Background: To study the effect of allogeneic umbilical cord mesenchymal stem cell transplantation on the structure and function of the thymus in aged C57 mice and provide a new method for the treatment of senile thymic atrophy.Results: The changes in the thymus cortex and medulla volume and the lymphocyte ratio were analyzed by immunofluorescence. For thymus tissue sections, immunohistochemical staining was performed to detect p16, p53, SOD, becline1, LC3b, p62, sirt1, and sirt3. Changes in CK5, CK8, CD4 and CD8 expression were observed. Treatment with mUCMSCs could promote hair regeneration in aging mice and regenerate the thymus structure.Conclusions: mUCMSCs inhibited senescence of the thymus and promoted structural and functional thymus regeneration by downregulating the senescence genes p53 and p16 and upregulating the SOD, Sirt1 and Sirt3 genes, but the mechanism requires further research.7 cells/kg twice per week for 3 weeks. Six weeks after the last transplantation, the thymus was weighed, and the thymus-to-body weight ratio was calculated. The thymus tissue was stained with HE.Methods: C57 mice were obtained and met the requirements of thymic aging. mUCMSCs were infused via the tail vein at a dose of 1×10 The immune system consists of immune organs, immune cells and immune molecules. Its functions include identifying and excluding antigenic foreign bodies and coordinating with other systems of the body to maintain the stability and physiological balance of the internal environment. As a central immune organ in the human body, the thymus is important for maintaining the stability of the immune system. However, the thymus is age-sensitive and is one of the earliest organs to age and atrophy in the human body. Therefore, whether it is possible to regenerate the thymus to slow its aging and shrinking is an important question.As a site of T cell development and maturation, the thymus often undergoes atrophy due to aging. The loss of thymocytes and destruction of the thymus structure caused by thymus atrophy reduce mature T cell output and limit T cell receptor (TCR) diversity. Maintaining normal thymic function is critical for reducing the morbidity and mortality of various clinical conditions, including infection and transplantation , 2.The mammalian thymus is generally divided into two leaves, and each leaf is divided into the central medulla and peripheral cortex. The main constituent cells are thymic stromal cells (TSCs), epithelial Mo-MΦ cells, delayed reaction T cells (TDCs), fibroblasts, and thymocytes. The thymus is at its largest and in its most active periods before birth and during puberty. After these periods, it gradually shrinks and is replaced by fat.+ T cell counts and intracellular GSH levels and decreased plasma levels of HIV RNA [The thymus is mainly composed of hematopoietic thymocytes and nonhematopoietic thymic epithelial cells (TECs) . To prov HIV RNA , which d HIV RNA . 2. Cyto HIV RNA , 11. 3.  HIV RNA . HoweverThe thymic microenvironment consists primarily of TECs and cells of mesenchymal origin. TECs are important in almost all stages of thymocyte development. The mesenchyme is involved in the functional development of epithelial cells and the maintenance of epithelial structure and function. The mesenchyme has been shown to be necessary for the successful reconstruction of thymus tissue . MesenchThis study aimed to systematically demonstrate the improvement of senile thymic atrophy induced by administration of MSCs in naturally aging C57 mice to provide a solution for the treatment of clinical thymic atrophy. This study provides additional experimental evidence for the clinical application of MSCs.Gross view with the naked eye: white hair appeared in C57 mice at 18 months of age , and theThe thymus weight, body weight, and thymus/body weight ratio of C57 mice are shown in After HE staining, the tissue was observed by inverted microscopy. (1) HE staining of the thymus in 2-month-old C57 mice: A thin connective tissue envelope was observed on the surface of the thymus tissue, the thymocyte leaflet interval was not obvious, and the cortex and medulla were clearly defined. The thymus cells in the cortex were dense, and its coloration was deeper. The medulla contained more TECs and had lighter coloration. A large thymus were observed in young mice . (2) HE The umbilical cord tissue pieces were inoculated in a 10 cm culture dish based on the characteristics of adherent mUCMSC growth. After 1 day, the cells were observed climbing out of the dish . After 6The cells obtained by adherent culture of umbilical cord tissue were long, spindle-shaped and fibroblast-like . After cCD29, CD90 and CD34 antibodies were used to label C57 mouse umbilical cord tissue adherent culture cells. The positive proportion of CD29 cells was 99.6% , and theGross view with the naked eye: The model control group showed white hair and partial hair loss on the back . The haiGross view with the naked eye: The thymus in the young control group was yellowish in color, soft in texture and normal in size. The thymus color in the treatment group and the model control group was darker, and the volume was reduced. The volume of the treatment group was significantly larger than that of the model control group . AccordiAfter HE staining, an inverted microscope was used to make observations. (1) The thin layer of connective tissue was visible on the surface of the thymus tissue of the young control group. The thymocyte leaflet interval was not obvious, the cortex and medulla were clearly defined, and the thymus cells in the cortex were dense, so the coloration was deep. The medulla contained more TECs, so the coloration was lighter, and the appearance of the thymus was consistent with that observed in young mice , 9B. (2)Cytokeratin 8 (cK8) and cytokeratin 5 (cK5) are markers of the thymic cortex and medulla, respectively, as shown by the results of thymus staining with immunofluorescent antibodies . (1) The+ and CD8+ cells in the thymus of the model control mice was low  , 7. The By comparing the levels of LC3b, becline1, P62 and other proteins that characterize the level of autophagy in the thymus, we found that the expression of LC3b, becline1, and P62 in the thymus tissue of the treatment group was increased to different degrees compared with that in the other groups. The LC3b activity was lowest in the young control group and highest in the treatment group, and the model control group showed intermediate activity  young c young c  The thymus volume of the C57 mice in the treatment group was significantly larger than that in the model control group. The thymus index was calculated and statistically analyzed. The mean value of the thymus index was compared . However, according to HE staining, the thymus tissue structure of the treatment group was significantly restored compared with that of the model control group. The thymus cortex structure of the model control group was unclear with respect to quality, and no glandular structure was observed. (2) The thymic medulla and cortex were labeled with the keratin antibodies ck5 and ck8, respectively. The statistical analysis showed that the cumulative optical density (IOD) of CK5 expression in the thymic medulla of the model control group was higher than that of the young group (p< 0.01). This result indicated that the density of epithelial stromal cells expressing CK5 in the medulla was increased, the proportion of epithelial stromal cells was increased, and the proportion of lymphocytes that did not express CK5 was decreased. This suggested that the size of the thymic medulla in C57 mice increases with age, the proportion of lymphocytes decreases, and the proportion of thymic medulla stromal cells increases. The expression level of CK5 in the thymus of the treatment group was lower than that of the model control group (p<0.01), indicating that the proportion of lymphocytes that do not express CK5 in the medulla of the senile mice increased after mUCMSC treatment, and the total number of cells as well as the thymus volume increased. CD4 and CD8 immunofluorescence staining revealed a thymic cortex with lymphocytosis. This indicates an increase in the number of lymphocytes that accumulated in the medulla. This suggested that mUCMSC treatment can promote lymphocyte homing to the medulla of aged mice or promote their proliferation in the medulla. The expression of CK8 in the thymic cortex of the model control group and the treatment group was higher than that of the young group. This suggested that the proportion of thymic cortex stromal cells expressing CK8 increases with age, and the proportion of lymphocytes in this region decreases. Compared with that in the model control group, the thymus CK8 expression in the treatment group was higher than that in the model control group (p>0.05), suggesting that the proportion of thymic cortical stromal cells after treatment of elderly mice with mUCMSCs was not significantly changed. The ability of mUCMSC treatment to increase the proportion of lymphocytes in the thymic cortex of aged mice was not obvious. In summary, mUCMSCs can improve senile sensitization, mainly by increasing the proportion and number of lymphocytes in the medulla of mice. mUCMSC treatment can promote lymphocyte homing to the medulla of aged mice or promote proliferation in the medulla region.+/CD8+ ratio decreases with age, which is mainly due to the rapid increase in the number of CD8+ cells, and the CD4+/CD8+ ratio in adulthood increases. This shows that young children and seniors show an immune imbalance. In the former, this reflects immune immaturity, and in the latter, this reflects weakened immunosuppressive function.How do mUCMSCs regenerate the thymus structure of aged C57 mice? A literature review showed that the percentages of lymphocyte subpopulations vary with age. The evidence shows that the changes from childhood to adulthood proceed as follows: the CD4+ T and CD8+ T cells in the treated group was significantly higher than that in the model control group, and the increase in CD8+ T cells was the most obvious. The change in the mUCMSC transplantation group compared with the model control group indicated that mUCMSC transplantation can restore the distribution of lymphocyte subsets from the old age state to the youth state. Intact thymus tissue was digested with type II collagenase into a single-cell suspension. The proportions of the T lymphocyte subsets were analyzed by flow cytometry, which showed that the number of CD4+ T and CD8+ T cells was increased significantly in the treated group compared with the model control group. The most obvious increase was observed in CD8+ T cells. The results obtained by fluorescence staining of CD4 and CD8 antibodies were consistent. Therefore, we asked whether these changes suggest that the mouse thymus tissue changes to a young state after mUCMSC transplantation.Therefore, we asked whether mUCMSCs also change the proportions of different subpopulations of lymphocytes in the thymus. In this study, fluorescence staining with CD4 and CD8 antibodies revealed that the number of CD4By immunohistochemical detection of P53, P16, SOD1, Sirt1, Sirt3 and other aging proteins, we found that the expression of p53 and P16 protein in the thymus of the treated group increased (p>0.05). The levels of SOD1, Sirt1, Sirt3 and other proteins with anti-oxidative stress and anti-aging functions increased to different degrees in the treatment group (p>0.05). This suggests that the degree of aging in tissues is reduced, indicating that treatment with mUCMSCs can confer a certain degree of anti-aging activity. p53 can cause endogenous apoptosis by activating proapoptotic genes . mUCMSCsBy comparing LC3b, becline1, P62 and other proteins that characterize the level of autophagy in the thymus, we found that the expression of LC3b, becline1 and P62 in the thymus tissue of the treatment group was increased to different degrees compared with that in the other groups. The LC3b activity was the lowest in the young control group and was the highest in the treatment group, and the model control group showed intermediate activity  young c young c .Pregnant C57 mice, which were raised in the SPF animal laboratory of the 920For the P4 generation mUCMSCs, the growth morphology during culture was observed under an inverted microscope. The positive expression rates of CD29, CD90 and CD34 in mUCMSCs were analyzed by flow cytometry. Using the induced differentiation assay kit, adipogenic, osteogenic and chondrogenic differentiation was performed according to the instructions of the manual, and the differentiation potential was identified.The C57 mice that met the requirements of thymic aging in the previous screening were randomly divided into the treatment group and the model control group. At the same time, 2-month-old C57 mice were used as the youth control group, with 15 mice in each group. They were all kept in the SPF animal laboratory.7 cells/kg twice a week (Monday and Thursday) for 3 weeks; the other 2 groups were injected with an equal volume of normal saline. After routine feeding and daily recording of mouse activity, the mice were sacrificed by cervical vertebra dislocation 6 weeks after the last transplantation, and the efficacy and mechanism were evaluated.For the experimental group, P4 generation mUCMSCs were infused through the tail vein at a dose of 1×10After assigning the mice to different groups, images were obtained under the same lighting conditions, and the average grayscale value of the head, back and hip in the photos was measured and tested by one-way ANOVA. The thymus specimens were arranged in groups and photographed. The body weight of each mouse and the corresponding thymus weight were recorded. The thymus index was calculated, and one-way ANOVA was performed.C57 mice were sacrificed by cervical dislocation. The abdominal cavity was cut open and cut along the rib cartilage on both sides to the upper edge of the thoracic spine. The thymus was exposed. After weighing and comparing the photos separately, the thymus was fixed with 4% paraformaldehyde. The thymus tissue was collected, embedded in paraffin, sectioned, and stained with HE. The changes in the tissue structure were observed under a light microscope.2). The positive cell density (n/mm2) was determined. The expression of CK8, CK5, CD4, and CD8 in the thymus was scored.A portion of the thymus was fixed with 4% paraformaldehyde, embedded in paraffin, sliced, and subjected to immunofluorescence staining. The green/red fluorescent nuclei with the same labeling were selected by ImagePro Plus 6.0 software as the unified standard for judging all photopositive cells, and each photo was analyzed to obtain the number of positive cells in each field of view , and independent samples were analyzed by t tests. Statistical comparisons between groups were tested by one-way ANOVA. P < 0.05 indicated a significant difference.The C57 mouse model with thymic atrophy showed partial whitening, shedding, alopecia areata, slow movement, decreased activity, atrophy of the thymic gland, disappearance of the medullary gland-like structure, and increased expression of the p53 and P16 genes.C57 mouse mUCMSCs with different growth characteristics, immunophenotypes and differentiation potential in accordance with UCMSC standards were prepared.After treatment with mUCMSCs, the thymus volume of the mice increased, the weight increased, parts of the thymic structure regenerated, the number of lymphocytes in the thymic medulla increased, and the functioning of CD8+ T cells improved.mUCMSCs inhibit the expression of the aging-related genes p53 and P16 by promoting the expression of autophagy- and anti-oxidative stress-related genes, such as LC3b, becline1, P62, SOD1, Sirt1 and Sirt3, thereby increasing the level of autophagy in the thymus tissue, inhibiting apoptosis and exerting therapeutic effects on thymus atrophy.th Hospital of the PLA Joint Logistics Support Force.The experimental protocols were approved by the Experimental Animal Ethics Committee of the 920


Video-based techniques for identification of structural dynamics have the advantage that they are very inexpensive to deploy compared to conventional accelerometer or strain gauge techniques. When structural dynamics from video is accomplished using full-field, high-resolution analysis techniques utilizing algorithms on the pixel time series such as principal components analysis and solutions to blind source separation the added benefit of high-resolution, full-field modal identification is achieved. An important property of video of vibrating structures is that it is particularly sparse. Typically video of vibrating structures has a dimensionality consisting of many thousands or even millions of pixels and hundreds to thousands of frames. However the motion of the vibrating structure can be described using only a few mode shapes and their associated time series. As a result, emerging techniques for sparse and random sampling such as compressive sensing should be applicable to performing modal identification on video. This work presents how full-field, high-resolution, structural dynamics identification frameworks can be coupled with compressive sampling. The techniques described in this work are demonstrated to be able to recover mode shapes from experimental video of vibrating structures when 70% to 90% of the frames from a video captured in the conventional manner are removed. Ensuring the reliable operation of critical infrastructure is going to require that we have persistent, autonomous sensing and analysis solutions. These analysis solutions must be capable of detecting, localizing and quantifying the structural integrity of large-scale infrastructure in harsh environments such as marine structures  over many length scales from the crack size up to the size of an entire wind farm. Mission-ready solutions for these problems do not currently exist. State-of-the art structural health monitoring solutions are expensive to install, do not have the spatial resolution to detect small, but potentially catastrophic, damage in large-scale structures ,2, and rPhotogrammetric experimental mechanics techniques that make use of digital imagers hold a lot of promise for structural health monitoring applications primarily because the measurements taken by imagers is inherently 2 dimensional. One of the main reasons being that it is much easier to get dense sensor coverage of a 3-dimensional structure using 2-dimensional sensing techniques as opposed to the 0-dimensional nature of contact sensors such as strain gauges or accelerometers. Furthermore, the recent emergence of 5G networking capabilities ,17,18 anFull-field, high-resolution, unsupervised learning-based structural dynamics identification frameworks based on decomposition algorithms such as principal components analysis and blind source separation have recently emerged as an alternative, non-contact optical measurement methods to achieve full-field, high-resolution structural dynamics measurements, which may significantly improve structural dynamics analysis and health monitoring. A recently proposed method , termed It is of note that the video of vibrating structures is inherently very sparse. Typically video of vibrating structures has a dimensionality consisting of many thousands or even millions of pixels and hundreds to thousands of frames. However, the motion of the vibrating structure can be described using only a few mode shapes and their associated modal coordinates. This means that the video measurement potentially contain large amounts of redundant data that increase the computational demand for video dynamics processing.ℓ1-minimization optimization problem, which exploits the sparsity of the signal over an appropriate dictionary of signals . The compressive sampling approach is applicable to the modal analysis problem, since the targeted monotone modal responses are spectrally most sparse over a Fourier representation, which is maximally incoherent with the non-uniform random sensing space.In this study we explore emerging techniques for sparse and random sampling such as compressive sampling (CS) ,43,44 toThis work presents how full-field, high-resolution, structural dynamics identification frameworks based on decomposition algorithms such as principal components analysis and blind source separation can be naturally and intimately coupled with compressive sampling techniques. The resulting low-data rate, random sensing framework can be summarized as follows. First, during the image/frame acquisition step, the frames are acquired using a conventional, uniform frame-rate imager. Next, frames are randomly selected for removal. The low-rate randomly sampled time series of motion for the pixels observing the motion of the vibrating structure are then directly decoupled by using principal component analysis and blind source separation algorithms, resulting in the recovery of a mode shape matrix, as well as the decoupled low-rate random samples of the modal coordinates. From the low-rate random samples of each modal coordinate, the L1 minimization recovers the original high-rate modal response, thereby enabling estimation of the frequency and damping ratio. Using this approach the mode shapes can be obtained directly without any change to the blind-source separation procedure for modal identification. However, if the modal coordinates are desired, an L1 minimization problem must be solved for each modal coordinate which requires knowledge of the measurement matrix. It is also possible to perform the L1 minimization step after using PCA and prior to performing blind source separation. The second approach tends to result in better performance, but it requires solving an L1 minimization problem for each PCA component retained to obtain both the mode shapes and modal coordinates. Solving these L1 minimization problems also requires knowledge of the measurement matrix. Both approaches will be demonstrated in this work. It must be noted that in this work, frames are captured from a conventional uniform frame rate imager and then frames are randomly removed. However other hardware or software process that results in frames randomly captured in time could also be analyzed using the techniques presented in this work.The contributions of this work include the presentation of a technique for reconstruction of mode shapes and modal coordinates from randomly sampled frames using L1 minimization. Another contribution is the demonstration that algorithms that solve the blind source separation problem can directly recover high-resolution mode shape information from randomly-sampled frames of video of vibrating structures without conventional L1 minimization, without knowledge of the measurement matrix, and without temporal order. A mutual-information-based algorithm for detecting and removing corrupted frames from video that would otherwise disrupt modal identification is presented. Finally, a relationship between structural dynamics, compressive sampling and cryptography is presented to illuminate a path toward privacy-preserving structural health monitoring and process monitoring. This work demonstrates that by using compressive sampling it is possible to reduce the number of frames needed to perform blind-source separation-based structural dynamics identification by about an order of magnitude. As a result, the approach described in this work is very attractive for deployment on video-based wireless sensor nodes for structural health monitoring. The output-only modal analysis algorithm for extracting full-field, high resolution structural dynamics information from video of vibrating structures can be summarized as follows , with FiConvert the intensity measurements at each pixel into a quantity that maps to the displacement at each pixel. This transformation can potentially be accomplished in a variety of ways. For in-plane motion, phase-based optical flow ,52,53, pPerform principle components analysis (PCA) across all of the displacement time series at each pixel in order to reduce the dimensionality of the data. It is expected that the number of non-trivial eigenvalues calculated from the displacement time series for each pixel generated from a video of a vibrating structure will be of the same order as the number of mode shapes that are observable from the displacement time series. For this reason it is only necessary to retain the number of top eigenvectors that correspond roughly to the number of non-trivial singular values. It is important to note that the principle components that are calculated in this step correspond to time series of displacement captured by the pixels in the image. Because principle components are eigenvectors these displacements are scaled arbitrarily. There are no strict units of measure associated with the principle components at this step. This step is illustrated in We now take advantage of the observation that the canonical form of the blind source separation problem has exactly the same form as the linear, multi-degree-of-freedom, structural dynamics equations when written in the modal form ,55. If tAn additional, accessible summarization of these steps without the compressive sampling component can be found in . After aA more detailed overview of the steps in the algorithm for extracting full-field, high resolution structural dynamics information from video of vibrating structures without the compressive sampling component will now be provided. The pre-processing component  is primaThe boxes with dashed lines with the labels “scramble,” and “unscramble,” indicate the points in the algorithm where scrambling of the order of the pixels would take place in the event it is desired to perform privacy-preserving structural identification. The dimensionality reduction and blind source separation process  is the pVideo reconstruction  is the pCompressive sampling theory has had a large impact on the fields of applied math, signal processing, and statistics over the last decade. The reason for the large impact is that compressive sampling techniques allow for high-fidelity reconstructions of signals from fewer samples than the Nyquist sampling criterion would suggest. This means that less energy and bandwidth is required to capture, analyze and transmit data. It also means that memory requirements are reduced for storing data. In the context of the structural health monitoring problem, compressive sampling suggests approaches that could be used to reduce the energy consumption of sensor nodes deployed in the field to measure structural response. In turn this reduction in energy would lead to longer-lifetimes for the structural health monitoring sensor nodes. These advantages become even more clear if compressive sampling can be effectively applied to video-based sensor networks for structural health monitoring. This is because processing video typically requires significantly higher computational resources than processing conventional time series. This is the result of video having higher dimensionality than time series. Tutorials that provide a good overview of compressed sampling theory can be found in ,62,63. Fx can be represented in a compressed form over some domain Ψ. Here a signal is considered compressible when the number of significant, non-zero elements in s is equal to K, and K<<N. K is referred to as the “sparsity” of the signal. A signal that is pure Gaussian noise is an example of a signal that would be excluded from consideration for compressed sampling. We now produce compressed sampling coefficients y by introducing a measurement matrix “Φ.”Here Ψ is an orthonormal basis and “s” is the coefficients of the signal over the Ψ basis. For compressed sensing applications we only consider the case where K<<N it is possible to reconstruct x from y assuming the measurements matrix possesses the restricted isometry property (RIP) and there exists a basis over which x is sparse  before adding the noise. After the addition of the noise samples, the noisy images were rescaled back to the original RGB scale of 0–255 and converted back into integers. Impulsive salt and pepper noise with a density of 0.05 was also considered. The density of 0.05 indicates that 5% of all the pixels in the randomly selected frames are replaced by either 0 or 255. Generally this noise occurs during the analog-to-digital conversion process, as a result of damage to the pixels. Finally, video frames corrupted by Poisson noise, also known as photon shot noise, were generated. Poisson noise is distinguished from the previous types of noise, in the sense that the noise is produced such that it is proportional to the image intensity. Poisson noise was also applied to the randomly selected frames.Videos of the cantilever beam corrupted by the four types of noise previously described were generated. The videos were generated such that 1.0%, 10%, 25%, 50%, 70%, 90%, 95%, and 99% of the frames were randomly selected and corrupted by noise. Throughout this paper results are presented for multiple values of frames being randomly removed in order to provide information on the robustness of the technique and to demonstrate where the performance drops off. The normalized mutual information was then calculated by the frames and the sum of the normalized mutual information was taken across all the frames. An example of a plot of the normalized mutual information for the video with 10% of the frames in the video corrupted by Gaussian noise is shown in Now that a technique has been developed for detecting the presence of randomly corrupted frames in the video of vibrating structure, we now show techniques that allow these frames to be removed from the video and still perform full-field modal identification. These techniques also work for the case where frames are simply randomly removed from the video of the vibrating structure. In this section, the techniques rely on the use of L1 minimization algorithms as is typically found in compressive sampling problems. As a result the measurement matrix indicating how frames have been removed must be known. Now a technique is demonstrated for performing modal identification on video with frames randomly removed, in such a way that the mode shapes can be recovered without any need for knowledge of how the frames are randomly removed , nor with any need for L1 minimization. In this approach knowledge of the measurement matrix is needed if a proper estimate of the modal coordinates is desired. It is worth noting that the modal identification results obtained when L1 minimization is not used are not as high of quality as those obtained when L1 minimization is used after the PCA step. However, these results are still noteworthy because they do not require any knowledge of how the frames are randomly sampled , and these results demonstrate that L1 minimization is not needed to implement compressive sampling on video when all that is needed is the mode shapes of the vibrating structure. These results could possibly lead to new insights for compressive sensing hardware for structural dynamics as well as new possibilities for privacy-preserving structural health monitoring. The previous section exploited the fact that the high-resolution mode shape information is a consequence of the mixing relationship between the pixel time series to show that mode shape information can be recovered from randomly sampled frames without any need for knowledge of the mixing matrix or the use of an L1 regularization algorithm to recover the mode shapes. The mixing relationship between the time series is preserved regardless of whether or not some of the frames are missing. An astute observer will also notice that the mixing relationship in the classical incarnation of the blind source separation problem is also invariant with respect to time. Theory would suggest that the temporal order of the frames could be completely shuffled and frames could be randomly removed, and it would still be possible to recover vibration mode shapes only using solvers for the blind source separation problem. To check the viability of this hypothesis the order of the frames in the video of the vibrating cantilever beam were randomly shuffled and then frames were randomly removed. The videos were then subjected to the full-field, high resolution decomposition algorithm for modal identification. The modal assurance criterion values for the mode shapes recovered from the randomly shuffled and randomly sampled videos are found in A careful examination of the blind-source separation approach for full-field, high resolution modal identification reveals that it is also possible to randomly shuffle the order of the pixels (after the motion detection step) and still obtain the same mode shapes and modal coordinates assuming a list of the pixel shuffling indices is maintained to rearrange the randomly shuffled mode shape back into the original pixel space at the end of the analysis. This is because no spatial information is needed for obtaining the mode shapes. The mode shapes are found using only the mixture matrix that relates the modal coordinate time series to the projection of the measured time series onto the dimensionality reduction matrix associated with the principle components analysis step. In fact unlike the case of randomly shuffling the frames, no degradation in performance is observed when randomly shuffling the pixel order. It is currently hypothesized that the degradation in performance associated with the random shuffling of the frames is an artifact of the numerical technique (complexity pursuit), used to find the solution to the blind source separation problem. It is possible that solutions to blind source separation exist or can be developed that mitigate the loss in performance, but finding such a technique can be considered in future work.The fact that randomly shuffling the spatial pixel order does not impact the ability to extract mode shapes and modal coordinates opens up some interesting possibilities for enabling privacy-preserving structural health monitoring and process monitoring. The problem of taking the randomly shuffling pixels and trying to rearrange them back into the original images is an example of the computational problem known as the “jigsaw puzzle problem.” It is actually a very extreme form of the jigsaw puzzle problem because the picture is broken down all the way into individual pixels. It has been shown that the jigsaw puzzle problem is NP-complete . This suThis work presents techniques for combining random sampling techniques with full-field high-resolution modal identification algorithms for purposes of data compression, denoising and privacy-preservation. A normalized mutual information technique is presented for detecting the presence of corrupted frames so they can be removed from consideration during modal identification. The paper presents a technique for recovering mode shapes from randomly sampled frames from video of vibrating structures that involve the use of L1 minimization algorithms as are typically used in compressive sampling as well as a technique that does not require L1 minimization. The paper also presents two strategies for recovering modal coordinates from randomly sampled frames from a video of a vibrating structure using L1 minimization algorithms. Interestingly, the results of this work suggest that under noisy field conditions it is generally conservative from the perspective of the MAC values of the mode shape estimates to remove frames from video that might be corrupted rather than to possibly allow them to remain and corrupt the modal identification analysis. Finally, the paper demonstrates how mode shapes can be recovered from randomly sampled, and shuffled frames captured from a video of a vibrating structure. The paper presents the reader with information on the tradeoffs in performance that are associated with the different approaches to using compressive sampling for video dynamics techniques in order to better select a specific approach for a given structural health monitoring application. The results of this work point to future applications such as privacy-preserving structural health monitoring, reducing phototoxicity/photobleaching effects during imaging of live cells for biological applications, and data compression for long-term monitoring of critical infrastructure such as wind turbines and bridges. This work also provides a path forward for research into learning high-dimensional models from small numbers of training examples.An interesting feature of the structural dynamics system identification technique presented here is that the unsupervised learning takes place directly over data that is represented in the randomly subsampled Dirac basis. It is shown that system identification can take place over far fewer samples than would be captured using conventional sampling schemes. This observation is important because contemporary deep-learning techniques tend to require large amounts of training data to achieve high levels of performance. Compressive sampling techniques combined with unsupervised learning may provide a path toward more general learning schemes that do not require large amounts of training data. The techniques described in this work are demonstrated to be able to recover mode shapes and modal coordinates from experimental video of vibrating structures when 70% to 90% of the frames from a video captured in the conventional manner are removed. The ability to remove such large percentages of frames and still be able to recover mode shapes makes blind source separation–based modal analysis techniques particularly attractive for deployment in video-based, low-power, wireless sensor networks that utilize emerging 5G network communication infrastructure for structural health monitoring applications. These techniques help work toward enabling video-based wireless sensor networks for structural health monitoring applications in real-world environments because the compression offered by the techniques in this paper greatly reduce the amount of data that potentially needs to be transmitted to central servers or cloud computing resources that aggregate data from across the sensor network. The results are lower bandwidth requirements, and less energy consumption associated with transmitting the data. Furthermore, the demonstrations of randomly shuffling the order of the pixels and the frames provide the ability to perform structural identification in a privacy-preserving mode which enhances the security of the over-all structural health monitoring system which is an important issue when monitoring critical infrastructure. Security is a known concern with emerging high-performance 5G networks, and these concerns must be addressed for critical infrastructure monitoring applications. This work also point to a path forward for learning high-dimensional models from a small number of training examples.


The boot camp aims to aid the progression of urology trainees. However, as a very new junior doctor I felt the opportunity to be involved in a training program would benefit my own growth as a doctor.1,2The urology boot camp is a 5-day course for doctors who are in their first year of surgical training for urology . During the course they take part in practical simulations, comprised of eight modules spanning technical and non-technical skills and covering the 12 As the junior doctor, I was part of the simulation, and was directed to be disruptive to the ward round to see how the delegate would respond. Of course, this added an extra element of pressure to the simulation but a pressure that does reflect the realities of working in a team.My role during this week was to facilitate the non-technical skills module which involved a simulated ward round, I would take the role of a first year junior doctor, whilst we saw a number of patients (actors) with urological problems led by the urology trainee doctor (delegate). We were accompanied by a nurse, health care assistant and another delegate acting as a second junior doctor. During the ward round the delegates had to deal with a number of realistic interruptions which included bleeps from various other wards requesting help; patients becoming acutely unwell; and other staff members trying to persuade the delegate to go elsewhere instead of the post-take ward round such as clinic.3,4 hence my apprehension towards this part of the job is unlikely to be unique as a newly qualified doctor. By helping at the urology boot camp, I was hopeful that it would help me become more confident and find ways to be more successful in this part of my role.Ward rounds are one of the most important aspects of a junior doctor’s role within the multidisciplinary team. During medical school, students take part in these regularly as part of their placement. However, this did not stop me from feeling apprehensive when as a junior doctor, I experienced my first surgical ward round. As seen in previous studies, final year medical students are often not confident in actively taking part in ward roundsThe scenarios were common urological problems that my team would often face, and the many interruptions are frequent occurrences that have to be dealt with by myself and my seniors. Observing my seniors manage the patients and distractions during the simulation, often in very different but effective ways, helped me to consider how I would act under the same stressors during a busy ward round. I was able to highlight actions I thought were done well and responses I felt could have been done differently. I even had the chance to feed this back during the debrief sessions after each delegate had been observed.A very positive part of the day for me was realising how important we are as junior doctors in ensuring a smooth and effective ward round. When I was playing a more disruptive and unhelpful junior doctor it led to the lack of cohesiveness within the team. In particular it created a much more difficult time for the urology trainee trying to manage the patients as well as the distractions. During the times that I was more helpful and take initiative to contribute more, the trainee would often give me feedback that it was a much more positive experience and they felt I eased a lot of the pressure they were feeling during the simulation. This contrast highlighted the importance of my actions during the simulations.The reason I found this so positive is that as the most junior member of the team it was easy to forget that you can be an asset and that people still value your opinion and help, despite being much less experienced than they are. Through the usual busy working day, people are often too busy to give feedback or thank you for your help. However, taking part in the boot camp reminded me that my role is valuable and can help to ease the pressures that my seniors face. This indirectly contributes to improved patient care. Being part of this simulation helped me consider how training for final year medical students leading up to the first day on the ward could be improved. At medical school I did take part in a number of simulations, however, they mainly focused on emergency situations focusing on the A to E approach to patient management.Placements are the best opportunity to take part in a ward round, but as the surgical round is so quick I think medical students shy away from taking an active role such as writing in notes as they do not want to slow the ward round down. The main issue here is that although observing a ward round is useful, more active participation, a hands-on approach, is the best way to learn and contribute.3-5 There is lack of consensus regarding how best to prepare doctors transitioning from medical school to the clinical environment5 and the approach taken in the urology boot camp is one I think could be adopted in training. The simulated ward round highlighted the need for 1st year junior doctors to become more proficient in being part of a surgical ward round.More training for final year medical students and new doctors is required to make them better prepared for ward rounds.


Such tasks also become more difficult as background noise levels increase. To overcome these difficulties, hearing aids (HAs) offer noise reduction (NR) schemes. The objective of this study was to investigate the effect of NR processing . The participants were instructed to listen to a target talker in front while ignoring a competing talker in front in the presence of multi-talker background babble noise.The results show that the neural representation of the attended speech envelope was enhanced by the active NR scheme for both background noise levels. The neural representation of the attended speech envelope at lower (+3 dB) SNR was shifted, approximately by 5 dB, toward the higher (+8 dB) SNR when the NR scheme was turned on. The neural representation of the ignored speech envelope was modulated by the NR scheme and was mostly enhanced in the conditions with more background noise. The neural representation of the background noise was modulated  by the NR scheme and was significantly reduced in the conditions with more background noise. The neural representation of the net sum of the ignored acoustic scene  was not modulated by the NR scheme but was significantly reduced in the conditions with a reduced level of background noise. Taken together, we showed that the active NR scheme enhanced the neural representation of both the attended and the ignored speakers and reduced the neural representation of background noise, while the net sum of the ignored acoustic scene was not enhanced.Altogether our results support the hypothesis that the NR schemes in HAs serve to enhance the neural representation of speech and reduce the neural representation of background noise during a selective attention task. We contend that these results provide a neural index that could be useful for assessing the effects of HAs on auditory and cognitive processing in HI populations. Selectively attending to a target talker while ignoring multiple interferers is more difficult for hearing-impaired (HI) individuals compared to their normal-hearing (NH) peers and becomes more difficult with increased background noise levels. To overcome such difficulties, hearing aids (HAs) offer noise reduction (NR) schemes. Here we aimed to investigate the effect of NR processing on the neural representation of speech envelopes across two different background noise levels by using a stimulus reconstruction (SR) method. The electroencephalogram was recorded while 22 HI participants fitted with HAs were performing a listening task. The participants were instructed to listen to a target talker in front of them while ignoring a competing talker also in front in the presence of multi-talker background babble noise. Measures of neural representation for the envelopes of the attended speech, the unattended speech, and the background noise were calculated separately. The results show that the neural representation of the attended speech envelope was enhanced by the active NR scheme for both background noise levels. The neural representation of the attended speech envelope at low signal-to-noise ratio (SNR) was shifted, approximately by 5 dB, toward the higher SNR when the NR scheme was turned on. The neural representation of the ignored speech envelope was modulated by the NR scheme and was mostly enhanced in the conditions with more background noise. The neural representation of the background noise was modulated by the NR scheme and was significantly reduced in the conditions with more background noise. The neural representation of the net sum of the ignored acoustic scene  was not modulated by NR scheme but was significantly reduced in the conditions with a reduced level of background noise. We conclude that, during a selective attention speech task, the active NR scheme enhanced the neural representation of both the attended and the ignored speakers and reduced the neural representation of background noise, while the net sum of the ignored acoustic scene was not enhanced. We contend that these results provide a neural index that could be useful for assessing the effects of HAs on auditory and cognitive processing in HI populations.Natural speech communication with multiple concurrent talkers requires a listener to be able to selectively attend to a talker while ignoring interfering talkers or background noise . BehavioTo compensate for the hearing impairment, aided hearing offers various advanced signal processing methods for digital noise suppression. Such noise reduction (NR) processing aims to reduce the level of interfering background noise to improve the signal-to-noise ratio SNR; . Previouvs. competing talker(s) during active listening , and magnetoencephalography (MEG), have demonstrated a strong attentional modulation of cortical responses by the substantial selective enhancement of neural responses to an attended talker istening . This stThree inter-related computational strategies to characterizestimulus–response correlation have been proposed in the literature . First, Stimulus reconstruction has several advantages over the other methods to shed light on the neural mechanisms being targeted by hearing aids (HAs). First, it has been investigated in an extensive body of auditory literature in recent years. Second, the estimated neural representation of the speech envelope (reconstructed speech envelope) may uncover information about the perception and the processing of speech signals such as speech intelligibility , focusedYet, to the best of our knowledge, there have not been attempts to evaluate the potential benefits of HAs equipped with NR schemes on selective auditory attention in complex settings that resemble everyday noisy social situations. The NR schemes in HAs may greatly benefit the HI listener’s ability to focus attention selectively by suppressing undesired background noise that is not the focus of attention. By improving SNR, fast-acting NR algorithms make the attended and the ignored talkers in front more audible, which could help the HA users to voluntarily switch attention between competing talkers while simultaneously suppressing background noise. This suggests that changes in NR processing in HAs may result in changes in the neural representation of speech envelopes.Importantly, fast-acting active NR processing may enhance selective auditory attention by enhancing the strength of the neural representation of the foreground (attended and ignored) talkers while ensuring that the neural representation of the background noise is suppressed when compared to the inactive NR processing. Additionally, associated with the neural representation of the ignored talker and the ignored background noise, the net sum of the ignored acoustic scene outside of the primary focus of the listener’s attention  should not be enhanced, i.e., either reduced or unchanged. Taken together, compared to inactive NR processing, fast-acting NR processing may be advantageous in that it may contribute to the improved “neural SNR,” which means that the fast-acting active NR processing may enhance the EEG responses to the attended talker while either reducing or keeping unchanged the EEG responses to the background noise and the ignored acoustic scene.Therefore, to test the feasibility of quantifying the user benefits of NR schemes in HAs, inspired by a previous study with normal-hearing (NH) listeners , we condThe NR scheme used in the present study improves the SNR of speech coming from the two foreground loudspeakers  by predominately attenuating the background noise coming from the four background loudspeakers. The back-facing cardioid was used to determine the levels and the spatial locations of noise and speech sources in the environment. Then, a fast-acting combination of minimum variance distortion-less response beam-former , which iThe NR scheme gives an overall SNR improvement of approximately +5 dB. For example, In combination with EEG-based speech reconstruction, this setup was designed to investigate whether NR processing in HAs affects the strength of the neural representation of different elements present in an acoustic scene and consequently supports selective auditory attention in HI listeners. We hypothesized that:enhance the neural representation of the attended speech masked by a competing talker and noise compared to when the NR is inactive and across low and high SNRs.(H1) The active NR scheme would enhance the neural representation of the ignored speech to a higher degree at a lower SNR than at a higher SNR.(H2) The NR algorithm would reduce the neural representation of the background noise across low and high SNRs.(H3) The active NR processing would 5-dB shift in the reconstruction accuracy toward the higher SNR.(H4) The effect of the NR scheme on the neural representation of the attended speech would correspond to a +Twenty-two native Danish speakers , aged between 40 and 80 years  years, were recruited from the Eriksholm Research Centre database see . All theThe study was approved by the ethics committee for the capital region of Denmark . The study was conducted according to the Declaration of Helsinki, and all the participants signed a written consent prior to the experiment.All the participants wore identical HA models, with two pairs of HAs fitted for each participant. The Voice Aligned Compression (VAC) amplification rationale  was applIn one pair, the NR scheme was turned off . The HAsIn the other pair, the NR scheme was activated. Technical measurements were done to verify the output SNR improvement in the HAs, which is defined as the difference between the input level of the environment  and HA output responses measured on a head and torso simulator (HATS). A pair of HAs was coupled to the HATS, and the output SNRs of the HAs were derived using the phase-inversion technique described in Danish news clips of neutral content were used for all speech streams. The two target streams were read by the same male and female talker for all 84 trials. The four-talker babble presented from each of the four loudspeakers in the back consisted of two female speakers and two male speakers, and none of the 16 streams were the same for each trial.The background noise was delivered from four loudspeakers. Each loudspeaker played a different four-talker babble, leading to an overall effect of 16-talker surrounding babble to be ignored. Each babble stream was made from four unique single talkers—two females and two males—each reading a different news clip. The long-term average frequency spectrum of the babble noise was matched with the target talkers. The two target talkers were always presented at 65 dB, which was obtained by a fixed level of 62 dB SPL for each of the loudspeakers during the entire experiment, as indicated in The SNR was defined as the ratio of signal power of the attended talker to the total signal power of the background noise, similar to that of via loudspeakers .Stimuli were routed through a sound card  and were played Our experimental design was inspired by a previous study with NH listeners . The parA total of 84 trials were conducted, with four trials used for training and 80 trials used for testing and analysis. Each trial consisted of a short period of silence, 5 s of background noise followed by 33 s of simultaneous stimuli from all speakers, as illustrated in The trials were randomized into a block design, with 20 trials for each of the four experimental conditions: “+3 dB OFF,” “+3 dB ON,” “+8 dB OFF,” and “+8 dB ON.” The target talkers consisted of one male and one female talker. The male and the female talkers were presented by separate loudspeakers, and the gender and the position (left/right) were randomized. The 20 trials in each experimental condition (block) were divided into sub-blocks of five randomized consecutive trials for each of “male right,” “male left,” “female right,” and “female left,” as illustrated in Each participant’s visit started with a training block in which the NR scheme was active (ON) and with one trial for each of the stimuli “male right,” “male left,” “female right,” and “female left” to ensure that the participants were confident with the experimental procedure.Electroencephalography (EEG) data were recorded using a BioSemi ActiveTwo amplifier system , with a standard cap including 64 surface electrodes mounted on the scalp according to the international 10–20 system. The cap included driven right leg and common mode sense electrodes, corresponding to the electrical reference, or “ground,” as reference for all other recording electrodes. To ensure stable connections to the scalp, the electrodes were prepared  such that the offset voltage was stable and below 50 mV. The EEG signals were recorded with a sampling rate of 1,024 Hz.Data analysis was done offline in Matlab R2018a (MathWorks) using the Fieldtrip toolbox , mTRF ToThe signals picked up by each EEG electrode were epoched from 8 s before to 33 s after the onset of the two target (attended and ignored) speech stimuli. Then, 0.5-Hz high-pass filter, 95-Hzlow-pass filter, and 50-Hz notch filter were applied. Afterward, the data were downsampled to 512 Hz and referenced to the average of the two mastoid electrodes. The EEG channels with excessive noise were identified visually and removed. On average, 3.1 ± 0.8 channels were rejected. The noisy channels were interpolated from the surrounding clean EEG channels by using the nearest neighbor method in Fieldtrip . The logUi was calculated by taking the absolute value of the analytic signal after a Hilbert transform of the raw sound signal at its original sampling rate (44.1 kHz), Butterworth low-pass filtering of the resulting waveform with a cutoff at 8 Hz (UA) and the envelope of the ignored talker is referred to as the ignored speech envelope (UI). In contrast, the envelope of the ignored background noise, comprising four different four-talker babbles B1, B2, B3, and B4 (see UIBN = UB1 + B2 + B3 + B4), and the envelope of the entire ignored acoustic scene, comprising both the ignored talker, and the ignored background noise (see UIAS = UI + B1 + B2 + B3 + B4). These envelopes are used to design the neural models in section “Decoder Designs.”The acoustic envelope  at 8 Hz , downsamd B4 see , is refeoise see , is refevia Pearson’s r correlation coefficient, which reflects reconstruction accuracy—a measure of the fidelity of the neural representation of that acoustic envelope  reconstruction (SR). The SR estimates the unknown model response  function or decoder, which best relates evoked neural responses to (spectro-) temporal information in speech such as acoustic envelope. This allows a direct comparison between the reconstructed acoustic envelope and the envelope of the actual sound stream envelope .With SR, the assumption is that the acoustic envelope can be explained as the convolution of the EEG signals with an unknown model response plus noise. Given the known acoustic envelope features and the measured EEG data, the model response is estimated in this study using dense linear regression, with an integration window set from 0 to 250 ms . This deIn order to quantitatively assess whether NR processing affects the neural representations of the sounds coming from different sound sources in an auditory scene, we estimated four different potential neural representations of sound elements in the multi-talker acoustic scene. To estimate the neural representations of the attended speech envelope, ignored speech envelope, ignored background noise envelope, and ignored acoustic scene envelope, four separate decoders were trained in a participant-specific manner for each experimental condition:(1)The attended talker decoder trained on the responses to the attended talker.(2)The ignored talker decoder trained on the responses to the ignored talker.(3)The ignored noise decoder trained on the responses to the ignored background noise.(4)The ignored acoustic scene decoder trained on the responses to the ignored acoustic scene consisting of the competing talker and background noise.via Pearson correlation coefficient r.Each of the four decoding approaches was used to reconstruct the corresponding acoustic envelope whose similarity with the actual acoustic envelope was assessed The attended talker decoder analysis tests the hypothesis that the active NR scheme enhances the neural representation of the attended speech. The ignored talker decoder analysis tests the hypothesis that the active NR processing enhances the neural representation of the ignored speech. The ignored noise decoder analysis tests the hypothesis that the active NR processing reduces the neural representation of the background noise. Finally, the ignored acoustic scene decoder analysis includes an additional exploration of the EEG responses to investigate whether the active NR processing either reduces or keeps unchanged  the neural representation of the ignored acoustic scene consisting of the competing talker and the background noise .r correlation between the reconstructed and the actual acoustic envelope  in a per-trial manner, i.e., treating each trial as a single mapping problem, estimating one decoder for each training trial separately, and averaging across all but the j-th decoder. Then, the averaged decoder was used to reconstruct the envelope of the left-out j-th trial as in Eq. (4). The CV procedure was then repeated for all trials, thus allowing one to reconstruct one envelope for each trial  and their joint effect on the neural speech representations. We fitted one LMM ANOVA model for each of the four decoders, modeling reconstruction accuracy as a function of NR type and SNR, their corresponding interaction treated as fixed factors, and the participants treated as a repeated measure, i.e., random effects. The probability level was p < 0.05. P-values for the individual follow-up pairwise comparison of the NR processing settings [inactive (OFF) vs. active (ON)] at each SNR level were based on t-values and used Satterthwaite approximation for degrees of freedom.All statistical analyses were conducted in R (version 3.6.1) using the R packages lme4  and lmerWe examined the effect of NR processing on the neural representation of the attended talker, ignored talker, ignored background noise, and ignored acoustic scene across different SNRs.rA with main factors of SNR and NR found a significant effect for NR . No significant effect was found for SNR . Furthermore, no significant effect for interaction between SNR and NR  was found, suggesting that NR was equally effective at enhancing the reconstruction accuracy r at both SNR levels. A follow-up pairwise comparison for each SNR level confirmed that the significant effect of NR processing was present at both SNR levels . In addition to this, we also tested whether the active NR scheme shifts the reconstruction accuracy by approximately 5 dB toward the higher SNR. post hoc pairwise comparison did not reveal the significant difference in the reconstruction accuracy values between these two conditions [p = 0.0782]. Given the non-significant interaction between SNR and NR, these results could be seen to suggest that the NR-enhanced neural representation also corresponds to a +5-dB shift . These results validated that a NR scheme can significantly improve the neural representation of attended speech in, for the HI individuals, challenging sound environments and that this improvement could correspond to the shift of 5 dB toward the higher SNR.To test the hypothesis H1, we used the attended talker decoder to reconstruct the attended speech envelope to assess the strength of the neural representation of attended speech across four different listening conditions see . As showF = 942.5845, p < 2.2e-16), which confirms that the attended talker is more strongly represented in the brain than the ignored talker.Prior to testing H2, we investigated how the neural representation of the ignored talker compared to the neural representation of the attended talker see . We applF419 = 6.767, p = 0.0094] and NR , with an interaction between SNR and NR , indicating that the reconstruction accuracy  of the ignored speech is affected by the differences in listening difficulty (SNR) and the NR processing algorithm. The interaction effect between NR scheme and SNR level implies that the NR effect of the reconstruction accuracy for the ignored speech envelope is more prominent in the difficult listening situation at +3 dB, as illustrated in p < 0.0005), but not at higher SNR (p = 0.1621).To test the hypothesis H2, we investigated whether the neural representation of the ignored speech envelope, reconstructed using the ignored talker decoder, depended on NR scheme and SNR level. F419 = 6.214, p = 0.013] and correlations were overall lower when the NR scheme was active. The LMM ANOVA also revealed a significant main effect of SNR  and correlations were overall lower when the SNR was increased. There was no significant interaction effect between NR scheme and SNR . Follow-up pairwise comparisons of the two NR scheme settings (OFF or ON) were applied at the two SNR levels. Significant differences in correlations were observed in the follow-up pairwise comparison between the NR schemes at lower SNR , but not at higher SNR . These results revealed a significant reduction of the neural representation of background noise when the NR scheme was turned on.To test hypothesis H3, Pearson correlation between the neural representation of the ignored background envelope estimated from the ignored noise decoder and the actual ignored speech envelope was calculated for each participant and experimental condition see . The resF419 = 4.3828, p = 0.03654]. However, no significant effect for NR scheme was observed , showing that the NR scheme did not significantly enhance the neural representation of the ignored acoustic scene. A significant interaction was also observed between SNR and NR, indicating that the NR dependency of the reconstruction performance differs according to the SNR level . A pairwise post hoc comparison for each noise condition revealed a significant difference between NR scheme settings at +8 dB SNR (p = 0.0153915), indicating a significantly reduced neural representation of the ignored acoustic scene. Hence, these results suggest that an active NR scheme should not enhance the ignored acoustic scene.Finally, we exploratorily investigated the neural representation of the ignored acoustic scene consisting of the ignored talker and the background noise. The neural representation of the ignored acoustic scene envelope was estimated using the ignored acoustic scene decoder see . Figure In this study, we systematically studied the effect on NR and SNR on neural speech representation during selective attention by means of SR methods applied to EEG responses. Taken together, we showed that active NR enhanced the neural representation of both the attended and the ignored speaker and reduced the neural representation of background noise, while the net sum of the ignored acoustic scene  was not enhanced. In addition, the condition with low SNR at +3 dB had increased neural background noise suppression as compared to the condition with high SNR at +8 dB. Hence, the overall neural representation of the foreground was enhanced as compared to the background noise during an active NR scheme. These findings were consistent across two SNR levels. Thus, these results suggest that the NR algorithms in HAs play an important role in enhancing the neural representation of speech and reducing the neural representation of background noise in HI listeners during a selective auditory attention task.vs. OFF) and SNR conditions. Our main finding was that the neural representation of attended speech was enhanced when the NR scheme was active as compared to inactive. Furthermore, as a complementary finding, our results revealed that the changes in SNR level were accompanied by changes in the reconstruction accuracy of attended speech in HI listeners. As expected, a lower SNR produced lower reconstruction accuracy, while a high SNR produced higher reconstruction accuracy of attended speech. This observation is in line with a recent study with NH listeners , the active NR processing reduced the overall neural representation of the background noise as compared to inactive NR. This result was observed by reconstructing the envelope of unsegregated background noise sounds rather than reconstructing the envelope for each background noise object and then averaging them. This approach was based on findings in recent studies suggesting that the background streams are more accurately represented as a single unsegregated background noise object rather than separated noise objects .Hence, the activation of a NR scheme suppressed the background noise features in the evoked neural responses in HI listeners. This finding confirms that NR processing plays a role in reducing background noise in the cortex and thus may lead the HA user to find the background noise less troubling . This reAn additional exploration of the response shows that fast-acting NR algorithms enhance the neural representation of the attended speaker while ensuring that the neural representation of the ignored acoustic scene is not enhanced, i.e., either reduced or unchanged. We observed that the neural representation of the ignored acoustic scene was reduced at high SNR levels with active NR, while it was unchanged between NR settings at low SNR level. This result was obtained by reconstructing the envelope of the unsegregated ignored acoustic scene based on previous findings .The experimental design introduced in this study allowed us to analyze the effect of NR processing on cortical responses to both the foreground  as well as the background noise across two different SNR levels using SR method. We hypothesized that, under challenging listening conditions, HAs can alleviate the impact of background noise while providing adequate access to foreground streams during selective auditory attention by applying high-end NR signal processing algorithms. It therefore appears reasonable to use the SR to objectively assess how well the talkers of interest in the foreground can be enhanced and the noise in the background suppressed in the brain with different HA settings. In our previous studies, we showed that NR scheme processing had a significant positive effect on sentence recognition and listening effort measured by peak pupil dilation . We thusOur results indicate that the NR processing alters the neural representations of sounds present in complex acoustic scenes across different SNRs, demonstrating the role of NR algorithms in natural sound environments. Crucially, we showed that the NR algorithm applied in this study enhanced the neural representations of attended and ignored talkers and reduced the neural representation of ignored background noise. We also give the evidence that the active NR corresponds to a shift in the neural representations of sound elements from 5 dB toward a higher SNR. Our results indicate that some aspects of selective auditory attention in HI listeners can be improved independent of SNR. Our study confirmed that the currently tested NR schemes enhance the neural representation of both the attended and the ignored talkers, leading to higher detail and audibility of the speech streams. This may ease selective auditory attention to enable the listener to attend to the speech of interest and switch attention if desired.The approach to quantitively assess the effect of NR processing on the representation of speech in the brain using SR applied to EEG responses may, in the future, provide a valuable tool to explore the user benefits of different HA settings. Whether age and degree of hearing loss would further influence the improved neural representations with a given HA setting should be explored. Determining how improved neural representations are linked to different perceptual benefits (such as improved speech perception and subjective listening abilities) would also have implications in prescribing amplification as well as providing insights into the design of new HA technology. With this approach in hand, we can now begin answering open questions concerning the benefits of HAs in solving the cocktail party problem in more realistic listening scenarios with continuous speech.In particular, the goal of our future studies will be to reveal how specific hearing-loss-related deficits in neural processing at various hierarchical levels in the auditory system  lead to A major limitation of the experimental design proposed in this study is the restriction on randomization. Overall, four experimental conditions  were tested in a randomized block design rather than a completely randomized design, which would allow us to avoid practice effects. This was decided for two reasons. First, each HI participant had a pair of HAs fitted for inactive (OFF) and active (ON) NR scheme settings. The HAs were removed and replaced at the end of each experimental condition, whether or not the NR condition actually changed, which would not be possible in a fully randomized design. Second, altering the experimental condition after each trial  may induce surprise and fatigue to the participants. Furthermore, the completely randomized design could have emphasized the two SNR conditions as the background noise level changed between SNR conditions, and hence the 5-s background noise prior to the onset of target talkers could have primed the participant on task difficulty. The randomization between gender and spatial position of the attended talker was likewise applied in a randomized block design to allow the HI participant to focus on the listening task rather than on the task instructions. This issue may be partially addressed by instructing the HI participant to attend to the same talker throughout all 80 trials. Nevertheless, a randomized block design was preferred in this study for the reasons that were described earlier.A related limitation specific to the present study is the spatial separation of the target (attended and ignored) talkers in the foreground. The two target talkers were positioned 44° apart, which was the maximum possible separation due to dimensions of the listening booth. Previous studies have shown that the separation of the speakers affects the mean decoding accuracy, with an advantage of having larger angular separation between the two target talkers due to spatial release from masking . HoweverWhile we provide strong evidence for the benefits of HA signal processing on the neural representation of speech during selective auditory attention, another limitation of this study is that we did our analyses on a population basis, and thus we did not explore the role of age or other factors that may affect selective attention. In our current sample, there is a considerable spread in age . Future studies are warranted to further investigate whether the benefits of the hearing aid signal processing vary across age and whether such benefits can be extended to hearing aid users with more severe hearing loss.Finally, content-related question-and-answer procedure may not be suitable to ensure sustained attention to one of the multiple talkers. In particular, the HI participants were asked a two-choice question after each trial about the content of the attended speech . For each question, there were two alternatives options: “True” or “False.” These questions served only to secure the sustained attention to one of the two competing talkers in the foreground (news clips). As the questions were only on a short snippet of the attended news clip, the participants may have heard the content but could not recall the correct answer. Similarly, the participants might have guessed the correct answer without attending or hearing the content of the news clip. Due to these uncertainties, we did not correlate our findings to behavioral performance.We demonstrated that a noise reduction scheme in commercial HAs can help listeners to focus attention in challenging listening environments by attenuating the neural representation of unwanted background noise and enhancing the neural representation of foreground sounds. Overall, we compared the reconstruction accuracy  for two different SNRs and two different noise reduction schemes. We found an improvement in the neural representation of attended speech with an active NR scheme, shifting the reconstruction accuracy by approximately 5 dB toward the higher SNR, indicating a selective enhancement of neural responses to the attended talker. In addition, a main effect of NR processing on the reconstruction accuracy of background noise was observed, indicating the suppression of neural responses to background noise. Furthermore, we found that the neural representation of the ignored speech envelope was also modulated by noise reduction scheme and was mostly enhanced in the conditions with more background noise, indicating the enhancement of the neural responses to the ignored talker and the improved ability to switch attention at will. Taken together, these results confirm that NR processing in HAs serves to support selective auditory attention in natural listening.clni@eriksholm.com.There are ethical restrictions on sharing the data set. The consent given by participants at the outset of this study did not explicitly detail sharing of the data in any format; this limitation is keeping with EU General Data Protection Regulation, and is imposed by the Research Ethics Committees of the Capital Region of Denmark. Due to this regulation and the way data was collected with low number of participants, it is not possible to fully anonymize the dataset and hence cannot be shared. As a non-author contact point, data requests can be sent to Claus Nielsen, Eriksholm research operations manager at The studies involving human participants were reviewed and approved by Journal number H-1-2011-033. The patients/participants provided their written informed consent to participate in this study.TL, EA, CG, DW, and RH contributed to study concept, hypothesis generation, and design of the experiment. EA, CG, and RH recorded the data. EA analyzed the data. EA, TL, CG, EN, LF, and DW interpreted the data. EA and CG drafted the manuscript. EA, CG, TL, EN, LF, and DW read the manuscript and provided critical revision. All authors contributed to the article and approved the submitted version.EA, TL, DW, LF, RH, and CG were employed by company Eriksholm Research Centre, Oticon A/S, Snekkersten, Denmark. EN was employed by company Oticon A/S, Smørum, Denmark.


Nefopam is a non-NSAIDs and opioid sparing centrally acting drug which is effective for a multimodal postoperative analgesia. The present study aimed to evaluate the analgesic efficacy of nefopam combined with parecoxib for gynecologic surgery. n = 72) who underwent gynecologic surgeries and divided them into either a nefopam or control group. The study group received parecoxib 40 mg plus nefopam 20 mg, while the control group received parecoxib 40 mg plus normal saline solution intravenously during open abdominal gynecological surgery. Both groups then received either nefopam or normal saline every 6 hours postoperatively for 24 hours. Intravenous patient-controlled analgesia with morphine was given for breakthrough pain within 24 h. The participants were evaluated for morphine consumption within 24 hours and postoperative pain using a verbal numerical rating scale (VNRS) at a postanesthetic care unit, at 6-, 12-, and 24-hour postoperative periods. Adverse effects were recorded.  This randomized double-blinded control trial recruited participants (P=0.97. The VNRS on movement at 6 hours after surgery of the nefopam group was significantly different from that of the control group . The VNRS of the nefopam group at 12 hours after operation during resting and on movement was significantly different from that of the control group (, ), respectively.  Morphine consumption within 24 hours and adverse effects were not significantly different between both groups. Mean difference and 95% confident interval of morphine consumption between both groups was 1.00 ,  The combined administration of nefopam and parecoxib during gynecologic surgery slightly reduced the VNRS at 6 and 12 hours postoperatively more than treatment with parecoxib. Postoperative pain is the most distressed adverse event occurred after major surgery which increases morbidity and prolongs the recovery period –3. MultiNefopam, a benzoxazocine derivative, was developed in the early 1970s as an antidepressant medication . It is aPrevious studies comparing more than one NOA combined with morphine for postoperative surgery are very limited, with the majority of the studies being on opioid and one NOA, either NSAIDs, paracetamol, or nefopam, which showed the morphine sparing effect. Therefore, we hypothesized that the combination of 2 NOAs and opioid would produce an additional effect for decreasing postoperative pain after major abdominal surgery. The aim of this study was to investigate the analgesic efficacy and side effects of nefopam combined with parecoxib in open gynecologic surgery.This prospective randomized controlled trial (RCT) was approved by the Ethical Clearance Committee on Human Rights Related to Researches Involving Human Subjects, Faculty of Medicine, Ramathibodi Hospital (MURA208/327).The study recruited patients who underwent gynecologic surgeries between August 2018 and July 2019. The participants and assessors were blinded to the treatment groups. This trial was registered at clinicaltrials.in.th (TCTR 20180808001).2, underlying diseases, i.e., liver failure , renal failure (glomerular filtration rate decrease ≥75%), heart diseases , history of convulsion, history of psychologic disorder or taking monoamine oxidase inhibitors, inability to understand the verbal numerical rating scale (VNRS) , chronic pain, or known allergy to drugs in our protocol.All seventy-two patients aged 20–65 years with American Society for Anesthesiologists (ASA) physical status 1–2 who were scheduled for open hysterectomy under general anesthesia were enrolled to the study. The exclusion criteria included patient refusal to participate in the study, a body mass index (BMI) > 35 kg/mThe patients were randomized into 2 groups using block-of-four computer-generated randomization. They blindly received either parecoxib and nefopam (nefopam group) or parecoxib and normal saline (NSS) (control group). In the operating room, the patient underwent general anesthesia and standardized monitoring of noninvasive blood pressure, heart rate, pulse oximetry, and electrocardiography. The baseline pain score and all vital signs were obtained. After preoxygenation with 100% oxygen for 3–5 minutes, anesthesia was induced with propofol (1.5–2.5 mg/kg), atracurium (0.5 mg/kg) or cisatracurium (0.2 mg/kg), and fentanyl (1–2 mcg/kg). Subsequently, anesthesia was maintained with oxygen, nitrous oxide, seveflurane, or desflurane ) with additional atracurium or cisatracurium as needed.h) for 24 h postoperatively to the participants in the nefopam group, whereas the ones in the control group received NSS 100 mL every 6 h. Neostigmine (0.05 mg/kg) and atropine (0.02 mg/kg) were administered for reversal of neuromuscular relaxation before finishing the operation.Nefopam 20 mg in NSS 100 mL and parecoxib 40 mg were administered intravenously to the participants in the nefopam group, while the control group received parecoxib 40 mg and NSS intravenously during closing the abdominal wall. Nefopam 20 mg in NSS 100 mL was injected intravenously every 6 hours  with morphine  was given for breakthrough pain within 24 h. The participants were then evaluated for postoperative pain using the VNRS at 6, 12, and 24 h after surgery by the nurses blinded to group assignment. Postoperative hemodynamic parameters such as blood pressure, heart rate, and adverse effects including nausea, vomiting, dry mouth, sweating, arrhythmia, and apnea were carefully evaluated and recorded.Primary and secondary outcomes were dosages of morphine consumption within 24 h postoperative and the VNRS at 1, 6, 12, and 24 h after operation, as well as adverse effects, respectively.The sample size was calculated based on our pilot study. The results showed that nefopam combined with parecoxib and parecoxib only reduced the 24 h postoperative morphine consumption from 15.0 ± 3.8 to 12.0 ± 4.7 mg. The number of 32 participants per group will provide 80% power to detect the equal difference in 24 h morphine consumption at a 2-sided alpha of 0.05. The definite number of participants per group was 36 after compensation of data loss.t-test or Mann–Whitney U test where appropriate. Categorical variables were compared between groups using the chi-square test. Pain scores were analyzed by mixed-effects maximum likelihood regression. A P value <0.05 was considered statistically significant.All analyses were performed by SPSS for Windows Version 20.0. The data were expressed as mean, median, standard deviation (SD), and percentage as appropriate characteristics. Between-group comparisons were analyzed using the independent samples P=0.058)   .. Interectively) . Multiplctively) .Our RCT study demonstrated the analgesic efficacy of multimodal analgesia using nefopam and parecoxib with IV-PCA over parecoxib with IV-PCA. It produced an additional efficacy by decreasing the postoperative pain score on movement at 6 h and the pain score both at rest and on movement at 12 h more than parecoxib only. However, no difference of morphine was found.Multimodal analgesia has been developed and widely used postoperatively for many type of surgeries. Drugs used in this strategy include paracetamol, NSAIDs, opioid, and a newly agent nefopam. The aims of using multimodal analgesia are to decrease postoperative pain and undesirable effects of opioids . Opioidsn, 27 vs. 125 per group). Therefore, the analgesic effect when comparing between NSAID and nefopam could not be analyzed due to the inadequate power of the sample size. Moreover, many kinds of operation were evaluated which was different from our study.Our RCT demonstrated the minimal enhancement of the analgesia of the combination of nefopam, parecoxib, and morphine IV-PCA for postoperative open major gynecologic surgery. The combined drugs significantly decrease pain intensity on movement at 6 h and both at rest and on movement at 12 h compared with parecoxib and morphine IV-PCA, but there was no significant difference of morphine consumption. Our results were inconsistent with the OCTOPUS study, a multicenter, double-blinded RCT, which compared different NOA combinations with morphine for postoperative analgesia . The treThe morphine consumption at 24 and 48 h between nefopam plus parecoxib and parecoxib only was not different but not the pain score on movement at 6 h and the pain score both at rest and on movement at 12 h. It could be possible because the pain score was not high, and then, the patients ignored administering morphine IV-PCA during changing the position. Therefore, a reduction in morphine consumption is not a good indicator of the benefit of adding analgesic. Moreover, data from a systemic study showed that morphine sparing was not changing parallel to morphine-related adverse effects . InteresPrevious studies have reported sweating, tachycardia, and hypertension as common side effects of nefopam , but theLimitations of the study were the subjective data of pain scores. Pain evaluation was a self-assessment using the VNRS that was individual dependent and multifactorial involvement such as pain evaluation at the bed time of the patients. Moreover, when the pain scores were low, it could not reflect the morphine consumption. Patient satisfaction should be evaluated in the future study for better analysis. Since we gave only 1 time of parecoxib which can maintain analgesia for 12 h, the latter 12 h postoperative analgesia could be explained by the effect of parecoxib and morphine IV-PCA. The future study may focus on other analgesic such as paracetamol, other kinds of NSAIDs, or even more multiple combined drugs.Administration of nefopam combined with parecoxib is slightly better than parecoxib only for acute postoperative pain control at 6 and 12 h for gynecologic operations. This could help patients to ease their early ambulation. Morphine consumption in 24 hours was not significantly different in both groups with comparable adverse effects.


Near field scanning optical microscopy exploiting differential interference contrast enhancement is demonstrated. Beam splitting in the near field region is implemented using a dual color probe based on plasmonic color sorter idea. This provides the ability to illuminate two neighboring points on the sample simultaneously. It is shown that by modulating the two wavelengths employed in exciting such a probe, phase difference information can be retrieved through measuring the near field photoinduced force at the difference of the two modulation frequencies. This difference in frequency is engineered to correspond to the first resonant frequency of the cantilever, resulting in improved SNR, and sensitivity. The effect of both topographical and material changes in the proposed near field differential interference (NFDIC) technique are investigated for CNT and silica samples. This method is a promising technique for high contrast and high spatial resolution microscopy. However differential interference contrast (DIC) microscopy has not been yet applied to SNOM.High resolution imaging, beyond the conventional diffraction limit has lead to the development of near-field microscopy (SNOM), in which the evanescent waves containing high spatial harmonic frequencies are collected in the near field region. Near-field microscopy, in its conventional form, delivers insufficient image contrast due to evaluating only field intensity as the image information. Inspired from far-field microscopy several contrast-enhancing techniques, including phase contrast6. Therefore, DIC provides the ability in visualizing weakly scattered samples which have low contrast images in conventional intensity contrast microscopy. The same is true for sharp imaging of edges on the samples. Several challenging issues have prohibited the implementation of DIC in SNOM. These include high resolution excitation of the two neighboring points on the specimen, near-field interference of the two scattered beams from the specimen, and detection of very low phase changes resulting from nanometric changes of optical path length during the near field scanning of the specimen’s topography.DIC microscopy, relying on detection of the phase change resulting from either topological or refractive index changes, is a powerful tool to provide high-contrast images using the phase information provided by the interference signal. In a conventional optical far field DIC system Fig. , the bea7. In spite of a great deal of work in designing innovative aperture10 and apertureless13 SNOM probes, none of them are capable of beam splitting in the near field region. Previously reported nanoantenna probes have been generally exploited to generate large near-field enhancement and optical confinement at the probe’s tip, as well as large optical throughput and detection efficiency of the probes. However, diffraction-unlimited excitation of the two neighboring points can be done through utilizing the novel SNOM probes reported in our previous works14, a new category of SNOM probes known as dual color probe. This kind of near-field plasmonic probes, relying on generating two hot spots at well-defined locations on the sample surface, is an excellent tool for splitting the beam of the light source in the near field region. The underpinning mechanism of this energy/frequency beam splitting is the hybridization of the plasmon modes due to the symmetry breaking of the nanoantenna structure on top of the probe15. It is worth mentioning that our proposed plasmonic dual color probe also has additional advantages features, including improvement in accuracy and speed of imaging, while doing its main job as a plasmonic nanoantenna probe providing large enhancement, and confinement of the illuminating field7.Here, we demonstrate the implementation of a near-field differential interference contrast microscopy (NFDIC) technique by the means of combining a dual color SNOM system and a photoinduced force microscope (PiFM). Diffraction-unlimited excitation of two neighboring points can be performed utilizing novel SNOM probes18, in which optically-induced localized polarizability of the specimen is measured by mechanical detection of the force gradient generated due to the interaction between a sharp polarizable tip and the specimen. Since in the PiFM the detection is carried out in the near-field region, it can be employed in our proposed NFDIC system to interfere non monochromatic scattered fields from the sample  experienced by the tip19:S is an arbitrary surface enclosing the tip, β direction  and generated by the αth hot spot, in Eq.  of the probe with two specific wavelengths . Figure I(x) and Iref are normalized output signal at the desired point and reference point  analysis technique. In the simulations, Johnson and Christy dielectric function data