The performance of the employed classifiers was analyzed using accuracy, recall, and precision, and compared to other findings in similar studies. Finally, the limitations and plans for further study are discussed.Although there is clinical demand for new technology that can accurately measure Parkinsonian tremors, automatic scoring of Parkinsonian tremors using machine-learning approaches has not yet been employed. This study aims to fill this gap by proposing machine-learning algorithms as a way to predict the Unified Parkinson’s Disease Rating Scale (UPDRS), which are similar to how neurologists rate scores in actual clinical practice. In this study, the tremor signals of 85 patients with Parkinson’s disease (PD) were measured using a wrist-watch-type wearable device consisting of an accelerometer and a gyroscope. The displacement and angle signals were calculated from the measured acceleration and angular velocity, and the acceleration, angular velocity, displacement, and angle signals were used for analysis. Nineteen features were extracted from each signal, and the pairwise correlation strategy was used to reduce the number of feature dimensions. With the selected features, a decision tree (DT), support vector machine (SVM), discriminant analysis (DA), random forest (RF), and  Despite the growing body of literature about tremor quantification for objective and quantitative diagnosis, automatic scoring of the Parkinsonian tremor severity using machine-learning algorithms for routine clinical assessments has yet to be investigated. Seeking to address this deficit in research, this paper expounds upon a machine-learning approach to objectively measure and accurately evaluate Parkinsonian tremors using the Unified Parkinson’s Disease Rating Scale (UPDRS). The aim of this study is to connect the automatic scoring system and current clinical rating scale in a more natural manner in order to attain a more objective and sophisticated diagnosis and to provide clinical convenience.As PD is a movement disorder; its symptoms mainly show clinical abnormalities of movements including tremor bradykinesia, rigidity, and postural instability . A ParkiThe assessment of a Parkinsonian tremor is usually accomplished by using rating scales. Various clinical rating scales have been used to quantify the symptoms of PD patients, of which the UPDRS is one of the best-known and most widely used methods . The UPDAlthough this method is widespread, the results obtained by this approach depend on the observer’s opinion. Ratings by trained observers and the patients’ own ratings have been surprisingly low, but there may also be poor reliability between raters ,6. In adMany previous studies have proposed measurable technologies and the analysis of the characteristics of Parkinsonian tremors using various techniques ,17,18,19Despite these studies obtaining good results for objective and quantitative approaches, most clinicians continue to use the clinical rating scale as a gold standard, and the currently available techniques have not yet found their way into routine clinical assessment ,22. MartSeveral approaches for automatically evaluating relevant features representative of the UPDRS using motion sensors have been presented for gait and gait-related tasks ,24,25,26To the best of our knowledge, however, machine-learning approaches have not yet been studied for the automatic scoring of Parkinsonian tremors. In this project, we aim to automatically assign the UPDRS of tremors using several machine-learning classifiers to obtain scientific and objective evaluations of Parkinsonian tremors. We designed, developed, and validated an automatic scoring system for PD that can easily be used in a clinical or home setting. We first describe patient participation, experiments, feature definition, and extraction, as well as multiclassification methods in , in thisEighty-five patients with PD  participated in this study. The patients met the diagnostic guidelines of the United Kingdom Parkinson’s Disease Society Brain Bank criteria. All of these patients visited the Department of Neurology at the Seoul National University Hospital (SNUH) in the Republic of Korea and were diagnosed as experiencing hand tremor symptoms in their daily lives (this does not mean that they definitely exhibited hand tremors during their visit). Patients with leg tremors or dyskinesia were not recruited. This study was conducted according to the principles of the Declaration of Helsinki (2008) with prior approval of the Ethics committee of the Seoul National University Hospital (SNUH).X, Y, and Z axes, and the gyroscope has ±2000 dps (degrees per second). The operating time of the device is 12 h when the battery is fully charged. The battery is Li-polymer with a capacity of 430 mAh and can be charged via a USB cable.A wristwatch-type wearable device was designed for this project to measure the acceleration and angular velocity of hand tremors at the same time. This is a small and low-power wireless wearable device, equipped with a triaxis accelerometer sensor  and triaxis gyroscope sensor , as shown in The device was attached to the wrist and the fingertips of the middle fingers of both the right and left hands. We used the signals of the fingers because they are mainly affected by tremor symptoms in most of the PD patients recruited in this study. The sensor position was changed when the patient had more severe tremor symptoms, specifically on another finger. Resting tremor signals were acquired when each patient was comfortably seated in a chair and after their forearms had rested on the arms of the chair for 1 min. A video camera  simultaneously recorded the patients’ hands extended to the front of the patient for later evaluation by neurologists. Both hands were recorded as large as possible within the screen of the camera for enhanced evaluation. Two neurologists, who had at least two years of subspecialty training in movement disorders, independently scored the hand-tremor severity by watching the video on the basis of the guidelines of the UPDRS. In total, 170 recordings of 85 patients’ hands were scored through video. We chose tremor recordings for which the two clinicians were in consensus about each other’s scores to design the automatic scoring system of tremor severity. As a result, 131 tremor recordings  were selected from a total of 170 tremor recordings, and each of them belonged to one of five classes ranging from 0 to 4, with a difference of 1. All signals were recorded at a sampling rate of 125 Hz and streamed via Bluetooth to a computer. After being scaled, the signals were band-pass-filtered between 1 and 16 Hz to remove artifacts such as drift and noise from the main electrical power line using a fifth-order Butterworth filter. Following that, the displacements and angles were calculated by integrating the accelerations twice and integrating the angular velocities once. The acceleration, angular velocity, displacement, and angle signals were segmented before calculating the features. A 30-s signal was segmented from the middle part of the entire signal after removing the first 10 s and the last 10 s in order to remove any unstable parts of the signal.To obtain features related to the characteristics of the tremors defined in the UPDRS guidelines, we defined 13 features from each of the signals . The defined features can be categorized into temporal and spectral features. For the temporal features, the root mean square (RMS) was calculated first from the three-axis signal. In the frequency domain, three spectra from the three-axis signal were first calculated and then averaged at each frequency to obtain one spectrum reflecting the three-dimensional (3-D) tremor movement before extracting all of the features.t) is a function of the magnitude over time)Mean amplitude: average amplitude of a tremor for a segmented periodAverage regularity: average time from the prior peak to the next peakWe first defined three features in the time domain. The mean amplitude of the tremor for a segmented period was calculated by averaging the peak-to-peak amplitude. In addition, the averaged regularity was computed to check the variability of the tremor rhythm. The standard deviation of the regularity for the segmented period was also added to the temporal features. These temporal features were calculated by the following equations and are illustrated graphically in i: a sample in a spectrum, if: a frequency at a sample i, and iP: a power value at a sample i.Mean frequencyIn the frequency domain, another 10 features were obtained. The peak frequency (PF), mean frequency (MF), peak power, and mean power were computed from an averaged spectrum. The peak frequency was defined as the frequency at the maximum power in an averaged spectrum. The mean frequency was defined as the value for assessing the center of the distribution of the power across frequencies. The peak power and mean power are the power values at the peak frequency and mean frequency, respectively.LowP), the tremor-frequency band Tr(P), and the high-frequency band (HighP). The relative power values (rlP) in these frequency bands were also computed. Relative power values signify the ratios of each frequency band to the total power value from 0 Hz to 16 Hz. In addition to the 13 features described thus far, we added the logarithms of the mean amplitude (log(mean amplitude)), the peak power value (log(peak power)), the mean power value (log(mean power)), and power values in the three frequency bands: (log(lowP), log(trP), and log(HighP)). As a result, 19 features were calculated from each set of four signals.The other six features were derived from three frequency bands in an averaged spectrum, as listed in With these features of the four signals described thus far, we implemented the pairwise selection strategy to reduce the dimension of the features ,34,35. Ak-nearest-neighbor (kNN) algorithm. When we employed an SVM, three kernels ) were used. When we employed the kNN classification method, odd numbers between 1 and 11 were considered for the k values. The reason why odd numbers were used is to avoid the ambiguity of selection when a k value is even. For validation, a leave-one-out cross-validation method was adopted to avoid bias in the classification performance . One data point among the dataset was used, in turn, for a prediction of the UPDRS, and the remaining data points were used to train the classifiers. The trained classifiers returned the estimated UPDRS classes of the tested points. We defined an absolute UPDRS classification error to evaluate the performance of the automatic scoring systems. The classification error is as follows [An automatic scoring system for the tremor severity based on the kinematic features described in  follows :(6)e≜| e of each optimized classifier for the selected features are shown in e value is shown, where the CDF values on the Y axis indicate the probability of obtaining a prediction with e ≤the corresponding X value. The highest accuracy of the automatic scoring of tremor severity corresponding to the CDF values at e = 0 was 85.5% and was achieved with the decision tree for the selected features by the pairwise correlation method. The lowest accuracy was 80.92%, obtained by the polynomial SVM for the PCA-projected data. The probability of an estimate with e ≤ 1 ranged from 94.66% to 99.24% depending on the classifiers. The decision tree returning the highest accuracy showed the highest probability of 99.24%, which means that the tremor severity can be estimated within a difference of one compared to the clinician’s decisions with a probability of 99.24% using our proposed method. The random forest and linear SVM also showed the same probability of 99.24%, although their accuracies were lower than that of the decision tree. The areas under the curve (AuCs) of the CDFs were also calculated. Here, we defined the normalized area under the curve (NAuC) of a CDF as the AuC divided by the total area. The performance, including the RMSE of each optimized classifier, is summarized in The CDFs of the classification error The performance of the automatic scoring system was investigated further with a confusion matrix from the automatic predictions of the decision tree. The recalls and precisions are presented in This paper proposed an alternative approach for the development of an automatic scoring system for tremors in PD using machine-learning algorithms. Compared to the existing methods, our approach can provide an estimated UPDRS, similar to the UPDRS already used in clinical practice with a high accuracy and the smallest margin of error yet. Plenty of researchers have studied tremor analysis to provide informative features with high and significant correlations to the UPDRS ,11,18, wThis proposed system focused on the automatic scoring of resting tremors for PD patients. This system should be expanded to include not only other tremor tasks such as postural tremors and kinetic tremors but also motor fluctuations of other extremities of patients as alternatives to classic methods in clinical practice for the quantitative and objective diagnosis of the movement disorders of PD patients. We plan to carry out related work with a more relevant dataset to develop a more perfect automatic scoring system of tremor severity with continuous feedback from neurologists working in the Department of Neurology at SNUH in the future.There are other limitations related to the underestimation of our proposed method. The prediction of each UPDRS tended to be biased toward UPDRS 0–2. Lower recalls and precisions resulted in a higher UPDRS, as presented in However, it is an inevitable occurrence, due to the population of patients with tremor symptoms in a typical hospital . There tFinally, the wearable device was used for the measurement of tremor symptoms in this study, but the incorporation of the proposed method on a wearable device may be considered in the future study. In this case, the required computational complexity on the wearable device should be taken into account for the online analysis of tremor severity on the wearable device.kNN algorithm for the selected features by a pairwise correlation strategy. These machine-learning algorithms were validated using a leave-one-out method and evaluated with various statistical methods. The main finding is a highly accurate automatic scoring system for Parkinsonian tremor severity using machine-learning methods. An RMSE of 0.034 was obtained for the measurement of five classes of the UPDRS compared to the traditional UPDRS measured by neurologists. This error is less than those of other methods that have been proposed, and the performance of our method has an accuracy of 85.5%, which is the best accuracy to the best of our knowledge for the automatic scoring of Parkinsonian tremors.This paper presents an alternative approach for the development of an automatic scoring system for the PD tremor using machine-learning approaches. We explored the use of a decision tree, an SVM with three kernels, a discriminant analysis, a random forest, and a The principal advantage of our approach is that it provides a predicted UPDRS with a high accuracy using a wearable device, which is most similar to neurologist-evaluated tremor scores in routine clinical practice using classical rating methods and can effectively be used in a home environment. Considering that existing studies have not yet been applied to real clinical practice in spite of the promising results, the application of the proposed method as a decision support tool is expected to naturally bridge new technology and the current subjective clinical rating scales in order to phase-out the present subjective clinical rating scales. Ultimately, the proposed approach could be highly useful for the effective diagnosis and management of PD.


Laparoscopic adjustable gastric banding (LAGB) is a well recognised and valid option in the treatment of morbid obesity. The objective of this procedure is to restrict the overall food intake. The technique has the reputation of being associated with a low morbidity and almost no mortality. We report the case of a 31-year-old woman, with morbid obesity, who complained from a chronic abdominal pain, mostly localized in the hypogastirum and a failure to lose weight, 13 months after a LAGB. An abdominal X-ray was obtained showing the disconnected tubing from the port, with the separated tube slipping in the pelvis. The patient underwent a laparoscopic retrieval of the band at her will, which was uneventful. Tube disconnection must be considered in patient with history of LAGB, presenting with chronic abdominal pain. A reasonable length separating the port from entrance to the peritoneal cavity may diminish the incidence of this rare LAGB complication. Retrieval of the LapBand is not mandatory in all cases, since reconnecting or changing the port can help solve the problem.


Pedetes capensis, the South African springhare. In this study, finite element analysis (FEA) was used to assess the lever mechanics of the springhare masticatory system, and to determine the function of the IOZM. An FE model of the skull of P. capensis was constructed and loaded with all masticatory muscles, and then solved for biting at each tooth in turn. Further load cases were created in which each masticatory muscle was removed in turn. The analyses showed that the mechanical advantage of the springhare jaws was above one at all molar bites and very close to one during the premolar bite. Removing the IOZM or masseter caused a drop in mechanical advantage at all bites, but affected strain patterns and cranial deformation very little. Removing the ZM had only a small effect on mechanical advantage, but produced a substantial reduction in strain and deformation across the skull. It was concluded that the masticatory system of P. capensis acts as a second class lever during bites along almost the entire cheek tooth row. The IOZM is clearly a major contributor to this effect, but the masseter also has a part to play. The benefit of the IOZM is that it adds force without substantially contributing to strain or deformation of the skull. This may help explain why the hystricomorphous morphology has evolved multiple times independently within Rodentia.The mammalian jaw is often modelled as a third-class lever for the purposes of biomechanical analyses, owing to the position of the resultant muscle force between the jaw joint and the teeth. However, it has been proposed that in some rodents the jaws operate as a second-class lever during distal molar bites, owing to the rostral position of the masticatory musculature. In particular, the infraorbital portion of the zygomatico-mandibularis (IOZM) has been suggested to be of major importance in converting the masticatory system from a third-class to a second-class lever. The presence of the IOZM is diagnostic of the hystricomorph rodents, and is particularly well-developed in  The mammalian jaw is frequently treated as a lever for the purposes of biomechanical analysis e.g., . More spIt has occasionally been proposed that mammalian jaws do not always operate as third-class levers , and canIn rodents, one muscle in particular has been identified as contributing to the jaw operating as a second-class lever. The infraorbital portion of the zygomatico-mandibularis (IOZM) is an anterior expansion of the deepest layer of the masseter, the zygomatico-mandibularis (ZM), which passes through the enlarged infraorbital foramen to take its origin on the lateral surface of the rostrum. The IOZM, also referred to as the maxillo-mandibularis  or mediaPedetes capensis—a rodent species in which the IOZM is notably well-developed P. capensis will demonstrate the masticatory system operating as a second-class lever along most of the molar tooth row. This is expected based on previous dissection work by It is hypothesised that a model of the skull of  (2)P. capensis. This hypothesis was previously proposed by It is hypothesised that the IOZM muscle has a major role in converting the masticatory system from a third to a second-class lever in Previous studies of the lever mechanics of the mammalian masticatory system have tended to focus on the mandible , owing tPedetes capensis, the South African springhare, were obtained from the University Museum of Zoology, Cambridge . The sex of the specimen was unknown, but sexual dimorphism has not been reported in this species . Bone and teeth were segmented as separate materials, but no differentiation was made between cortical and trabecular bone, nor between different materials within the teeth. These simplifications of the model geometry were felt to be justified as several previous studies have indicated that, whilst absolute strain magnitudes are impacted by the presence or absence of trabecular bone and different tooth materials, the large-scale patterns of deformation are relatively insensitive to such changes . In ordeMaterial properties were assigned to the model based on previous nano-indentation work on rodent skulls . Both bo−2  and minimum (ε3: predominantly compressive) principal strains across the skull were examined using contour maps. Geometric morphometric methods were used to analyse deformation patterns across the skull (www.evan-society.org).The model was solved for biting at each tooth along the dental arcade. Based on experimental work by he skull . A set ohe skull , based ohe skull , not a Phe skull . This waP. capensis are given in The absolute bite forces and joint reaction forces predicted by the model during biting at each tooth in The effect of removing each of the masticatory muscles on the overall mechanical advantage is given in P. capensis during biting on the incisor and first molar are shown in 1 strains than ε3 strains, and thus is predominantly under tension, whereas the orbital wall seems to be experiencing greater ε3 strains and is likely mostly in compression. Strains are generally greater during molar biting than incision, and there is an overall caudal shift of the most highly strained regions away from the rostrum towards the orbit as the bite point moves posteriorly along the tooth row.The contour maps of principal strain distribution across the cranium of 1 and ε3 strains across the skull during bites at all teeth.The geometric morphometric analysis highlights differences in the magnitude and mode of deformation between the different loadcases solved in this study. Pedetes capensis operates as a second-class lever during biting along almost all of the cheek teeth (first hypothesis), and this effect can be largely ascribed to the presence of the IOZM muscle (second hypothesis), although the masseter is important in this regard as well.The results of this study support both of the hypotheses proposed here. The skull of P. capensis indicates that the mechanical advantage of the masticatory system is greater than one and the reaction forces at the temporo-mandibular joints are negative during bites on all three molars. Furthermore, the mechanical advantage is almost one and the joint reaction force is very close to zero during premolar biting. Thus, as the bite point moves distally along the tooth row, the system switches from a third-class to a second-class lever somewhere between the premolar and first molar. In an analysis of the mandibles of two murid species, Apodemus speciosus and Cleithrionomys rufocanus, such an effect was calculated to occur between the first and second molars  and reducing tensile strains at the symphysis .P. capensis, each providing less than 11% of the total adductor muscle force. Hence, the impact of their removal on bite force and mechanical advantage was minimal. Similarly, removal of these muscles had a very limited impact on the overall deformation of the skull . Previous research has suggested that, amongst rodents, sciuromorphs are adapted for efficient gnawing at the incisors, whereas hystricomorphs are adapted to efficient grinding at the molars (The masticatory system of e molars . Druzins10.7717/peerj.3741/supp-1Table S1Landmark numbers correspond to Click here for additional data file.


Energy-resolved neutron imaging enables non-destructive analyses of bulk structure and elemental composition, which can be resolved with high spatial resolution at bright pulsed spallation neutron sources due to recent developments and improvements of neutron counting detectors. This technique, suitable for many applications, is demonstrated here with a specific study of ~5–10 mm thick natural gold samples. Through the analysis of neutron absorption resonances the spatial distribution of palladium  is mapped within the gold samples. At the same time, the analysis of coherent neutron scattering in the thermal and cold energy regimes reveals which samples have a single-crystalline bulk structure through the entire sample volume. A spatially resolved analysis is possible because neutron transmission spectra are measured simultaneously on each detector pixel in the epithermal, thermal and cold energy ranges. With a pixel size of 55 μm and a detector-area of 512 by 512 pixels, a total of 262,144 neutron transmission spectra are measured concurrently. The results of our experiments indicate that high resolution energy-resolved neutron imaging is a very attractive analytical technique in cases where other conventional non-destructive methods are ineffective due to sample opacity. The gold samples were mounted at ~15 mm distance from the detector active area. The non-relativistic energy E of each neutron is calculated from its time-of-flight (TOF) T, measured by the detector relative to a trigger that is synchronized to the time of spallationThe principle of energy-resolved imaging utilized in the present study is explained schematically in m is the mass of the neutron, and ΔT0 is the time delay of the trigger pulse relative to the time of spallation. Each pixel of the detector operates independently, enabling the detection of tens of thousands of nearly simultaneous events. Multiple neutron pulses were acquired in TOF mode, collecting several thousand time resolved images, with each image corresponding to a specific energy calculated with 2 pixel size. In the cases of insufficient neutron statistics for a single pixel that is required for a quantitative analysis of the sample properties, neighboring pixels can be combined in the post-experimental analysis in order to reduce the statistical fluctuations of measured spectra  and microstructures  of crystalline materials. Neutron diffraction occurs for thermal and cold neutron energies for which the corresponding wavelengths of neutrons are comparable to interplanar distances within the crystal structure. In a diffraction experiment, the intensities and shapes of diffraction peaks, formed by neutrons scattered out of the incident beam are used for the reconstruction of texture, strain, and phase compositions of interrogated samples121101223A little studied characteristic of naturally-occurring gold samples is their bulk crystallinity, which cannot be examined non-destructively with conventional X-ray or even synchrotron methods for centimeter-scale samples due to their opacity. Thermal and cold neutrons can penetrate such samples  and can reveal the presence of large grains or texture within the sampleThe shape and distribution of the spots observed in the diffraction images can reveal the presence of multiple large grains if present in the sample, as demonstrated in previous studiesλhkl is the wavelength of neutron, dhkl is the interplanar spacing for a given set of crystal planes with Miller indices (hkl), and E according to where The transmission image and two diffraction images from sample N1 are shown in The neutron attenuation of a sample with a given elemental composition and thickness can be calculated from the tabulated attenuation cross section values given as a function of neutron energy in the ENDF database27Quantification of the elemental composition was performed in our analysis by fitting the calculated sample transmission to the experimental data. For a given sample thickness and composition (both fitted parameters), the theoretical sample transmission was obtained from the tabulated attenuation cross sections for the natural isotope abundance. In the case of an ideal neutron beam , the transmission for a given neutron energy can be calculated from the equationl is the thickness of the sample, N is the number of atoms per unit volume, ωi is the atomic fraction of the i-th element, σij(E) is the neutron attenuation cross section for the j-th isotope of element i, and Aij is the abundance of isotope j for the element i. The number of atoms per unit volume can be obtained from the equationwhere ρ is the sample density and mij is the atomic mass of isotope j of element i. The finite time-width of the neutron pulse changes the measured sample transmission and broadens the resonances, especially at higher energies where the width of the neutron pulse becomes comparable or larger than the width of neutron resonanceswhere S is the function describing the shape of neutron pulse as a function of neutron energy for a given distance L from the source. The shape of the neutron pulse at a given spallation facility is determined by the proton pulse and the moderator used to modify neutron energies. In our analysis the function S was approximated by a Cole-Windsor function with parameters corresponding to the NOBORU beamline described in referencewhere The high resolution energy-resolved neutron imaging employed in this study demonstrates a unique possibility to investigate bulk properties of samples that are opaque to other non-destructive testing techniques. It is the combination of fast neutron counting detectors and collimated bright neutron beams available at spallation neutron sources that now allow measurement of spatially-resolved neutron transmission in a wide range of energies, spanning from epithermal neutrons  to thermal and cold neutrons . It is important to note that different bulk material properties can be reconstructed from one measurement and with a ~100 μm spatial resolution. At present, such experiments can be conducted at very few facilities only. The unique capability of neutrons to penetrate objects opaque to other more conventional interrogation methods make these studies very attractive for valuable samples, which can only be studied non-destructively .How to cite this article: Tremsin, A. S. et al. Non-Destructive Study of Bulk Crystallinity and Elemental Composition of Natural Gold Single Crystal Samples by Energy-Resolved Neutron Imaging. Sci. Rep.7, 40759; doi: 10.1038/srep40759 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


The sensitivity of traditional diffraction grating sensors is limited by the spatial resolution of the measurement setup. Thus, a large space is required to improve sensor performance. Here, we demonstrate a compact hexagonal photonic crystal (PhC) optical sensor with high sensitivity. PhCs are able to diffract optical beams to various angles in azimuthal space. The critical wavelength that satisfies the phase matching or becomes evanescent was used to benchmark the refractive index of a target analyte applied on a PhC sensor. Using a glucose solution as an example, our sensor demonstrated very high sensitivity and a low limit of detection. This shows that the diffraction mechanism of hexagonal photonic crystals can be used for sensors when compact size is a concern. Optical sensors have attracted a great deal of attention because they offer several advantages, such as non-invasive measurement, high specification, high sensitivity, real-time monitoring, and low cost, compared to other conventional analytical techniques . Among vPhC represents an intriguing solution to achieve high sensing performance. Sensors employing photonic architectures include ring resonators , surfaceIn this work, with the purpose of designing a miniature optical sensor for a handheld device  and IoT 2. The scanning electron micrograph (SEM) images are shown in The PhC sensor was fabricated on a Si substrate. The process started from first depositing a 250 nm-thick layer by Plasma Enhanced Chemical Vapor Deposition (PECVD) as the hard mask. The hexagonal 2D PhCs (nanohole arrays) were patterned by electron beam lithography. The patterned hard mask enabled the precise transfer of the PhC pattern to the Si substrate by Reactive-Ion Etching (RIE). The dielectric was then removed by buffer oxide etchant (BOE) wet etching. A schematic diagram of the PhC pattern is shown in There were two steps of measurement in this work. We first characterized the light diffraction behavior of the PhC structure, then performed glucose sensing. In the first part, to analyze the diffraction modes of the hexagonal lattices, broadband white light emission from a Xenon lamp was coupled into a multi-mode optical fiber and then was collimated before shining on the PhC surface. The incident plane of the light was chosen to be aligned with the Γ-K direction, which corresponds to a grating period of 350 nm see . The spox-axis, as shown in For periodic optical grating, the reflective modes fell on the same plane as the incident light. The 2D PhCs allowed incident light to be diffracted in various directions, as long as the conservation of momentum was satisfied. For the hexagonal PhC structure, the diffracted beams appeared at various azimuth angles above the PhC surface, in addition to the same incident plane. m is the harmonic order of diffraction; n is refractive index of the dielectric; and G is the reciprocal lattice vector given by PhCs. Light can be extracted from PhCs and radiated into the air, which is attributed to the coupling of the in-plane wavevector and the reciprocal lattice vector x,yG. Because of the symmetry of the lattice structure, the direction of the primitive cells in reciprocal space were a key factor of concern. k1 to Gk6) existed in the first Brillouin zone [m) increased, the number of lattice vectors (from Gm1 to Gm6) grew larger. When the phase-matching condition was fulfilled, the guided light could be diffracted into the air. In our measurement, as the incident angle , the cut-off wavelength is correlated to the refractive index. When the incident angle or refractive index increases, the cut-off wavelength will shift to a longer wavelength. Traditional optical biosensors characterize the refractive index of target materials by measuring the angular shift or wavelength shift of the reflected light. Spatial resolution has a tremendous influence on sensitivity. It means that the longer the distance between the reflected light and detecting instrument, the higher the sensitivity is. The cut-off wavelength approach in our hexagonal PhC avoided the limits of spatial resolution. We were able to detect the refractive index change by determining the cut-off condition from the spectra of the diffracted beams.Equation (1) also implies that diffraction behavior is dependent on the refractive index of the material applied on the PhC sensor surface. All of the diffraction patterns that were visible on top of the sensor surface met the phase matching conditions. As the wavelength of the incident light increased to a certain value where the corresponding bers see . Since kWe explored the detection capabilities of the hexagonal PhC structure using a glucose solution. As shown in The cut-off wavelength shifts of water and glucose solutions are shown in The optical detection properties of the sensor could be quantitatively estimated by the sensitivity parameter, We demonstrated the evanescent properties of optical diffraction using a 2D hexagonal PhC structure. The device can be used for sensor applications by correlating the refractive index with the measured cut-off wavelength. For glucose solution above 10 mM, the sensitivity was around 378 nm/RIU, while a much higher sensitivity of 3091 nm/RIU was achieved for concentrations below 10 mM. The limit of detection was 0.1 mM. The sensitivity of our PhC sensors was compatible or even superior to that of other PhC-based sensors. The advantage of the cut-off wavelength approach is that large spaces of measurement setup can be avoided in the high-resolution sensing of typical grating sensors.


The reliability of musculoskeletal diagnostic ultrasound imaging (MSK-DUSI) for the evaluation of neck musculature has been sparsely documented in the research literature. Until now, research has featured a limited number of subjects and only few studies have tested for both inter- and intra-reliability using appropriate methodology.Four examiners conducted an inter- and intra-rater reliability and agreement study. Fifty females with and without neck pain (NP) between the ages of 20–70 were recruited from October 2014 to April 2015. The muscles that were evaluated were the longus colli (Lcol), the rectus capitis posterior major (Rcpm), the deep cervical extensors (Dce) and the semispinalis capitis (Sscap). Each of the examiners captured ultrasound images of their allocated muscle and measured the thickness of that muscle twice, on separate occasions, for the first part of the intra-rater reliability study. For the second part, a second image of the same muscle was taken on the same subject and measured by the same examiner. The four examiners then met to measure on each other’s images, to test inter-rater reliability. Their results were compared pair-wise using Interclass Correlation Coefficients (ICC) and Bland-Altman plots. Linear regression analysis was performed to evaluate for possible bias.Inter-rater reliability was found to be good for Lcol and Sscap muscles and moderate towards poor for the deeper Rcpm and Dce muscles. Intra-rater reliability was good for all the muscles, with the exception of the Dce, which was found to be moderate in the second part of the study. The B&A plots showed good agreement, few outliers, and no bias. However, the agreement intervals indicated a measurement error within the variance of the method that may not have been acceptable for these small muscles if the aim is to evaluate change in thickness.This study found that MSK-DUSI had variable reliability in assessing the thickness of the Lcol, Rcpm, Dce, and Sscap muscles. No bias was demonstrated, but agreement intervals were wide. Neck pain (NP) is common and represents a disabling and costly problem to society . It is aThe longus colli (Lcol) function as a stabiliser and flattener of cervical lordosis , 17. TheIn recent years, MSK-DUSI has emerged as a method to evaluate morphological changes within neck muscles . The amoJavanshir et al.  reviewedThe main objective in this study was therefore to investigate one aspect of clinical utility by determining the inter-rater reliability and degree of agreement of determining the thickness of the Lcol, Rcpm, Dce and Sscap, by four raters on the same ultrasound image. It was also deemed important to ascertain the repeatability between days and between scans by investigating the intra-reliability of MSK-DUSI in measurement of the thickness of the same muscles.Intra- and inter-rater reliability and agreement study.Four raters, living in different parts of Norway, were involved in the study. The raters were chiropractors with at least 4 years of clinical experience in MSK-DUSI and had post-graduate certificates and diplomas in MSK-DUSI, from a CASE accredited University. This article is based on the four raters separate thesis submitted in partial fulfilment of the requirements leading to the degree of MSc Ultrasound. Their method was the same, but each rater had separate muscles to concentrate on. Beforehand the raters had agreed on which four muscles they considered most appropriate to investigate according to the literature describing muscle impairment in neck pain disorders , and theAn a priori decision was made to include a total of at least 50 female subjects for each muscle investigated. This was considered an accessible size as the subjects were invited into the study from the four raters’ private chiropractic clinics from October 2014 to April 2015. The subjects were enrolled by consecutive invitation over the period of one to three months at each clinic. See details for inclusion/exclusion criteria in Table The ultrasound machines used were the one the raters had available in their clinics. For the Rcpm and Sscap, the Esaote MyLab5 ultrasound machine was used, while a Medison X 8 was used for Lcol and Dce muscles. The scanning was performed in B-mode. A linear probe applied with a 40 mm footprint and high frequency  was used. The radiological principal ALARA (as low as reasonably achievable) was followed to obtain the necessary information, with minimal settings and examination time. No standard protocol (from EFSUMB or BMUS) existed for ultrasound scanning of the neck muscles. Thus, prior to testing, scanning procedures were based upon extended knowledge about anatomy from books and scientific articles. An excursion with a professor in anatomy at a dissection lab, including dissection and ultrasound scanning of a female cadaver, as well as training sessions and discussions within the study group were also a part of preparations prior to commencement of the study.Subjects were supine in a neutral position with a small towel placed under the neck to support the cervical lordosis, knees and hips were bent, and arms lying along the sides of the body. The thyroid and cricoid cartilages were palpated and the ultrasound probe was placed in the sagittal plane in the midline of these cartilages. The cricoid cartilage corresponded to the C6 level , while tSubjects were placed in a prone position, as it has previously been shown to give more reliable measurements . ForeheaFor the Dce, containing the semispinalis cervicis (Sscerv), the cervical multifidus (Cxmult), and the rotators, the transverse process on one side of C7 was identified in the transverse plane. The probe was moved medially to visualise the articular pillar and was then turned longitudinally, to identify the cervical facet joint of C5-6. The articular facet between C5-6 was placed in the middle of the image and the probe was again turned transversely. In this position, the lateral insertion of Cxmult on the articular facet and capsule was identified, while the probe was moved medially toward the base of the SP. The probe was angled up- or downwards to make the anterior and posterior borders as sharp as possible, before the image was captured. Thickness of the deep cervical extensors was determined as the measurement between the two echogenic lines of the lamina of C5 and the echogenic line of the hyperechoic fascia between Sscap and Sscerv. The calliper was positioned at 90° in relation to the laminae. The measurement was performed where the rater considered the muscular unit to be at its thickest Fig. .Fig. 3UlSscap, the third muscle in the layer, was recognised by its medial and lateral parts with aponeuroses visualised internally. To identify Sscap, the transducer was placed transversely to the level of C4. The bifurcation of the carotid artery usually occurs at the level of C4. The transducer was placed transversely to the SP and was moved laterally and anteriorly to identify the carotid artery on both sides, to ensure that the C4 level was in the image. The thickness of the muscle was measured by APD, at its thickest part over the midline of the lamina of C4, in the longitudinal view. An image in transverse plane was saved to decrease measurement error. This was achieved due to it giving dynamic visualisation of the fascia layers, thus clarifying which bright lines were actually within the muscle or fascial layer dividing the muscles  was obtained for each muscle from the left and right sides. Once the first two images were taken, the subject stood up from the bench, walked around and was re-positioned and the procedure was repeated for two more images (image B). In the intra-rater reliability part of the study, rater one measured the muscle’s thickness as image A was captured, and randomly again one week after all of the images had been collected. Thickness measurements performed by rater one on image B of the same subject, captured after re-positioning, were performed one week after all the data was collected. For the inter-rater reliability part of the study, the other raters measured muscle thickness on the entire A images and these were plotted together with the first measurements from rater one. Each of the raters’ measurements was compared pairwise to the other raters’ measurements. Thus in total, six ratings were collected for each muscle. This procedure was repeated for all of the muscles. The measurements were performed using the calliper software on the machine. The mean of two or more ratings has been recommended to increase reliability . HoweverAll of the data were analysed with IBM SPSS version 23 software. Descriptive statistics were used to describe the study population. The intra- and inter-rater reliability was analysed by calculation of the ICC, known as analysis of variance (ANOVA), which reflected both the degree of consistency and agreement among ratings. ICC was determined by a two-way mixed model, type absolute agreement, with a 95% CI , for single measures (ICC 3.1). For the estimation of the level of agreement and illustration of measurement error, the Bland-Altman plot was considered most relevant . The ratA description of the study subjects is seen in Table Separate analyses were made for the right and left sides. As the results were similar, only the right side is reported. When measurements from the four raters were compared, the ICC values for the Dce and the Rcpm were moderate towards poor, and generally lower than for the Lcol and Sscap muscles, where inter-rater reliability was good, see Table P-values were all > 0.05, so there was no proportional bias.The Bland-Altman plots for inter-rater agreement are shown in Figs. There was found to be good intra-rater reliability for all four muscles when measurements were done on the same image, see Table The aim of this study was to establish the reliability of MSK-DUSI in measuring the thickness of the Lcol, Rcpm, Dce, and Sscap by four clinicians. The lower reliability found for the Rcpm and Dce may be because morphological changes, as fat infiltration in the deepest extensor muscles including the Rcpm, may make anatomical landmarks and muscle borders more difficult to define. The ICC values were higher in the intra-reliability part of the study, which was expected as the same rater who took the images also did the measurements, and hence probably had a greater understanding of that muscle and its borders. For a test to be useful on a consistent basis in clinical practice reproducibility would be considered of more importance than repeatability . HoweverStatisticians maintain that one should not seek agreement between different methods or measurers; instead one should focus on disagreement or bias . This stTo improve the quality of the study, the methodology employed was tailored according to proposed recommendations in the literature –50. It hUnlike most previous studies both the ICC and the B&A test with LoA were used. An advantage of the B&A plot is that the graph provides a representation of the magnitude of the degree of agreement. One can easily identify bias, outliers, and other relationships between the variance in measure .The small thickness of these muscles may have amplified errors, thus influencing the variability of measurements . With laAs the cervical muscles are complex and anatomy may vary between individuals, differences in consistent anatomical landmarks represented a challenge. Measurements were only taken at one spinal level, considered consistent for each muscle. The images were two dimensional (2D), so the entire muscle could not be visualised. It was also challenging to reproduce the muscle image in the exact same plane. There were issues regarding accurate documentation of tissue boundaries and anatomical landmarks. Either because the transition between the different muscles layers was blurred or because of thickened fascia and aponeuroses were difficult to distinguish from each other. A cause for this might be muscular degeneration where decreased water content and increased fat and fibrous content may give a greater echogenicity and change in the architectural features of muscles , 54. TheIt is difficult to directly compare previous studies with the current study, primarily due to methodological differences. In these studies, the ICC has often been considered, more often intra-rater reliability of measuring muscle size of various cervical muscles, with a range from 0.60–0.99 –64, 70. We are uncertain whether further improvement of measurement procedures or more training will allow the raters to better agree and reduce errors, especially on images featuring difficult anatomical borders unless new technology with use of different ultrasound apparatus applications can improve this. Nevertheless, our study has provided clinicians with a recommendation for an ultrasound scanning protocol and measurement procedure for four different neck muscles. Intra-rater reliability was greater than inter-rater reliability and therefore our recommendation so far would be that the same examiner performs all ultrasound examinations, especially if repeated exams are being performed on each individual. We recommend the use of orthogonal views. Access to a video clip of the scanning may also be useful. More anatomical landmarks than the SPs should be used to identify cervical levels, as described in the methods, as differentiation otherwise may be difficult. However, the validity of this must be investigated further. The levels of investigation may also need to be reconsidered depending on muscle function at different spinal levels. In a study by Skeie et al. (2015), grading the degree of contraction of the lumbar multifidus, not measuring the exact thickness change, was suggested . This maThe results of this study suggest that MSK-DUSI, as an imaging tool to assess the thickness of various neck muscles, had good inter-rater reliability for Lcol and Sscap muscles and moderate towards poor for the deeper Rcpm and Dce muscles when tested by experienced raters on females with and without NP. Intra-rater reliability was found to be good for all the muscles, except for the Dce, which was moderate towards poor, for between scans repeatability. However, the agreement intervals indicated measurement errors within this method for all muscles that probably are not acceptable, especially if one should look for thickness changes in clinical practice or clinical studies. Future enhancement of ultrasound technology may solve some of the challenges with defining anatomical landmarks and tissue variables, and hence improve both the ICC and the LoA.


Avascular necrosis (AVN) of the bones of the wrist most commonly involves the lunate followed by the proximal pole of the scaphoid and the capitate. Trapezium avascular necrosis is extremely rare with only two cases reported in the literature, both of which were treated surgically. In this article, we report a unique case of trapezium avascular necrosis treated conservatively. A 38-year-old man complaining of a 4-month history of mild pain on the base of his right thumb. MRI scan was performed. The clinical presentation and the imaging findings indicated avascular osteonecrosis of the trapezium. The patient was treated with immobilization of the wrist joint for a period of six weeks. Three months later, the patient was free of symptoms and the MRI scan revealed a normal trapezium. AVN of trapezium is extremely rare. Our case shows that immobilization of an early stage avascular necrosis of the trapezium might be a treatment option. Avascular necrosis (AVN) is a disease where there is cellular necrosis of bone and marrow elements due to an interruption of the blood supply. It is a disease documented in several bones throughout the human body and most commonly affects the femoral head , 2.AVN of the carpal bones is an uncommon condition that most commonly involves the lunate  and the Trapezium AVN is extremely rare with only two cases reported in the literature, both of which were treated with bone excision and arthroplasty or vascularized bone graft , 7.In our case, we report a trapezium AVN that was treated conservatively.A 38-year-old man was presented in the orthopaedic department of our hospital complaining of a 4-month history of mild pain on the base of the right thumb. The patient had no history of trauma, no systemic disease was reported, and he had not taken any corticosteroids. He is a white-collar bank worker and reported continuous mild pain that impaired his ability in everyday activities.There was no inflammation and the mobility of the wrist and fingers was normal. Physical examination revealed tenderness over the trapezium without any swelling.The patient underwent an X-ray examination which proved to be normal. Further investigation with an MRI of the wrist revealed an area of abnormal signal intensity affecting the whole trapezium. On T1-weighted MR images, the bone demonstrated low signal intensity while being hyperintense on PD and STIR sequences . The imaDue to the mild symptoms, the age of the patient, and the blood supply of the trapezium, we decided to proceed with conservative treatment. The patient's wrist and thumb were immobilized with a thumb thermoplastic splint for six weeks and he was prescribed nonsteroidal anti-inflammatory drugs. Right after that period and because most of the symptoms were faded, he applied the splint only during the night for additional four weeks.After three months, the patient's symptoms subsided and an MRI scan revealed a normal trapezium .AVN is a condition defined as bone necrosis due to interruption of blood supply –10. AVN The disruption of blood supply leads to bone oedema as seen on MRI scans.Gelberman et al. described in detail the blood supply of the carpal bones –13. The The role of MR imaging in the early diagnosis of AVN is well established. Findings include signal drop of the whole trapezium on T1WI and increased signal on T2WI and STIR images.Its clinical presentation includes chronic pain, swelling, reduced mobility, and stiffness. An early diagnosis is vital due to the fact that it can lead to bone salvage if the correct treatment is applied.The differential diagnosis of “mild” types of trapezium AVN should include bone oedema secondary to trauma, infection , or basilar thumb arthritis, in which case the Χ-ray and MRI imaging would have been different. In our case, there was also no history of trauma or any clinical or laboratory findings of infection.With this case report, the authors would like to emphasize the excellent results of conservative treatment (immobilization) in early stages of trapezium AVN, especially when the X-ray is diagnosed as “normal.” Actually, there is no specific classification for trapezium AVN as a result of the very few cases reported in the literature. We characterised this incident as a stage I AVN based on Steinberg et al.  and ARCO2 [There is no literature regarding trapezium AVN treated conservatively. However, there are articles documenting conservative treatment of early AVN stages, such as in hip, using teriparatide, alendronate , or pros2 . The imm2 , whereasTo our knowledge, only two cases of AVN of the trapezium were reported so far and both of them were treated surgically either by suspension arthroplasty or by vascularized bone grafts , 7. In tAvascular necrosis of the trapezium is extremely rare with only two cases reported in the literature so far, both of which were treated surgically. In our case, taking into consideration the diffuse blood supply of the trapezium, we decided to treat the patient conservatively resulting in a normal bone after three months. Conservative treatment should be considered as an option before surgery.


A deep understanding of multipath characteristics is essential to design signal simulators and receivers in global navigation satellite system applications. As a new constellation is deployed and more applications occur in the urban environment, the statistical multipath models of navigation signal need further study. In this paper, we present statistical distribution models of multipath time delay, multipath power attenuation, and multipath fading frequency based on the experimental data in the urban canyon environment. The raw data of multipath characteristics are obtained by processing real navigation signal to study the statistical distribution. By fitting the statistical data, it shows that the probability distribution of time delay follows a gamma distribution which is related to the waiting time of Poisson distributed events. The fading frequency follows an exponential distribution, and the mean of multipath power attenuation decreases linearly with an increasing time delay. In addition, the detailed statistical characteristics for different elevations and orbits satellites is studied, and the parameters of each distribution are quite different. The research results give useful guidance for navigation simulator and receiver designers. The high-precision differential technique of global navigation satellite system (GNSS) has prompted the development of applications such as unmanned aerial vehicles (UAVs), autonomous land vehicle driving, and precise farming. The differential positioning technique can remove most of the errors, such as satellite ephemeris and clock, ionosphere, and troposphere, by using spatial or temporal correlations between the mobile receiver and the reference station. However, multipath is an exceptional interference because of its dependency on specific environments. Unfortunately, there is no method that can solve the multipath problem completely, especially in a severe multipath environment, such as an urban canyon area. Therefore, multipath is the last major error source that may prevent high accuracy in some circumstances.An important multipath error elimination strategy is to design a suitable filtering according to multipath statistical features . A similOver the past several decades, researchers worldwide have made much progress in characterizing multipath signals. Normally, the study methods can be divided into two types. One type of method uses a ray tracing technique to precisely calculate all possible multipath signals for a specific environment. This type is very suitable for studying multipath characteristics under specific carriers, such as fighter and warship, since the 3-dimensional structure model of carriers can be built relatively precise . The rayAnother type of method uses signal estimations on sampled real multipath signals to directly study the characteristics of multipath parameters for interested environments. Since multipath code error is periodic for the static receiver, the error model is often used to mitigate the multipath error of pseudorange ,9. TheseAlthough many achievements have been made in previous research, further research efforts in multipath channels are still required, especially for the urban environment. First, as new constellations are deployed, different orbit satellites, such as geosynchronous orbit (GEO), inclined geosynchronous satellite orbit (IGSO) and medium earth orbit (MEO), are put to work. There are not enough studies on the statistical multipath channels of different orbits, especially for the BeiDou Navigation Satellite System (BDS). Second, most researchers have focused on kinematic multipath channel models. Research on static multipath channel models is seldom seen in the literature. Third, the models developed by research groups such as DLR are based on data obtained from emulated signals that are emitted from a Zeppelin instead of a real GNSS signal. A research method based directly on real GNSS signals has not been widely used. Fourth, no empirical formulas have been proposed to describe the statistical characteristics of multipath parameters based on the experimental data. Targeting these goals, a signal sampling device is used to collect BDS B1I and GPS L1CA signals in a static urban canyon environment. Statistical models about multipath core parameters, including the time delay, the power attenuation and the fading frequency, are developed by analyzing and fitting those experimental data.The paper is organized as follows. First, the tools that are used to extract raw multipath parameters from the real signal are introduced, and the performance is tested by a GNSS simulator. Next, the urban canyon environment, where the real multipath data are collected, is described, and the method used to process multipath raw data is illustrated. Then, the statistical analysis of multipath time delay, multipath power attenuation, and multipath fading frequency is described. Finally, some conclusions are summarized based on the experimental results.x(.) represents the product of the navigation code and the spreading code. N is the multipath number. The parameter k-th multipath ray’s time delay relative to LOS, and k-th multipath ray’s carrier phase difference relative to LOS.In the multipath environment, the received signal is composed of the LOS signal and multiple multipath rays. The compound signal can be expressed as :(1)s(t)=According to (1), it can be seen that the main parameters of multipath signal are To obtain multipath parameter features from the real satellite signal, a broadband intermediate frequency (IF) data sampling and recording device is designed to store both GPS L1CA and BDS B1I raw IF signals at the same time. A one-stage, the direct down-conversion in-phase/quadrature orthogonal sampling technique is adopted with a local oscillator (LO) frequency of 1568 MHz. The sampling frequency is 62 MHz complex samples per second, with 8-bit quantization resolution. The 1 TByte capacity is able to support more than 2 h of continuous signal recording. The specifications of the signal recording device are shown in N of multipath detection is ten in one chip. However, according to the analysis of experimental data, five channels for one satellite are enough to track most powerful multipath signals. Normally, the power of the rest multipath is too low to interfere with the positioning performance.After collection in the field, the IF data were exported and processed off-line with a software receiver developed by our group. One of the algorithms implemented in this receiver is the Coupled Amplitude and Delay Lock Loop (CADLL) multipath estimation method, which can estimate multipath parameters by processing the raw IF data ,23. The k-th multipath ray, with respect to the LOS signal, is calculated ask-th multipath, respectively. The signal amplitude of each path ray isk-th multipath, respectively. Then, the power attenuation proportionality coefficient is defined asAccording to (1), the code phase delay of the The carrier phase of each path ray is computed ask-th path ray is computed asTherefore, the multipath frequency fading of the One hundred and twenty-seven correlators are used in CADLL to make the multipath-detection scope extend to 4 chips, which cover most of the possible multipath delays encountered in the urban environment. A Spirent GSS8000 simulator is used to test the performance of the CADLL algorithm. The configuration of the case is shown in From We chose Lujiazui, Shanghai, which is one of the most populated skyscraper areas in China, as the target urban canyon environment to study. This experiment area is located around 31°14′19.09′′ N, 121°29′58.77′′ E and covers approximately 1.7 square kilometers. We divided this area into 16 even cells, each of which covered approximately 0.1 square kilometers. On-field data collection occurred 26 times, all of which were marked on the Google map shown in Among all the multipath detected, it was necessary to design a principle to separate different types of multipath signals before conducting a statistical analysis. We used two different sets of separation criteria for the GEO and non-geosynchronous orbit (NGEO) satellites because their motion status and multipath characteristics differed.(1)The difference of code delay is larger than 0.1 chip;(2)The difference of power attenuation is larger than 3 dB;(3)−4 Hz (for GEO)/1 × 10−2 Hz (for NGEO).The difference of multipath fading frequency is larger than 1 × 10(4)The interruption time is more than 1 min (only for NGEO).The principle of separating a multipath signal refers to time delay, power attenuation, and fading frequency simultaneously. First, the multipath is segmented into different sections when any characteristic changed significantly, so many sections are obtained for the whole period. Then, some sections are combined and considered one multipath if the mean value of all three parameters is similar. The multipath characteristics of the NGEO satellite fluctuate more heavily than the GEO multipath, so the methods of separating the multipath are slightly different between GEO and NGEO satellites. The boundary parameters of segmenting and combining sections are shown as follows,i and multipath j are considered two multipath signals, even though all of their feature parameters are similar.In In addition, if only non-line-of-sight (NLOS) signals can be received, this satellite signals will be excluded from the data set. For the NLOS signal, the pseudorange error is usually very large and the signal power is much lower. Thus, it can be easily detected by the signal power and residual value of pseudorange especially in the static case ,25.We built some statistical models of multipath characteristics by analyzing the experimental data. The characteristics included multipath time delay, multipath power attenuation and multipath fading frequency. The validity of these models was proven by the chi-square test. The raw multipath data of all collection spots were mixed in the following analysis to achieve reasonable statistical models. According to the experiment results of all three satellite orbits, the statistical characteristics of time delay and power attenuation are the similar, while the characteristics of fading frequency have significant differences. Thus, the model comparison of three satellite orbits were analyzed only for the multipath fading frequency.We build the statistical distribution models for different elevation angle ranges because the multipath characteristics are closely related to the satellite elevation angle. x is the time delay. In ith interval and ith interval. n is the sample size, and k is the number of intervals. The result should follow a chi-square distribution with To verify that the fitted distribution is acceptable, the chi-square test is used in every probability distribution model . The forSince this paper mainly focus on the empirical model based on the experiment measurements, a common method of studying distribution function is to use all potential functions with similar trend to fit the statistical histogram. The chi-square test result is used to represent the fitting consistency of each function. It can be found that the overall probability distribution of time delay first rise and then drop, so the following six distribution functions are chosen to fit the data. The test result of time delay distribution fitted by these functions are shown in The chi-square test of time delay with different elevation fitted by the Gamma distribution are shown in x is the elevation angle. The parameters x is the time delay, and the parameters a and b are given in In this section, the multipath power attenuation will be studied. All of the fitted parameters are shown in During our experiments, the statistical characteristics of time delay and power attenuation are not distinct for different orbit satellites. This is reasonable because the time delay and power attenuation are largely related to the distribution and materials of surrounding reflecting/scattering objects other than the satellite orbits. However, when the antenna is static, the multipath fading frequency mainly depend on the satellite velocity relative to earth. Since the satellite velocities to earth of GEO, MEO, and IGSO are different, the different fading frequency behaviors for different orbits are discussed.Multipath fading frequency affects the periodic behavior of observation errors caused by multipath. There are three major factors that influence multipath fading frequency: the position and velocity of the satellite, the position and velocity of the receiver antenna, and the reflector position. In this paper, the statistical multipath fading frequency characteristics for MEO, IGSO and GEO orbits are discussed.x is the fading frequency. The parameter Considering the probability of the multipath fading frequency with a positive sign and negative sign is the same, the fitted probability distribution function is given as follows:The GEO satellite is almost static with respect to earth, and its elevation angle and azimuth angle change slowly. There are five GEO satellites in the BDS system, and the variation range of their elevation angle is less than 4 degrees. The experimental statistical distribution of the multipath fading frequency for GEO satellite is given in The chi-square test is also used to test the goodness of fit in the fading frequency distribution in X and Y coordinates are the horizontal position of reflection points with respect to the receiver. Although longer distance from reflector to receiver does not necessarily produce larger multipath delay, it has large possibility that further reflector corresponds to large delay. Thus, it is reasonable to compare the overall trend of these two distributions. To compare the models in only one dimension for the time delay and mean power, we choose the DLR model with the coordinate interval To give deeper insight into the statistical models developed in this paper, we compared our models with the models developed by the DLR group. The DLR group studied multipath models in several types of carriers and environments, and we chose the one obtained from the urban environment for comparison. The left three plots of Y axis has physical meanings that corresponded to the delays, and the X axis do not contain any information about the distribution. The distributions are supposed to form a line in the two-dimensional thermodynamic charts. In order to make thermodynamic charts more readable, we use strips to replace the supposed lines.We present the delay distribution and the power attenuation distribution from our research in a thermodynamic chart (shown in the right three plots of According to the time delay models (top three plots), the possibility of very short delays (or very near reflectors) from the antenna is quite low (dark blue shown in the charts). Then, the possibility increases as the delay increases (or the distance of reflector increases), but after a certain peak, the possibility decreases as the delay increased further. It can be seen that this trend occurs to the models of both the DLR and this paper. When we look at the power attenuation distribution (middle three plots), it can be found that both the models of the DLR and this paper follows decreasing trend as the delay increase. For fading frequency model (bottom three plots), since the DLR models are developed based on a moving carrier but the models in this paper focused on the static platform, the Doppler (or the multipath fading) distributions cannot be compared. However, we still determine that both models regarding the multipath Doppler are symmetrical around the zero axis.Overall, although the raw data are collected in different types of environment and different cities, the multipath delay and power attenuation derived in this paper are consistent with the distribution trend found by other research groups. Thus, in other types of environment, it can be believed that the distribution functions are also suitable for the multipath characteristics, but different parameters are needed.The probability distribution of multipath time delay followed a gamma distribution, and the mean time delay is inversely proportional to the elevation angle.The mean multipath power attenuation linearly decreases as the multipath time delay increases, and the multipath attenuation is normally less than −17 dB.The probability distribution of the multipath fading frequency is axisymmetric around 0 Hz, and it follows a double-sided exponential distribution.For different elevations and different satellites orbits, the type of distribution function to characterize each core parameters is the same, but the feature parameters are different.We mainly studied the statistical distribution models of multipath characteristics based on the experimental data in an urban canyon environment. The characteristics contained the multipath time delay, multipath power attenuation, and multipath fading frequency. In addition, the relationship between the statistical distribution and elevation or orbits was analyzed. Several main conclusions can be drawn:The contribution of this work provides some complements to the existing multipath models. The novel probability functions of multipath time delay and fading frequency are proposed. The results can be used in some research fields, such as multipath simulator, multipath mitigation, and spoofing detection. For example, the statistical model can help us to design the initial parameters for algorithms based on filter theory or estimation theory. The distribution characteristics can also be used to distinguish between a spoofing signal and multipath. In the future, we will continue this research in different types of environments.


Pulmonary drug delivery is currently the focus of accelerated research and development because of the potential to produce maximum therapeutic benefit to patients by directly targeting drug to the site of pathology in the lungs. Among the available delivery options, the dry powder inhaler (DPI) is the preferred device for the treatment of an increasingly diverse range of diseases. However, because drug delivery from a DPI involves a complex interaction between the device and the patient, the engineering development of this medical technology is proving to be a great challenge. Development of DPI systems that target the delivery of fine drug particles to the deeper airways in the lungs using a combination of improved drug formulations and enhanced delivery device technologies means that each of these factors contributes to overall performance of the aerosol system. There are a large range of devices that are currently available, or under development, for clinical use, however no individual device shows superior clinical efficacy. A major concern that is very relevant in day-to-day clinical practice is the inter- and intra-patient variability of the drug dosage delivered to the deep lungs from the inhalation devices, where the extent of variability depends on the drug formulation, the device design, and the patient’s inhalation profile. This variability may result in under-dosing of drug to the patient and potential loss of pharmacological efficacy. This article reviews recent advances in capsule-based DPI technology and the introduction of the ‘disposable’ DPI device. The benefits of inhaled therapy for the treatment of asthma and chronic obstructive pulmonary disease (COPD) have been recognised for many years. In comparison with oral or parenteral formulations, minute but therapeutic doses of drug are delivered topically into the airways where the active drug exerts its beneficial effects locally within the lungs. Unwanted systemic effects are minimised because the medication acts with maximum pulmonary specificity together with a rapid onset of action. As a result, aerosol formulations of bronchodilators and corticosteroids are the mainstay of modern treatment for asthma and COPD , 2. CentPressurised metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) are the devices most commonly used for drug delivery in the treatment of asthma and COPD. The pMDIs, which first became available in the mid-1950s, are globally the most widely-prescribed inhaler devices because they are cheap and use consistent technology to deliver a variety of medications. However, pMDIs do have some disadvantages in terms of effectiveness and usability. Most patients cannot use pMDIs correctly, even after repeated tuition , becauseThe main types of DPI systems are shown in Fig. This brief review focuses on recent improvements in capsule-based DPI technology and on the recent introduction of capsule-based disposable inhalers.Although therapeutic application of capsule-based DPIs began in the middle of last century with the introduction of the Aerohaler® for the delivery of antibiotics, the SpinDPI formulations may either be fine powder drug (particle size <5 μm) blended with larger carrier particles  to prevent aggregation and increase powder flow prior to aerosolization, or it may consist of drug alone Fig. . In all The role of the technology in DPI devices is to disperse the powder mixtures into a respirable fine drug particle fraction by aerodynamic means. The aerodynamic behavior of a DPI is affected by its design, dimension, and geometry of the functional engineered device parts, such as the air-inlet/air-outlet, inhaler resistance, mechanisms of disaggregating powder mixtures  and emptying the dose . For instance, the air-inlet size has been shown to have a significant impact on powder dispersion at different inhalation flow rates by varying the inlet jet flow turbulences and particle interaction velocity , 19. TheFurthermore, the shape of the drug particle affects DPI performance. For instance, elongated particles have been found to achieve higher fine particle fractions released due to the unstable particle interactions . FinallyParticle engineering using additional excipients, such as amino acids or sugar derivatives, in the drug-carrier formulations is another field of research to design the particle and surface characteristics for use in carrier-based and carrier-free DPI systems . An examThe performance of DPI formulations is also related to the characteristics of the primary packaging, from which the formulation is released upon activation in the device. Due to the ease and availability of capsule filling, DPIs use hard gelatin or hypromellose capsules as pre-metered monodose unit systems . CapsuleThe quantity of drug powder retention in the capsule depends on the interplay between the surface properties of the capsule shell, the characteristics of the interactive powder mixture, and the functioning of the device. With a given formulation and device, powder retention can be modified by changing the surface characteristics of the capsule to achieve the optimal performance target . This pe2O/L/min [All currently available passive DPI systems rely solely on the inspiratory force of the patient to disperse drug powders. When the patient activates the DPI and inhales, airflow through the device creates shear and turbulence; air is introduced into the powder bed which is fluidized and enters the patient’s airways. Thus, the drug particles, separated from the carrier particles, are carried deep into the lungs, while the larger carrier particles impact in the oropharynx and are cleared. As a result, deposition into the lungs is determined by the patient’s variable inspiratory airflow . However2O/L/min . To prod2O/L/min . Of note2O/L/min  however,2O/L/min) than that of other capsule–based DPIs such as the HandiHaler device (0.22 cmH2O/L/min). Due to its low intrinsic internal resistance it requires high inspiratory flow rates (100 and 117 L/min) to obtain a mean pressure drop of 4 kPa within the device [The Breezhaler device Fig.  is a sine device . Howevere device  and Singe device  have shoe device , studiese device , 30 corre device . In eldee device  who demoe device  recommenwithin the inhaler are required for effective dispersion rather than high airflow through the inhaler. The higher the airflow, the higher the powder dispersion generating a fine particulate, even if such a high airflow leads to a higher impaction losses in the proximal airways and, as a result, to a lower dose reaching peripheral airways [High air velocities  airways , 34. On  airways , 34. Fur airways .Ease of use and the presence of reliable feedback is considered by the majority of patients as the most important features of an inhaler. Patients are in general not assured that they have taken the full dose correctly with most inhalation devices and want ease of device use to increase their acceptance of the device. Healthcare practitioners emphasize an increase in patient satisfaction because this potentially increases adherence. To properly operate the Breezhaler device, patients must load the device by inserting the capsule of powder into a chamber . After cCapsule-based DPI requires that single doses are individually loaded into the inhaler immediately before use: this is inconvenient for some patients and does not allow direct dose counting. The device then needs to be primed by breaking the capsule, and then, depending on the patient’s breathing profile, the inhalation process must be continued or repeated until the capsule is emptied: this may result in under-dosing and high dose variability. In addition, the sequence of steps required to properly load the device may not be easy for children or elderly patients with diminished dexterity. It has been shown that patients were more confident of the medication being taken correctly when using the Breezhaler, and found it more comfortable and simpler to use compared with the Handihaler ; howeverIt has been shown that the air inlet size and grid structure of the Aerolizer capsule-based DPI were found to impact significantly on aerosolization of the carrier-based powder . More spIn inhalation medicine, from an economic perspective, the trend of the past two decades indisputably has been the introduction of a large number of generic devices for administration of ICS and beta2-agonists for the treatment of asthma and COPD . In manyIn the last decade, we have observed an increasing interest in DPI technology in response to the need for alternatives to ozone-depleting and greenhouse gas-propelled inhaler devices, and new approaches to the delivery of potent drugs of biological origin. The characteristics and dynamic interaction between fine drug particles and carrier particles, as well as the interaction between particles and inhaler characteristics, have now been elucidated . The fut


However, this approach is limited to urban areas, while a large portion of the world’s population still lives outside cities and rural areas dominate land use worldwide. Here, we extend the concept of SAMs to population density scale-adjusted metrics (DSAMs) to reveal relationships among different types of crime and property metrics. Our approach allows all human environments to be considered, avoids problems in the definition of urban areas, and accounts for the heterogeneity of population distributions within urban regions. By combining DSAMs, cross-correlation, and complex network analysis, we find that crime and property types have intricate and hierarchically organized relationships leading to some striking conclusions. Drugs and burglary had uncorrelated DSAMs and, to the extent property transaction values are indicators of affluence, twelve out of fourteen crime metrics showed no evidence of specifically targeting affluence. Burglary and robbery were the most connected in our network analysis and the modular structures suggest an alternative to “zero-tolerance” policies by unveiling the crime and/or property types most likely to affect each other.Scale-adjusted metrics (SAMs) are a significant achievement of the urban scaling hypothesis. SAMs remove the inherent biases of  Crime is a long-standing problem for society and its understanding has challenged scientists from a wide range of disciplines. From a sociological perspective, crime is treated as a deviant behavior of individuals and the goal of sociologists is often to find the conditions that lead to or favor criminal behavior. There is a vast literature on the sociology of crime seeking to find such conditions. An example is the “broken windows theory”  that corurban scaling hypothesis ).(PDF)Click here for additional data file.S4 Fig2), for the DSAMs values after shuffling their values among constituencies, and for uniform random numbers . Error bars are one standard deviation of the quantity (MIC-Pearson2). We note that the average value for original DSAMs is small and fully explained by chance. Thus, we can assume that correlations among the DSAMs are linear.The bar plot show the average value of the difference between the maximal information coefficient (MIC)  and squa(PDF)Click here for additional data file.S5 Figp-value of the two-sample bootstrap test (at 95% confidence)for the equality of mean values of the Bayesian information criterion (BIC) obtained by adjusting the DSAMs pairwise relationships with a linear and a quadratic model. We have bootstrapped the BIC values over 100 realizations and considered only the pairwise relationships in which the BIC for quadratic model is smaller than the one obtained for the linear model. Among the 231 possible relationships, the BIC of the quadratic model is smaller than BIC of the linear in 90 cases. However, the difference between the BIC values is significant only in 19 cases (indicated in the plot), that is, only in ≈8% of all relationships. (B) The same analysis comparing the linear model with the cubic model. In this case, the BIC of the cubic model is smaller than BIC of the linear in 71 cases, but in only 23 there is significant difference, only in ≈10% of all relationships.(A) Each dot corresponds to the (PDF)Click here for additional data file.S6 Figρij between the metrics, and the edge label shows the value of ρij. The edges are arranged so that negative correlations are above the gray nodes, and positive ones are below; also, the closer the edge is to the vertical position, the more intense is the correlation/anti-correlation between the metrics.Each gray node (circle) represents a crime or a property type, and the connections indicate the metrics that are negatively (blue) and positively (red) correlated with the particular crime or property type. The edge thickness is proportional to the absolute value of Pearson correlation (PDF)Click here for additional data file.