Traditional symphony performances need to obtain a large amount of data in terms of effect evaluation to ensure the authenticity and stability of the data. In the process of processing the audience evaluation data, there are problems such as large calculation dimensions and low data relevance. Based on this, this article studies the audience evaluation model of teaching quality based on the multilayer perceptron genetic neural network algorithm for the data processing link in the evaluation of the symphony performance effect. Multilayer perceptrons are combined to collect data on the audience's evaluation information; genetic neural network algorithm is used for comprehensive analysis to realize multivariate analysis and objective evaluation of all vocal data of the symphony performance process and effects according to different characteristics and expressions of the audience evaluation. Changes are analyzed and evaluated accurately. The experimental results show that the performance evaluation model of symphony performance based on the multilayer perceptron genetic neural network algorithm can be quantitatively evaluated in real time and is at least higher in accuracy than the results obtained by the mainstream evaluation method of data postprocessing with optimized iterative algorithms as the core 23.1%, its scope of application is also wider, and it has important practical significance in real-time quantitative evaluation of the effect of symphony performance. At present, most of the research processes of orchestral performance effect evaluation are based on the traditional “performance type and melodic characteristics research and vocal appreciation” type, supplemented by the “performance audience evaluation” research . In receThe innovation of this paper is that the multilayer perceptron genetic neural network algorithm is used in the evaluation of symphony performance. On this basis, it can make full use of a large amount of symphony performance data and extract appropriate symphony performance information from it. Data quantification, information extraction, and analysis of the audience's facial expression changes, emotional performance, and so forth are carried out dynamically to achieve an overall closeness in the audience evaluation data. Compared with the current mainstream performance evaluation methods of data analysis and postprocessing, the symphony performance evaluation management and analysis model proposed by this research uses multitransformed neural network factors to quantitatively describe the quantitative characterization characteristics of different performance processes. The degree of agreement between the similarity of the dimensional vocal analysis model and the expected evaluation index is to complete the ranking of the influence on the performance melody with the quantitative index, which can efficiently analyze the characteristics of the factors that affect the performance of the symphony.This paper investigates the normalization scheme of audience evaluation and analysis of orchestral performance effects and is divided into five sections. It is known that it is relatively backward in symphony performance analysis model innovation and quality evaluation using computer techniques . At presIn summary, it can be seen that most of the current orchestral music in performance effect analysis models does not involve an intelligent evaluation method based on performance effect and audience evaluation. In the evaluation of the delay effect of symphony in mainstream scientific research, most of researches are unified collection of data in the performance link, followed by postprocessing and analysis of the data, but rarely realize the “data collection” of the symphony performance link. Data analysis effect evaluation integrated real-time dynamic processing analysis. On the other hand, although the multilayer perceptual genetic neural network algorithm has been gradually applied in music evaluation, it has not been quickly and efficiently widely used in the stage of multianalysis and dynamic real-time processing of data. Therefore, it is important to study the orchestral performance effectiveness evaluation method based on multilayer perceptron genetic neural network algorithm.There are no more successful intelligent models applied in the world for studying optimization problems and simulation in the field of teaching quality assessment compared to genetic algorithms, particle swarm greedy algorithms, and local optimization neural network algorithms –26. The Based on this, in the orchestral performance effect analysis and evaluation model based on multilayer perceptron genetic neural network algorithm, the genetic neural network algorithm based on multilayer perceptron factors is firstly designed; that is, by combining neural network factors based on the level variability and audience evaluation effect in the process of orchestral performance, the quantitative evaluation of orchestral performance effect is realized. Then, the multilayer perceptron genetic neural network algorithm is used to precisely divide the information in a series of teaching processes expressed in the symphony performance analysis, so as to achieve a high degree of categorization of different qualities in the process of symphony performance analysis and melody research and to generate targets  with a very high degree of synergistic correlation, which are pushed to the next stage of the process to be optimized to achieve a quantitative effect evaluation.In constructing the orchestral performance effect evaluation model and evaluation link based on the multilayer perceptron genetic neural network algorithm (GA-MLP-NN), the multilayer perceptron genetic neural network algorithm is used to categorize different types of symphonic music at different stages according to the similarity of vocal analysis patterns and the synergetic similarity of musical instruments, and then the melodic information in the analysis process of different symphonic performances is divided into secondary divisions, and, through the multilayer perceptron genetic neural network algorithm, the effect of symphonic performances of different degree types is selected for secondary division and update to ensure the stratification and update of effect analysis and management of different types of symphonic performances. Its data processing process is shown in The steps are shown below.In the first step, in the data analysis and processing link, the neural network data is classified according to the degree of association between the data and the difference of the modulus length after the data is vectorized, and a label is generated for each classified group for subsequent use. Supervised learning and then a neural network coding strategy are selected to transform the parameter set (feasible solution set) into a multilayer perceptron structure in a multilayer perceptron genetic neural network algorithm. In order to realize the process, this study combines a new multifactor coupling model-based orchestral performance process evaluation method, which uses the deformed coupling sequence to randomly displace common orchestral content and melody types, and then decouples it to achieve the optimal determination of different types of orchestral performance and performance process schemes and conducts simulation verification to evaluate this orchestral performance analysis quality evaluation scheme. It has a good objective evaluation capability. In this process, the simulation results of the relationship between the number of iterations of analysis and the coupled hierarchical perceptron are shown in From Q(x), dimensional function W(x), and hierarchical function E(x) used in this process are given below, and they are often applied to some fields like image processing, image recognition, and image classification [x is the original input data. The results of the simulation analysis between different numbers of perceptrons and the number of neuron nodes in this stage are shown in The expressions of the perceptual function fication –31:(1)QxQ′(x), the true degree matching function R(x), and effect analysis function T(x) are expressed asx is the original input data. The results of the simulation analysis of the relationship between the analysis strategy and the analysis quality factor for different dimensions in this stage are shown in As can be seen in As can be seen in s=. Thus, the neural network node function isIn the second step, a neural network node function is defined. We take a sequence of symphony types that conform to the algorithm rules s= symphonic performance object. The results of performing layer 1, layer 2, layer 3, and layer 4 variants areA, B, C) is the different variation rule. m is the n-dimensional information.The basic implementation of this step is as follows: neuronal encoding of the individual We then perform the regular recursive or neighborhood operation in the multilayer perceptron genetic neural network algorithm, such as swapping the last three, and then the variation results under 1, 2, 3, and 4 layer variation factors at this time areThe results of the simulation analysis of the relationship between different levels of variables and the effect evaluation index factors in this stage are shown in As can be seen in In this orchestral performance effect evaluation model, in order to make different types of evaluation methods to maximize the evaluation level of different orchestral music types based on the existing melodic timbre and characteristic information status in the process of orchestral performance, the orchestral performance effect evaluation model is optimized by combining neural network algorithm and greedy optimization rules, and its optimization analysis process is shown in The specific optimization process is divided into two steps.First, the existing level information of common symphony types is first used to determine the appropriate recursion strategy according to the corresponding feature values and adaptations to achieve random generation of initialized neuron nodes. When the linguistic feature values of any two symphonies in the group are not the same, it means that the performance performative melodies of the two symphonies are extremely different, and automatic separation is achieved to calculate the number of symphonies in the group, perform the recursive postadaptation values, and compare them with the feature values and adaptations of the next target to be tested for analysis. When the multilayer perceptron genetic neural network algorithm is processed in deep mining for different symphonic performances, it generates different similarities in the types of symphonic melodies corresponding to the expression methods of the symphonic performances.Second, in the optimization process of this multilayer perceptron genetic neural network algorithm-based orchestral performance effect evaluation model, the multilayer perceptron genetic neural network algorithm, in the actual evaluation process of a specific orchestral performance, transforms the timbral characteristics level information of the target orchestral performance type into computer-recognizable data information (such as vector groups and matrices) through specific processing, and then uses it in this process; the relationship between the different numbers of pointer patterns and the degree of difference of symphonic performance effect is shown in As can be seen in Assembling a comprehensive evaluation model based on symphonic performance analysis and symphonic performative melody analysis enables a more accurate assessment and analysis of the differences and characteristics of different types of symphonic music. Therefore, before conducting the experiment, a consistency assumption of noncore factors is required in order to reduce the interference of random factors.In the experimental design link, this evaluation model can carry out feature monitoring when obtaining feature information of different orchestral performances, then realize feature information extraction from the monitored data, carry out further study through the analysis process of melodies and evaluation carriers in the process of multiple orchestral performances, and, finally, through data analysis of dynamic detection and experimental process, compare with the feature values of the standardized analysis model to realize in evaluation in terms of core indicators. The format of the input data in this experimental process and the previous simulation analysis process is the data matrix filled by the quantitatively evaluated data vector group, which uses the function of how to extract the input data. The dimensions of the data matrix are dynamically adjusted . The input layer, hidden layer, and output layer have an upper limit of 100 nodes. In addition, the data intervals in terms of crossover rate and data mutation rate are both 0.2–1.0.In the evaluation session, the stored information about the characteristics of the symphony in terms of language and melody will be stored for further comprehensive evaluation of the quality of different vocal music analysis modes at a later stage, so as to achieve an intelligent analysis of the quality of symphony performance analysis and thus an objective evaluation under the innovative mode of symphony performance analysis based on the multilayer perceptron genetic neural network algorithm.According to the multiple influential indicators, it is possible to achieve the optimization and high-quality development of each vocal music analysis model scheme, to quickly enhance the data recording for each symphony type, and thus to achieve intelligent recording for different students. This orchestral performance evaluation model analyzes four indicators  for the first group of objects and the second group of objects, and the experimental analysis results of the deep recursive processing of neural networks at different levels are shown in As can be seen in The comparison results of the objective indexes for the evaluation of orchestral performance effects combining multilayer perceptron genetic neural network algorithm and intelligent fuzzy evaluation are shown in The analysis of the error degree of the results during the experiment under the multilayer perceptron genetic neural network algorithm is shown in From Therefore, combining the results of In order to better realize the quantitative evaluation enhancement of symphony performance effect, the innovation of the current symphony performance effect evaluation and analysis model in China is imperative. Based on this, this paper uses genetic neural network algorithm based on multilayer perceptron and fuzzy evaluation model and firstly selects three characteristic parameters related to symphony performance-related analysis and proposes an evaluation system based on the characteristic parameters of symphony performance effect. This orchestral performance effect evaluation model is evaluated from multiple perspectives by studying the type of orchestral performance, vocal playing ability, vocal coordination ability, audience evaluation effect, and timbre feature extraction analysis in the analysis process. The final experimental results show that the use of multilayer perceptron genetic neural network algorithm to characterize the effectiveness of the innovation model can achieve comprehensive evaluation. However, this study did not evaluate the effectiveness of specific types of orchestral performances in a targeted manner, so in-depth research can be conducted on the scope of application and customized analysis.


In the original article, there were errors in the text.Discussion, Future Direction. The corrected paragraph is shown below:A correction has been made to Several randomized control trials investigating the efficacy, safety, and utility of MMA embolization for cSDHs are underway . Additionally, various embolisates for MMA embolization are currently being studied. The SQUID Trial for the Embolization of the Middle Meningeal Artery for Treatment of Chronic Subdural Hematoma (STEM) is a randomized control trial that is investigating the safety and efficacy of SQUID for the management of cSDHS (61). Another embolisate currently being analyzed is Onyx, which is being evaluated in the Embolization of the Middle Meningeal Artery with ONYX Liquid Embolic System for Subacute and Chronic Subdural Hematoma (EMBOLISE) (62). Both of these trials are comparing medical management alone to MMA embolization, and surgical treatment with embolization to surgical treatment alone. Because the literature on MMA embolization of cSDHs includes a large number of patients who also received surgical intervention, randomized control trials will need to be conducted in a manner to also elucidate the appropriate patient selection for either MMA embolization alone or in combination with surgical intervention.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.


The use of principal component analysis (PCA) for soil heavy metals characterization provides useful information for decision making and policies regarding the potential sources of soil contamination. However, the concentration of heavy metal pollutants is spatially heterogeneous. Accounting for such spatial heterogeneity in soil heavy metal pollutants will improve our understanding with respect to the distribution of the most influential soil heavy metal pollutants. In this study, geographically weighted principal component analysis (GWPCA) was used to describe the spatial heterogeneity and connectivity of soil heavy metals in Kumasi, Ghana. The results from the conventional PCA revealed that three principal components cumulatively accounted for 86% of the total variation in the soil heavy metals in the study area. These components were largely dominated by Fe and Zn. The results from the GWPCA showed that the soil heavy metals are spatially heterogeneous and that the use of PCA disregards this considerable variation. This spatial heterogeneity was confirmed by the spatial maps constructed from the geographically weighted correlations among the variables. After accounting for the spatial heterogeneity, the proportion of variance explained by the three geographically weighted principal components ranged between 85% and 89%. The first three identified GWPC were largely dominated by Fe, Zn and As, respectively. The location of the study area where these variables are dominated provides information for remediation. Soil pollution; Heavy metals; Principal component analysis; Spatial heterogeneity; Geographically weighted principal component analysis The conThe sources of these metals in soils may be natural components or due to anthropogenic activities . HoweverDue to different sources of contamination, an assessment of soil heavy metal pollution may be difficult . In an aThe PCA has been widely applied for soil heavy metals pollution characterization and offers considerable benefits of understanding multiple sources of soil pollution . These bTo account for spatial heterogeneity in soil heavy metals data, the geographically weighted principal component analysis (GWPCA) was used. The use of the GWPCA does provides additional information which is obscured in the conventional PCA . For ins22.10 North and longitude 1.60 West of Ghana  with n representing the number of observations and p represents the number of individual variables. The The GWPCA which was introduced by fined as :(2)wij={o retain . The numo retain . With tho retain . The deci for two given variables . location, The outputs from GWPCA are extensive and provide detailed information which will be obscured in the conventional PCA. For example, a spatial map of the winning variable which corresponds to the variable with the largest absolute loading in each GWPCA can be used to describe the dominant variable in each component and where they are located. The spatial map of the cumulative proportion of total variance (PTV) gives information on where the PTV are highly concentrated. In addition, the spatial map of the GW correlation among the variables can be used to describe the interaction of the variables at distinct spatial locations. Similar to the conventional PCA, the geographically weighted correlation coefficient at location yi is defined as:R version 4.0.2  at the sampling points are presented in The results of the conventional PCA are presented in 3.2Following, the conventional PCA, the GW correlation was conducted to investigate the local relationship between the first three most correlated variables and determine if such relationship is heterogeneous in the study region. The results, as presented in Since three PCs accounted for 86% of the total variation in the data as observed in the conventional PCA, it was reasonable to retain these same three components for the GWPCA . The spaThe heavy metals dominating in each GWPC (winning variables) are presented in 4The characterization of heavy metal pollution in soil has increasingly become important to understand the sources of pollution and contamination. The present study explored the use of GWPCA as oppose to the conventional PCA to account for spatial heterogeneity and connectivity in soil heavy metals in Kumasi, Ghana. The results from the GWPCA confirm the existence of local relationship among the soil heavy metals in the study area. In addition, the distribution of these variables was found to be spatially heterogeneous in the study area. The identified GWPCs and the spatial distribution of their influential heavy metals can inform the future trajectory of soil pollution and contamination research, allowing for identification of different locations in which these are likely to manifest. The results also have policy implications to alleviate aspect of polluted areas. The use of GWPCA has improved the results of the conventional PCA by providing information on the spatial distribution of the percentage of variance explained in the data and also the distribution of the most influential metals in each identified principal components. Such information gives better understanding of the relationship between the different heavy metals and their distribution across the study area.Eric N. Aidoo: Conceived and designed the experiment; Performed the experiment; Analyzed and interpreted the data; Wrote the paper.Simon K. Appiah: Conceived and designed the experiment; Analyzed and interpreted the data.Gaston E. Awashie: Analyzed and interpreted the data; Wrote the paper.Alexander Boateng: Conceived and designed the experiment; Wrote the paper.Godfred Darko: Contributed reagents, materials, analysis tools or data.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.The authors do not have permission to share data.The authors declare no conflict of interest.No additional information is available for this paper.


Earlier research suggests that educational attainment up to early adulthood are crucial for the development of cognitive reserve, while intellectually stimulating activities later in the life course are of limited impact. We sought to explore the effects of educational attainment and occupational factors (occupation type and currently having work) across the distribution of cognitive performance for adults aged 45-65 years in South Korea. We analysed scores from the Korean Mini Mental State Exam (MMSE) provided in the 2006 wave of the Korean Longitudinal Study of Aging. We used quantile regressions to both investigate relationships across the distribution and to reduce bias for measures of the central tendency as the MMSE is known for its ceiling effects. The quantile function at the lowest conditional decile of MMSE scores suggested that education level was the dominant significant factor for adult performance on the MMSE . All occupational factors were non-significant. Further factors with a significant association with the MMSE were hearing loss, the log-transformed household income, and age squared. With the conditional median function, occupational factors became significant in the middle of the distribution but remained much less important than education levels. In summary, educational levels were more important to explain variation in cognitive functioning than occupational factors, echoing studies with Western samples. We discuss the findings with regard to the historically gender unequal educational and occupational opportunities in Korea.


The neuromuscular junction (NMJ) is a tripartite synapse in which not only presynaptic and post-synaptic cells participate in synaptic transmission, but also terminal Schwann cells (TSC). Acetylcholine (ACh) is the neurotransmitter that mediates the signal between the motor neuron and the muscle but also between the motor neuron and TSC. ACh action is terminated by acetylcholinesterase (AChE), anchored by collagen Q (ColQ) in the basal lamina of NMJs. AChE is also anchored by a proline-rich membrane anchor (PRiMA) to the surface of the nerve terminal. Butyrylcholinesterase (BChE), a second cholinesterase, is abundant on TSC and anchored by PRiMA to its plasma membrane. Genetic studies in mice have revealed different regulations of synaptic transmission that depend on ACh spillover. One of the strongest is a depression of ACh release that depends on the activation of α7 nicotinic acetylcholine receptors (nAChR). Partial AChE deficiency has been described in many pathologies or during treatment with cholinesterase inhibitors. In addition to changing the activation of muscle nAChR, AChE deficiency results in an ACh spillover that changes TSC signaling. In this mini-review, we will first briefly outline the organization of the NMJ. This will be followed by a look at the role of TSC in synaptic transmission. Finally, we will review the pathological conditions where there is evidence of decreased AChE activity. The overall organization of the neuromuscular junction (NMJ) contains three partners : (1) a nvia a collagen-like tail [collagen Q (ColQ)]. It should be noted that AChE anchored by ColQ is an enzyme that limits not only the lifetime of ACh in the synaptic cleft but also the spillover of ACh outside of the synaptic cleft.Synaptic transmission results in several sequential steps: (1) depolarization of the motor neuron membrane triggers the simultaneous release of dozens of vesicles filled with acetylcholine (Ach) and ATP; (2) synchronous activation of nicotinic acetylcholine receptors (nAChRs) clustered on the crest of the post-synaptic membrane that depolarizes the membrane and triggers an action potential; (3) termination of the action of ACh by hydrolysis with acetylcholinesterase (AChE) localized in the synaptic cleft and anchored in basal lamina In mammals, AChE and butyrylcholinesterase (BChE) are enzymes that hydrolyze ACh and have similar molecular forms , both coThe PRiMA/AChE that is presented at the NMJ can be produced by the motor neuron because in ColQ KO mice, which have only PRiMA/AChE, very fine staining of AChE was detected at the plasma membranes of the motor neuron but not at the surface of the muscle . HoweverButyrylcholinesterase (BChE) is also detectable at the NMJ , more spThese enzymes (AChE and BChE), localized and clustered in different compartments of the NMJ, efficiently eliminate ACh and thus prevent ACh spillover and limit the action of ACh to a single shot to the post-synaptic receptors.+ ions. When an action potential is generated, the accumulation of K+ ions released by nerve and muscle cells into the extracellular environment can lead to the depolarization of the cell membrane and consequent inactivation of Nav1.4 sodium channels. Thus, the timely removal by TSC K+ ions prevents the development of muscle fatigue . The short-term exogenous application of neurotrophin-3 or BDNF in newborn animals leads to an increase in the level of intracellular Ca2+ ions in the TSCs, which correlates with an increase in the release of ACh through the activation of presynaptic receptors of the tropomyosin receptor kinase (Trk)  into TSCs reduces the induced release of the ACh, while the microinjection of GDPβS  reduces the synaptic depression caused by high-frequency stimulation (In addition to controlling the concentration of extracellular Kse (Trk) . The conmulation .It has been shown that TSCs can influence ACh release from the motor nerve . Since a2+ in TSC  has been described (In response to the release of ACh, the release of Caescribed . HoweverIt is important to note that in general, the effect of the activation of mAChRs on ACh release in mammalian NMJs has been studied mainly in the presence of exogenous agonists , 2015 orThese mechanisms, demonstrated experimentally in the context of mature NMJ, are observable only after the inhibition of AChE and BChE. The depression of ACh release triggered by ACh spillover could be activated in physiological contexts where AChE density is significantly decreased. For example, during motor unit remodeling, some neuronal terminals are no longer connected to the muscle fiber that accumulates AChE and thus ACh spillover can be detected by TSC and thereby limit ACh loss. These mechanisms are useful during tissue remodeling and may accentuate pathological alterations in NMJ when the AChE level is reduced.To date, over 60 mutations have been identified in the human ColQ gene, all of which lead to a congenital myasthenic syndrome with endplate AChE deficiency . ColQ isThe C-terminal domain of ColQ interacts with the receptor tyrosine kinase MuSK, master organizer of NMJs , and couIn addition to these post-synaptic mechanisms, the probability of ACh release is changed in ColQ KO mice . During Around 5–15% of patients with myasthenia gravis carry autoantibodies directed against MuSK . It was The endplate AChE deficiency has been described in the mouse model of Schwartz-Jampel syndrome. It results from mutations of the gene encoding perlecan .It was shown that AChE deficiency contributes to NMJ dysfunction in a mouse model of type 1 diabetic neuropathy . DiabetiIn this mini-review, we have analyzed the function of cholinesterases in tripartite NMJ. In this light, AChE deficiency or inhibition results in an ACh spillover that can be detected by the TSC. Therefore, a better understanding of the molecular and cellular mechanisms of these communications could lead to the discovery of new possibilities for the development of therapeutic methods. On the other hand, the further study of pathological conditions associated with AChE deficiency could help to better understand the contribution of TSC to neuromuscular synaptic transmission.All authors contributed equally to the writing and editing of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The results of strain measuring experiments, with the help of rosettes consisting of fiber Bragg grating sensors (FBG) embedded at the manufacturing stage in a polymer composite material are considered in this paper. The samples were made by the direct pressing method from fiberglass prepregs. A cross-shaped sample was tested under loading conditions corresponding to a complex stress state. A variant of strain calculations based on experimental data is discussed. The calculations were performed under the assumption of a uniaxial stress state in an optical fiber embedded in the material. The obtained results provide a reasonable explanation of the absence in the conducted experiment of two peaks in the reflected optical spectrum, the presence of which follows from the known theoretical principles. The experimental result with two peaks in the reflected optical spectrum was obtained for the same sample under a different loading scheme. The proposed variant of the numerical model of the experiment and the results of numerical simulation made for FBG rosettes embedded in the material allowed to estimate error in the strain values calculated on the assumption of the uniaxial stress state in the optical fiber and in the presence of two peaks in the reflected optical spectrum. Fiber-optic strain sensors (FOSS) based on fiber Bragg gratings (FBGs) are currently considered one of the most promising sensitive elements for strain measurement . These eThe general solution to the problem of strain measurement by various sensors, including fiber-optic sensors, is associated with obtaining information about all components of the strain tensor. One way to solve this problem is to use special sensor layouts called rosettes ,4,5,6,7.Various works are devoted to the description of the strain measurement by rosettes made from Bragg grating sensors. One of the first is the work by , which pA number of works focus on studying the problems concerning the use of rosettes from FBG sensors and new possibilities of their practical application. In , FBG rosA number of works discuss technologies for creating sensor networks, including those with the implementation of FBG-based rosettes. An example of such studies is in work , which pOne of the key problems associated with application of FBGs embedded in the material is the evaluation of strains based on information about the registered physical quantity. The known relations establish the direct relationship between the measured strains and the readings of sensors only in the case of a uniaxial stress state in the location of the Bragg grating. In review paper , which eThe authors of  describeIn the present work, experimental results on the strain measurement by rosettes made from FBG sensors embedded in a polymer composite sample under a complex stress state are presented. The schemes and results of numerical simulation that interpret the experiment are considered. A variant of estimating error limits of strain, obtained using assumptions that allow calculating the strain values on the basis of measured physical quantities, is considered.A cross-shaped PCM sample was used in the experiment on strain measurements with the embedded fiber Bragg grating sensors arranged in a rosette configuration . A complThe selected shape of the sample, under the condition of elastic material behavior in the range of the tested loads, makes it possible to obtain experimental results for the complex stress state when tested on uniaxial tensile machines. This case was used in the present work. The equivalent of biaxial tension by forces PCM samples were manufactured by direct pressing method from 20 layers of fiberglass prepreg with the following mechanical properties: tensile modulus of elasticity along the warp direction A rosette consisting of three fiber Bragg grating sensors was embedded into the PCM during the technological process of material formation at the stage of stacking the prepreg layers on the molding tool. The sensor rosette was placed between the second and third layers of prepreg. The single-mode bend insensitive germanosilicate optical fibers of the SM1500(9/125)P series with photosensitivity were used. Silica glass optical fiber has the following mechanical properties: elastic modulus k method , followeThe main property of a Bragg grating consists in reflecting the part of a broadband optical signal transmitted through an optical fiber. The value of strains measured with the FBG sensors is obtained by processing information about the resonant wavelength of the reflected signal recorded by the interrogator. The resonant wavelength of the reflected signal is determined by the effective refractive index The interaction of the fiber-optic sensor with a deformable material causes the length of the Bragg grating to change, leading to a change in the resonant wavelength of the reflected signal. The relationship between the change in the resonant wavelength of the reflected spectrum and the strain of the fiber in the Bragg grating zone is determined by the relations :(2)Δλ1λ*12=0.270 .In the uniaxial stress state, the strains in the optical fiber, which does not interact with the environment, are, For used optical fibers, Relations (2) and (4) show that an unambiguous relationship between the experimental data on the change of the resonant wavelength of the reflected signal, and the component of the strain tensor in the fiber along its length, takes place only in the case of a uniaxial stress state in the region of the Bragg grating. In the general case, a complex stress state with three different components of the strain tensor: ss state . Despitess state . In addiRelation (2) shows that for fiber Bragg gratings embedded into the material in a complex stress state, there will be two resonant wavelengths of the reflected spectrum The tension is applied to the studied sample in direction 1 by gripping zones 1 and in direction 2 by gripping zones 2 . The loax, y, z axes The absence of two peaks in the reflected spectrum can be explained by the results of the following numerical experiments. Consider a PCM element shown in The presented results demonstrate that under loads acting along the optical fiber, in contrast to the load acting perpendicular to the fiber, a stress state close to uniaxial takes place in the zone of the Bragg grating. In this case, relation (2) shows that Known theoretical and experimental results have shown that embedding of an optical fiber in a PCM can produce a technological defect called a resin pocket . This deFor the refined PCM model with an embedded optical fiber and a region filled with matrix, the strains in the Bragg grating zone were calculated and the corresponding theoretical values of The obtained results show that in the case of applying loads along the optical fiber, value λ*  is less The difference between the theoretical values  surface , at a loTo obtain the strain values based on relation (4) for the sample subjected to tensile loading in directions 1 and 2, the maximum values of the resonant wavelengths in the reflected spectrum were used. For the loading scheme shown in For the sample under consideration, and equivalent loads applied in directions 1 and 2, the readings of sensors The obtained close values for strains This relation shows that the value of the angle These results demonstrate that when using rosettes embedded into the material, small errors in the information about the orientation angle of the sensors lead to an additional error in the determined strains.Relation (2), which determines the relationship between the strain tensor components in a fiber Bragg grating and the characteristics of the reflected spectrum, generally demonstrate the presence of two peaks in the spectrum. In the case of a uniaxial stress state in an optical fiber, relation (4) determines an unambiguous relation between the strain in the optical fiber and one resonant wavelength in the reflected optical spectrum. The assumption of a uniaxial stress state, which is used for strain calculations in an embedded optical fiber and the presence of two peaks in the reflected spectrum may cause a problem with their choice for relation (4).Numerical experiments can provide additional information on the error limits, in the case of using in relation (4) the information about each of the peaks in the reflected optical spectrum. A plate with an embedded rosette a is consThe results of the numerical experiments are the values of the characteristics of the reflected optical spectrum The values Analysis of the results of numerical experiments showed the fulfillment of one of the main properties of the rosettes, namely, the strain values Comparison of the strain values From the presented results, it can be seen that, according to (6), the error of the calculated values of strains is much less when Experimental and theoretical results on the strain measurement by FBG-based rosettes embedded into PCM are presented. The rosette was embedded into the material at the technological stage of its manufacturing by the method of direct pressing of fiberglass prepregs. A cross-shaped sample was loaded by forces applied in its plane in different directions. The strains were calculated based on the measurements of physical quantities of the reflected optical spectrum under the assumption of a uniaxial stress state in an optical fiber embedded in the material. The reliability of the presented results of strain measurements with FBG sensors is confirmed by satisfactory agreement with the results obtained by the VIC-3D optical system.In contrast to the theoretical results predicting the existence of two peaks in the reflected optical spectrum, the spectra obtained in the experiments only have one peak. To clarify this contradiction, the results of numerical simulations are presented, which qualitatively and quantitatively explain the difference between the theoretical and experimentally obtained values of resonant wavelengths of the reflected optical spectra. On the considered sample under loads acting perpendicular to the plane of the sample, a variant with two peaks in the reflected optical spectrum was experimentally obtained. The analysis of the obtained experimental results using numerical simulation methods shows that the error in the information about the angles of orientation of the sensors has a significant effect on the results of strain calculations based on the relations for rosettes. It should be noted that the numerical simulation conducted under the assumption of a uniaxial stress state in an optical fiber embedded in the material and the existence of two peaks in the reflected optical spectrum poses the problem of selecting one of them to calculate the strains. A numerical model of an experimental sample with an embedded rosette was developed. The numerical simulation results of the error in the strain calculations under the assumption of a uniaxial stress state in an optical fiber, as well as information on the theoretical reflected spectrum with two peaks, were analyzed. The obtained results demonstrate that information about one of the peaks provides a significantly smaller error in calculating the strain values. However, there were no adequate methods for selecting a peak, securing a smaller error in the strain values. Therefore, in the case when the reflected spectrum has two peaks, it is suggested that the strain calculations are made using their arithmetic mean value.


Self-assembled phospholipid bilayers are ubiquitous in biology and chemistry. In biological systems they constitute membranes that act as cell barriers that mediate the exchange of compounds, energy and information with the extra-cellular environement and essentially act as a host for membrane proteins that carry out a multitude of critical taks. In modern chemistry, self-assembled surfactant or lipid membranes in dispersed lamellar or non-lamellar phases  or bicontinuous microemulsions are frequently used in health care or consumer products to encapsulate and deliver active substances for controlled pharmacokinetics. Thanks to their generally well defined structure and properties, and using nature as an inspiration they can also be used to formulate nano-scale reactors for sustainable synthesis.Neutron scattering provides a unique view on nanoscopic and mesoscopic structure of self-assembled membranes, for example with Small Angle Neutron Scattering (SANS) in solution or with Neutron Reflectivity (NR) using contrast variation through deuterium labelling . ThermalContrast variation by deuteration in neutron scattering provides a tool to get insight into the properties of individual components in the liquid state on nanometer length scales that is not accessible through other techniques.The collection of papers in this issue only covers a fraction of the plethora of membrane properties that can be studied with state-of-the-art neutron scattering techniques.Sharma et al. ILs as solvents with increasing importance in chemical engineering processes of various kinds are generally toxic to living organisms. The article aims therefore in a better understanding of the interaction if ILs with lipid membranes by studying the influence of ILs on the membrane fluidity and molecular motion and learning in this way how to work with or use safely ILs. Quasi elastic neutron scattering was the method of choice to get insight into the molecular dynamics at the membrane-IL-interface.The interaction of ionic liquids (ILs) with cellular membranes is studied in the Article of LoRicco et al. with neutron diffraction. Apolar molecules stabilize the membrane of archea for survival in the most extreme conditions of high temperatures and pressures.A completely different environment is studied in the contribution of Engelskirchen et al. in view of understanding and improving lipase catalyzed reactions. Combining structural and spectroscopic investigations were essential for getting hints on the residence time of the lipase at the surfactant membrane.The interaction of lipase with microemulsion membranes has been investigated by Conn et al. to study membrane proteins, here in the bicontinuous cubic phase of phospholipid bilayers.The strength of neutron scattering in soft matter and biology is the accessibility to parts of a complex sample through contrast variation. This has been used by Thermally driven motion of membranes or incorporated proteins can be investigated with neutron spin echo (NSE) spectroscopy on nanometer and nanosecond length- and time-scales under physiologically relevant conditions. Subtleties of modern NSE experiments are discussed in the Article of Hoffmann.Jaksch et al., where, in combination with reflectometry, the influence of salt on phospholipid membranes is studied.An example of studies of the membrane dynamics with NSE is found in the contribution of Jakubauskas et al..Also plant cells contain membranes, and photosynthetic membranes are eminently important for nature and thus studied since long time. Combining different techniques such as microscopy and x-ray or neutron scattering provides an added value helping to understand nature, when the experimental results are properly modelled, as is shown in the paper of Waldie et al.).Use of  deuteration is a strong argument for neutron scattering techniques, which is applied for studying the interplay between high density lipoproteins (HDLs), cholesterol and the lipid membrane to help understanding the factors for deseases as Altzheimer’s or atherosclerosis in the article by Luchini et al. to characterize different preparation methods, an important prerequisite for reliable data analysis, and further on the existence of different lipid phases could be proven by the diffraction data attributed to the heterogeneity of their acyl chain composition. Using natural extracts with the ability of producing deuterated lipid mixtures plays again with the power of adjustable contrast for biological samples.Neutron diffraction on stacks of lipid multilayers allowed Krugmann et al. in order to investigate the nanoscopic details of the role of myelin basic protein in the formation of the sheath that wraps around axons. Combination of static and kinetic measurements together with theoretical arguments provide insights concerning the myelination process.Neutron reflectivity is mainly used in the contribution by Kinnun et al. highlights the advantages of contrast variation availiable in various neutron methods for accessing structural and dynamic information about the in-plane and out-of-plane structure of a variety of biomembrane systems.Finally the review article by With this research topic we hope to provide a useful and interesting overview over some recent advances in membrane studies with different neutron scattering techniques and to illustrate the potential of the different techniques of diffraction, reflectivity and spectroscopy measurements which allow together with the unique contrast variation possibilities with isotope substitution a nanoscopic view into the details of artificial and natural self assembled membranes.


Glomerulopathy is generic disease of the renal glomerulus, impairment of which can lead to hematuria or proteinuria due to injury or dysfunction of the endothelium, glomerular filtration barrier or podocyte . The NepThe most primitive ki dney was the pronephros, evolved as a urea-secreting organ in a multicellular animal  that wasDiagnosing pathology and assessing etiology on the basis of dysfunction of evolutionary adaptations is a promising approach to analyzing contemporary disease and injury . An evo-


This Research Topic represents a collaboration between the International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine (IFAPP) and Frontiers in Pharmaceutical Medicine and Outcomes Research aimed to create further awareness of Pharmaceutical Medicine (PM) as a profession and meet the new challenges of medicines development.The advancement in biomedical sciences extended the concept of medical products to including biological agents, gene and cell therapies as well as drug-medical device combinations. The development and application of these new products can be efficiently done only in complex, multidisciplinary teams combining the know-how of pharmaceutical physicians, clinical investigators, basic and applied bio-medical scientists and other non-medically qualified professionals.This Research Topic covers 11 articles focusing on the evolving challenges in medicines development as related to the standards for performing with competence and the application of ethical principles while working in the pharmaceutical industry, academia, research sites and regulatory agencies.systems approach integrating research into healthcare systems has been proposed to overcome the current barriers to a cost/effective cooperative process and appropriate management of the risks involved  with an urgent call to address these disparities using a multi-stakeholder approach and building consensus for change.However, a host of challenges confront healthcare authorities worldwide. The challenge is particularly great in therapeutic areas where, despite significant medical need and economic impact, the technical challenges and commercial risk of development serve as disincentives to sponsors. Currently the development and approval of new active substances, with its disproportionate focus on oncology and rare diseases is not in alignment with health care needs in most geographic regions. The origins of this misalignment and approaches to overcome this situation are discussed  indicating low and variable levels of perceived competence for the various domains regardless of the seniority in the job. Similar results were reported among individuals involved in clinical research . Core Competencies in Clinical Research have also been identified and proposed as a model for E&T and improving the quality and accountability for specific functions involved in the drug development process (Sonstein and Jones) including the challenges for implementation and lessons learned.The evolution of postgraduate vocational E&T in pharmaceutical medicine along with the development of the full set of core competencies  for pharmaceutical physicians and drug development scientists within the competence framework of seven domains are now established (Chisholm) whereas the process of adoption of the scope of the above Framework to reflect such roles in academic institutions or regulatory bodies in Switzerland is part of the lessons learned .Many of the disruptive forces affecting the healthcare industry today are also impacting education. The increasing voice of the patient and the rise of patient engagement in drug development are mirrored by the increasing student voice and student focus on education. The process for curriculum transformation from didactic to competency based programs in Pharmaceutical Medicine in Australia is thoroughly described  with recommendations to all other countries and institutions which may consider establishing this program.There is a growing consensus of the role of vocational training to gain competence . SpecifiBridges).Regulatory Affairs professionals play pivotal roles to ensuring healthcare products adhere to regulations and in gaining regulatory approvals for product manufacture and sales. Although they perform complicated work connected to the entire product lifecycle, only 14% of regulatory professionals come to the field with a degree related to the work  and moreKerpel-Fronius et al.) with the intention to provide recommendations to both professional groups to make joint ethical decisions during various situations occurring during clinical trials. Mutual trust and respect between the various experts is emphasized as the basis of effective multi-professional team work.The complexity of developing and applying increasingly sophisticated new medicinal products has led to the participation of many medical and non-medically qualified scientists in multidisciplinary non-clinical and clinical drug development teams worldwide. Revising the IFAPP International Code of Ethical Conduct for Pharmaceutical Physicians written in 2003, the Ethics Working Group prepared the IFAPP International Ethics Framework .These revised recommendations add to the list of Codes of Practice for pharmaceutical physicians prepared by professional organizations like the Faculty of Pharmaceutical Medicine, CIOMS and the World Medical Association. Jointly they provide clear and detailed guidance for correct behavior of pharmaceutical medicine experts in specific research situations .An alignment of the Declarations of Helsinki with that of the Declaration of Taipei is recommended for the better protection of both biological materials and data derived from clinical studies when their secondary use is intended. Furthermore, it is emphasized that any future plan for data and/or material sharing should be explained in the protocol, signed by the research participants and should be made publicly available (This Research Topic intended to create further awareness of the complex set of competencies and ethical considerations required for clinical drug development and the need to foster education and training at the undergraduate, postgraduate and continuing professional development levels to ensure the pharmaceutical industry is fledged with competent professionals able to bring better and valuable medicines to the market place and contribute to leveraged health in their communities.


Blood blister-like aneurysms (BBAs) are rare and usually appear at nonbranching sites in the supraclinoid portion of the internal carotid artery (ICA). Because it is difficult to obtain histological specimens of the aneurysm wall and because experimental models are challenging to establish, the pathogenesis of BBAs remains uncertain. In this paper, we reviewed the diagnostic, radiological, and pathophysiological characteristics of patients with BBAs. We also summarized the existing evidence and potential mechanisms related to the causes of BBAs. Current evidence indicates that atherosclerosis and dissection are the main prerequisites for the formation of BBAs. Hemodynamics may play a role in the process of BBA formation due to the unique vascular anatomy of the supraclinoid ICA. Further research on histopathology and hemodynamics is warranted in this field. Blood blister-like aneurysms (BBAs) usually appear at the anteromedial or anterior wall of the supraclinoid segment of the internal carotid artery (ICA) BBAs typically have a thin, fragile wall and unidentifiable neck In clinical practice, patients are usually diagnosed with BBAs due to the acute symptoms caused by SAH, and they typically have no complaints until rupture occurs From the digital subtraction angiography (DSA) images, a typical BBA is usually observed as a small irregular hemispherical protrusion on the anteromedial wall of the supraclinoid ICA. Sometimes, BBAs may be accompanied by dissection of the ICA; the lumen of the parent artery can be narrowed or dilated during angiography The diagnosis of BBAs should not be confirmed only by radiological images and clinical symptoms. Although the imaging manifestations of an aneurysm and the patient's clinical symptoms are consistent with the characteristics of BBAs, the pathological manifestations may be a true aneurysm Although numerous treatment strategies have been proposed, including microsurgery, endovascular treatment, and combined options, the optimal therapeutic strategy for BBAs is still under debate. Wrapping only has a limited effect on preventing postoperative re-rupture, and direct clipping carries a high risk of intraoperative rupture and subsequent ICA sacrifice From the endovascular treatment perspective, the small size and unidentifiable broad-based neck of BBAs limit the effectiveness of coil embolization Saccular intracranial aneurysms (sIAs) are pathological pouch-like dilatations of the intracranial arteries. Although BBAs can grow from a small protrusion to a saccular shape in a short period, the pathological features of BBAs are different from those of sIAs.Under normal physiological conditions, the intracranial artery usually consists of three layers Compared with the rarity of BBAs, sIAs are a common disease, with a prevalence of 5%-7% in the general population Therefore, a true aneurysm is formed by the gradual degeneration of the artery wall, and there are usually one or two layers of typical arterial structures in the aneurysm wall. BBAs cannot be considered an early stage of saccular aneurysm development. BBAs do not have a complete arterial wall and lack the IEL and media instead of having thin adventitia and fibrous tissue BBAs usually show a thin, fragile wall and unidentifiable neck from the intraoperative view; these features make it challenging to obtain a specimen of the aneurysm wall, and experimental models are difficult to establish Dissection weakens the artery wall, making it unable to resist hemodynamic stress and eventually leading to rupture of the artery wall Atherosclerotic remodeling, degeneration of the artery wall and loss of the IEL lead to the formation of BBAs There exist only a few reports of traumatic-related BBAs. Haji et al. sIAs commonly arise at the bifurcations of the cerebral arteries. In contrast, BBAs usually appear at nonbranching sites in the surpraclinoid portion of the ICA The large curvature of the carotid siphon is one of its essential characteristics. In a computational fluid dynamics (CFD) simulation study, high curvature tightness resulted in a significantly higher wall shear stress (WSS) on the outer wall than on the inner wall of the bend The OA is one of the main branches of the paraclinoid ICA. The branching vessels can affect the hemodynamic characteristics of the ICA trunk through shunting. Indo et al. In this study, we reviewed the diagnostic, radiological, and pathophysiological characteristics of patients with BBAs. We also summarized the existing evidence and potential mechanisms related to the causes of BBAs of the supraclinoid ICA. Current evidence indicates that atherosclerosis and dissection are the main prerequisites for the formation of BBAs. Hemodynamics may play a role in the process of BBA formation due to the unique vascular anatomy of the supraclinoid ICA. Overall, the pathogenesis of BBAs is not entirely clear and further research on their histopathology and hemodynamics is warranted.


To the Editor,Onishi et al. responded productively to our research by adding the importance of the relationship between symptoms and vitamin B1 deficiency.The vagueness of the symptoms regarding vitamin B1 deficiency can make the diagnosis of vitamin B1 deficiency challenging. As the authors of the letter suggested, Wernicke encephalopathy can be critical because of high mortality and is diagnosed on the basis of typical symptoms, blood tests, and magnetic resonance imaging.The perception and degree of symptoms can be dependent on patients’ background, clinical settings, and their help‐seeking behavior (HSB), which can make it difficult to investigate the relationship between symptoms and vitamin deficiencies. Older patients tend to experience symptoms in varying degrees because aging impinges on the sensitivity of perceiving symptoms.I appreciate the letter of the authors regarding the present challenges for the clarification of the relationship between symptoms and vitamin deficiencies. In the present era, aging societies can lead to the exacerbation of the prevalence of vitamin B1 deficiencies, which may drive the progression of dementia and frailty in future. Future studies should investigate the prevalence of vitamin B1 deficiency in various contexts and improve older people's HSB for improvements in their quality of life.The authors declare no conflicts of interest with regard to this article.


After this article  was publPLOS ONE website at the time of retraction.The authors requested that PLOS remove the article from online publication, and informed PLOS that the University of Ottawa library and representatives of Factiva (Dow Jones) had both requested this action. Following an internal assessment of this case, PLOS agreed to remove the article from the All authors agreed with retraction.


Our senses receive a manifold of sensory signals at any given moment in our daily lives. For a coherent and unified representation of information and precise motor control, our brain needs to temporally bind the signals emanating from a common causal event and segregate others. Traditionally, different mechanisms were proposed for the temporal binding phenomenon in multisensory and motor-sensory contexts. This paper reviews the literature on the temporal binding phenomenon in both multisensory and motor-sensory contexts and suggests future research directions for advancing the field. Moreover, by critically evaluating the recent literature, this paper suggests that common computational principles are responsible for the temporal binding in multisensory and motor-sensory contexts. These computational principles are grounded in the Bayesian framework of uncertainty reduction rooted in the Helmholtzian idea of unconscious causal inference. We receive sensory information from the environment and the body through several distinct senses. For a coherent and unified representation of information, our brain needs to group the multisensory features emanating from an object or event  for solving the causal inference problem  congruency between pairs of cues, and attentional allocation are all known to influence temporal perception  actions Buehner, , machineA number of recent studies have begun to investigate IB mechanisms from the perspective of Bayesian cue integration (Moore and Obhi, This review explored the temporal binding mechanisms in multisensory and motor-sensory contexts. By critically evaluating the recent empirical evidence, this paper suggests that the common computational mechanisms grounded in Bayesian causal inference models are responsible for the temporal binding in multisensory and motor-sensory contexts. Moreover, the extent of temporal binding depends on the strength of prior and the precision of sensory likelihoods. Future studies are required to understand the independent and interactive roles of multiple priors and sensory likelihoods on temporal binding across the multisensory and motor-sensory features.The author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In recent years, the development of interface debonding defect detection methods for concrete-filled steel tubes (CFSTs) using stress wave measurement with piezoelectric-lead-zirconate-titanate (PZT) actuator and sensor has received significant attention. Because the concrete core in CFSTs is a heterogeneous material with randomness at the mesoscale, the size, position and distribution of aggregates unavoidably affect the stress wave propagation and the PZT sensor response. In this study, to efficiently investigate the influence of the mesoscale structure of the concrete core of CFSTs on the response of embedded PZT sensors, a multi-physics substructure model of CFST members coupled with a PZT actuator and a PZT sensor, where a single circular aggregate with different size and position and randomly distributed circular aggregates are considered, are established first. Then, multi-physics simulations on the effect of the local mesoscale structure of the concrete core on the response of the embedded PZT sensor excited by both a sinusoidal signal and sweep frequency signal are carried out. Moreover, corresponding multi-physics and mesoscale simulations on the embedded PZT sensor response of substructures with different interface debonding defects are also carried out for comparison. The amplitude and the wavelet packet energy of the embedded PZT sensor response of each mesoscale substructure are employed to distinguish the influence of the concrete core mesoscale structure and interface debonding defect on sensor measurement. The findings from the results with the multi-physics coupling substructure models are compared with those of the full CFST-PZT coupling models and the tested members of the previous studies to verify the rationality of the embedded PZT sensors measurement of the established substructure models. Results from this study show that the effect of interface debonding defect on the amplitude and the wavelet packet energy of the embedded PZT sensor measurement of the CFST members is dominant compared with the mesoscale heterogeneity and randomness of the concrete core. As a typical concrete-steel composite structure, concrete-filled steel tube (CFST) members have been widely used as significant vertical and axial load-carrying members in long-span bridges and super high-rise buildings due to their advanced mechanical behavior under strong dynamic loadings, such as earthquakes, where the confinement effect of the steel tube on the concrete core plays a key role. However, the possible interface debonding defect between the concrete core and the steel tube has been a common concern due to shrinkage or apparent hydration heat. This is because the interface debonding defect weakens the confinement effect of the steel tube on the concrete core and finally leads to a negative effect on the load-carrying capacity, the stiffness and the ductility of CFST members. Therefore, it is particularly critical to develop effective interface debonding defect detection approaches for CFSTs .In recent years, non-destructive testing (NDT) techniques, including the acoustic echo method, electromagnetic method, infrared thermal imaging method, ultrasonic method and the X-ray method have been proposed to detect different defects, including cracks and debonding between concrete and rebars in reinforced concrete (RC) structures ,3,4,5,6.Investigation of the mechanism of defect detection for complex structures, including CFST members using PZT patch actuation and sensing technologies, is desired. Recently, numerical simulations on the stress wave propagation and the response of the PZT sensor embedded in or bonded on different structural members have been carried out to investigate the defect detection mechanism using stress wave measurements. The concrete core in most of the CFST numerical studies on stress wave propagation is usually modeled as a kind of homogeneous material ,8. In faEven though a variety of mesoscale modeling methods for the purpose of numerically investigating the effect of the mesoscale structure of concrete on both local and global behavior of concrete materials and structures have been proposed ,16,17,18PZT materials have been used as either actuators or sensors for defect detection of different engineering structures. A low frequency bending piezoelectric actuator with integrated ultrasonic non-destructive evaluation (NDE) functionality was embedded in a composite laminate to detect damage using ultrasonic pulse excitation qualitatively . In ordePerera et al. ,27 used Most recently, in order to consider the mesoscale structure of the concrete core of CFST members, Xu et al.  first peIn this paper, in order to efficiently investigate the influence of the mesoscale structure of the concrete core of CFST members on the output voltage response of the embedded PZT sensor and to compare it with that of the interface debonding defect, the multi-physics mesoscale simulation on the stress wave propagation of a substructure of CFST-PZT coupling models, considering different circular aggregate size, position, distribution and interface debonding defect, are carried out. The proposed mesoscale CFST-PZT coupling substructure model can not only study the influence of the mesoscale component, including aggregate dimension, position and distribution between the PZT actuator and embedded sensor on the response of the embedded sensor, but can also significantly improve the simulation efficiency.In the mesoscale and multi-physics simulation on the stress wave propagation of the substructure, both sinusoidal excitation signals with different frequencies and sweep excitation signals are considered. The effect of the size, position of a single circular aggregate and the distribution of circular aggregates on the embedded PZT sensor response and the corresponding wavelet packet energy of healthy CFST members are investigated in detail. Then, the effect of the size, position of a circular aggregate and the distribution of circular aggregates on the embedded PZT sensor response and the corresponding wavelet packet energy of the corresponding CFST members with interface debonding defects are demonstrated and compared. Finally, the effect of the mesoscale structure of the substructure on the response of embedded PZT sensors is compared with the interface debonding defect and the finding from the numerical results with the substructure proposed in this study is compared with that of the previous experimental study by the authors. The rationality of the proposed mesoscale substructure model for stress wave propagation is demonstrated. Mesoscale substructure simulation results show that the mesoscale structure of the concrete core has a certain effect on the embedded PZT sensor response, but the effect of the interface debonding defect on the embedded PZT sensor measurement is dominant. The results imply that the interface debonding detection approach with stress wave measurement for CFST members is reasonable even though the concrete core is a heterogeneous material.t is the time variable, The control equations for elastic stress wave propagation simulation in a solid medium excited by a PZT actuator are shown in Equations (1)–(5) ,38,39,40The direct and inverse piezoelectric effects of the PZT sensor and actuator are considered in the coupling model composed of PZT patches and CFST members. The mechanical balance equation of PZT patches is consistent with the force balance equation of conventional solid materials except for the stress tensor shown in Equation (6).The charge conservation equations of the PZT material in the electrostatic effect are shown in Equations (7)–(11) ,38,39,40Different from the previous multi-physics mesoscale simulation studies by Xu et al. ,36, in tThe low reflection boundary condition used for the substructure of the CFST member coupled with the PZT actuator and sensor meets the following Equations (12) and (13) ,30,31.The steady output voltage amplitudes of the embedded PZT sensor of the mesoscale substructure coupling models showed that the size, lateral and longitudinal positions of a single aggregate and the aggregates distributions differently affected the response of embedded PZT sensor of the mesoscale substructures without the interface debonding defect under continuous sinusoidal excitation signal. The effect of the size, lateral position of a single aggregate and the aggregates distributions on the response of embedded PZT sensor of the mesoscale substructure without interface debonding was limited, but the aggregate longitudinal position had the most obvious influence.(2)The effect of the size and position of a single aggregate and the distribution of aggregates on the response of the embedded PZT sensor of the mesoscale substructure coupling models with interface debonding defect was comparatively limited when compared with that of the mesoscale substructures without the interface debonding defect under sweep frequency excitation signal. The existence of interface debonding defect led to an obvious decrease in the output voltage amplitude of the embedded PZT sensor no matter what size and position of the single aggregate and distribution of aggregates were considered.(3)The wavelet packet energy of the embedded PZT sensors is also dominantly affected by the interface debonding defect rather than the mesoscale structure of the concrete core of the substructure coupling models with different single aggregate sizes, positions and aggregates distribution. Additionally, the length of the interface debonding defect had an obvious effect on the wavelet packet energy of the embedded PZT sensor in the mesoscale substructure coupling models and its wavelet packet energy of the models with the interface debonding defect was always much lower than that of the healthy substructure.In this study, a multi-physics simulation with mesoscale substructures of CFST-PZT coupling models composed of a surface-mounted PZT actuator, an embedded PZT sensor, aggregate, mortar and a steel tube was carried out, and the effect of the size, lateral and longitudinal positions of a single aggregate, the distribution of aggregates and the interface debonding defect on the response of the embedded PZT sensor was investigated in detail with the proposed mesoscale substructure coupling models. The output voltage response of the embedded PZT sensor of different mesoscale substructure coupling models without and with debonding under a continuous sinusoidal excitation signal or sweep frequency excitation signal was discussed. Based on the multi-physics mesoscale simulation results on each substructure, the following conclusions could be drawn:In this study, the distance between the PZT actuator and the PZT sensor was constant. In order to demonstrate the effect of the measuring distance between the PZT actuator and sensor on the embedded PZT sensor of the mesoscale substructures without interface debonding defect, further investigation on the response of the output voltage signal of the PZT sensor with different measuring distances could be carried out in future. Moreover, the mesoscale structure of concrete with aggregate shapes other than the circular shape can also be considered further.


Teaching Point: In the absence of a clear history of trauma, avulsion of the lesser trochanter should raise a high index of suspicion of an underlying malignancy. Figure 1, arrows). The initial diagnosis of an avulsion fracture of the lesser trochanter was made, in accordance with the professional activities of the patient. Because of aggravating pain and the onset of nightly pain, a follow-up radiograph was performed a few weeks later, showing an expansile radiolucency of the lesser trochanter with an adjacent layered periosteal reaction at the medial cortex of the proximal femoral diaphysis . These findings were suggestive of an aggressive osseous lesion. Repeated MRI showed an osseous lesion causing destruction of the medial cortical bone and a large soft tissue component posteromedial the proximal femoral diaphysis. There was heterogeneous enhancement of the mass . Perilesional edema was present in the iliopsoas and vastus intermedius muscles. The combination of the age of the patient, the absence of a history of trauma, and the aggressive appearance of the osseous lesion with a large soft tissue component was suspicious for Ewing’s sarcoma. After histopathological confirmation, the lesion was treated with neoadjuvant chemotherapy, followed by resection of the proximal femur shaft and placement of a femoral prosthesis. Further follow-up was uneventful.An 18-year-old cyclist was admitted to our hospital for spontaneous onset pain in the left groin for the past months. Computed tomography (CT) showed a fracture at the lesser trochanter of the left femur, which was confirmed on the subsequent magnetic resonance imaging (MRI) (Ewing’s sarcoma is a highly aggressive neoplasm and the second most common bone tumor in children and adolescents with a peak incidence between 10–20 years. The metaphysis of the long bones is most involved (80%), and the femur is the most affected (25%) [Location in the lesser trochanter may rarely mimic an avulsion fracture. The imaging appearance of Ewing’s sarcoma is highly variable and often presents as a large permeative lesion, with lamellated periosteal reaction. Conventional radiography shows an aggressive osteolytic lesion. Computed tomography (CT) is more sensitive for the detection of bony destruction in more complex regions. Magnetic resonance imaging (MRI) is the modality of choice for evaluating local tumor extension and staging. Typically, there is bone marrow replacement with heterogeneous enhancement and a large soft tissue mass. Systemic chemotherapy is the keystone in treatment; additional surgery or radiotherapy can be performed depending on the location and size of the lesion.Underlying malignancy should be excluded in case of avulsion fracture of the lesser trochanter, particularly in the absence of trauma.


The SARS-CoV-2 pandemic has swiftly and firmly implanted itself within our communities and countries. Multiple countries have faced numerous waves of the virus and have paid the price with death counts totalling in the hundreds of thousands, and globally now millions. The novel nature and rapidity of the SARS-CoV-2 spread throughout the globe has resulted in health institutions finding themselves in a quagmire as they battle with the lack of the necessary equipment but more importantly battle the lack of an established and universally accepted treatment protocol for the COVID-19 infection [The drugs thus used throughout the progression of the pandemic have varied and waivered as more research and data for better treatment of the infection has become available. Corticosteroids are however, one such group of drugs that are almost always a constant among most treatment regimens and protocols. The off label use and implementation of various regimens and high doses of certain drugs have led to some deleterious adverse effects .Corticosteroids and immunosuppressants of such a nature have long been used in viral infections and have been a mainstay in the treatment protocol and regimens used in COVID-19 patients. Popular corticosteroid drugs and therapies that are being prescribed in patients suffering from COVID-19 are dexamethasone, methylprednisolone and or hydrocortisone with IV (intravenous) and/or oral administration. The use of such high doses of corticosteroids have shown very positive results and have been lifesaving in many cases . The basCorticosteroid therapy has a multitude of side effects and they vary dependant on the dosing, duration and potency of the particular species being prescribed. When used in short durations at high doses the side effects may vary and include hypertension, electrolyte abnormalities, cutaneous effects, pancreatitis, hematological dyscrasias, hyperglycemia, neuropsychologic and immunological adverse effects . In the Reports have surfaced with new side effects developing in patients post recovery from COVID-19 infections. Severe systemic mucormycotic infections causing orbital compartment syndrome and severe multiorgan infections have been partially attributed to the extensive use of systemic corticosteroids in the treatment of the initial COVID-19 infection. A factor further superadded to the complications experienced is the fact that the majority of patients being treated with corticosteroids have pre-existing conditions and severe comorbidities. The nature of these pre-existing conditions are often exacerbated and accelerated via the use of the lifesaving steroid treatment. A textbook example being the reduced and worsened glycaemic control in diabetic patients whom are treated using corticosteroids ,9.As in the case of mucormycotic infections and their relationship with the immunosuppressive nature of corticosteroid therapy used in the treatment of COVID-19; a rise in cases of avascular necrosis of the femoral head is being reported and is being attributed to the sustained and aggressive corticosteroid therapy being implemented ,11.The severe and life-threatening nature of the COVID-19 infection, the ARDS (acute respiratory distress syndrome) as well as the cytokine storm induced by the infection, commands lifesaving high doses of steroid therapy. As in all pharmacological therapies adverse effects are present. One such adverse effect which is being reported is corticosteroid induced avascular necrosis of the femoral head/ osteonecrosis of the femoral head (ONFH) .The mechanism by which steroids induce avascular necrosis of the femoral head is underpinned by the collective actions of the drug therapy. It must be noted that AVN principally affects the femoral head and most commonly the anterolateral aspect thereof as it is the crux of weight bearing. Corticosteroids induce fat mobilization and this thus innately enhances the likelihood of fat emboli developing from the liver to occlude minor blood vessels in the femur, this thereby compromises the microvascular environment. Superadded to this the steroid therapy disrupts calcium metabolism and homeostasis which induces hypertrophy in the intramedullary fat cells, Gaucher cells and inflammatory cells; whilst increasing the activity of osteoclasts, thus increasing bone resorption and decreasing calcium uptake and deposition; ultimately leading to an insufficiency in the trabecular and cortical bone. This insufficiency thus equates to an increased intraosseous pressure which impedes intramedullary circulation and results in avascular necrosis .Agarwala et al, conducted a study on three cases whom had recovered from COVID-19 after being treated with corticosteroid therapy and subsequently developed AVN. The patients were found to be prescribed a mean dose equivalent to 758mg of prednisolone. The patients were subsequently symptomatic with bilateral femoral hip pain. The great importance of this study is that the patients were diagnosed with AVN after receiving a dosage much lower than the 2000mg equivalent ceiling which current guidelines dictate to avoid AVN. Superadded to this; it was noted that the patients presented with the features of AVN at a mean of 58 days after their initial COVID-19 diagnosis and treatment. This is in contrast to the current literature which states that AVN takes 6 months to 1 year to develop post corticosteroid therapy ,17.It has been long established that steroids induced AVN, however reports of AVN developing rapidly in COVID-19 patients post treatment where specific treatment guidelines to avoid steroid induced AVN have been adhered to suggest that the COVID-19 infection itself may also be instrumental in the development of AVN and that steroid use is not the sole benefactor to inducing AVN post steroid therapy ,16.Current guidelines suggest that a cumulative ceiling dose of 2000mg of prednisolone or its equivalent should not be breached in order to prevent the development of AVN, however as seen in the research conducted by Agarwal et al it is evident that AVN is being induced in patients treated far below the 2000mg ceiling. It is thThe use of steroid therapy in COVID-19 is invaluable and lifesaving in nature. The adverse effects of such steroid therapy are however profound and well established. It is evident that avascular necrosis is directly caused by high dose steroid therapy, however the case reports have very clearly indicated that the rapid onset of AVN post recovery from the COVID-19 infection cannot be solely attributed to steroid therapy and that another benefactor induced by the COVID-19 infection is at play. It is thus vital for treating physicians to take cognisance of this adverse effect post recovery and therefore should ensure that prophylactic bisphosphonate therapy is initiated timeously and congruently.


Temporo-mandibular joint (TMJ) joint and the condyle of mandible are observed in the radiographs of the skull and the jaw. Therefore, it is of interest to assess the predictability of four different shapes of condyle in skeletal class I, II and IIImalocclusion. The four commonly visualized shapes are oval, bird beak, diamond and crooked were assessed using an ortho pantomogram (OPG). Each of the malocclusion was visualized for different shapes of the condyle. 987 OPGs were radiographically evaluatedand the morphology of 1974 condylar heads was visualized. The shapes of the condyles were grouped under four different types. Data shows that oval shaped condyle was most common followed by bird beak. There was variability in the diamond and crooked shape andwas lesser than the other types. Thus, the shapes of the condyle are useful predictable guide in deciding the nature of the occlusion. Temporomandibular joint (TMJ) is a ginglymoarthroidal joint that is formed by articulation between two bones, the condyle part of mandible and glenoid fossa at the base of the skull . The variation and the pattern noticed among individuals in the morphologicalvariations in the condyle and the fossa has now become an area of research . The treIn literature there are various studies that have assessed the various condylar morphology. There is difference in condyle morphology in various malocclusions. There are variations in male and female with men having a larger condyle than woman. The malocclusionthat has a major change in the condyle is the transverse malocclusion. Another important finding Tadej et al had pointed out was the medio-lateral dimension as compared to anterior- posterior  . SeymouThe predictability of condylar morphology is of significant importance. Data showed that all three types of skeletal malocclusion I, II and III, the oval shaped condyle was found to show the maximum occurrence. The next common shapes are diamond and bird beakand the crooked shaped condyle is the least common. There was no significant difference between the left and right side of the condyle. Results of the study suggest that reasonable predictability of condylar morphology with nature and any deviation from the ovalshape would require the need for further investigation with relevance to any clinical significance.


Breast carcinoma metastasis can involve any ocular structures, but involvement of the optic nerve is extremely rare. Choroidal metastasis is usually multifocal as well as bilateral and occurs late. We report an unusual initial presentation of metastasis from breast cancer; unilateral infiltrative optic neuropathy with concurrent choroid metastatic deposits in an adequately treated middle-aged female. Our present case, wherein for the first time in the literature, we illustrated unilateral infiltrative optic neuropathy and choroidal metastatic deposits secondary to breast carcinoma, will increase our knowledge about the various potential ocular presentations of this relatively common malignant disease. A 41-year-old woman with a history of invasive ductal type of adenocarcinoma of her right breast presented with diminution of vision in the right eye of 15 days duration. The diagnosis of her right-sided stage IIIc breast carcinoma was made 6 years ago when she developed a lump and pain in the right side of her chest. She subsequently underwent a right-sided modified radical mastectomy followed by eight cycles of chemotherapy and external beam radiation of the thoracic wall. She remained stable thereafter and presented with diminution of vision in the right eye, six years after initial diagnosis of breast cancer.On evaluation, the best corrected visual acuity (BCVA) was 3/60 in the right eye and 6/6 in the left eye. Examination of the right eye was completely unremarkable except for the presence of a relative afferent pupillary defect (RAPD). There was also the presence of trace vitreous cells on the anterior vitreous surface in the right eye. Fundus examination of the right eye revealed a diffuse enlargement of the optic disc, and disc oedema with splinter haemorrhages in the surrounding retina (blue arrow) suggestive of optic nerve infiltration. There were multiple, homogenous, creamy yellow lesions with interspersed alterations of the retinal pigment epithelium along the supero-temporal vascular arcade (yellow arrows) associated with serous detachments of the fovea characteristic of choroidal metastatic deposits (Figure 1A In view of the patient’s present condition, her past history of breast cancer, optic nerve head infiltrative and characteristic choroidal metastatic features on fundus examination, and imaging findings, the diagnosis of infiltrative optic neuropathy with concurrent choroidal metastasis of the right eye secondary to breast carcinoma was made. The patient was referred to an oncologist to rule out other system involvement and necessary interventions.Metastatic tumor is the most common ocular malignancy, and uveal tissue is the most favored site where cancer metastases develop . The oveOptic nerve head involvement in metastatic disease of the breast is seen in less than 5% of all intraocular metastases; appearing as a diffuse enlargement of the optic disc in about 84% of cases with a degree of secondary disc oedema and splinter haemorrhages [Optic disc infiltration is known to occur either due to direct extension of a choroidal tumor which is located close to the optic disc, or due to a spread of neoplastic cells to the circulation of the optic nerve head by blood route . The hemTo conclude, breast carcinoma is a relatively common source of ocular metastasis and can have varied presentations depending on the site of metastasis. Unilateral infiltrative optic neuropathy with concurrent choroidal deposits as initial manifestation needs to be considered as differential diagnosis and potential cause of severe diminution of vision due to metastasis in patients of breast carcinoma.The authors declare that they have no competing interests.