This paper presents a multipurpose and low cost sensor for the simultaneous monitoring of temperature and ullage of wine in barrels in two of the most important stages of winemaking, that being fermentation and maturation. The distributed sensor subsystem is imbedded within the bung of the barrel and runs on battery for a period of at least 12 months and costs around $27 AUD for all parts. In addition, software was designed which allows for the remote transmission and easy visual interpretation of the data for the winemaker. Early warning signals can be sent when the temperature or ullage deviates from a winemakers expectations so remedial action can be taken, such as when topping is required or the movement of the barrels to a cooler cellar location. Such knowledge of a wine’s properties or storage conditions allows for a more precise control of the final wine quality. Over the past decade, the development and integration of wireless sensor networks (WSN) within the agriculture and food industry, along with a greater understanding of the theory and potential application of such devices, has seen considerable growth ,6,7,8,9.Surprisingly, the use of WSN in vineyards and wineries is still quite rare. In terms of vineyard monitoring, several reports have appeared recently detailing the use of WSN to monitor not only a vineyard’s microclimate but also the risk of vine damage due to frost, pests and disease ,11,12. Ti.e., the space between a bung in a barrel and the surface of the wine, or the space between a cork or screw cap in a bottle and the surface of the wine. Given that this air contains around 20.95% oxygen, minimising ullage is very important to avoid chemical oxidative damage or bacterial damage of the wine [Another key parameter that is monitored for wines in barrels is the extent of ullage. Ullage is defined as the empty space that lies between the wine and the closure, the wine . For exathe wine . To our In this paper, we demonstrate a WSN platform that can be embedded inside wine barrels bung and used to monitor the temperature and ullage of the wine in each individual barrel during both the fermentation and maturation stages of winemaking. Similar pioneer works of potential for the deployment of WSN in wineries have been reported in recent years ,21. HoweThe distributed wine monitoring platform consisted of a small central node and a subsystem where sensor modules may be attached, a schematic of which is depicted in The subsystems acquire data, push it to the central node and power off immediately at a fixed interval. The central nodes receive the data from the subsystems, identify the source barrels of the data, conduct preliminary data processing and upload the data to the server in the computer room. The server logs and analyses the data, puts them on the web interface and sends out alerts when necessary.Specifically, a FriendlyARM Mini210s single computer board computer was used as the basis of the central node whilst an ATMega328 chip based Arduino-like single chip microcontroller (Moteino) was used as the basis of the subsystem. An additional Moteino chip was connected to the Mini210s via a USB port serving as a FM radio transceiver. Currently, the Moteino software supports 65,280 chips in its networks, but there is no hardware limitation. The ullage and temperature modules were built using a SHARP GP2Y0A41SK0F (measures 4–30 cm) infrared distance sensor and Dallas DS18B20 1-wire temperature sensor (measures from −55 °C to +125 °C with ±0.5 °C from −10 °C to +85 °C), respectively. et al., bluetooth was used as the wireless network interface and an analogue temperature sensor TM35DZ for temperature measurement. Such modules suffer from several drawbacks including that the usual transmission range for bluetooth devices is only a few meters which makes the monitoring system unsuitable for practical use in large wineries where the barrels are constantly being moved around, whilst the accuracy of the analogue temperature sensor would not be as good if a digital temperature was used [et al. employed high-precision digital temperature sensors (DS1631 ±0.5 °C from 0 to 70 °C) and an XBee wireless interface with a range of 20–30 m [In the work by Sainz was used . Consequ 20–30 m , it is nThe assembly of the subsystem was rather straightforward. As shown in the top left photo in etc. To the right of this menu is a pane, which displays each individual barrel of wine and graphically or numerically displays what the current status of that parameter is. This setup allows users to access the sensor data using any remote web browser with early warning messages being sent out via emails to the winemakers if pre-set parameters are not being adhered to. For example, if the winemaker wished the wine to be stored in barrels at 15 °C for six months and the temperature deviated by more than 2 °C (pre-set in the software by the winemaker), then an alert would be sent wirelessly to warn of such an instance so remedial action could be taken. The ullage readings were not calibrated to physical units, however, it could be given that the ullage values are inversely proportional to the voltages read from the IR distance sensors. To calibrate the inversed voltage to physical units, one may use the relationship: L = a * 1/V + b, where L is the distance, and V is the voltage, to fit the voltages manually measured for different wine levels to obtain the calibration coefficients a and b, and input them into the software. The code on Moteino was developed using the Arduino toolkit. Moteino is fully compatible with the Arduino Uno platform.Specific software was designed which would run on both the central node and computer server. It was written in C/C++ utilizing Qt  and Wt  packagesAfter building the bungs with associated temperature and ullage sensors incorporated and designing the software, we then tested the system under several real world winemaking conditions. The first was to monitor the temperature and ullage of still wine on the cellar floor over time (maturation in barrels) whilst the second test was to monitor the same parameters during fermentation. In both test trials, four barrels of wine were monitored simultaneously. The sampling rate in our tests was set to once every 8 s for both temperature and ullage.The first trial was performed on four barrels of red wine stored on the cellar floor for a period or nearly three months, where the temperature was not actively controlled, It can be clearly seen that the readings from the individual temperature sensors within each bung are remarkably identical except for some minor variations due to small differences in the heat capacity of each barrel. Given that the winemaker wished the wines to be kept in the range of 10–15 °C during maturation, which was observed by our WSN, it provided confidence to the winemaker that the cellar hands did not need to manually measure the temperature of each barrel. On occasions, we opened one of the barrels and manually measured the temperature with a thermometer and found the same values for the temperature of the wine. Furthermore, the barrels did not need to be opened which aids in avoiding potential contamination, and oxidative spoilage. During this first trial, one of the subsystems  can be simply added in the future to the “smart bungs” upon development. Finally, we anticipate that in the future these “smart bungs” could be manufactured via the use of 3D printing which may further reduce the cost and allow installation in thousands of barrels in each winery.In this work, we have designed a simple low-cost energy saving wireless distributed sensor network that allows for the simultaneous monitoring of a wine’s temperature and ullage both in the fermentation and maturation stages of wine making in barrels. The distributed sensor subsystem runs on battery for a period of at least 12 months and costs around $27 AUD for all the parts. In addition, software was designed which allows for the remote transmission and easy visual interpretation of the data for the winemaker, displaying “virtual barrels” that can be monitored remotely. Early warning signals can be sent when the temperature or ullage deviates from a winemaker’s expectations so remedial action can be taken, such as topping up or the movement of the barrels to a cooler cellar. Such knowledge of a wine’s properties or storage conditions will allow for a more precise control of a final wine’s quality. Moreover, the WSN has been designed so that additional modules of analysis (e.g., pH, sulfur levels, ethanol content


The use of video cases to demonstrate key signs and symptoms in patients (patient video cases or PVCs) is a rapidly expanding field. The aims of this study were to evaluate whether the technical quality, or judgement of quality, of a video clip influences a paediatrician’s judgment on acuity of the case and assess the relationship between perception of quality and the technical quality of a selection of video clips.Participants (12 senior consultant paediatricians attending an examination workshop) individually categorised 28 PVCs into one of 3 possible acuities and then described the quality of the image seen. The PVCs had been converted into four different technical qualities .p = 0.4564). Agreement between actual acuity and participants’ judgement was generally good at higher acuities but moderate at medium/low acuities of illness . Perception of the quality of the clip was related to correct assignment of acuity regardless of the technical quality of the clip .Participants’ assessment of quality and the actual industry standard of the PVC were independent (333 distinct observations, spearmans rho = 0.0410, It is important to benchmark PVCs prior to use in learning resources as experts may not agree on the information within, or quality of, the clip. It appears, although PVCs may be beneficial in a pedagogical context, the perception of quality of clip may be an important determinant of an expert’s decision making. The potential benefits of patient video cases (PVCs) are being increasingly realised , with a Quality issues are clearly relevant to the validity of assessments of learning outcomes however there is no universal definition of what constitutes high quality video. In a medical context most investigation of video quality has been in relation to telemedicine. The focus of this research has been either in the transfer of single pictures (such as in tele-dermatology ), communThe aim of this study was to assess paediatricians’ perceptions of video quality and acuity of illness in a selection of PVCs of unwell children. The null hypothesis being the technical quality of a video case of an acutely unwell child does not influence a paediatrician’s judgement on the child’s acuity.Assess the relationship between senior paediatricians’ perception of quality and the measured technical quality of a selection of video cases.Define the correlation between the paediatricians’ judgments on the acuity of patients clinical signs via video cases and the actual patient acuityEvaluate whether the technical quality, or judgement of quality, of a video case influences the paediatricians judgment on acuity.The objectives of the study were to:The video cases used in this study were taken from the “Spotting the Sick Child” educational project  and addiParticipants were asked, for each clip, to assess a range of clinical relevant features across 5 categories  from the pro-forma designed by McFaul  Table 22. They tThe principal investigator had directly observed the majority of the children in a clinical context as they were videoed, and made a clinical judgement of PVC quality against the McFaul system, which was used as the gold criterion standard. The scenario described to all participants was that they were making a telemedicine judgement based on a video clip shown to them by a member of junior medical staff. They were asked to grade each clip. If they would be comfortable making a clinical decision based on the clip then this would be graded as at least 4 . The participants all viewed the clips from the same angle on the same computer screen (an LCD screen with 1366x768 pixel frame) in the same lighting conditions. No clips were longer than 20 s and the entire time needed per participant to complete all the questions was approximately 25 min. Clip length was chosen pragmatically to clearly demonstrate the clinical sign in question and allow for a manageable amount of cases to be studied in the available time.p < 0.05. Spearman’s rho was used to determine relationships between image quality standards and raters’ quality of assessment. This non-parametric test was chosen as the results were not normally distributed. In order to assess whether the level of significance of the correlation coefficient was affected by the clustering of ratings within the same video clips, corresponding tests were carried out using linear regression with random effects for the clips. Spearman’s rank correlation was used to determine the relationship between gold standard assessment and the raters’ assessment.Given the novel nature of the methodology power calculations were not undertaken as there were no prior studies with data to enable an estimation of effect size. Stata version 13 was used to analyse data with significance set at Twelve participants undertook the study. The total number of clips with quality scores was 333 (27 clips in 4 different versions seen by 3 participants at each version and 1 clip seen in 3 different versions by 3 participants at each version). There were three instances where a participant  was unable to make an acuity judgement on the clip. So there were 330 responses with acuity and quality scores for analysis.p = 0.45) (Table p = 0.469) and one without it (p = 0.677).There was no relationship between image quality and raters’ quality of assessment  Table . This laThere was a better match between the rater’s assessment of acuity and the gold standard  at high acuities (89.9 %) than at the low acuity (67.6 %) Table . The oveThe paediatrician’s acuity score versus gold standard varied across the five clinical sign domains. A difference of two levels in either direction (+/− 2) means that the gold standard rated the abnormality as normal or severe and the rater judged the opposite. This is likely to be a clinically significant difference. Social interaction showed the greatest variability with 7 (11.7 %) cases showing a +2 difference and Respiratory showed the least (zero) +2 differences Table .Table 5Pp = 0.0196), and this relationship was stronger when the repeated clip was not included . The corresponding random effects models were less strongly significant, with p = 0.038 and p = 0.034 respectively.The raters’ ability to correctly score acuity showed little variation at the four levels of technical image quality Table . Given tAlthough quality assurance of videos in respect of descriptive information content has been defined this has not occurred for video image quality . In thisThese results imply that the clinicians had a different meaning of “quality” from the technical industry standards. In other words the technical video quality measures do not match the factors which the paediatricians perceived as important in being able to judge acuity in PVCs. Further studies are needed to elucidate the factors underlying a clinician’s perception of video quality. The reasons why the paediatricians may be influenced by their perception of quality rather than the technical quality are complex. Polanyi  is crediContext has shown to be very important in decision-making. Croskerry cites examples of system 1 and 2 processing, a psychological theory regarding cognitive reasoning . SherbinIt is possible that certain clinical signs were more difficult to interpret than others and this may have influenced the relationship between video quality and outcome. There is some evidence for this as there was a greater proportion of agreement with the gold standard for the domains of alertness (75.0 %) and colour (79.3 %) than there was for hydration (61.7 %) or respiratory (61.4 %). This could be considered surprising as colour gradation is affected by the quality of the image and has poor inter-observer reliability even when examined in direct clinical practice . The facIn order to confirm these findings a validation of this study is needed as a number of factors may have influenced the results. The participants may not be representative of typical clinicians as they were all experienced in assessment. It could also be argued that the gold standard was not adequate as less than 70 % of the participants were correct for hydration and respiratory. However, even if the gold standard was accepted to be incorrect, it would still be the case there was large variation in the answers. The purpose of the study was to benchmark quality and observe variability between experts rather than test clinical accuracy, so this pragmatic gold standard was thought to be sufficient. Similarly other measures of video quality could have been varied, such as signal-to-noise ratios, but bitrates were practically the easiest to alter with available resources. However it would be useful to replicate the study using a reference point video as a control to confirm the clinical significance of the bitrates used. A further study altering clip length may also be useful as this may have impacted on the judgement of the paediatrician and it is possible showing the clips for a longer period may have altered the acuity and quality score given.Preference for a particular cinematic film compared to another has been shown to affect the perceived quality of the video . It is uA recent study has demonstrated considerable variability in the assessment of breathing difficulty in wheezy children between professionals . UtilisiIt is important to benchmark PVCs prior to use in learning resources as experts may not agree on the information within or quality of clip. Although PVCs may be beneficial in a pedagogical context their translation into an assessment methodology or clinical use via telemedicine must be further examined as perception of quality of clip was an important determinant of an expert’s decision-making.


These include targeted drug delivery, local measurement, biopsy or microassembly. Studying mobile microrobots inside microfluidics is an essential step towards such applications. But in this environment that was not designed for the robot, integration process and propulsion robustness still pose technological challenges. In this paper, we present a helical microrobot with three different motions, designed to achieve these goals. These motions are rolling, spintop motion and swimming. Through these multiple motions, microrobots are able to selectively integrate a chip through a microfluidic channel. This enables them to perform propulsion characterizations, 3D  maneuverability, particle cargo transport manipulation and exit from the chip. The microrobot selective integration inside microfluidics could lead to various  Wireless mobile robots at the micro or nano-scale have promising applications in closed and liquid environments such as microfluidic channels or human blood vessels. Indeed, in such environments, installing transducers or sensors require for the moment invasive interventions. Different manners to propel such microrobots exist using electric234681011in-vitro or in-vivo applications, they have not yet been applied to such closed microfluidic environments. The main reason is their high surface-to-volume ratio, which is a handicap for robustness as they can be stuck on the substrate/channels walls or carry away by external flow (e.g. in a blood vessel). Indeed, we consider microrobots to be robust enough to be applied in such environments if they can be used for a long period of time without being damaged or lost during normal control.But even if such 3D controlled microrobots are promising for A way of overcoming these problems is to make the robot capable of interacting with the surface. In fact either the friction directly created by the surface1617The integration of microrobots on a microfluidic chip has two important consequences on the field. First it provides a well controllable environment in terms of flow and boundaries condition to investigate the physics of microrobots. Second it brings the microrobot to a challenging testbed. Indeed, to offer some practical applications, we think microrobots need to work in an environment designed for another purpose. Finally, the microfluidic chip is a common platform that requires manipulation and characterization at the micron scale. Microrobots could help fulfil this need.μm. Indeed at this scale injecting a single robot by fluidic inlet or by manual integration during the chip fabrication need a lot of technological development. However to support the drastic change of environment of the self-integration manoeuvre, both high robustness and mobility are required. Unfortunately, those cannot be provided by any single 3D corkscrew or surface motion independently. Therefore we investigate multimodal motion for microrobot as it increases the robustness and mobility by taking benefit of each motion advantages presented above while suffering less by their specific inconveniences. With this technique, we were able to perform self-integration of a microrobot in a microfluidic chip without fluidic injection or manual integration.This integration was demonstrated with milli-19The In this paper we first show how using three different motions enables us to integrate selectively the RTS in a microfluidic chip. The microfluidic chip is a well-controlled environment with minor fluid perturbation and it also simplifies the long term analysis of single microrobot. Therefore we use this platform to investigate the advantages and make a full characterization of each of the robot's motion. Finally we demonstrate useful microfluidic applications of multimodal motion which are: particle manipulation, 3D maneuverability inside a microfluidic chip and exit out of the chip.Microfluidic chip integration of a microrobot is an important step. It proves the robustness of the RTS and brings helical robots closer to application and characterization by making them available on a widely used biological platform. In this section, we first describe the design and fabrication of the RTS and the microfluidic chip. Then we explain how we carried out this integration by using different motions.μm long for a 5 μm diameter. Fabrication uses 3D two-photon laser lithography for patterning and e-beam nickel evaporation for ferromagnetic property. The method section presents more details on fabrication steps. A rotating homogeneous magnetic field produces the rotation of the robot, which is the base of the three motions. This is explained in μm high, 1 mm wide and 11 mm long microchannel makes the connection between the two separate chambers.As shown in For the integration process, we place in the open chamber of the chip a substrate with a field of RTSs on top of a thin PDMS layer. This substrate can be removed after the integration and used again to supply robots in different microfluidic chips. The first step is to detach a single RTS from the fabrication substrate  and are made with a two-photon 3D laser lithography (Nanoscribe GmbH) using IPG 780 resist on a glass substrate. Metallization of 200 nm ferromagnetic layer (Ni) and 10 nm thick adhesion layer (Cr) were done by electron beam evaporation. Both 0 and 75 degrees of deposition inclination were used to make the RTS ferromagnetic in a more uniform way. The RTS is detached from the substrate with a tungsten tip fixed on a micromanipulator (kleindiek mm3A-EM).−3 Tesla. As it is impossible for dimension reasons to give the same size to each pair of coils, each one has different dimensions. However, the Helmholtz condition, which states that the radius of the two coils must be equal to the distance between the two coil centers, is respected. Therefore, the coils provide a homogeneous field at their center. The smallest dimension of the coil radius is 22.5 mm. The containing microfluidic chip is placed on a moving platform that is manually commanded in 3 translational axes. This keeps the RTS in a cube with 2 millimeters-long edges around the common center of the 3 pairs of coils and ensures that the RTS stays in a homogeneous region of the field.A pair of Helmholtz coils in each of the three space directions provide a quasi homogeneous 3D rotating magnetic field. These three pairs are linearly combined to provide a field in any wanted direction. Thus the ferromagnetic RTS aligns in this direction. The intensity of the field is constant and set to 12·10In the manual control mode, the user can directly control the RTS with the keyboard. For that purpose, the arrow keys are mapped to the commands forward, backward, turn right or turn left. Four other keys are used to control the frequency of the rotating field and the pitch angle between the rotating magnetic field and the surface. The computer turns the command of the user into the corresponding changes in the parameters of the rotating field (angle and frequency). These changes are then updated in another thread which directly controls four linear amplifiers (Maxon motor 4-Q-DC) via a S626 card, with a refreshing time of 1 ms. Feedback is performed with a camera (Pike F032B) mounted on a microscope optic. The assembling of the camera and the optic allows a maximum precision of 0.5 micrometer per pixel. The image is sent back to the computer with a frequency of 20 frames per second to be displayed on the screen. Lighting of the sample can be made both by front light arriving through the optic or from back light depending if the RTS is on a opaque surface (nickel) or a transparent one (glass). Closed-loop control uses the same loop except that the video is also sent to a tracking algorithm that detects the robot position. Then a simple PID controller is used to control the RTS in position via the control of the pitch angle around When a ferromagnetic object is placed under a magnetic field, a resulting torque T is created. Its expression is :T the torque, M the magnetization of the object and B the magnetic field.with et al.The meaning of this equation is that the torque tends to align the magnetic axis with the magnetic field, just as a compass aligns with the magnetic field of the Earth. A rotating magnetic field will therefore make the object rotate at the same frequency. We used this rotation for the three motions of the RTS. However, this article will not focus on the primary axis of magnetization which is longitudinal to the RTS and result in a woobling. In fact, this axis makes the robot rotate around an axis that is perpendicular to its directions and is not used in the paper. To use only the second axis of magnetization, we increase the rotational frequency. Indeed, the rotation along the first axis of frequency reduces when the frequency rises. This is mainly due to a bigger increase of the drag force associated to the first axis of magnetization. Details of this phenomenon for a magnetic helical swimmer were described by Man cm2. When the fabrication substrate is put on this chamber, a thin PDMS layer is placed between this substrate and the chip. The first function of this layer is to prevent the fabrication substrate to slide when the robot is detached by the tungsten tip. The second is to facilitate the removal of this substrate by manually handed tweezers.A first open chamber. It allows the introduction of the RTS fabrication substrate as well as the tip to remove a single RTS. This square chamber is large enough to allow manipulation with human hand precision and its surface is 1 μm and a width of 1 mm. The total length is 11 mm. The shape is designed to allow for the channel to be closed by applying a pressure on the top of the chip. Thus the closed part of the chip can be isolated from the exterior. A 2 mm diameter plastic screw is fixed just above the chip and can apply this compressive pressure.A micro channel. It connects this chamber to a closed chamber. The section of this channel is a circular arc with a maximum height of 100 μm height. It is used for all the characterizations of the RTS. This chamber is also connected to a fluidic input and output. These connections can fill the chamber with liquid at the beginning and can be used to set a flow in the chamber to perform dynamics measurements or inject micro particles.A closed experimental chamber. Its dimensions are 7 mm over 5 mm with a 850 μm high for a width of 0.5 mm.An other microchannel. It is connected to the closed chamber and is used to store the RTS during the flushing period. Its dimensions are 50 All experiments with the RTS were made inside a microfluidic chip after a self-integration of the robot. This allows a better control of parasite flow and provides a way of stocking the RTS with high yield reliability. The chip has 4 main parts:μm high channel, has been used for the particle trapping and transport manipulation.Another microfluidic chip, with two closed chambers instead of one, linked together by a 100 2 plasma (90 seconds at 70 Pa). Finally, the chip is put for 24 hours in a 60 °C oven to reticulate the PDMS entirely.The chip is made with Polydimethylsiloxane (PDMS) and glass. First, a negative mold is made with a micro milling machine with a 0.5 mm diameter flat drill on Polymethyl methacrylate (PMMA). Then PDMS is poured on the mold and is put at least for 2 hours in a 60 °C oven in order for it to reticulate. Then the replicated PDMS channel is removed from the PMMA mold and bonded to a 1 mm thick glass substrate using an 0μm·s−1. It corresponds to a Reynolds number inferior to 6.10−3 in isopropyl alcohol and therefore the laminar flow is guaranteed.All the experiments were carried out using isopropyl alcohol at 21 °C. The range of the maximum speed for the robots is below 300 How to cite this article: Barbot, A. et al. On-chip Microfluidic Multimodal Swimmer toward 3D Navigation. Sci. Rep.6, 19041; doi: 10.1038/srep19041 (2016).


An appropriate nonlinear blood flow model under the influence of periodic body acceleration through a multiple stenosed artery is investigated with the help of finite difference method. The arterial segment is simulated by a cylindrical tube filled with a viscous incompressible Newtonian fluid described by the Navier-Stokes equation. The nonlinear equation is solved numerically with the proper boundary conditions and pressure gradient that arise from the normal functioning of the heart. Results are discussed in comparison with the existing models. At present the investigation of blood flow analysis in a stenosed artery is very important in the medical domain because of the fact that many of the diseases such as heart attacks and strokes are related to blood flow and the physical characteristic of vessel wall. Nowadays the leading causes of the death in the world are due to heart diseases such as atherosclerosis. Atherosclerosis involves an accumulation of low-density lipoprotein in the wall of large arteries, typically where the wall shear rate is low and oscillatory .Investigation of blood flow modeling through arterial multistenosis is very challenging. Accuracy of the simulation depends mainly on suitable numerical approach, realistic model geometry, and boundary conditions. Many investigators have focused their attention on blood flow through stenosed arteries with single stenosis by Mekheimer , 3, ChakWith the above motivation in our mind we have worked on numerical simulations of nonlinear pulsatile unsteady Newtonian blood flow in a rigid cylindrical tube through cosine-shape stenosis under the influences of periodic body acceleration. It appears that a few studies address the issue of that nonlinear terms present in Navier-Stokes equation govern blood flow with periodic body acceleration associated with an atherosclerotic plaque. The numerical solutions are obtained of the nonlinear model using appropriate finite difference method. A comparison of the axial and radial velocities, wall shear stresses, flux rates, and the streamlines with other existing model  has beenr0. The blood is modeled as a homogeneous incompressible viscous unsteady Newtonian fluid of density ρ and kinematic viscosity ν. Therefore, the blood flow is governed by the incompressible Navier-Stokes equation.The segment of the artery is modeled as an axisymmetric cylindrical tube with radius r, θ, z) is chosen, where  is the coordinate in the radial and circumferential direction, while z is taken along the axis of artery as shown in u and v, respectively. The flow is driven by a prescribed dimensional oscillatory axial pressure gradient given by [p0 and p1 are the steady component of the pressure gradient and pulsatile component, respectively. The frequency ω = 2πf, and   f is the heart pulse frequency. The pressure gradient in the radial direction is negligibly small as the lumen radius of artery is small compared to pressure wave length so that ∂p/∂r≃0. Also because of the human body acceleration, the axial flow is subject to an external force Fext. For the present model, we consider the periodic acceleration force given bya0 is the amplitude of the pulse.A cylindrical coordinate system (given by (1)−∂p∂z=v)u)r0u∞ρ/ν is the Reynolds number and u∞ is the average velocity of the blood.According to the above assumptions, the blood flow dynamics is governed by the equation of continuitylocity v)∂v∂t=−u∂vlocity u)∂u∂t=−v∂uh(z):λ is a dimensionless constant and the geometry of this axisymmetric stenosis in the cross section of the artery is shown in Finally, to model multiple axisymmetric stenosis, we define the following mathematical function We numerically simulate –5) subj subj5) sv.We use the finite difference scheme to study the dynamics of blood flow through the cylindrical shape artery. To employ this method, first we transform our cylindrical domain into the rectangular domain by using the following radial transformation:ntinuity  and the ntinuity  and axiantinuity , respectondition  and no-sondition  due to rx=rhz.Undtinuity i,jn is obtained from  in the domain of interest at any time tn with the help of the following discretize initial and boundary conditions (discretization of (Fext from relations (v)i,jn is obtained from u)i,jn iation of ):(16)ui,ned from  and 11)u)i,jn iμ is the viscosity. The discretize version of Q and τ is given by the following equations:Finally, we determine the volumetric flow rateormation , where μl = 2.00, d = 3.00, λ = 0.5, Re = 400, 600, and 800, p0 = 0.1, and p1 = 0.2 × p0. The results obtained for axial velocity by solving explicit finite difference scheme with various grid sizes are taken in order to achieve the convergence and stability. We perform the experiments for grid size 60 × 60 and 100 × 100 with dt = 0.01 and 0.001. The results are found to be very similar in both cases.In this section, we shall discuss the numerical simulation of the nonlinear equations to study the influence of stenoses and body acceleration on the blood flow for different values of the physical parameters. The simulation parameters are as follows , 14: l =t = 10 without and with body acceleration, respectively. Both figures are drawn for Re = 400 at different z. The comparative study between the figures , the velocity is low and in presence of body acceleration, the velocity sharply decreases in this stenosed zone. z enters into the stenosed zone the axial velocity starts decreasing from its maximum value in nonstenosed zone until the first constriction attaint its maximum value near z = 4 and then it gradually increases up to z = 5.2 and again it starts decreasing till the maximum height of the second stenosis and gradually starts increasing thereafter and finally again flows with maximum velocity in nonstenosis region. The three curves here indicate that the axial velocity increases in the constricted part of the artery as Reynolds number increases under the influence of body acceleration. Figures  Figures  reveals x = 0.8 and then it decreases gradually in negative direction.The curves in u and v are shown in different region with different colors representing the value of velocity with the help of color bar. One can see from these plot that velocity profile is divided into different layers due to the constriction of the artery and changes in the plot also can be observed in case of no body acceleration. We have shown the distribution of axial and radial velocities in Figures t = 10 for Re = 400. One can see that the velocity profile is constant in the nonstenosed zone and varies over the constricted area. In case of body acceleration the profile is shown in To test the effects of body acceleration on axial and radial velocities profile several simulations have been carried out using the contour plot as shown in Figures Wall shear stress plays an important role in the creation and propagation of arteriosclerosis. If the wall shear stress is high then it may damage the arterial wall and is the main cause of the intimal thickening. On the other hand, the plaque formation in an artery is created in the regions of low arterial wall shear stress. Atherosclerotic lesions are associated with low and high wall shear stress. So it is important to study the wall shear stress distribution in the multistenosed artery. Figures The streamlines of the blood flow in the artery with multistenosis are found in the transformed rectangular domain with grid 60 × 60 in the upper half zone and same grid also taken for lower half portion. We have plotted the different types of streamlines in Figures For the purpose of model validation, the axial velocity profile is compared with , and as A nonlinear mathematical model for blood flow in a multiple stenosed arterial segment has been developed under the influence of body acceleration. The numerical simulation of blood flow is investigated in this study. As the Reynolds number increases, the wall shear stress increases. The multiple stenosis has significant effect on the wall shear stress in such a way that it develops more at the constricted locations than all other sites of the artery. The streamline pattern shows the distinct boundary layer characteristics in the arterial segment. This is validated by the flow visualisation observed by the simulation studies of . The res


Patient safety research has focused largely on hospital settings despite the fact that in many countries, the majority of patient contacts are in primary care. The knowledge base about patient safety in primary care is developing but sparse and diagnostic error is a relatively understudied and an unmeasured area of patient safety. Diagnostic error rates vary according to how ‘error’ is defined but one suggested hallmark is clear evidence of ‘missed opportunity’ (MDOs) makes a correct or timely diagnosis to prevent them. While there is no agreed definition or method of measuring MDOs, retrospective manual chart or patient record reviews are a ‘gold standard’. This study protocol aims to (1) determine the incidence of MDOs in English general practice, (2) identify the confounding and contributing factors that lead to MDOs and (3) determine the  impact of the detected MDOs on patients.We plan to conduct a two-phase retrospective review of electronic health records in the Greater Manchester (GM) area of the UK. In the first phase, clinician reviewers will calibrate their performance in identifying and assessing MDOs against a gold standard ‘primary reviewer’ through the use of ‘double’ reviews of records. The findings will enable a preliminary estimate of the incidence of MDOs in general practice, which will be used to calculate the number of records to be reviewed in the second phase in order to estimate the true incidence of MDO in general practice. A sample of 15 general practices is required for phase 1 and up to 35 practices for phase 2. In each practice, the sample will consist of 100 patients aged ≥18 years on 1 April 2013 who have attended a face-to-face ‘index consultation’ between 1 April 2013 and 31 March 2015. The index consultation will be selected randomly from each unique patient record, occurring between 1 July 2013 and 30 June 2014.There are no reliable estimates of safety problems related to diagnosis in English general practice. This study will lay the foundation for safety improvements in this area by providing a more reliable estimate of MDOs, their impact and their contributory factors.The online version of this article (doi:10.1186/s13012-015-0296-z) contains supplementary material, which is available to authorized users. Patient safety has received considerable global attention since the publication of the landmark report ‘To Err is Human’ in 1999 . This isData about the incidence, types and causes of errors encountered in primary care are scant and there are no large-scale epidemiological studies in the UK to reliably quantify error and harm rates in this setting. However, among the different types of errors, medication-related errors and diagnostic errors (DEs) are the most common in primary care , 9. DespCase analysis reveals evidence of a missed opportunity to make a correct or timely diagnosis. The concept of a missed opportunity implies that something different could have been done to make the correct diagnosis earlier. The missed opportunity may result from cognitive and/or system factors or may be attributable to more obvious factors, such as lapses in accountability or clear evidence of liability or negligence.A missed opportunity is framed within the context of an ‘evolving’ diagnostic process. The determination of error depends on the temporal or sequential context of events. Evidence of omission (failure to do the right thing) or commission (doing something wrong) exists at the particular point in time at which the ‘error’ occurred.The opportunity could be missed by the provider, care team, system, and/or patient. A preventable error or delay in diagnosis may occur due to factors outside the clinician’s immediate control or when a clinician’s performance is not contributory .DE rates are likely to vary substantially according to the criteria used to define ‘error’. A central issue in the reliable measurement of DE is therefore how it is defined. Some studies define diagnostic error as any diagnosis that is (i) wrong, e.g. another diagnosis was made before the correct one; (ii) delayed, e.g. insufficient information was available to make an earlier diagnosis; or (iii) missed, e.g. no diagnosis was ever made. The decision as to whether a diagnostic error occurred or not is judged from a subsequent assessment of more definitive information, regardless of whether an error in the diagnostic process occurred , 15. To In this study, we define and conceptualise diagnostic errors therefore as ‘missed diagnostic opportunities’ (MDOs).Patients may suffer preventable harm, for example through conditions which remain untreated or by receiving inappropriate and unnecessary treatment;Doctors may be subject to malpractice claims  in the UK); andAdditional financial costs are incurred by health care systems.Research suggests that the aetiology of the vast majority of MDOs is multi-factorial and arises via a complex interplay of system and cognitive contributory factors . One potThe lack of progress in understanding and determining MDOs and in particular MDOs in primary care may be attributed to several factors. The diagnostic process often spans multiple health care settings and involves different professional staff groups, which in turn introduces myriad challenges, such as co-ordinating care and managing the timely and secure communication of patient information. Furthermore, diagnoses are made during time-pressured consultations within primary care settings, where providers are often remain unaware of ultimate patient outcomes . As a reIdentifying, measuring and understanding MDOs in primary care is the first step in developing policies and interventions to reduce harm and improve patient safety in this area. At present, we have no reliable estimates of diagnostic error in English general practice with which to formulate any such policies or interventions, hence the need for this work.To determine the incidence of MDOs in English general practice;To identify the confounding and contributing factors that lead to MDOs; andTo determine the impact or potential impact of the detected MDOs on patientsThe study has three specific aims:To test for significant associations between MDO rates and specific patient, index consultation, practice and diagnostician variables.To compare the MDO rates of the participating practices and different professional groups.To describe the types of diagnoses clinicians made during the study period as well as the types of MDOs.The secondary objectives of the study are:The study design is a retrospective review of electronic medical records that will be undertaken in two consecutive phases. In the first phase, clinician reviewers will gain experience and confidence in the review method and at the same time calibrate their performance in identifying and assessing MDOs against a gold standard ‘primary reviewer’ through the use of ‘double’ reviews of records. Thus, a primary goal of this phase is to maximise consistency of ratings across reviewers. The review findings from phase 1 will then be used to calculate a preliminary estimate of the incidence of MDOs in general practice. This preliminary rate will be used to calculate the number of records to be reviewed in the second phase in order to estimate the true incidence of MDO in general practice to a specified degree of precision and reliability. In other words, the MDO rate from phase 1 will ensure that no more than the required number of records is reviewed during phase 2. This is an essential requirement of the study to ensure that the available resources are used efficiently.The study will be conducted in the Greater Manchester (GM) area. More specifically, the electronic patient records of general practices in the GM Clinical Commissioning Groups (CCGs) will be considered for potential inclusion. However, practice staff and patients will not directly be involved in any aspect of the study.i.The sampling strategy will involve random selection of sets of electronic health records from a stratified sample of general practices.A sample of 15 general practices is required for phase 1 of the review process. An additional sample of 35 practices may be required for phase 2. However, this is an estimate that will be revised as described in ‘ii.Electronic health recordsPurposeful sampling will be used to select a sample of practices stratified by size and neighbourhood deprivation. Practice size will be based on the number of registered patients and coded as ‘large’, ‘medium’ or ‘small’. Neighbourhood deprivation will be based on the national quintiles of the English Index of Multiple Deprivation (IMD) for 2010 , based oElectronic health records for 100 unique patients that meet the following four inclusion criteria will be randomly sampled from each participating practice: (1) age ≥18 years old on the 1 April 2013; (2) registered continuously with the same practice from 1 April 2013 to 31 March 2015 (thus excluding records of temporary residents); (3) availability of the complete medical record for review; and (4) must have attended a face-to-face ‘index consultation’ during this period.Each patient’s index consultation represents the ‘anchor’ of the review process and marks the reviewers’ starting point for that patient. A single index consultation will be randomly selected from each unique patient record, occurring within the 12-month period commencing on 1 July 2013 and ending on 30 June 2014. Across the patient sample within each practice, the index consultation dates will be spread over the course of the defined 12-month period to account for potential seasonal effects on reasons for consulting and hence MDOs. This will be done by assigning four week-long sampling ‘windows’ to the practice and randomly selecting 25 index consultations from all patient consultations within each window. The first sampling window will be randomly chosen from the first 13 weeks of the period and each subsequent window will be 13 weeks later.Five GPs will be recruited and trained as clinician reviewers and will meet the following inclusion criteria: (1) currently working as a GP or has worked as a GP in the last 12 months; and (2) a minimum of 5 years’ experience as a GP. Based on previous experience and knowledge of safe practice, one of the five GPs will be designated the ‘primary reviewer’ and will undergo additional training and calibration with clinical members of the project research team group. The primary reviewer will then act as the gold standard against which the performance of the four remaining GPs in identifying and evaluating MDOs will be calibrated.The primary objectives of phase 1 are to calibrate the reviewers with the primary reviewer and to collect sufficient data to reliably estimate the sample required for phase 2. For these purposes, we have determined that a phase 1 sample of 15 practices and 100 records at each will be required. For calibration, the study uses overall sensitivity and specificity of the reviewers of 75 % or better as acceptable and 60 % or less as fully unacceptable, assessed using the latter 50 % of records ) to estimate the required sample at phase 2. Assuming a fairly high ICC of 0.05 , this sample will yield an MDO rate with a 95 % confidence interval of 2.3–7.7 % when the true rate is 5 %; and 6.2–13.8 % when the true rate is 10 %.The number of electronic patient records to be sampled and reviewed at phase 2 will depend upon the estimates of the MDO rate and the ICC obtained from phase 1. In addition, to allow estimation of the relative rates of different forms of MDO, we aim to pick up a minimum of 100 MDOs in total across phase 1 and phase 2 combined . As a pre-check that sample sizes will be sufficient for this purpose, we have made estimates for three true MDO rate scenarios: 1, 5 and 10 % (at an ICC of 0.05). The results are shown in Table If the overall MDO rate from phase 1 is 5 %  approvals for the study and will continue until we have recruited the requisite number of general practices as described in the ‘The recruitment process will begin by contacting the GM CCGs and meeting with their leaders in order to seek their support and approval for participation in this study. Each GM CCGs has many general practices with diverse geographical spread and wide-ranging socio-economic conditions and all of them will be considered once we have obtained senior leadership support.We will send practices an introductory letter  in each participating practice as the first step in the review process.One reviewer will be recruited from each of the three participating CCGs if feasible. Two additional reviewers will be recruited, one as the ‘primary reviewer’ and the other as a ‘floater’ to allow for holidays and unforeseen eventualities in the lives of the other reviewers. The reviewers will be remunerated for their time in accordance with locum rates.n = 100) of unique and eligible index consultations will be selected by using the Random Integer Set Generator.1The administrator will visit each practice to create a list of ‘index consultations’ (one per patient record) and to complete the ‘patient demographic’ section on the data extraction form  and time of day of the selected index consultation ;The age of the patient on the day of the index consultation;The patient’s gender;This part of the data collection will be performed by the administrator while steps 2–4 will be performed by the clinician reviewers. The following information will be extracted by the administrator from the index consultation in each record:The number of repeat medication items prescribed;The type and number of documented morbiditiesThe following information will be extracted by the administrator from each record on the day the search is conducted:During this part of the data collection, the clinician reviewers collect information on the diagnosis or diagnoses that were made during the index consultation. If there were no diagnosis made, the review for that specific record is effectively over, and the reviewer continues with the next record.Reviewers will systematically gather information about the index consultation diagnosis or diagnoses in order to make professional judgments in step 4 about (i) the accuracy of each diagnosis and (ii) whether there had been missed diagnostic opportunities. The systematic approach involves searching for the presence of seven predefined ‘triggers’ or prompts in each record and considering eight questions about potential MDOs  will be paired with the primary reviewer in 5 of the 15 practices .For analysis purposes, the data from phases 1 and 2 will be pooled together, with the data for each phase 1 practice being the agreed final ratings between the two reviewers.Simple descriptive statistics, including means, standard deviations, medians and inter-quartile ranges, will be used to characterise the overall MDO rate and individual practice and subgroup rates, e.g. professional group and month of year. The precision of the MDO rate estimates from each analysis will be expressed in terms of the confidence interval around the rate. The overall rate of MDOs will be calculated by aggregating all practice data from phases 1 and 2. In addition, we will compare the distribution of the sample of practices in terms of key practice variables  to all practices in GM and in England and derive weights from this in order to compute weighted estimates of the mean rates for these larger geographical areas.Analysis of free-text data will be undertaken by the reviewers, research team and steering group. We will produce an output similar to Singh  to outliWe will use multilevel logistic regression (records within clinicians within practices) to investigate a wide range of variables potentially associated with MDOs Table . The anaInter-rater agreement will be assessed through calculation of specificity and sensitivity for each of the four secondary reviewers relative to the primary reviewer using the phase 1 data. Agreement will be based on ratings for the latter 50 % of records in each case; with the first 50 % being regarded as principally a training set. Sensitivity and specificity rates of ≥75 % will be considered as acceptable, ≤60 % as requiring further calibration and 60–75 % as requiring input from the research team steering group to decide whether further calibration is required or not.The study started with literature review, planning, consultation, preparation and finalising this protocol. We have full ethical and R&D approvals, and data collection will begin soon. Data collection in all of the participating practices is estimated to last a maximum of 12–16 months. The study endpoint, including analyses and write-up is estimated to be December 2016 to March 2017.Ethical approval for the study was obtained from NRES Committee North West-Lancaster on 23/03/15 (reference: 14/NW/1491). Approval was also obtained from the Confidential Advisory Group on 9/03/15 (reference: 14/CAG/1041).We do not plan to seek individual patient consent for access to patient records. This is because the records will be reviewed by GPs who are currently, or have been within the last 12 months, employed by the NHS and no patient identifiable information will be collected or used in any part of the analysis or reporting of the study findings. In addition, GPs regularly perform and are expected to perform clinical audit as part of their normal work activities.There are no reliable estimates of the incidence of MDOs in English general practice. Current estimates are based often on anecdotes, personal experience and a number of small studies conducted, for example in the UK  There are many challenges in measuring diagnostic error and MDOs and in developing and using good measurement instruments; and the ability to reduce diagnostic errors hinges on the ability to overcome measurement-related challenges , 24. Asi


The main objective of this paper is to study the mechanical influence of the tympanic cavity (TC) in the auditory system (AS). It is done for a frequency range from 0.1 to 20 kHz and the pressure source was applied in the external ear canal (EEC) entrance.Numerical simulations were developed for seven different models by means of finite element model. On the basis of an EEC finite elements model, the additional elements are coupled and removed in order to evaluate the contribution of the TC. Tympanic membrane, ossicular chain, simplified cochlea and TC were modeled and simulated in four different combinations.Pressure, velocity, and displacement measures were obtained in AS key points in order to be compared with experimental results. Umbo and stapes transfer functions have been represented.The main conclusion is that we find evidence that the presence of the TC in the AS introduces a second resonance in middle ear transfer functions at frequencies above 3 kHz. The mechanics of the outer and middle ear have been the objective of much research and many publications. There is a common position regarding the main behavior of the system, especially at lower frequencies, however at higher frequencies there are still some controversies. At lower frequencies (at the range below 1–2 kHz), the classic piston-like motion model is widely accepted to described the mechanics of the sound transmission. Experimental and numerical research confirms this basic model.Nevertheless, at frequencies above this range, different coupled mechanisms appear which are difficult to identify. Aspects as how the tympanic cavity (TC) couples to the tympanic membrane (TM), the influence of the ossicular system on the dynamic of the membrane or the effect of the external ear canal (EEC) over the eardrum motion and transfer functions are certainly unclear nowadays.There are some common surgical interventions, as tymplanoplasties or bone substitution by prosthesis, which solve hearing problem but sometimes derive on an audition quality lost. For the patient, it becomes manifest in limitation on the speech intelligibility or difficulties to appreciate music. This is normally due to changes on the transmission of higher frequency sounds. A better understanding of the sound transmission mechanisms at these frequencies is the base for proper interventions or therapies. For instance, in the case of a tympanoplasty, the change on the membrane thickness change its behavior at higher frequencies.The main objective of this paper is to find evidence of the TC role in the transfer function. This has a double benefit, on the one hand we obtain a better comprehension of the behavior of the system, on the other hand we can shed light on the interpretation of experimental work which commonly has to manipulate the TC in order to carry out the experiment.There is a great deal of work published about the influence of the ear canal (EC), TM and ossicular chain (OC) in the auditory system (AS). Some papers show experimental measurements varying TC conditions in order to deduce the TC role in the AS. Otherwise, experimental difficulties limit their finding and it is not clear how the TC affects TM motion at high frequencies.Regarding numerical model and particularly in finite element method (FEM), only a few papers have included TC in their Models –6, and oRegarding experimental researches, there is evidence that changing middle ear cavities produce changes in middle ear impedances , so it sThis paper is based on outer and middle ear numerical simulations developed by means of FEM. The maximum number of possible combinations of different outer and middle ear subsystems have been modeled and simulated: EEC, TM, OC, TC and simplified cochlea (SC). Four main different combinations have been modeled: EEC only attached to TM; EEC coupled to TM and TC; EEC coupled to TM, OC, and SC; and the full model: EEC coupled to TM, TC, OC and SC. Other three combinations have been simulated on the basis on the full model: The TC was opened to an air-filled domain with open boundary conditions that do neither reflect nor dampen the outgoing waves. These situations try to simulate experimental setups at the laboratory tests.The model presents a complete fluid–structure interaction among EC, TM, TC and oval window. The TM modeling presents a crucial innovation respect to previous models; the elements used in the TM have an improved formulation, the formulation enhanced strain , which eBefore continuing with the following section of the paper it must be stated what our numerical model does and what it does not. Which results are useful and which can only be considered qualitative.Apart from geometry uncertainties dues to natural variability, the maximum level of inaccuracy is due to the difficulty to obtain the mechanical properties of some components . In this paper, these values have been obtained from bibliography and has been assumed. There is no attempt to discuss its accuracy. In previous works , they haDespite this, there are two key aspects in the numerical model that must be remarked due to its strong influence on the mechanisms studied. The first one is the proper fluid–structure interaction modeling. Even when there could be some delay effect (phase differences) due to some material viscoelasticity, it is negligible compared with the reflection effect of the cavities and the TM. So this coupled effect must be correctly simulated.The second one it is related with the difficulty of modeling and meshing the membrane. A proper structure interaction with the fluid at both sides of the membrane requires the use of solid elements. It is a task that can introduce important errors in the model, depending on the mesh size and the finite element formulation.Numerical simulations have been performed by means of the FEM using the commercial software ANSYS 13. All numerical simulations consist of harmonic analysis in a frequency range from 100 to 20,000 Hz. All models use a unit value pressure at the entrance of external auditory canals an input signal.The geometries of the different subsystems have been obtained from the bibliography. Differences in the geometric and material properties should affect the transfer functions. A previous work  presenteThe geometric model of the TM was obtained from the surface eardrum data, using moiré interferometry , with thThe auditory canal was obtained with data from nine cross sections obtained from the work published by Egolf . With thThe anatomic measures and functional properties of middle ear were based on published geometric data of human normal middle ear elements. The geometrical model is divided into three parts: the TM or eardrum, the OC , and the system of ligaments, tendons and joints that include superior, lateral and anterior mallear ligament, incudal ligament, tensor tympani tendon, stapedial tendon, tympanic annular ring, stapedial annular ligament, incudomallear joint and incudostapedial joint. To achieve the model of each part, a different methodology is used due the differences in physiology, anatomy and mechanical behaviour.The OC was drawn using three-dimensional CAD tools from the orthogonal views obtained by Weistenhöfer and Hudde  as shownThe TC geometry is based on published photomicrographs . ReconstThe geometry of the cochlea has not been modeled. It has been used as an equivalent system consisting of damper-mass-damper inspired in the literature , and pro3. Speed of sound: 343 m/s. The acoustic absorption coefficient for the TM and canal wall are 0.007 and 0.02 respectively [Fluid: the EEC and TC are modeled emulating the air. The element used is the Fluid 30 of ANSYS 13.0 [Eardrum and annular ligament of the eardrum: The TM and the annular ligament tympani have been modeled with hexahedral solid element 185 of ANSYS 13. The TM must be meshed as solid elements in order to do a proper fluid–structure connection among EEC, TM and TC. The element uses an improved formulation (formulation enhanced strain) which eliminates the problems of “shear locking” of the elements used in thin membranes. The mesh size used was 200 μm.Figure In addition, some mesh convergence analyses were performed to confirm the optimal mesh size. A convergence analysis of TM size elements is shown in Fig. −4 s for all solid components. The mechanical properties of the membrane are different for the pars tensa and pars flaccida. Table The damping coefficient β was 1 × 10−4 s for all solid components. These property values were subjected to a previous sensitivity analysis [OC: the malleus, incus, and stapes have been modeled with the Solid45 element in its tetrahedral shape. The mesh size used is 400 μm. The same elements and mesh size have been used to model incudostapedial and incudomallear joints, incudal ligament, and stapedial tendon. The tensor tympani tendon and posterior, anterior and superior ligaments are modeled as linear elements with the Beam4 element (six degrees of freedom at each node). The stapedial annular ligament is assumed to be an elastic band around the footplate 0.1 mm wide and 0.1 mm thick using Shell43 elements. Table analysis  in orderThe cochlea is modeled as an equivalent load , consistThe boundary conditions of the model include the suspensory ligaments and tendons of the OC, which is joined at one end with the nodes at the intersection of each bone and at the other end is fixed to simulate the union with the middle ear cavity. The nodes of the outer edge of the ‘tympanic annular ring as well as nodes of the periphery of stapedius annular ligament are fixed to simulate the connection with the middle ear cavity.Seven different combinations have been simulated in order to discern what the impact of each subsystem in the human AS is. In Table The results show the TMP to umbo and stapes footplate displacement and velocity transfer function. The comparative of FEM results and experimental results from literature are shown first in order to validate the proposed model. The experimental results are divided in open-cavities (OC) and close-cavities (CC).Figure Figure It is evident that both the presence of the TC and the OC and cochlea pairing have an effect on the response, but it should be noted that the shape of the responses is similar in all cases. Therefore the TM is undoubtedly the most influential sub-system in the UD/TMP transfer function. A second resonance is only observed when the TC is modeled.Figure Figure Figures Figure Figure Figure Figure In this subsection, the effect of the gradual TC opening is presented. The TC is connected to an air-filled domain with open boundary conditions that do neither reflect nor dampen the outgoing waves.The results of three open cavities FEM are shown in this subsection together to the full model FEM. There are many possibilities to consider cavity apertures depending on the experiment setup. For this study, the opening is situated in the Eustachian tube side and different sizes have been analyzed. The open cavity-1 model has the smallest opening just at the Eustachian tube. The open cavity-2 model has a medium size opening, the TC has been cut 2 mm from the Eustachian tube. The open cavity-3 model has the biggest size opening, the TC has been cut 4 mm from the eustachian tube.Figure Figure The results of Figs. As described in the “There are differences in the results of eardrum and stapes transfer functions presented in experimental papers. This is justifiable because there are differences between operational methods in the preparation of the temporal bones, the measurement instruments used, and the inherent geometry of each analyzed AS . If we fWhen there are more open cavities the second resonance is less noticeable. Kringlebotn results (closed cavities)  show theVolandri   presentsTherefore, there is a controversy on this fact. There are at least two considerations to be taken into account for explaining this issue: most of experimental results show the mean of several measurements in different individuals and the second resonance frequency can be different due to geometrical and boundary conditions differences of the middle ear cavities. This fact could lead to a cancelation for the resonance. Another important fact is that opening the middle ear cavity does not imply the elimination of the cavities (this FEM paper models closed cavity or nonexistence of cavity), but it implies a change in boundary conditions. The middle ear cavity remains with different conditions and most of the middle ear walls remain reflecting waves. Evidently, the resonance frequencies will change.This second resonance in transfer functions is also observed in other mammals. Chien et al.  shows a There are also representative jobs in FE in mammals like the cat. Tuck-Lee  presentsThe difference between experimental and numerical results above 2 kHz observed in Fig. Due to the complexity of these numerical models is difficult to conduct experimental–numerical work to obtain robust conclusion in this matter. Only with simplified and limited experimental setups we can fit the numerical model with the experimental data .In any case, what is relevant in this discussion is that this difference does not affect the specific objectives and conclusions of this research, which is not to assess the effect of mechanical properties of tissues on the response of the AS, but to assess the influence of the auditory subsystem. In this sense, those properties related to the stiffness and mass of the system are very sensitive  as they change the dynamics of the system. But those related to energy loss only present a limited influence on the magnitude of the response.Otherwise, it must be recall that once the mechanical properties have been fixed and justified in our research, FEM results are inside the standard deviations reported by Nishihara .This study has found evidences resulting that the presence of the TC in the AS introduces a second resonance in middle ear transfer functions at frequencies higher than 3 kHz. It is in coherence with the experimental results even when the experiments have limitations at higher frequencies.The gradual TC opening affects to the middle ear transfer functions at high frequency. This fact could have a clinical impact, in some common surgical interventions, the size of the TC is modified, deriving on an audition quality lost at high frequencies. On the other hand, the gradual TC opening should be studied deeper to understand interpretation of experimental work which commonly has to manipulate the TC in order to carry out the experiment.The TM must be carefully meshed when EEC and TC are modeled. Solid element with a determined size  and enhanced strain formulation (which eliminates the problems of “shear locking”) must be used to avoid an excess of stiffness.The eardrum is the most influential subsystem in the Umbo transfer functions shape . UD/TM and UV/TMP magnitudes are also strongly affected by the OC and the cochlea attachment, but phase magnitude is only slightly affected. A cascade-like phase distribution is observed in UD/TMP and UV/TMP transfer functions.