Human motion analysis is crucial for a wide range of applications and disciplines. The development and validation of low cost and unobtrusive sensing systems for ambulatory motion detection is still an open issue. Inertial measurement systems and e-textile sensors are emerging as potential technologies for daily life situations. We developed and conducted a preliminary evaluation of an innovative sensing concept that combines e-textiles and tri-axial accelerometers for ambulatory human motion analysis. Our sensory fusion method is based on a Kalman filter technique and combines the outputs of textile electrogoniometers and accelerometers without making any assumptions regarding the initial accelerometer position and orientation. We used our technique to measure the flexion-extension angle of the knee in different motion tasks . The estimation technique was benchmarked against a commercial measurement system based on inertial measurement units and performed reliably for all of the various tasks (mean and standard deviation of the root mean square error of  Human posture and movement analysis is fundamental for a wide range of applications and disciplines, such as physical and neuro-rehabilitation, sports medicine, human performance assessment and virtual training. Although standard motion analysis instruments are widely used in these fields, the development and validation of ambulatory and unobtrusive sensing systems, which provide a reliable measurement of human motion and activity in out-of-lab daily life, are still open issues in the current literature. The development and validation of wearable technologies aimed at allowing physicians and therapists to remotely supervise and coach the patients during their rehabilitation exercise in their recovery phase are some of the current challenges.Recently, as anticipated by De Rossi and Veltink in , wearablOver the last decade, inertial measurement units (IMUs), based on the integration of accelerometers, gyroscopes and magnetometers, have gained the reputation of being at the cutting edge of wearable motion tracking ,5,6,7,8.Several wearable motion analysis systems based on IMU technology are now on the market. The well-known XSens MVN system ,14 uses Beside their widespread adoption in the field, IMU-based systems suffer from a loss of accuracy due to magnetic disturbance; they can be bulky, and their cost can be considerable. The contribution of inertial and translational accelerations can limit the accuracy of the accelerometer update . Most imThus, the new approach described in this work exploits only the acceleration components of IMUs in combination with other measurement sources taken from a particular class of e-textile sensors.Textile-based or e-textile solutions have been developed, and their possible application for ambulatory and unobtrusive motion detection has been described in several research papers, including ,26,27,28The aim of this paper is to show that by combining e-textiles and low cost inertial sensing, unobtrusive and reliable human motion monitoring is possible. This can be achieved by addressing the drawbacks of the two measurements, by fusing the information derived from KPF goniometers and tri-axial accelerometers. The idea behind this is that single triaxial accelerometers are less expensive and complex compared to the current complete IMU technology and do not suffer from magnetic interference. In addition, they can be easily attached or integrated into the extremities of the KPF goniometer in order to obtain a reliable and unobtrusive measurement system.Without loss of generality, we demonstrated our concept on the movement of the femoral-tibial joint, which along with the hip and ankle is one of the three major articulations of the lower limb that allows ambulation.Several research groups have investigated performing reliable knee joint kinematic assessments through simplified and reduced sensing systems based on accelerometers and gyroscopes and avoiding the use of the magnetometer information. Relevant studies are reported in ,35,36,37i.e., the full orientation matrix extracted by fusing accelerometer, gyroscope and magnetometer information) was employed as the standard reference for benchmarking our new approach. In the experimental session, the prototype was employed to acquire goniometer and IMU data while subjects performed different tasks involving moving their knee joints. To introduce the sensing fusion technique, the KPF device and inertial sensing system working principles are described in vs. the reference measurements). In addition, note that no hypotheses were made on the accelerometer position and orientation with respect to the joint reference frame. Note also that the system can be easily calibrated, through the dedicated procedure conceived of within this work, without requiring the user to perform complex tasks. These achievements and the promising measurement performance make the hybrid system a good candidate for ambulatory and unobtrusive wearable measurement systems.In this work, we propose an innovative solution for the implementation of a simplified and reduced sensing system for knee joint flexion-extension assessment. We exploit a hybrid system that combines the non-inertial angular measurement of the textile goniometer with the inertial information derived from the two accelerometers. More specifically, we developed and conducted a preliminary evaluation of a dedicated sensory fusion approach, based on a Kalman filter implementation. This method exploits the accelerometer measurement to correct the angular estimation performed by the KPF goniometer by continuously adjusting its calibration parameters. We demonstrated the capabilities of the new hybrid measurement system, which is made up of KPF goniometers and tri-axial accelerometers, through the experimental setup described in θ) was defined as the angle between the two consecutive segments of the model  was integrated into the garment to entirely cover the considered joint. The working principle of the goniometer, produced by SMARTEX  and baseIn the same knee band, two inertial measurement units  were fiens MTws  used in ens MTws ,14. The In order to collect data on the knee kinematics, in the experimental sessions, the band was worn by five healthy subjects, who were asked to perform several tasks, grouped into a set of six trials and repeated three times. In the first two trials, the subjects were asked to perform knee flexion-extension movements at different velocities in monopodalic contralateral standing. During these phases, the subjects were asked to flex/extend the knee approximately in the 0–θ), defined in KPF goniometer output was gathered through a dedicated wireless electronic unit, and data were sampled at 100 Hz and transmitted to a remote PC for elaboration. The IMU sampling rate was set to 100 Hz, and the data (raw accelerometer outputs and orientation expressed as the rotation matrix) were transmitted via a wireless link to the same PC. IMU and goniometer data were synchronized through a dedicated XSens software tool. After recording the sensor outputs, our algorithm for the estimation of the knee flexion-extension angle, which fuses data from the KPF goniometer and the accelerometers , except for a second order infinitesimal function [Ideally, if the two KPF layers were geometrically and electrically equivalent, the sensor output, represented by the resistance difference between the two sensing layers (function :(1)ΔR=kθθvs. θ can be explained by Equation .For this reason, we designed the sensor-to-segment calibration procedure outlined in In the first step, using the accelerometer output in a static position, it is possible to determine the transformation that maps the To gather static information from the accelerometers, the subject was asked to stand upright in a natural position. In this position, the To test the reliability of the accelerometer calibration procedure, let us introduce the following metric:R), and it is possible to prove, thanks to the triangle inequality, that its values lie in the range R and S are completely aligned, while for R and S are “intuitively” completely misaligned. Function Where R, S are a special orthogonal matrix and I the identity in While the accelerometer calibration matrix derived by the method described above and built using  was defined as the angle between the x unitary vectors of the reference frames of the hinge joint segments . The state vector (ξ) is defined as follows:The Kalman filter developed within this study  state and its covariance are calculated as follows:ν) and minus and plus symbols indicate a priori and a posteriori estimates, respectively.In the measurement update, according to the Kalman filter theory , the a pIn the angle update phase, the calibration parameters and the angular estimation are corrected taking into account the measurement update results:According to the indirect formulation of the Kalman filter ,45, in tTo define the process model, we simply supposed that the calibration parameter errors were random walk processes, and consequently, the state transition matrix (ζ) is defined as the difference between measured and estimated sensor input. Following [a priori angular estimation:In the indirect formulation, the observation  and the errors committed by the individual sensors is presented .In this section, the knee flexion extension angle estimated by the hybrid system, obtained by fusing goniometer and accelerometer data as described in i-th trial , we calculated the deviation between the estimation performed by the proposed technique applied to the hybrid system 2RMSEmi=1NOur hybrid system’s reliable performance is confirmed by the results reported in the first row of luations ,48, showluations . The redluations ,35,36,37i.e., accelerometers and goniometer applied individually without fusing the information). The RMSEs related to the goniometer estimation of the knee flexion-extension angle are reported in the second row of vs. the reference for the fusion method made on the hybrid system and the corresponding estimation made with the goniometer and accelerometers individually .We performed a further analysis to quantify the improvement introduced by the sensor fusion technique with respect to the single sensing subsystems (surement ). In addIn the accelerometer signal, the errors are due to the acceleration spikes that are present when changing movement direction and when interacting with the environment  and, thus, justify the large mean RMSE and the related standard deviation. Conversely, the goniometer signal is affected by errors due to the limitation introduced by the use of the nominal calibration parameters and slight hysteresis, which produced the error reported in One limitation of the current study is that the hybrid system and the fusion technique were evaluated against inertial measurement units. It is well known that the golden standard in biomechanics is marker-based optical tracking. Optical motion capture systems based on external markers have been extensively used in gait analysis and have shown, for the knee flexion-extension angle, RMSE deviations in the order of  markers . However markers , the estA second limitation, which we are currently addressing, is that only one degree of freedom can be monitored per joint. We did not consider the rotation of the knee on the horizontal plane, since KPF goniometers are not influenced by twisting. From , where tWe have developed and conducted a preliminary evaluation of a new sensing concept aimed at unobtrusive and ambulatory human motion monitoring that combines e-textile and accelerometer sensors. Our hybrid system is based on textile goniometers and low cost accelerometers whose outputs are fused through a Kalman-based algorithm specifically developed for this work. The fusion technique continuously adjusts the goniometer electromechanical parameters using the information taken from the triaxial accelerometers. The method was applied in the measurement of the flexion-extension angle of the knee through the dedicated setup described in this paper. An important feature of the proposed method is that the initial position and orientation of the accelerometer with respect to the joint segments are unknown. Our calibration procedure aligns the accelerometer frames as required by the fusion technique. This procedure is easy to perform and is compatible with the ambulatory context that we are targeting. The estimation performance was compared to a reference measurement system during different motion tasks . Our method showed a reliable performance and good capabilities in following dynamic knee movements (mean and standard deviation of the RMSE equal to


Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a new technique for measuring the in vivo autofluorescence intensity decays generated by endogenous fluorophores in the ocular fundus. Here, we present a software package called FLIM eXplorer (FLIMX) for analyzing FLIO data. Specifically, we introduce a new adaptive binning approach as an optimal tradeoff between the spatial resolution and the number of photons required per pixel. We also expand existing decay models  to account for the layered structure of the eye and present a method to correct for the influence of the crystalline lens fluorescence on the retina fluorescence. Subsequently, the Holm-Bonferroni method is applied to FLIO measurements to allow for group comparisons between patients and controls on the basis of fluorescence lifetime parameters. The performance of the new approaches was evaluated in five experiments. Specifically, we evaluated static and adaptive binning in a diabetes mellitus patient, we compared the different decay models in a healthy volunteer and performed a group comparison between diabetes patients and controls. An overview of the visualization capabilities and a comparison of static and adaptive binning is shown for a patient with macular hole. FLIMX’s applicability to fluorescence lifetime imaging microscopy is shown in the ganglion cell layer of a porcine retina sample, obtained by a laser scanning microscope using two-photon excitation. It produces quantitative images based on the lifetimes of the different fluorophores in the fundus and thus extends standard autofluorescence intensity imaging [Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a new technique based on fluorescence lifetime imaging (FLIM) that measures the  imaging , 2. EachThe goal of FLIO in the human eye is the early detection of eye diseases and other diseases, which might be possible using measurements at the fundus. Another application of FLIO is in basic research, where it can be used, for example, to reveal pathological mechanisms for metabolic diseases . FLIO atin vivo tissue characterization and diagnostics [FLIO is based on fluorescence lifetime imaging . fluoresgnostics . To extrgnostics  is oftengnostics  developegnostics  performsgnostics  extends Fluorescence of the Eye and Approximation of the Fluorescence Lifetime for One Pixel). In addition, software for performing an in depth analysis of the fluorescence lifetime parameters of a single patient or for performing statistical comparisons of groups of patients is not available. To address these issues, a software package called FLIM eXplorer (FLIMX) has been developed and is introduced in this paper. FLIMX implements known multi-exponential and stretched exponential [None of the available software packages can be adapted to the layered structure of the eye, nor can they account for artifacts or correct for the influence of the crystalline lens fluorescence on the retina fluorescence . Fundus images  are recorded in high-speed mode at 8.8 frames/s. A pulsed diode laser with a wavelength of 473 nm , a pulse width of approximately 70 ps  and a repetition rate of 80 MHz is fiber-coupled (single-mode) into the cSLO to excite the autofluorescence. The laser power in the corneal plane is circa 150 μW, well below the exposure limits set by the ANSI standards for durations of up to 8 h . A multiThe instrument response function (IRF) was measured using a 25 μM Eosin Y solution which additionally contained 5 M potassium iodide. The Eosin Y solution was prepared by dissolving Eosin Y powder  in a small volume of dimethyl sulfoxide (DMSO) first. Then water was added to obtain a stock solution of 2 mM which finally was further diluted down to 25 μM using a solution of 5 M potassium iodide. The Eosin Y fluorescence can be excited from 350 to 500 nm and ranges between 450 and 680 nm with a sufficient intensity. Based on the reported Rose Bengal fluorescence lifetime of ca. 16 ps when dissolved in 5 M potassium iodide  it is retc caused by the distance d between the crystalline lens and the retina is defined as:n is the refractive index and c is the speed of light. For the average Gullstrand Schematic Eye [d is 22.2 mm  and n of the vitreous is 1.3668. From these parameters, the 12.2 ps time resolution of the FLIO instrumentation is sufficient to resolve the resulting tc of 202.3 ps. The autofluorescence of the crystalline lens is visible as a shoulder in the rising edge of the fluorescence signal (see section Approximation of the Fluorescence Lifetime for One Pixel).To measure the fluorescence of the retina using the FLIO instrumentation discussed above, the excitation light has to pass through the lens. A crystalline lens emits a strong autofluorescence when excited at 473 nm , which latic Eye , d is 22l of the window is:f is the binning factor. Static binning is effectively a moving average filter in the spatial dimensions. Often, a binning factor of one is used for multi-exponential approximation with two exponential functions, and a binning factor of two is used for multi-exponential approximation with three exponential functions.In FLIO, the spatially and time resolved TCSPC datasets are typically collected with an average number of 1000 photons per pixel in the macular region. This number is a compromise between signal-to-noise ratio (SNR) and acquisition time. If the number of photons is too low, e.g., for a multi-exponential approximation using three exponential functions, the photons of neighboring pixels are combined. This process sums up the decay signals for a square shaped window around each pixel and is called static binning. The edge length The fluorescence intensity of the human retina is not homogeneously distributed. The optic disc is generally weakly fluorescent. High concentrations of macular pigment in the fovea centralis absorb more of the excitation light than is absorbed in the outer regions, and vessels block the excitation light, prohibiting retinal fluorescence from underlying tissue. Another important factor that can contribute to the inhomogeneous distribution of fluorescence is suboptimal alignment of the instrument to the patient. In darker regions with low fluorescence signals, static binning with a fixed binning factor may not collect enough photons for the chosen approximation model, resulting in inaccurate estimates of the fluorescence lifetimes. Choosing a higher static binning factor would collect a sufficient number of photons in darker regions, but at an unnecessary cost of spatial resolution in brighter regions. Furthermore, the number of pixels involved in static binning increases with the binning factor by a power of two, making high binning factors unfavorable.2  is the weighting in time channel j, IM(tj) is the number of measured photons, Ic(tj) is the number of calculated photons using one of the models discussed above and p is the number of free parameters in the model. The ideal weighting is w(tj) = ϭj2, where ϭj is the standard deviation of the number of measured photons, which is the square root of the expected value for data with a Poisson distribution. To approximate the weighting, the Neyman approach [To approximate the fluorescence lifetime parameters, a global optimum characterized by the smallest possible figure of merit must be found. To quantify the figure of merit, the approach  is used:In addition, other weighting approaches such as Pearson , fitted χr2, a minimization scheme is required. The summation of the exponentials is a linear operation. Thus, a linear minimization algorithm can determine the amplitudes as well as the background. The remaining parameters must be determined by a non-linear minimization algorithm. Generally, there are two types of non-linear minimization algorithms: stochastic approaches, such as the evolution strategies [To find the global optimum of rategies  and the rategies , and detrategies  and the rategies . DetermiThe following minimization algorithms are implemented in FLIMX: differential evolution , a partiAll minimization algorithms implement parameter constraints to allow only positive values for the fluorescence amplitudes, the fluorescence lifetimes and the background. The stretching exponent is restricted to values between zero and one. Custom constraints can also be defined to exploit a priori knowledge, e.g., if a certain fluorescence lifetime is expected to occur in the sample.Reflections in the optical pathway cause artifacts in the photon histogram of the fluorescence decay. The fluorescence signal decreases over time, starting at the excitation. A reflection of the fluorescence photons at two or more reflective surfaces/interfaces, e.g., at the surface of a detector or an optical filter, causes a sudden increase in the fluorescence signal at some point in the decay because the reflected photons travel an additional distance and, therefore, arrive at a later point in time. An example of a reflection artifact is shown in 2 per pixel, the fluorescence lifetime properties of a biological tissue are expected to change only moderately from pixel to pixel. Thus, the fluorescence lifetime parameters for a certain pixel should also provide reasonable initial approximation for its surrounding pixels. To model a pixel, a figure of merit may also be computed for the adjacent pixels to achieve a spatially smoother fluorescence lifetime approximation. The resulting n is the number of adjacent pixels.A number of factors affect the approximation of the fluorescence lifetime parameters when utilizing the model function and minimization algorithm discussed above. For example, noise due to a low number of measured photons can lead to unstable results in the approximation. An ill-posed model function, e.g., due to a higher number of excited fluorescent substances than employed exponential functions, can increase the ill-posedness of the problem. Furthermore, the minimization algorithm may be stuck at a local minimum and, thus, will not be able to find the global minimum. Spatial a priori information can be used to improve the approximation. In FLIO with a spatial resolution of circa 34 x 34 μmBecause outliers in the fluorescence lifetime images may be present, a separate treatment of these outliers might be needed to improve the fluorescence lifetime approximation. To search for outliers after the fluorescence lifetime is approximated for all of the pixels of an image, a sliding window of a user-defined size is moved over the image. A window size of 7 x 7 pixels showed good results in practical tests. The window is moved through the images of the fluorescence lifetime parameters and the figure of merit. In each window, the central pixel is compared to the median of all of the pixels inside the window. If the relative difference between a pixel and the median is above a user-defined threshold, the approximation of this pixel is repeated using the fluorescence lifetime parameters from the pixel with the best figure of merit inside the window as initial values. The result of the repeated fluorescence lifetime approximation is accepted only if its figure of merit is better than the original approximation. The applied threshold depends on the application and the expected changes in the parameter space. Thresholds of circa 30 percent demonstrated good results in our applications. τm is a good overview parameter. It can be derived from the fluorescence amplitudes and lifetimes:For some applications, the average fluorescence lifetime To reduce noise in the fluorescence parameter space, spatial mean- or median-filtering can be applied to the obtained images. A reasonable size for the filter kernel is either 3 x 3 or 5 x 5 pixels, depending on the amount of noise in the data. The statistics discussed in the section below are calculated using the filtered data.Although visual analysis is important for a general judgment of the image quality, quantitative analysis is required for the detection of pathologic alterations. Dysli et al.  proposed1, is computed for each volunteer. Then, for each class in the histogram, a two-sided Wilcoxon rank sum test [th:s is the significance level and nC is the number of histogram classes for the fluorescence lifetime parameter. Histogram classes with p-values smaller than the threshold possess a significant difference in medians between the patients and controls. If such a significant difference is found for a histogram class, it can be used as a classifier. Subsequently, its specific cut off point as well as its sensitivity and specificity are determined. The Holm-Bonferroni method can then be applied to the full image or to a region of interest, such as a subfield of the ETDRS grid. In the latter case, only pixels inside the ROI are used for the histogram and for the statistics of the Holm-Bonferroni method. The Holm-Bonferroni method is applied to an exemplary group comparison in experiment 4.The Holm-Bonferroni method  is used sum test  is perfoFLIMX was implemented in MATLAB , mostly in an object-oriented programming style, as shown in A tool for generating synthetic, time-resolved fluorescence data is also included in the software package. It can be used for the simulation processes, e.g., for the construction of the fluorescence decays based on the fluorescence lifetimes of known fluorophores. In addition, a batch job manager is included, which allows for the assembly and batch processing of approximation jobs. The software can handle an arbitrary number of studies and patients with different parameter sets. The computation of the fluorescence lifetime parameters can be very time consuming, depending on the selected minimization algorithm. Thus, FLIMX is able to run the computation on different pixels in parallel, utilizing multiple CPU cores. A custom built backend allows for the user-transparent distribution of work units across multiple compute servers. Therefore, a slave process is started on each server, which scans a network folder for the work unit files generated by the FLIMX software. Each work unit can contain several pixels, which are computed in parallel by the slave process using up to 12 CPU cores . The results of the computation are saved in the shared folder, and FLIMX uses the results to assemble the images of the fluorescence lifetime parameters. File access is synchronized using semaphores. The CPU core activity and memory requirements for a typical distributed fluorescence lifetime approximation using the lens-corrected approach on a 256 x 256 pixel dataset, obtained from a healthy volunteer, are given in To analyze the approximation results, fluorescence lifetime parameters can be visualized in two- and three-dimensions. The three-dimensional view can be freely rotated. Arithmetic operations between different fluorescence lifetime parameters and different spectral channels enable an in-depth analysis of the approximation results.All research procedures were performed according to the Declaration of Helsinki. Approval for the study was obtained from the ethics committee of the Jena University Hospital. Written informed consent was obtained from each volunteer prior to participation in the study.The following methods were used for all experiments. For Eqs FLIO data were measured in the left eye of a 39-year-old male patient with diabetes mellitus type 1 without diabetic retinopathy and a crystalline lens. The motivation of this experiment is to demonstrate the abilities of our adaptive binning approach in comparison to static binning. Therefore, static binning with a binning factor of two and adaptive binning with a threshold of 100,000 photons per pixel were applied to the FLIO data. The fluorescence lifetime parameters were determined using the lens-corrected approach , with twa multi-exponential model using three exponential functions the spectral global analysis approach  using ththe layer-based approach  using ththe layer-based approach in combination with two stretched exponentials , with onthe lens-corrected approach , with thFLIO data were measured in the left eye of a 59-year-old male healthy volunteer with a hemorrhage located in the superior temporal region. The patient had a crystalline lens. The adaptive binning approach with a threshold of 100,000 photons per pixel was utilized. To determine the fluorescence lifetime parameters, the following approaches were applied separately:The results were compared using descriptive statistics.FLIO data were measured in the left eye of a 68-year-old female patient with a macular hole without overlying operculum. A macular hole is a structural defect in the sensory retina at the site of the highest visual acuity. The patient had a crystalline lens. The FLIO data, which were binned by static binning with a binning factor of two, were analyzed using a multi-exponential model  with thr1 of 5 ps, fluorescence lifetime τ2 of 20 ps, fluorescence lifetime τ3 of 100 ps.The motivation of this experiment is to show the ability of our analysis chain to provide group comparison for groups of patients or volunteers. This is important because the high inter-individual variability might not allow for subject specific discrimination for all FLIO applications. We exemplify this group comparison on 20 diabetes mellitus patients without diabetic retinopathy, aged 63.9 ± 8.2 years, and 21 controls, aged 59.1 ± 11.3 years. All volunteers had a crystalline lens. The FLIO data, which were binned by static binning with a binning factor of two, were analyzed using a multi-exponential model  with thrAutofluorescence of porcine fundus samples was measured ex vivo using two-photon excited fluorescence imaging. The technical setup was based on an inverted multi-photon laser scanning microscope . A femtosecond Ti:Sapphire laser  with a pulse width of 140 fs, a pulse repetition rate of 80 MHz and a wavelength of 760 nm was used to excite the autofluorescence. To measure the time-, space- and spectrum-resolved fluorescence decay datasets (FLIM data), the technical setup for the fluorescence lifetime imaging was similar to the FLIO instrumentation. The system also splits the fluorescence photons into two spectral channels (500–560 nm and 560–700 nm). Young porcine eyes have been obtained from a local slaughterhouse and kept on ice in Dulbecco's Modified Eagle's Medium (DMEM) cell culture medium  shortly after enucleation. The ocular fundus samples were taken from a paramacular region and placed into a sample holder filled with DMEM, which was placed onto the object mount of the microscope with the retina facing towards the excitation laser. Technical setup and sample preparation have been described in detail elsewhere . The FLIm  and a multi-exponential model with three exponential functions  and the lens-corrected approach with two exponential functions and a separate measurement of the crystalline lens  curve is given next to the histogram. The area under the ROC curve (AUC), as a measure of the ROC curve’s accuracy, achieves the largest value of 0.85 for fluorescence lifetime τ1 in spectral channel 2. Thus, its cut-off point as best trade-offs between true positive rate and false positive rate would result in the best achievable diabetes detection using only the FLIO data from this experiment.As stated above, the motivation of this experiment is to show the ability of our analysis chain to provide group comparison for groups of patients or volunteers because of the high inter-individual variability. Normalized histograms comparing the diabetes patients and controls for all of the fluorescence amplitudes and lifetimes, as well as for both spectral channels, are shown in m for spectral channels 1 and 2 are shown in The fluorescence intensity and the average fluorescence lifetime τin vivo measurements from volunteers and one experiment using an ex vivo microscopy measurement.In this work, a new software package called FLIMX is introduced. This software implements a new adaptive binning method, a number of known as well as new approaches for modelling FLIO data, new methods for the treatment of artifacts and outliers, visualization and group comparison abilities specifically useful for FLIO, but generally also for other means of imaging fluorescence lifetimes. The abilities of FLIMX were demonstrated in four experiments using Static binning smoothes all of the image parts with the same strength. In contrast, adaptive binning smoothes dark parts more and bright parts less, better preserving spatial detail. Static binning and adaptive binning also use different window shapes. Because of the circularly shaped window used in adaptive binning, only the closest pixels are used for binning. In the case of static binning, a square window shape is used, and pixels at the edges of the square shaped region are farther away from the root pixels than the other pixels. The circular window is isotropic, while the square window is anisotropic. The calculated fluorescence lifetimes in Figs FLIMX implements a number of known approaches  to modelThe benefits of the new approaches proposed in this work are observable in the results of experiment 3, which compares the standard static binning in combination with the three-exponential approach to our adaptive binning in combination with our lens-corrected approach. These data indicate, that adaptive binning is able to preserve small structures such as the macular hole (circular shape with a diameter of circa 15 pixels), which are clearly visible in the average fluorescence lifetime in In this work, fluorescence lifetimes are related to different fluorophores for simplification reasons. However, excited-state dynamics and potential excited-state depopulation pathways also influence the fluorescence decay. The method proposed to correct for artifacts caused by reflections in the optical pathway removes only the most important part of the artifacts. The time range of the detected artifacts is not entirely corrected, as the reflections possess an exponential decay that is as long as the entire FLIO signal. An accurate modelling of the reflections was not implemented because the anticipated benefits are rather small and the necessary increase in the complexity of the minimization algorithm may reduce the robustness of the fluorescence lifetime approximation, leading to unstable fluorescence lifetime estimates. Another method used to remove artifacts in FLIMX is the iterative algorithm for the treatment of outliers. This method is effective at rectifying errors in single pixels surrounded by presumably correct pixels. A similar effect may be achieved by median filtering the fluorescence lifetime images instead. However, median filtering can remove small fluorescence lifetime alterations, e.g., from drusen, and could introduce new artifacts into the fluorescence lifetime images.An important step for the quantitative analysis of FLIO data is the adoption of the ETDRS grid proposed by Dysli  because The Holm-Bonferroni method used in experiment 4 with 41 measurements, each consisting of two spectral channels, required 452 MB of memory. In this example, a single subject required approximately 11 MB of memory for the data structures in FLIMX. The amount of memory per subject may vary due to spatial resolution, ROI size and the number of spectral channels. Consequently, group comparisons in FLIMX are limited by the memory of the computer being utilized. In the era of 64 bit operating systems and common memory sizes of at least 4 GB, this limitation does not seem critical. Another computational resource is CPU time, which is especially important for the fluorescence lifetime computations. As seen in FLIMX permits the simulation of multiple decay processes, which might be helpful for interpretation of experimental data or for estimation of required number of photons .http://www.flimx.de.A new public domain software package called FLIMX has been demonstrated. This software has been optimized to extract and analyze fluorescence lifetime data from time-resolved autofluorescence measurements of the human eye, but it is not restricted to this FLIM application. FLIMX enables detailed investigations of single patients, as well as statistical analysis on groups of patients, and is most suited for FLIO research. FLIMX, is available under an open source license at S1 FigThe gray boxes are related to data storage, the blue boxes symbolize computational modules and the orange boxes symbolize graphical user interfaces. To reduce the complexity of the figure, only the most important connections between the modules are shown.(EPS)Click here for additional data file.S2 FigThe FLIMX data structure is divided into groups of subjects called studies. Each subject may contain multiple spectral channels. Inside a channel, the measurement data (TCSPC) and a set of corresponding results from the fluorescence lifetime approximation, such as amplitudes and lifetimes, can be saved. A channel can also contain approximation results imported from third-party software.(EPS)Click here for additional data file.


Recent investigations emphasized the role of communication features on behavioral trust and reciprocity in economic decision making but no studies have been focused on the effect of communication on affective states in such a context. Thanks to advanced methods of computational psychometrics, in this study, affective states were deeply examined using simultaneous and synchronized recordings of gazes and psychophysiological signals in 28 female students during an investment game. Results showed that participants experienced different affective states according to the type of communication . In particular, participants involved in personal communication felt more relaxed than participants involved in impersonal communication. Moreover, personal communication influenced reciprocity and participants' perceptions about trust and reciprocity. Findings were interpreted in the light of the Arousal/Valence Model and self-disclosure process. Recently attention has been focused on the study of the effects of different types of communication on behavioral trust and reciprocity. Typically, the trust game is one of the preferred contexts to study trust and reciprocity in decision-making situations , 2. communication effect [ identification (humanization) of other agents. When another subject is perceived as being similar to ourselves—even if the similarity is vague and generic—we have the tendency to be kinder and more generous than we would be if the other part were completely anonymous. Identification reduces what is called “social distance” and therefore may increase the scope for reputation effects, which in turn may yield more cooperation [As far as the role of communication in decision making is concerned, it is possible to identify two different perspectives. On the one hand, Bicchieri and colleagues definedn effect , 4 as thperation . In partperation , 6 distiperation .Within the game-irrelevant communication, Buchan and colleagues  introducAs far as we know, the effects of communication on decision have been studied only in terms of behavioral results, such as the amount of money sent by the proposer (trust) and the amount of money sent by the responder (reciprocity). No studies have been focused on what happens during the communication process between participants in terms of affective and cognitive states. a posteriori the communication experience.To investigate this process we used computational psychometrics that has several advantages. First, this approach allows extracting several critical pieces of information related to subjective processes, without asking directly individuals. Second, thanks to the availability of brand-new technologies and paradigms researchers can investigate communication without interfering with the communication flow. Third, the use of computational psychometrics allows overcoming limits related to the use of the classic psychometrics questionnaires, where individuals are asked to recallAt our best knowledge no study investigated yet the relationship between affective states and communication type. On the other hand several studies investigated the relationship between affective states and psychophysiological correlates in individuals by using biosensors .To classify participant's affective states during communication, we referred to the well-known Arousal/Valence Model , 11, basThis approach has been extensively used in psychophysiological research as an objective way to measure affective states during a mediated experience –23. MoreTo identify the affective and cognitive states with regard to the type of communication, we followed the process tracing paradigm  and we uThe general goal of this study was to investigate the effects of personal and impersonal communication on participants' affective states during the communication phase and their implications for trust, reciprocity, and participants' perception about trust and reciprocity after the trust game. For this reason we used an investment game as a typical decision-making task and we considered only the affective states during the communication phase . This is the first study carried out by using double eye-tracker synchronized with double psychophysiological biosensors.(H1)There are significant differences between participants' affective states depending on the topic of communication ; since no study investigated this specific issue we decided to explore this relationship by referring to the Lang Model.(H2)There are significant differences between participants' behaviors in terms of trust and reciprocity depending on the topic of communication . According to Buchan et al. , we expeIn particular, we formulate two hypotheses:Ethical Committee of the Psychology Department of the Catholic University of Milan approved the study. All participants gave written informed consent to the experimental procedure according to the rules of the scientific review board.The experimental investigation relies on the investment game, introduced by Berg and colleague , which pThirty-two students  attending the Faculty of Psychology at the Catholic University of Sacred Heart of Milan, Italy, took part in the experiment. All the participants were students in psychology or communication, but without previous knowledge of decision science and in particular with no knowledge of the investment game used in the experiment. Social, economic, cultural, and historical background were all similar since all the participants were students in the same university and with similar background. To avoid differences in money perception the level of incomes was similar (student workers have been excluded). They were first met by one of the researchers during academic courses and then contacted via mail and/or telephone to schedule a meeting at the psychophysiology laboratory. The topics associated with the experiment were not mentioned during academic courses.We selected only women in order to reduce the effects due to confounding variables associated with gender, such as sexual attraction, and control a priori effect of identification .The participants were informed that the reimbursement for their attendance was related to their choices in the game.Four of the participants failed to complete the experimental session due to personal or technical problems and were excluded from statistical analyses. The final sample was composed of 28 students, who were randomly coupled and assigned to one of the two experimental conditions (PC versus IC).The experimenters attached the following biosensors: a respiration belt (RSP), positioned on the chest; a facial EMG on corrugator supercilii muscle , placed on the forehead after the researcher cleaned the skin with abrasive paste; two EEG sensors located on the frontal lobes, on the right and on the left, respectively, attached with conductive paste to improve signal detection , with the reference electrodes attached to the respective ear lobes after they had been cleaned with abrasive paste by the experimenter; two SC adhesive patches applied on the nondominant palm; a BVP sensor placed on top of the index finger of the nondominant hand.Finally, participants' eye movements were calibrated by asking participants to follow a small point on the screen. The EEG and the physiological signals of BVP, GSR, respiration, and EMG-CS were acquired using a ProComp Infiniti device from Thought Technology, including Biograph Infiniti 5.0.2 software to record all signals. Every channel was synchronously acquired at 2048 Hz and exported at a 256 Hz sampling rate (every 3.90625 milliseconds).In order to analyze deeper the affective states related to different types of communication content during the communication phase in FtF condition, we used video-conferencing technologies. According to Brosig et al. , video-cBoth members of each pair were separately welcomed in different rooms by two experienced experimenters, who assisted them for the duration of the laboratory session. The experimenters were instructed to maintain a neutral voice tone and a neutral behavior while the subjects were being exposed to experimental stimuli. Participants did not know each other and could not talk to each other before the beginning of the experiment. First of all they were informed about the general purpose of the research  and received all the instructions about the nature of the investment game (including the switch of the roles). Then, they signed the written informed consent and were prepared in order to collect the psychophysiological data. When a participant indicated feeling comfortable, the researcher asked her to try to remain still during all the experimental conditions in order to avoid artifacts in signal acquisitions as a result of movements. A baseline measure of the psychophysiological parameters was obtained with a 5-min registration in a steady state .At this point the experimental task started. The two participants were allowed to get to know each other, meeting their partner in the virtual context of Google video chat. The communication lasted 3 min. They were asked to converse about specific arguments among authorized topics, according to the experimental condition to which they belonged (PC versus IC).After this step, the decision phase started and participants knew that the game was played with real monetary payoffs and the winnings were converted in a proportioned way.The proposer was asked to choose how much money she would give to the partner from an initial amount of 2000 Euros by choosing one of the following alternatives: 100, 500, 1000, 1500, and 2000 Euros. According to the investment game procedure, the responder was then asked to choose how much of the triple of the amount received she wanted to give back to the proposer, selecting one of the following options: nothing, 1/4, 1/2, or 3/4 of the final amount and all the final amount.After the decision, the video chat was closed and participants completed a brief questionnaire about the choice they had made and related personal motivations and the partner's choice and related motivations.The second phase of the experiment started with another 3-min video-chat communication, when the game was repeated, by inverting the roles.The experiment was carried out in two labs, each one equipped with two portable PCs, one for delivering the stimuli and acquiring eye-tracker data and the other for psychophysiological signal recording.The physiological signals were acquired using a ProComp Infiniti device from Thought Technology, including Biograph Infiniti 5.0.2 software to record and export all raw signals. Every channel was synchronously acquired at 2048 Hz and exported at least a 256 Hz sampling rate (every 3.90625 milliseconds) or higher where needed.The pupillometry data were acquired using two Tobii x-series, including Tobii Studio software to record all raw signals, then exported, and resampled at 60 Hz.In our study, by using the eye-tracker data extraction, we obtained for each participant a matrix of gaze and pupil data corresponding to stimuli presentation (such as the webpage for Google video chat); in particular, we collected 50 rows for each second (sampling to 50 Hz), thereby making it possible to establish the exact period previously indicated.Then, the synchronization of the psychophysiological signals allowed us to identify the communication period. In this case, we used several algorithms to synchronize eye-tracker systems with a ProComp Infiniti device from Thought Technology by using the TT-AV Sync sensor, which was configured through a physical channel on ProComp capturing the light  thanks to a photodiode actually applied on the screen . MoreoveAll collected biosignals were analyzed using Matlab 7.0  for the signal processing and computation of psychophysiological measures.Data were analyzed with the aid of the statistical software SPSS, version 18 .According to the classic valence-arousal model , 11 descPhysiological arousal can be measured by using electroencephalogram (EEG), galvanic skin response (GSR), cardiovascular activity (ECG or BVP), and respiration signal (RSP); emotional valence can be measured by using EEG, self-reports, facial expression identification, eye-blink startle, and facial EMG corrugator and/or zygomatic. According to Blumenthal and colleagues , facial Frontal EEG activation asymmetry has been generally used, giving evidences that greater left frontal activity seems to be higher related to positive emotional valence, whereas greater right frontal activity seems to be more involved in negative emotional valence . Alpha iFurthermore, we used pupillometry to investigate emotional responses. Because pupil dilation indicates a higher cognitive load or emotional processing , 27, stuAs recently showed by Mojzisch and colleagues , the selCardiovascular and respiratory activities were monitored to evaluate both voluntary and autonomic effect of respiration on heart rate, analyzing IBI , respiration (from chest strip sensor), and their interaction. Following the guidelines of task force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, typical Heart Rate Variability (HRV) temporal and spectral method indexes were used to evaluate the autonomic nervous system response –52. TempSC and skin resistance recorded through GSR sensors are units of electrodermal activity, which are expressed in either conductance (microsiemens) or resistance (microohms). SC reflects a fairly slow physiological process and can be sampled at 32 Hz without distortion. The signal is expressed in microohms. We considered mean and standard deviation of the sampled signal.μV (microvolts). As the participant contracts the muscle, the number and amplitude of the lines increase; as the muscle relaxes, it decreases. We considered the Root Mean Square (RMS) for rectifying the raw signal of the corrugator supercilii muscle and converting it to an amplitude envelope, following EMG-CS. We were not interested in frequency related to this muscle fatigue.The raw electromyography is a collection of positive and negative electrical signals. Their frequency and amplitude gave us information on the contraction or rest state of the muscle. Amplitude was measured in EEG signals need to be extensively worked to remove ocular artifacts and blinks using automatic algorithm and subsequent visual inspection. Then the corrected matrixes have been computed to calculate means of the Slow Alpha bands (at 7–10 Hz) for the FP1 and FP2 EEG channel, through spectral analyses –56. Eye-How do you consider the amount of money you gave to the responder? ;Why did you give to your partner this amount of money? .After the decision, the video chat was closed and participants completed a brief questionnaire. In particular, proposers were asked about their choice and the personal motivations for it through two questions:How do you consider the amount of money you gave back to the proposer? ;Why did you give to your partner this amount of money? .Responders too were asked about their choice and the personal motivations for it through two questions:Psychophysiological measures : heart rate, EMG corrugator, skin conductance, EEG Alpha Asymmetry, EEG Slow Alpha waves, EEG Beta waves, LF/HF, pupil dilation, NN50, and RMSSD.Trust: the amount of money sent by the proposer to the responder.Reciprocity: the amount of money returned by the responder to the proposer.Perceived trust: the individual's evaluation of fairness of personal decision about the amount of money sent to the responder.Perceived reciprocity: the individual's evaluation of fairness of personal decision about the amount of money sent to the proposer.The dependent variables considered were defined as follows:Analyses were carried out in order to test the hypotheses. For this reason we analyzed differences between participants' affective states depending on the topic of communication (H1) and differences between participants' trust and reciprocity and their perceptions about trust and reciprocity depending on the topic of communication (H2).We analyzed the effect played by the independent variable “role” (proposer versus responder) on all dependent variables: since it resulted not statistically significant in both main and interaction effects, it was not further considered in the subsequent analyses. t-tests in a between-factor design (PC versus IC) to compare the two groups of participants. t-test correction has been done whether or not dependent variable variance between groups was homogeneous, based on Levene's test.The impact of communication type on psychophysiological measures of affective states was evaluated by running a series of independent samples t-tests in The descriptive statistics summarized in Finally, Slow Alphas were lower in participants in the PC condition, highlighting their higher sustained attention than in IC.A power analysis was used to anticipate the likelihood that our study yielded significant effects. The goal of our post hoc power analysis was to compute achieved power, given significance level, effect size, and sample size. The analysis showed a good power (above 80% per each measure). These results also demonstrated that our sample is at the fair size. t-tests . As far as reciprocity was concerned, results suggested that responders returned a higher amount of money to the proposers in the PC condition . Nobody gave back zero or the total final amount.The impact of communication type on trust and reciprocity was evaluated by running a series of independentWe investigated also the participants' perceptions about their choices by using Kendall tau-c and we compared them depending on the communication condition.c = −0.384, df = 26, and P = .032): the proposers in PC condition considered the responders more trustworthy than in IC condition.Analyses showed that differences exist between participants' perceptions about trust depending on the topic of communication. In particular, the motivations related to the proposer's play were different between PC and IC .As a consequence, responders evaluated the personal decision about the amount of money returned to the proposers as fairer in the PC condition  versus the repeated talk about generic topics (in IC) change the trust over time?The present results suggest that a personal conversation is more oriented to positive affective states and to positive perceptions related to the partner of communication. Implications could be relevant for many purposes, since many communication processes made in both FtF and online settings can precede decision making. Vivid examples are related to the physician-patient communication , 63, botThanks to the use of computational psychometrics we have been able to investigate communication processes and their effects on decision making. In particular, the use of double systems synchronized to record the related psychophysiological correlates and eye movements has shown great potential.The extended use of new computational psychometrics paradigms represents a promising approach and future researches aiming to investigate communication processes are encouraged to follow these advances methods.


In human movement analysis, 3D body segment orientation can be obtained through the numerical integration of gyroscope signals. These signals, however, are affected by errors that, for the case of micro-electro-mechanical systems, are mainly due to: constant bias, scale factor, white noise, and bias instability. The aim of this study is to assess how the orientation estimation accuracy is affected by each of these disturbances, and whether it is influenced by the angular velocity magnitude and 3D distribution across the gyroscope axes. Reference angular velocity signals, either constant or representative of human walking, were corrupted with each of the four noise types within a simulation framework. The magnitude of the angular velocity affected the error in the orientation estimation due to each noise type, except for the white noise. Additionally, the error caused by the constant bias was also influenced by the angular velocity 3D distribution. As the orientation error depends not only on the noise itself but also on the signal it is applied to, different sensor placements could enhance or mitigate the error due to each disturbance, and special attention must be paid in providing and interpreting measures of accuracy for orientation estimation algorithms. One of the main issues in human movement analysis is the accurate estimation of the three-dimensional 3D) orientation of a body segment, relative to a global Earth-fixed reference frame. In fact, body segment orientation is needed to estimate both kinematic and kinetic joint parameters in a variety of contexts: for instance, in clinical contexts, they allow to assess the functional outcome of treatments ,2; in spD orientaAmong the technologies currently available for the estimation of a rigid body 3D orientation in human movement analysis, Magneto-Inertial Measurement Units (MIMUs) are becoming increasingly popular. Recent advances in the field of Micro Electro-Mechanical Systems (MEMS), in fact, have allowed manufacturing sensors characterized by reduced dimensions, relatively low-cost, and easy set-up, which enable unconstrained motion monitoring ,7. MIMUsIn principle, the 3D orientation of the MIMU (and therefore of the body it is attached to) can be obtained through the gyroscope signal alone, by numerically integrating the non-linear kinematic equations that relate the angular velocities with the time-derivative of the orientation, regardless of the formalism employed for its description . HoweverNevertheless, there are cases in which the sensor fusion approach has been proved not to represent a real added value with respect to the numerical integration alone . This ocMEMS gyroscope measurements are affected by errors, due to several types of noise, which may be classified as deterministic or stochastic . DetermiThe constant bias is the angular velocity value provided by the gyroscope when it is not undergoing any rotational movement with respect to an Earth-fixed frame. In order to compensate for this offset, its value is usually estimated through a procedure called bias capture, which consists in averaging the gyroscope signals obtained during a static acquisition , when the expected angular velocity is null. Although most of the gyroscope offset can be accounted for with this procedure, the averaging process can entail uncertainties which lead to a residual bias that remains uncompensated. Its effect is that of a steadily growing angular error in time ,12.The scale factor is the ratio between the gyroscope-measured values and the actual angular velocity and is due to errors affecting the sensor’s calibration performed during its manufacturing. To assess how far the gyroscope scale factor is from the ideal conditions (unity), the sensor can either be rotated at a predefined angular velocity, which is then compared to the measured signal, or it can be rotated by a known angle, which is then compared to the integral of the kinematic equation relating the angular velocity with the time-derivative of the orientation . The forThe white noise is a sequence of zero-mean uncorrelated random values, which fluctuate at a much greater rate than the sampling frequency of the gyroscope and are due to thermo-mechanical causes. Its integration leads to a zero-mean random walk process, with a standard deviation that grows with the square root of time .Finally, the bias instability is a stochastic error that indicates how unstable is the bias of a gyroscope over a certain specified period of time (gyroscope drift rate) ,14. SeveAlthough the effect of the mentioned noise types on the estimated orientation over time has already been studied in the literature ,16, to tIn light of the above considerations, the main objective of the present study is to assess the influence of the magnitude and 3D distribution of the angular velocity signal on the orientation error due to the four above-mentioned types of noise that affect MEMS gyroscopes, in reference to the human motion analysis context. To this aim, a simulation approach was followed to corrupt reference angular velocity signals, considered noise-free, with each considered noise type, and both the reference and corrupted signals were integrated to obtain the corresponding orientations. Two different types of angular velocity signals were examined: on the one hand, signals that are representative of a typical human motion analysis context; on the other, constant signals that allow to investigate the separate influence of angular velocity magnitude and 3D distribution. For what concerns the former, signals consistent with the angular velocity of pelvis and shank during level walking were chosen, as they are characterized by significantly different magnitudes and distributions. For what concerns the constant signals, several magnitudes and 3D distributions were considered in order to span the range of typical values encountered in human motion analysis.The methodology presented in this study is based on the definition of a simulation framework developed using the MATLAB software . The simulator receives as input a reference 3D angular velocity signal and corrupts it with different types of disturbances (noise). The types of noise considered in this study are: residual bias (RB), scale factor (SF), white noise (WN), and bias instability (BI). The deterministic noise types (RB and SF) are represented by the uncompensated angular velocity offset and by the ratio between the measured and actual angular velocity, respectively. For what concerns the stochastic noise types, WN is described in terms of the standard deviation (STD) of the underlying process on each gyroscope axis, whereas BI is defined in terms of the bias instability coefficient as defined in . For boti.e., orientation matrices and Euler angles), among which the lower computational load [The reference and the corrupted angular velocity signals were considered as those measured by an ideal and a noisy MEMS gyroscope, respectively. To obtain the orientations of these gyroscopes over time, the kinematic equation that relates the angular velocity with the time-derivative of the orientation was integrated, with an integration step within the typical range of MEMS gyroscope sampling frequencies. The integration of the kinematic equation was performed assuming that the angular velocity signals are constant within each interval of time between two subsequent samples . To descnal load  and the nal load . The relnal load . FinallyThe above-described approach was used in this study with angular velocity signals of different nature: representative data of healthy gait and constant signals. Each of the considered types of noise was homogeneously distributed across the three gyroscope axes. In the cases in which the obtained results suggested that different noise distributions could be of interest, further tests were performed to assess the influence of noise directionality on the orientation error.To obtain reference signals representative of healthy gait, two synchronized MIMUs  embedding tri-axial MEMS gyroscopes were attached to the pelvis (L4–L5) and to the distal part of the right shank of a healthy male subject  as shown in i.e., human motion analysis), were thus generated for both pelvis and shank segments.Stride segmentation was performed by considering the angular velocity measured by the shank MIMU about its X axis, roughly corresponding to the medio-lateral direction ,21. AssuThe reference signals were then corrupted with each individual noise type modelled within the simulation framework. In order to cover the range of typical values of commercially available MEMS gyroscopes, eleven levels  were assigned to each noise type. The range of values was selected based on the literature  and on t samples , the varU as a non-parametric method. Otherwise, in case of normal distribution, the differences were tested through an unpaired t-test (α = 0.05). For the deterministic noise types (SF and RB) the differences between the two locations were quantified through the RMS difference. To investigate the trend with which the orientation error due to each noise type increases with the noise levels, polynomial curve fittings were performed (for WN and BI both on their means and STDs) and their adequacy described in terms of coefficient of determination (R2). The statistical analysis was performed using IBM SPSS Statistics .The orientation error previously defined was evaluated for each level of each noise type and for both pelvis and shank locations. For the stochastic noise types (WN and BI), the testing for differences between the pelvis and shank locations was carried out using inferential statistics. First, the normality of the distribution of the orientation errors was checked with the Shapiro-Wilk test. In case of skewed distribution, differences between the two locations were tested through a Mann-Whitney The procedures implemented to single out the effect of the angular velocity magnitude and 3D distribution on the orientation error due to each individual noise type are described in the following sections.To assess the effect of the 3D distribution of the angular velocity ed above , were geed above . Five hut-test or a Mann-Whitney U test was performed, according to the normality test. On the other hand, when testing for differences among angular velocity magnitudes, a one-way ANOVA or a Kruskal-Wallis H test was carried out, since more than two datasets were compared. If a significant magnitude effect was found, post-hoc comparisons were performed between each pair of angular velocity magnitudes using either the Bonferroni correction or a Mann-Whitney U test. For what concerns the deterministic noise types (SF and RB), the differences in orientation error were assessed through the RMS difference.To assess the individual contribution of the angular velocity magnitude to the orientation error due to each noise type, the magnitude of the angular velocity was varied to cover the range of typical values observed in gait at pelvis and shank levels (from 0 to 10 rad/s). For each magnitude value, the angular velocity was studied for the 3D distributions that were found to be most paradigmatic  according to the results of the previous section . ConstanThe differences in the angular velocity observed at the pelvis and shank during a stride are shown in The effect of homogeneously distributed individual noise types on the orientation error and the influence of the angular velocity 3D distribution and magnitude are presented in the following sections.The orientation error due to different levels of homogeneously distributed individual noise types, affecting the angular velocity signals representative of the motion of pelvis and shank during gait, is shown in R2 = 0.99), in agreement with [R2 = 0.99), similarly to WN. However, in this case, significant differences between the pelvis and the shank locations were found (t(998) = 2.81, p < 0.01), with greater errors associated to the pelvis with respect to the shank.For what concerns the stochastic noise types, the mean orientation error due to WN and its standard deviation were found to increase with the values of the noise levels following a linear trend (ent with . MoreoveR2 = 0.99), the slope of which was found to be different for the pelvis and shank locations (RMS differences = 2.4°). In fact, since the shank experiences mean angular velocities (µ = 1.76 rad/s) that are greater than those of the pelvis (µ = 0.53 rad/s) (R2 = 0.99), in accordance with [As for the deterministic noise types, linear trends were observed for the orientation errors due to SF (3 rad/s) a, the fonce with . The effnce with  are reveFor what concerns the effect of the angular velocity 3D distribution, assessed considering different directions of a constant unit angular velocity vector, it was found to affect the orientation error due to homogeneously distributed noise types only in the case of RB. The distribution of the orientation error due to RB across the sphere is shown in The effect of the angular velocity magnitude on the orientation error due to homogeneously distributed noise types is reported in 2(10) = 6.93, p = 0.73). On the other hand, a significant magnitude effect was observed for BI (χ2(10) = 619.51, p < 0.001). A Mann-Whitney U test, performed between each pair of angular velocity magnitudes, confirmed the presence of significant differences between the first angular velocity magnitude  and each remaining magnitudes , with larger errors associated to low magnitudes. This result matches with the above mentioned larger orientation error displayed by the pelvis with respect to the shank, when BI was considered . This result supports the fact that, for these noise types, the 3D distribution of the angular velocity vector does not affect the orientation error.For what concerns the stochastic noise types, no significant difference was encountered among the orientation errors corresponding to the different angular velocity magnitudes for WN , except in the case limit of null magnitude, where the orientation error corresponds to the integration of the sole residual bias and its value is constant d, Max RBd for BI b. This cIf only homogeneous distributions of noise types are considered, it is unclear whether the maximum errors associated to RB depend on the direction of the angular velocity vector or rather on the relative orientation of the angular velocity vector with respect to the RB vector. For this reason, an RB vector with non-equally distributed components across the three axes was selected, with which the three tests considered in this study  were repThe effect of different levels of RB noise on the orientation error, considering the distribution defined above, was evaluated for the angular velocity signals representative of the motion of pelvis and shank during gait . With reThe distribution of the orientation error due to the maximum noise level of the considered non-equally distributed RB components is shown in −8 degrees.Finally, the effect of the angular velocity magnitude on the orientation error due to the maximum level of the non-equally distributed RB components was evaluated. The paradigmatic directions were defined following the same criterion as for the equally distributed RB case, in order to represent the conditions of maximum error, minimum error, and the two intermediate conditions. For this, a transformation was applied to the paradigmatic directions identified on the sphere in The present study focuses on the effect of the most relevant stochastic and deterministic noise types typical of MEMS gyroscopes on the accuracy of the orientation estimated through numerical integration in the context of human movement analysis. Reference signals representative of the angular velocity of pelvis and shank during gait were considered, and corrupted with each of the four considered noise types: white noise, bias instability, scale factor and residual bias. As the signals differ significantly in the two locations in terms of both magnitude and 3D distribution across the gyroscope axes, the influence of each of these two parameters was assessed, in order to gain further insight into the effect of each noise type on the accuracy of the estimated orientation.For what concerns WN, both angular velocity magnitude and 3D distribution were found not to affect the orientation error, indicating that this error is determined exclusively by the white noise STD, regardless of the angular velocity signal it is applied to.Regarding BI and SF, not only the orientation error increased with the noise level, similarly to WN, but also it was found to be influenced by the angular velocity magnitude. In this respect, a different trend was observed for the two noise types: while larger orientation errors were associated to low angular velocity magnitudes for BI, the opposite behavior was obtained for SF, in agreement with . On the Interesting results were obtained for RB, for which the orientation error was found to be strongly influenced by both angular velocity magnitude and 3D distribution, as it was found to vary up to 8° in the tested conditions. Specifically, the results obtained for an RB vector with equally and non-equally distributed components . The facThese results expose the inadequacy of the signal-to-noise ratio as a figure of merit of the angular velocity signal when it is employed for orientation estimation. Additionally, they point out the substantial contribution of the spatial orientation of the gyroscope, determined by its positioning, to the orientation error due to RB. In fact, given an angular velocity vector, which is determined by the movement under analysis, the condition of alignment or misalignment between the measured angular velocity and the RB vectors is determined by the spatial orientation of the gyroscope. However, it must be noticed that in real experimental conditions, the direction of RB is unknown, and therefore it is hardly possible to provide practical guidelines to establish the conditions of minimum error in terms of optimal gyroscope positioning.For what concerns the alignment/misalignment of the pelvis and shank angular velocity vectors with RB, it may be noted that the error due to RB vectors with equally and non-equally distributed components . TherefoIt should be noted that, due to the varying magnitude and direction of the pelvis and shank angular velocities during gait, the effect of different RB component distributions on the orientation error is slighter than when constant angular velocities are considered. Nevertheless the considerations presented in this study are still valid in principle as integration methods generally consider the angular velocity constant in each time interval between two subsequent samples . AdditioThe present study is based on a simulation approach and focuses on the individual effect of four types of noise, typical of MEMS gyroscopes, on the accuracy of the orientation estimation through numerical integration, applied to a human movement context. Additionally, the influence of the angular velocity magnitude and 3D distribution on the orientation estimation accuracy was assessed considering appropriate constant signals.All noise types were found to affect the orientation error that increases with the noise levels. The magnitude of the angular velocity was found to affect the orientation error due to all noise types except for the white noise. The error due to the scale factor increases proportionally with the angular velocity magnitude, whereas, for what concerns both the bias instability and the residual bias, the error decreases with a horizontal asymptote when the angular velocity magnitude increases. Only the error due to the residual bias was found to depend on the distribution of the angular velocity about the three gyroscope axes. Specifically, the orientation error depends on the mutual alignment of the angular velocity and residual bias vectors: maximum errors occur when the two vectors are aligned and minimum errors correspond to a condition of orthogonality between the two. The same angular velocity and residual bias were found to yield an orientation error that varies significantly (up to 8° in the tested conditions) depending on their mutual alignment.These results lead to two main conclusions. First, the angular velocity signal-to-noise ratio alone cannot be used to represent the accuracy with which the orientation can be estimated. Second, special attention must be paid in providing and interpreting measures of accuracy for orientation estimation algorithms, as orientation accuracy measures have been proven to be meaningless unless appropriately contextualized. Specifically, static accuracy information can be provided by a single value, as is currently done in gyroscope datasheets, whereas dynamic accuracy requires to specify the conditions in which it was assessed, as it is affected by the very angular velocity signal being measured. Standardized conditions could be defined, under which producers should carry out the dynamic accuracy assessment, in order to allow users to compare gyroscope performances on equal terms.


This manuscript describes a new type Ka-band airborne double-antenna microwave radiometer (ADAMR) designed for detecting atmospheric supercooled water content (SCWC). The source of the measurement error is investigated by analyzing the model of the system gain factor and the principle of the auto-gain compensative technique utilized in the radiometer. Then, a multipoint temperature correction method based on the two-point calibration method for this radiometer is proposed. The multipoint temperature correction method can eliminate the effect of changes in environmental temperature by establishing the relationship between the measurement error and the physical temperatures of the temperature-sensitive units. In order to demonstrate the feasibility of the correction method, the long-term outdoor temperature experiment is carried out. The multipoint temperature correction equations are obtained by using the least square regression method. The comparison results show that the measuring accuracy of the radiometer can be increased more effectively by using the multipoint temperature correction method. However, all of these radiometers use negative feedback control and synchronous detection circuits, which add great complexity and cost to the systems. For this reason, the digital auto-gain compensation microwave radiometer (DGCMR) was proposed [Microwave radiometers have been widely used in many remote sensing applications in recent decades –3. It isproposed .The DGCMR adopts fast analog-to-digital conversion and a software compensation technique, which can compensate the output value of the receiver according to the detected change of the system gain and greatly simplify the system structure. The remote sensing application experiments show that the DGCMR has high sensitivity and stability . HoweverIn this paper, firstly, a new type Ka-band (frequency is 31.65 GHz) airborne double-antenna microwave radiometer (ADAMR) is introduced. The ADAMR based on the digital auto-gain compensation technique is developed for detecting atmospheric supercooled water content. The detailed results of the sensitivity and stability experiments for this radiometer can be found in . Secondl2.The ADAMR is designed for detecting the radiation brightness temperature from sky. It has been successfully used to retrieve the spatial distribution of SCWC using tomography due to the high sensitivity and the optimized double-antenna structure . The bloThe heterodyne receiver uses a modularization structure, which consists of the radio frequency front end unit (RF unit), intermediate frequency amplifier unit (IF unit), noise source unit and digital circuit unit. In order to detect ultralow (<10 K) effective brightness temperature signals from the sky, the noise coupled technique is used . The theIn order to obtain more observation information, we equip the radiometer receiver with two fixed antennas. The double-antenna elevation angles are 30° and 90°. This has proven to be the best combination of elevation angles according to the results of numerical simulations . Figure LFg is the gain of low pass filter, DAg is the gain of differential amplifier, dC is the power sensitivity of the square-law detector, G is the pre-detection gain, k is Boltzmann's constant, B is the IF amplifier bandwidth. The RF switch which is controlled by the digital control unit alternately connects the antenna ports and the reference source port to the receiver periodically. In a switch period, the corresponding output voltages of the radiometer when RF switch connects respectively antennas and the reference source can be expressed as:RECT is the receiver noise temperature, NST is the reference noise source temperature, and AiT  is the antenna temperature. When the system gain fluctuates, the corresponding output voltages become:The system gain factor of the radiometer can be expressed as following:In order to eliminate the effects of the system gain fluctuation, we define a compensation coefficient α ≠ 1, considering the system gain is changed. Through digitizing the voltages and calculating the compensation coefficient by the digital circuit unit and computer, we can real-timely compensate the output voltage of system connecting the antenna by multiplying When AiT can be estimated by the two-point calibration equation:a and b are the calibration coefficients. However, the auto-gain compensation method mentioned above is based on the assumption that the receiver noise temperature and reference noise temperature are unchanged during the measuring procedure. In fact, a shift in physical temperature of the receiver causing changes in receiver noise temperature and reference noise temperature. Supposing the system gain keeps constant, when the receiver noise temperature and reference noise temperature change, the Comparing Substituting α ≠ 1, the system output voltage will be compensated incorrectly which causes the measuring error in observed brightness temperature. In order to correct this error, deriving from the physical temperature variation of the receiver, we define the measuring error as ΔAiT. The corrected antenna temperatureAiT and the physical temperatures of the temperature sensitive units above. The internal structure of the radiometer is shown in AiT with the multiplication of temperature functions related to each unit as:NST, RFT and IFT are the physical temperatures of the noise source unit, RF unit, and IF unit, respectively. We can expand each of the temperature functions above in a first order power series and retain the second order terms only:1a, 2a, 3a,…7a can be determined by regressing the result of the temperature experiment using the least square method.Because the compensation coefficient is 3.Before the experiment, we calibrated the radiometer system using two-point calibration method which combines the blackbody and the meteorological calibration. In the calibration curve, the high-temperature point is the black body temperature and the low-temperature point is the clear sky brightness temperature collected from a weather station. The calibration equations of the two antenna channels are The connection block diagram of this temperature experiment is shown in 3.1.30V is the output voltage from the 30° antenna channel, B30T is the corresponding brightness temperature of the observed target. The black body target physical temperature and the brightness temperature estimated by the two-point calibration method are shown in B30T = targetT − B30T.The temperature of the target ranges from 276 K to 311 K. The uncorrected two-point calibration equation is:NST and the measurement error ΔB30T by using the 2nd-order polynomial fit method:We obtain the relationship between the temperature of reference source The one-point temperature correction equation can be expressed as:We use the temperatures of the units shown in The results of the corrected calibration are shown in 3.2.The black body target physical temperature and the brightness temperature estimated by the two-point calibration method are shown in NST and the measurement error ΔBT90 is:The relationship between the temperature of reference source The one-point temperature correction equation can be expressed as:We can extract coefficients of the multi-point temperature correction equation by least squares method using the temperatures of the units and the measurement error. The corrected calibration equation is:The results of the corrected calibration are shown in 4.This paper introduces a new type Ka-band airborne double-antenna microwave radiometer for detecting atmospheric supercooled water content. Although the auto-gain compensative technique can eliminate the effect of the system gain fluctuation and greatly simplify the structure of the radiometer receiver, it also imports measurement errors when the radiometer operates in varying temperature environments. For this reason, we propose a new multi-point temperature correction method and carried out a long-term outdoor temperature experiment with the radiometer. The results demonstrate that the temperatures of the two antenna channels corrected by using this method have higher correlation with the target temperatures than the uncorrected two-point calibration and the one-point temperature correction methods. Since the brightness temperature is the key parameter for retrieving SCWC, it is important to obtain highly accurate flight observation brightness temperature data. This new multipoint correction method will be able to eliminate the effect of the dramatic changes caused by the aircraft cabin temperature on the airborne radiometer and improve SCWC retrieval accuracy effectively in further flight observation experiments.


The purposes of the study were to examine relative age effects (RAEs) in Spanish female soccer and to identify the influence of a playing position. The sample comprised all female players (n=4035) of five different competitive levels in the 2010–2013 seasons: First, Second and Third divisions , and National and Regional  teams were included. Differences between the observed and expected birth-date distributions were tested based on data from the general Spanish population, using the chi-square statistic followed up by calculating odds ratios and 95% confidence intervals. Results revealed that the birth-date distributions of almost all groups of football players showed an overrepresentation of players born in the first quartile. Only in the lowest level was age distribution not significantly different from that of the general population. Moreover, the RAE risk progressively increased with a higher level of involvement. It was also observed that at some playing positions the birth-date distributions were significantly biased. That was the case for goalkeepers and defenders. It could be concluded that in the current structure of Spanish female soccer there is a relative age effect, probably due to the early processes of talent identification. To guarantee equal competition, sports governing bodies for youths generally allocate participants to chronological age groups based on a specific cut-off date. As a result, there are age differences among youth of the same age born shortly after the cut-off date relative to those born almost one year after the cut-off date . In streMost of the studies related to the RAE are focused on male sports and it seems to be a persistent and repeated problem both in youth and in senior soccer categories . HoweverThe presence of RAE in female soccer is still unclear since authors have revealed inconsistent results. For instance, Certain sport structures, for instance those in which talented athletes are identified, selected, and developed from a young age, could benefit from inequalities if the number of people wishing to participate grossly exceeds the infrastructure available . This coMoreover, if RAE is related to physical advantages, it could be assumed that the magnitude of this phenomenon varies according to the players’ position, with stronger RAEs at more physically demanding positions . To our Because of the lack of related studies and the presence of unclear results, the main purposes of the present study were to examine RAE in the overall setting of Spanish female soccer and to identify if playing positions modified the prevalence and size of RAEs. More specifically, we hypothesized that the present developmental structure of female soccer, with early talent identification procedures, could stimulate the appearance of RAEs at the lowest level of selection and would be even more pronounced in higher competition levels, which could lead to a reduction of the overall quality of these levels. On the other hand, we also hypothesized that the RAE varied according to the players’ position with stronger RAEs in positions with higher physical demands.The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethical Committee of the European University Miguel de Cervantes.- First division group (FDG) (n=936)- Second division group (SDG) (n=1711)- Third division group (TDG) (n=870) .- National team (NT) (n=232): Players selected for the national teams .- Regional team (RT) (n=286): Players selected for Castilla y León regional teams (U17 and U19).The study comprised a total of 4,035 female soccer players that had played for teams registered in competitions organized by the Spanish Royal Federation of Soccer (SRFS) for the 2010–2013 seasons. They were allocated to one of the five subgroups, which included the total amount of players registered in each competitive level.Only players born after 1980 were included in the study .All data were acquired from the SRFS database. Player’s birth-dates were categorized into quartiles bearing in mind that the selection year corresponds with the regular calendar year. Additionally, the playing position for players in NT, RT, FDG and SDG were registered. The playing position data from TDG players were not available. Expected birth date distributions were calculated for the available Spanish female population birth statistics between 1980 and 1999 .Differences between the observed and expected birth-date distributions were tested with the chi-square statistic. Significant chi-square values were followed up by calculating odds ratios and 95% confidence intervals (CI) for the quartile and half-year distributions in order to examine subgroup differences with respect to the bias of the birth-date distribution. The odds ratios compared the birth-date distribution of a particular quartile  or semester (S1) with a reference group, who consisted of the relatively youngest players (Q4 or S2). A higher odds ratio indicated an increased risk of players who were born in that particular quartile compared to the reference quartile. The level of significance was set at p<0.05.This study examined the relative age effect in the overall setting of Spanish women’s soccer. As predicted, the main findings confirm the existence of a RAE at almost all competitive levels of female soccer with an overrepresentation of players born in the first quartile of the year. Moreover, findings revealed that the RAE was more pronounced as the level of competition increased.The RAE is a persistent problem in male team sports  and seemAlong the same line, The main cause of RAE in soccer might be attributed to the talent identification processes . Female A RAE was not found at the lowest level. This could be related to the so called “depth of competition hypothesis”, since that level might support universal enrollment and there is no great competition for limited posts on a team .On the other hand, as predicted, results revealed that the birth-date distributions at specific levels, in some playing positions, were significantly biased towards a higher number of births during the early part of the selection. To our knowledge, no strategies have been implemented to combat the negative consequences of the RAE in female soccer. However, as mentioned before, a decrease in RAEs might substantially enhance the overall quality of female soccer. Several alternatives have been proposed to reduce the impact of the RAE: rotating cutoff dates or grouping according to physical characteristics . HoweverIn conclusion, the current study shows the presence of RAE in the present structure of Spanish female soccer. Moreover, RAE is more pronounced as the competitive level increases, which might lead to a reduction of the overall quality of the competition due to waste of talent. Consequently, it is necessary to implement strategies to reduce the problem. One of the first steps could be to change the mentality of the coaches when they select players, finding better balance between short-term success and a more process-oriented approach to instruction. On the other hand, it could be interesting to delay the selection process until late teens, when players reach physical maturity, however, this is rather difficult as specialization starts very early in elite sport. Moreover, coaches should keep in mind that they normally select relatively older defenders and goalkeepers because of physical maturity, what could reduce future progress of a player.


A common method for conducting a quantitative systematic review (QSR) for observational studies related to nutritional epidemiology is the “highest versus lowest intake” method (HLM), in which only the information concerning the effect size (ES) of the highest category of a food item is collected on the basis of its lowest category. However, in the interval collapsing method (ICM), a method suggested to enable a maximum utilization of all available information, the ES information is collected by collapsing all categories into a single category. This study aimed to compare the ES and summary effect size (SES) between the HLM and ICM.A QSR for evaluating the citrus fruit intake and risk of pancreatic cancer and calculating the SES by using the HLM was selected. The ES and SES were estimated by performing a meta-analysis using the fixed-effect model. The directionality and statistical significance of the ES and SES were used as criteria for determining the concordance between the HLM and ICM outcomes.No significant differences were observed in the directionality of SES extracted by using the HLM or ICM. The application of the ICM, which uses a broader information base, yielded more-consistent ES and SES, and narrower confidence intervals than the HLM.The ICM is advantageous over the HLM owing to its higher statistical accuracy in extracting information for QSR on nutritional epidemiology. The application of the ICM should hence be recommended for future studies. A quantitative systematic reviews involving meta-analysis may be applied as an efficient solution to inconsistencies in the outcomes of epidemiological studies ,2. HowevIn observational studies related to nutritional epidemiology, dietary intake levels are grouped into 3 to 5 quantiles depending on the predefined categorization, and the effect size (ES) is presented accordingly. As this methodology inevitably poses the problem of inter-study discrepancies in reference points and interval units, only the ES of the highest intake quantile is used for meta-analyses . This ESTo overcome these limitations of the HLM, Islami’s collegues presented the interval collapsing method (ICM) ,11, in wThe meta-analysis performed by Bae et al.  was selei=1) and assume that each k interval has an odds ratio (ORi) and 95% CI, and the ES value obtained by using the HLM is the k-layered OR (ORk). On the other hand, the ICM was applied after obtaining the ORi and its standard error (SEi). The ES values of the respective studies were calculated by using the generic inverse-variance weighted-average method [Let the reference group be the lowest intake group  and no fluctuations in statistical significance occurred based on 95% CI. In addition, the differing patterns were examined by calculating the standard error of log effect size (SElogES) by using the 95% CI of the SES.An FEM meta-analysis was performed on the extraction values obtained from each paper to estimate the SES values and their respective 95% CI obtained when the HLM and ICM were applied. The differences in heterogeneity patterns were tracked by calculating the Taking these results together, the ICM is advantageous over the HLM in that its outcome values have lower standard errors, hence narrower CIs, while maintaining the directionality and statistical significance of ES and SES.As a limitation of this study, it should be pointed out that the two methods were comparatively analyzed based on a single meta-analysis. To improve the validity of the conclusions drawn in this study, more validation tests and application examples are required. In particular, as shown in Another limitation of this study is the difficulty in interpreting the results obtained by using the ICM, as is the case with the HLM. Islami’s collegues interpreted ICM-estimated ES values as a dietary risk factor for prevalence in comparison with non-intake ,11, but In nutritional epidemiology, the application of study results to concrete measures for disease prevention and health promotion projects, and its implementation for the general public can be achieved only when a clear answer can be given to the question of how much of a certain food item should be taken to increase the risk of prevalence. DRMA is currently used, whereby the intake level is converted into a portion size such as daily intake (g/d) . HoweverIn conclusion, of the methodologies of extracting information for meta-analysis on nutritional epidemiology, the ICM is advantageous over the HLM owing to its higher capacity for statistical accuracy based on a broader information base and should hence be recommended for future research.