magnetic disturbance on the heading estimation. Simulation and experimental tests were conducted to verify the performance of the proposed methods in resolving the magnetic noise effect on attitude and heading. The results showed that the proposed method performed better than complimentary, gradient descent, and single quaternion-based EKF. The attitude and heading reference system (AHRS) plays a significant role in navigation applications. Vehicles with any degree of navigation autonomy require an AHRS to continuously monitor their orientations with respect to a specific reference system . One of An AHRS consists of MEMS-based tri-axis sensors, including gyroscopes, accelerometers, and magnetometers, to collect important information about the angular rotation speed, gravity, and Earth’s magnetic field, respectively. The AHRS can potentially determine the 3D orientation of a sensor device by integrating the gyroscope output from known initial conditions with gravity and magnetic field measurements from the accelerometer and magnetometer . HoweverPoulose et al.  addresseDespite the findings of the previously mentioned studies, some problems remain. One of the most serious concerns in the UAV industry is the lack of accurate and reliable information about attitude and heading, especially in environments where external magnetic fields may present such as in warehouses, tunnels and other indoor environments. In such an environment, the magnetometer’s reading of the Earth’s magnetic field is tempered by unexpected magnetic fields in its surroundings ,13,14. TDifferent methods are used to represent a rigid body orientation in three dimensions (3D). Euler used three sets of angles  to describe the definite rotation of an object frame, which is called the body frame, with respect to a given reference frame . Unlike the Euler representation, four parameters are used in quaternion representation for 3D rotation quantification, with the constraint that the sum of squares for each parameter equals unity ,16,17.V be a vector pointing to the initial front direction of the object and let the final object orientation be represented by VVV and the Euler rotation angles, as indicated in Equation ..3). Let Equation .(1)V=v1The strength of the gravitational field measured by the accelerometer along its vertical and horizontal axes can help determine the vehicle’s roll and pitch angles if the accelerometer’s and the vehicle’s axes are aligned in the same direction. The direction of gravity is always vertically downward, and its magnitude is constant. Therefore, depending on the current orientation of the sensor, the component of the gravitational field detected along the sensor axes varies, and this change is used as input to calculate the roll and pitch angles ,12. The If there is no linear acceleration H=HxThe value of declination angle Equation .(9)mxmySubstituting Equation  into EquThe Earth gravitational field vector measured with respect to the sensor frame and NED frame is related to the vector rotation formula presented in Equation . The graEquation  has infiEquation  becomes Similarly, the equation that relates the heading quaternion representation to the magnetometer readings can be derived. It is clear that the heading component of the orientation quaternion parameter is independent of any rotation about the X- and Y-axes. Therefore, the quaternion parameters representing the axis of the rotation vector should be constrained only in the vertical direction. As a result, quaternion The magnetic field measured by the magnetometer can be mapped to the horizontal and vertical components of the Earth’s magnetic field using Equation (14)mxmyFinally, a single quaternion representing both attitude and heading is the product of the two quaternions Equation .(16)q=qThe gyroscope measures the rate of orientation change about each axis of the sensor frame. The relative orientation at the time of interest is obtained by integrating the raw measurement data for all rotational axes. The Euler angles are updated based on the gyroscope readings as follows:The time derivative of quaternion isIt follows thatThis means that q yields the differential equationLeft multiplication by Converting Equation  to discrEquation (23)qk=IAs discussed in In The EKF is an iterative prediction/correction approach for estimating the state of a discrete time process or measurement. Before moving on to the algorithm, it is important to select either the quaternion or Euler representation method. In this work, the quaternion-based approach is preferred because this approach does not introduce the gimbal lock problem. The EKF process relies on a state prediction model that mathematically defines how the state variable The EKF algorithm follows three major sequential steps: initialization, prediction and correction.At this stage, the state values are set to their original orientations, which in most cases start at zero rotation about all axes, described with quaternions R) and the process noise covariance matrix (Q) can be time-varying or time-invariant. The heading estimation is highly sensitive to magnetic noise. Therefore, in this study, simulations and practical experiments were conducted to determine how to minimize magnetic disturbances in heading estimation by using a disturbance-dependent measurement covariance matrix; this topic is further discussed in Q and R are given in Equation R=σνA mathematical model of quaternion-based orientation estimation is presented in Additionally, the prediction error covariance isThe observation model, as shown in Equations  and 11)11) for tThen,This is the last step of every single iteration of the EKF. The states and covariance matrix were corrected using the Kalman gain.In this study, a double quaternion configuration was proposed to represent the attitude and heading separately. A single quaternion consists of four parameters Hk=HThe measurement and processing of noise covariance matrices obviously changes according to the current number of measurement and state variables.An observability analysis approach was applied to test the impact of faulty readings of the magnetometer sensor on attitude estimation. The observability of the quaternion parameters by the magnetometer sensor was analyzed by considering the observation model and state model given in Equations  and 27)27), respFor a single quaternion representation case, by using the system state model in Equation  and the Similarly, for the double quaternion representation case, based on the state model from Equation  and the The observability matrix A magnetic sensor measures the strength of Earth’s magnetic field in the sensor frame. Earth’s magnetic field varies across geographic locations. According to the literature, the approximate magnetic field of the Earth can be referenced from the world magnetic model . TherefoAssume that Based on the error calculated in Equation , a rule For functional verification of the proposed algorithm, an embedded inertial navigation system (INS) prototype was developed in this study. The prototype was equipped with an ICM-20948 9-axis MEMS TDK InvenSense The PCB of the prototype included a sensor board with sensor chips and a main board with an MCU, a power source, and external interface connectors. The sensor board and the main board are connected by a flexible flat cable and are designed to be physically secured with double-sided tape made of a soft ethylene propylene diene monomer (EPDM) sponge material. This is to minimize the effect of vibration due to the actuator operation of the INS mounted targets, such as drones and ground robots. Simulated IMU sensor data were generated to compare the performance of complementary, gradient descent proposed by Madgwick, EKF, and the proposed double quaternion-based EKF algorithms in estimating attitude and heading, and in eliminating environmental magnetic disturbance. MATLAB software was used to generate the IMU sensor data using the parameters listed in In order to carry out a validation experiment for the proposed algorithm, an experimental environment was set up as shown in Motion table: This machine was used to rotate the sensor around the X-, Y-, and Z-axes to an orientation angle required by the computer software. The software was developed as real-time harware-in-the-loop simulation (HILS) testing tool for small UAVs . The speComputer: A command is sent to the motion table from the computer. The raw data measured by the sensors and the estimated orientation angles are also logged into a file on the computer;Permanent magnet: We used a permanent magnetic bar to create a magnetic disturbance in the environment.In the experiment, the magnetometer was carefully calibrated, as the workplace area was filled with different tools that could contain metallic materials that would create magnetic interference and affect the output of the experiment. Then, the motion table was operated to rotate around the X-, Y-, and Z-axes in sequence for specific times, under conditions with no significant magnetic disturbance, and in a magnetically disturbed environment by placing a magnetic bar in close vicinity to the motion table. Experiments were also carried out when the motion table was not moving to compare performance under static and dynamic conditions. Simultaneously, all raw measurement data from the sensors and estimated rotation trajectories were recorded.In this simulation experiment, comparisons of the complementary , gradienThe validation procedure was carried out using the experimental setup specified in This study covered all of the processes needed to create a fully working AHRS sensor, including algorithm development and simulation validation, as well as sensor hardware design, manufacturing, and experimental verification. Furthermore, the common algorithms complementary, gradient descent, and EKF were examined with the identical magnetic disturbance conditions as the double quaternion-based EKF to confirm the required performance by the developed algorithm and hardware.As seen in the simulation results demonstrated in Regarding heading estimation, DQEKF performed better than EKF in rejecting the magnetic disturbance, even if the same magnetic disturbance rejection algorithm was used in both cases. This is because the error in attitude due to disturbance also affects the heading. As the magnetic disturbance algorithm developed in this study could not be directly applied to the complementary and gradient descent algorithms, only the EKF and DQEKF comparisons were performed. Overall, it can be concluded that the EKF and DQEKF algorithms surpass the complementary and gradient descent algorithms in terms of the accuracy and reliability of the attitude and heading estimation. DQEKF is better than EKF in preventing the effect of magnetometer noise in both attitude and heading estimation.The experiments were carried out for static and dynamic statuses of the INS sensor. The results of the two experimental scenarios were consistent with one another and also with the simulation results discussed in The divergence of the heading (yaw) value from the reference value in In this work, two complementary methods are presented for rejecting the effect of magnetic disturbance in determining a reliable 3-D orientation of a moving object such as a UAV. The first method addressed the issue of attitude estimation error due to the magnetic noise by using a double quaternion representation of an object orientation in the EKF algorithm process. With this method, the attitude and heading are set to update with independent quaternion parameters, where the quaternion parameters correspond to the attitude calculation decoupled from magnetometer readings. In the second method, the inaccuracy of the heading under magnetic interference is reduced by an online adjustment of the measurement error covariance matrix. The experimental tests proved that the deviation of attitude and heading values from the ground truth better reduced with the proposed methods than commonly used algorithms: complementary, gradient descent, and the conventional use of EKF, during the period of magnetic disturbance. Thus, in an environment where magnetic interference has a significant impact on the performance of attitude and heading sensors, the suggested approaches are solutions.


This paper uses the panel data of 15 countries from 2009 to 2020 to construct the time-varying parameter panel vector error correction model for testing the hypothesis of dynamic hedging characteristics of gold on exchange rate. As the existing literature has never considered that the foreign exchange risk hedged by gold is dynamic, this study can fill the research gap in this area. The empirical results show that: First, gold can partly hedge against the depreciation of the currency in the long run; second, gold is unable to hedge against the risk of the exchange rate when considering dynamic hedging effects in the short run; third, when facing unexpected shocks, the impulse response shows that the gold returns have reversible reactions compared to exchange rate fluctuations; therefore, gold can regard as a safe haven for foreign exchange markets; Finally, the government, as well as investors should always be concerned about these dynamic risks and formulate effective hedging strategies to control the currency uncertainty. It is critical for multinational companies, export–import businesses, and investors making foreign investments to understand the impact of exchange rate risk on their profitability of trade and investment deals. How to mitigate the exposure risk of the exchange rates is an issue that is often discussed or tried to solve empirically and theoretically by economists. Due to the uncertainty of domestic and international stock markets and the fact that the bond yields of developed countries are relatively lower than those of developing countries, investors continue to increase their investment in new assets of emerging markets. They have to deal with the risks related to international investment and domestic assets. The risks of domestic inflation and capital flow are relatively substantial when facing exchange rate fluctuations. To effectively manage the dynamic risk of foreign exchange rates, investors and governments must exercise centralized oversight over their foreign exchange hedging strategies where gold is essential. It acts positively in times of uncertainty and market volatility.Bordo and Rockoff  argued tThis study aims to find a solution for dynamic risk management for policymakers, corporate managers, and investors. For many years, gold has been regarded as a tradable financial asset and a safe haven from market turmoil. As gold added to the asset portfolio can reduce the volatility of returns and avoid the exchange rate's fluctuation risk, maintaining a positive return on the portfolio is one of the main reasons why gold attracts investors and managers. At the same time, changes in market information continuously occur. According to the principle of the asset portfolio, assets with low or negative correlations are select to form a portfolio in the hope of reducing risks and maintaining returns. Investors put a portion of their portfolios in gold mainly because other financial assets, such as stocks and bonds, cannot hedge against the depreciation of their currencies. Hence, if gold can hedge against exchange rate risk, putting gold in the portfolio will make it more efficient.Moreover, economies engaged in global trade and international finance might be influenced by their gold holding levels. Governments hold gold in their reserves for three primary reasons; risk mitigation, inflation hedge, and facilitation on economic stability and growth. National banks of many countries seek to purchase gold for hedging against a weakening dollar or any other fiat currency. In other countries where their domestic currencies are weak, central banks add gold to their holdings for seeking the hedge by purchasing dollar-denominated gold.The ability to hedge against the exchange rate risk of gold is based on two perspectives. First, gold can resist the change in the purchasing power of a country's currency. When the price index rises, the gold price expressed in its currency increases simultaneously and at the same level, which is called the perfect internal hedge. If the increased level in gold price is less than the increase in the price index, it is the partial internal hedge. Second, the rise of gold price in the domestic currency is equal to the decrease in the rate of the domestic currency to the foreign currency per unit, which is regarded as the perfect internal hedge, conversely in the same way, if the increase is less than the depreciation level, it is a partial external hedge. The main focus of this study is the first prospective, and it further examines whether gold is a safe haven for foreign exchange markets and if gold can evade the impact of foreign exchange market shocks.The best way is to examine the relationship between gold and other assets and realize gold investment performance from a global perspective. So far, however, the existing empirical literature has not considered that the correlation or risk factor changes dynamically. Also, it may not be appropriate to discuss gold hedge against the exchange rate for a single country as the risk factor under international risk sharing and financial integration may change with time and state. How to propose relative risk diversification strategies and measures at the right time and condition for the dynamic relationship is very important in practical operations.Therefore, this study uses a multinational model based on the time-varying TVP-PVECM that can explore the hedging characteristics of gold on the dynamic risk of the exchange rate and further analyze the risk hedging performance and impulse response. This study first tests whether gold can hedge the devaluation of a country currency in the long run; then, examine whether gold can hedge against the risk of a country currency depreciation in the short run; finally, explore whether gold is a safe haven for the foreign exchange market.Three main empirical findings emerge. First, significant evidence shows the power of gold in hedging currency depreciation in the long run. Second, the hedge of gold against the short-term risk of the exchange rate is not supported by estimating the linear model. Third, the effect of the short-term impulse response is more significant than the long-term, and gold is the safe haven of the foreign exchange risk. This study contributes to the literature in several ways. In terms of research topic, it designs multinational research and involves the impact of cross-national contamination effects. In terms of research methodology, compared to the traditional fixed-parameter model, the estimation of the variable parameters can better grasp the influence of dynamic time and state and provide investors with a reliable gold diversification mechanism on exchange rate risk in practical operation. Besides, to analyze the response of variables to the other shocks with different lengths of time and intensity, we perform impact response analysis. The impulse response analysis is a crucial tool for testing the dynamic effects between variables in VAR models. As traditional model parameters do not change over time, we develop the TVP-PVECM to test the dynamic interaction between variables in another dimension. The impact response effect at all-time points can compute using the estimated time change parameters.Our empirical findings reveal the safe haven of gold on exchange rate risk and focus on its dynamic hedging effectiveness compared to previous research. The remainder of the paper is organized as follows. In "Discussing the interactions between the gold price and macroeconomic variables , Ariovich , FortuneHowever, studies relevant to gold nexus dynamic exchange rate risk are few. Joy  found thThe seminal article of Ranaldo and Soederlind  uses theRecent research on the gold issue of Omane-Adjepong and Boako  examinesIn this study, we extend the research method of gold-related literature by Wang and Lee , Wang etTo estimate the innovation process of deferred variable regression, we use the current to future period to compute the time-varying coefficient. The time level and time point are selected in the final period of the sample, and a multi-dimensional impulse response graph is generated. Minimal effort has been made in the prior literature to use multinational panel data in which a specific country at a particular time is selected for impulse response analysis. In the empirical process, we can verify the impulse response of exchange rate fluctuations to the gold price interference at different frequencies in the future, compare the effects of short-term and long-term impulse responses, and provide pieces of evidence to the existing literature.We build a model based on Wang and Lee , which ientclass1pt{minimaR will indicate the real appreciation of the local currency (gold-producing country). Equation , Eq.  is derivThen, the real PPP reflected in the relationship between domestic and foreign gold prices is ork, Eq.  can be dentclass1pt{minimaork, Eq. , and \doAll other terms and conditions remain unchanged, the relationship between gold price changes and exchange rate fluctuations is:We incorporate the elasticity of demand and supply into Eq. , and theSuppose the domestic and foreign price indices remain unchanged. The price change is 0 . \documt in Eq. ). If the0 in Eq. , the golwhere Based on the above inferences, we establish the following hypotheses to test: (1) when This study uses 15 countries as the sample, including major currency countries, major gold demand countries, and major gold-producing countries. The variables are the gold price index in each country's currency per ounce, and the exchange rate is domestic currency/SDR. The benefit of using SDR is that the impact of the U.S. can be estimated independently. A total of 720 observations are collected from the first quarter of 2009 to the fourth quarter of 2020 for the study period. The gold price and exchange rate data are from the AREMOS database. The country and code of variables are shown in Table Examining the trend of gold prices in countries, as depicted graphically in Fig. Using unstable variables for the empirical model would lead to spurious results. Therefore, the stationarity of variables is necessary to be verified with the panel unit-root tests. Table To get a preliminary understanding of the basic statistics of data used for the model, Table After determining that all variables are stationary at the first difference, we perform a cointegration test. Table mentclass2pt{minimTo test whether gold can avoid the dynamic risk of the exchange rate, we further estimate the TVP-PVECM. The period lag of the TVP-PVECM model selected by the AIC criterion is 1. Figure Observing the variables to simulate the fluctuation trends of variables randomly, Fig. , i = 1, 6), and have the inverse matrix of posterior distribution estimation The synchronization correlation trend  gold can partly hedge against the depreciation of a country's currency in the long run; (2) in the short run, gold cannot hedge against the exchange rate risk when considering dynamic hedging effects; (3) the short-term impulse response effect is greater than long-term effect; (4) when facing the unexpected shocks, the gold returns have reversible reactions compared to exchange rate fluctuations; therefore, gold can regard as a safe haven for foreign exchange markets; (5) the government and investors should always be concerned about these dynamic risks and formulate effective hedging strategies to control the currency uncertainty.Prior literature such as Wang and Lee , Wang etManaging relative risk dispersion and policy timely in a dynamic relationship is the main contribution of this study. The TVP-PVECM model is proposed to help clarify whether gold can hedge against the devaluation of a country's currency in the long run. Besides, the impulse response analysis is applied to examine if gold can stay away from the depreciation risk of a country's currency in the short run and if gold is a safe haven for exchange rate risk when an unexpected or unpredictable event occurs. Although the TVP-PVECM model does not classify the market conditions as previous literature, the impulse response analysis shows that when facing unexpected shocks, the gold returns have reversible reactions compared to exchange rate fluctuations. Therefore, gold can regard as a safe haven for foreign exchange markets. Also, we analyze the impact of the Covid-19 pandemic event and find gold is a safe haven for exchange rate risk after the second quarter; the effect then slowly diminishes over time.Through the empirical analysis of the integration and the relationship between variables, the globalization factors of transnational dynamic time and state risks are focused, which help investors and the government deal with the reliable mechanism of the golden hedge on exchange rate risk and challenge the unexpected event. The empirical evidence of this paper provides investors and policymakers some suggestions that long-term holding of gold can partly avoid the depreciation of currencies. The dynamic risk hedging effect facing the greater risk is better than the fixed one in the short term. Also, suffering the impact of unexpected events, gold can be used as a safe haven for foreign exchange risk. Therefore, adding gold to a portfolio can help investors and legal entities reduce the volatility of returns and avoid exchange rate fluctuations. We moreover expect that the evidence provides the reasons for governments to purchase gold as an official reserve asset. In future research, the major currency countries, major gold demand countries, and major gold production countries will be classified and compared.