Recent studies have proposed that the diffusion of messenger molecules, such as monoamines, can mediate the plastic adaptation of synapses in supervised learning of neural networks. Based on these findings we developed a model for neural learning, where the signal for plastic adaptation is assumed to propagate through the extracellular space. We investigate the conditions allowing learning of Boolean rules in a neural network. Even fully excitatory networks show very good learning performances. Moreover, the investigation of the plastic adaptation features optimizing the performance suggests that learning is very sensitive to the extent of the plastic adaptation and the spatial range of synaptic connections. Models of neural network attempting to contribute to the understanding of learning in the brain usually look at a task where for a specific set of inputs the network has to adapt to generate a desired result. Error back propagation4, one of the most popular algorithms proposed, can however not serve as a candidate for learning in a biological sense5. A teaching signal which transmits information antidromically with memory of all neurons it has passed before, seems unlikely to exist in the brain.The brain is a large neural network, where sensory information is processed, possibly triggering a specific response. If this response turns out to generate a result, that is different from the expected one, error signals cause changes in the synaptic weights attempting to minimize further mismatches7, where forward and backward connections have to be chosen symmetric. Another interesting approach is to calculate error gradients by using an alternation of two activity phases, where one is determined by a teacher8. A similar performance, as the back propagation algorithm, can also be achieved by using exact error gradients only for the last synapses and the synapses in the hidden layers are modified only in the same direction as with back propagation9. There exist also interesting models, called liquid state machines or echo state machines, where the weights of the main network remains unchanged and the inputs are connected to a large recurrent neural network, thereby mapping the input to a higher dimensional space11. These models are mainly used for spatiotemporal problems like speech recognition, but their capability for recognizing handwritten digits has also been demonstrated12.Different studies have proposed a variety of models for a neural network able to learn without passing error gradients antidromically. It has been suggested that errors could propagate backwards through a second network13. In particular for dopamine, it has been verified, that its release can mediate plasticity15. In several recently proposed models these ideas are implemented by the assumption that spike-timing-dependent plasticity (STDP) and dopamine induced plasticity are directly coupled18. These models assume that dopamine serves as a rewarding signal. In an other model it has been proposed19 that the transmitted feedback signal changes the vesicle release probability of previously activated synapses.The variety of model reduces if we insist on the assumption that synaptic changes have to be triggered by a specific error signal. Since there is no evidence that a neural network can transfer feedback information antidromically, such a signal should propagate through the extracellular space. A feedback signal to change the strength of synapses in a larger region could for instance be delivered by monoamine releasing neurons. It is known that these neurons release their transmitters deep into the extracellular space22. Based on such ideas, de Arcangelis et al.24 proposed a model of spiking integrate-and-fire neurons which is able to learn logical binary functions in a neural network. For wrong responses by the neural network, activated synapses are modified proportionally to the inverse number of synaptic connections on the signal path to the output neuron. This method implies that the feedback signal propagates backwards on the synaptic connections and decreases in strength depending on the number of neurons it has passed before. In this article we extend these ideas by a model, where the strength of the feedback signal does not depend on a network distance, but on the euclidean distance. By this model we study the importance of the localization of a teaching signal, i.e. if a localized learning signal can represent advantages over one acting widely in space. This is the case, for instance, of dopamine whose effect covers a finite range of tens to thousands of synapses13.Opposite to rewarding reinforcement it has been argued that negative feedback signals, which change synapses only if mistakes occurred, are more biologically plausible and preserve the adaptability of the systemN neurons in the hidden network, which are placed randomly in a square, with side length L. The area is chosen to scale proportional to N, such that the density of neurons remains constant  and when applying the input patterns, as long as no input leads to firing of the output neuron, all synapses are strengthened by a small amount . As soon as the first input leads to the output neuron firing, the network is considered to be close to the “critical point” and the learning procedure starts.Whether the activity reaches the output neuron depends solely on the strength of the synapses. If the average strength of the synapses is too low, the propagation of the activity stops soon and only a fraction of the entire network will fire. On the other hand for very strong synapses almost all neurons will fire several times and the output neuron will fire for each input pattern. Therefore an optimal choice for the average synaptic strength is a “critical value” where on average for each input pattern there is an equal chance that the output neuron fires or does not fire. We approximate this “critical point” by initially choosing weak synapses . The ωij and the nact dependence are considered since they lead to an increase in learning performance. A maximum synaptic strength (ωmax = 2) is imposed. If the activity is so weak that the voltage of the output neuron remains unchanged, the system is not able to provide an answer and therefore we increase all the weights by a small amount (Δωij = αωij).Learning proceeds as follows: All inputs of the rule are fed into the network one after the other, where the value of the neurotransmitters and the voltages are restored back to ωij ≥ 0) and inhibitory (ωij ≤ 0) synapses. It has actually been shown that a certain percentage of inhibitory synapses can increase the learning performance24. The importance of inhibiting signals can be seen by looking at the XOR-rule  the success rates are close to zero. This is not surprising as only the synapses leading to the output neuron are modified by a noticeable amount. For larger r0 the learning adaptation penetrates deeper into the network and the success rate rapidly increases up to s = 1.0 for r0 = 10 and Tmax = 100,000. Interestingly, when r0 exceeds the system size (r0/L = 1), which implies that all synapses in the network are adapted, the learning performance strongly decreases. Overall, we find that the learning performance can strongly be optimized by the spacial extent of the teaching signal.We first investigate the role of the learning length see Fig. . For verr0 at which the learning performance increases shifts towards larger values the more patterns the network has to learn. This suggests that the more patterns a network has to learn the deeper the learning signal has to penetrate into the network.Figure r0 increasing proportionally to L, whereas the s-decay shifts towards larger r0 for larger system size. This result confirms that the learning capabilities decrease when r0 exceeds the system size L and the adaptation changes all activated synapses in an almost uniform way. In Fig. d0 and study its effect on the learning performance. When r0 exceeds the system length, d0 strongly affects the learning performance. For longer synapses (higher d0) the performance drops much faster as r0 increases. This result is in agreement with the abrupt decrease of the performance for plastic adaptation acting over a range larger than the system size L. For very large d0, the synaptic network also undergoes quite uniform plastic adaptation over large distances. The maximum performance appears to weakly depend on d0, except for very localized connections.Next we investigate, the role of the network size on the performance. Indeed, we find a monotonic increase in performance see Fig. . InteresWe also ask the question whether the space dependence of the adaptation influences the presented results. Therefore we perform simulations using a plastic adaptation that decrease in space as a Gaussian. Results are very similar (data not shown) to those obtained for a synaptic adaptation decaying exponentially, except that for the Gaussian adaptation the peaks are slightly narrower.trefr = 1 and trefr = 2. For trefr = 10 the performance decreases almost to zero. This might be related to the fact that for larger refractory times it becomes less likely that a single neuron fires more than once, therefore preventing the occurrence of activity loops. This result shows that the refractory time is an important ingredient to generate inhibition, but also the activation function (Heaviside step function) causes dissipation which can create inhibition. We could reduce this type of dissipation by using an activation function that is proportional to the voltage of the firing neuron. Equation Further, we tested the influence of the refractory time on the learning performance see Fig. . When thtrefr = 0 to learn, but with a low performance.To eliminate dissipation completely we would need to set the firing threshold to zero. However, this would make learning impossible as every input will make all successive neurons fire and nothing can stop the output neuron from firing. In Fig. pinh = 0.2 of inhibitory neurons. Inhibitory neurons noticeably increase the maximum learning performance and the performance decay for larger r0 is slightly less pronounced. In Fig. In each case of Figs r0 exceeds the system length L, where the performance decreases. When 27 and EEG data29 shows that a greater brain signal variability indicates a more sophisticated neural system, able to explore multiple functional states. Signal variability also reflects a greater coherence between regions and a natural balance between excitation and inhibition originating the inherently variable response in neural functions. Furthermore, the observation that older adults exhibit less variability reflecting less network complexity and integration, suggests that variability can be a proxy for optimal systems.We show that a neural network trained by a distance dependent plastic adaptation can learn Boolean rules with a very good performance. The spatial extent of the learning signal was found to have a huge impact on the learning performance. A very localized plastic adaptation, which only modifies the synapses directly connected to the output neuron, results, unsurprisingly, in poor performance. For deeper adaptation signal, the performance strongly increases, until the learning length Interestingly, we show that a network with only excitatory neurons can learn non-linearly separable problems with a success rate of up to 100%. In this case, the neural refractory time generates inhibition in the neuronal model. If we include additional inhibitory neurons the performance still increase noticeably.Regarding the network structure we find that the synaptic length also has an impact on the performance: For networks dominated by local connections the performance is worse compared to networks with long range connections. We conclude that the structure of the network and the locality of the plastic adaptation have an important role in the learning performance. To assess the generality of our results it will be necessary to study more complex forms of learning like, for example, pattern recognition. Further investigations should also try to improve the learning performance to become comparable to machine learning algorithms.


In this work we theoretically and experimentally analyze the resonant behavior of individual 3 × 3 gold particle oligomers illuminated under normal and oblique incidence. While this structure hosts both dipolar and quadrupolar electric and magnetic delocalized modes, only dipolar electric and quadrupolar magnetic modes remain at normal incidence. These modes couple into a strongly asymmetric spectral response typical of a Fano-like resonance. In the basis of the coupled mode theory, an analytical representation of the optical extinction in terms of singular functions is used to identify the hybrid modes emerging from the electric and magnetic mode coupling and to interpret the asymmetric line profiles. Especially, we demonstrate that the characteristic Fano line shape results from the spectral interference of a broad hybrid mode with a sharp one. This structure presents a special feature in which the electric field intensity is confined on different lines of the oligomer depending on the illumination wavelength relative to the Fano dip. This Fano-type resonance is experimentally observed performing extinction cross section measurements on arrays of gold nano-disks. The vanishing of the Fano dip when increasing the incidence angle is also experimentally observed in accordance with numerical simulations. The electromagnetic excitation of conduction electrons in metallic nanoparticles results in the well-known localized surface plasmon resonances (LSPRs)12578101112Interestingly, particular arrangements of metal nanoparticles give rise to magnetic plasmon modes16162021In some cases, coupling effects in plasmonic structures may lead to the formation of Fano-type resonances2425272829253132353637In this work we theoretically characterize a planar oligomer of gold nanoparticles, consisting of a regular array of 3 × 3 particles that presents a Fano-like resonance when illuminated under normal incidence. In the basis of the fully analytical Mie theory generalized to interacting particles, the electromagnetic field scattered by the overall structure is expanded in terms of a multipolar basis. As a result, the oligomer is considered as an effective scattering particle. Resonances in the different multipolar contributions to the total extinction are then considered in order to investigate the origin of the Fano-like resonance. We rely on the coupled mode theory to interpret the Fano-type resonance as resulting from a hybridization process between electric and magnetic resonant modes of the structure. The effect of the structure size as well as the illumination on the oligomer optical response is then explored. The near-field effects, especially magnetic and electric field enhancements on the structure, at normal incidence are also theoretically studied and interpreted according to the previous analysis. Experimental characterizations of gold nano-disk arrays will also be carried out to confirm the effect of the incident angle on the emergence of a Fano-like resonance. To the best of our knowledge, Fano-type resonances on a single plasmonic oligomer under normal incidence have never been reported from the coupling between an electric and a magnetic mode. This result could lead to a revival of interest for this kind of structure, particularly as building blocks for optical metamaterials.We theoretically investigate the optical properties of a finite array of gold nanoparticles. All results are obtained using the Mie theory generalized to interacting particles41Let us consider a 3 × 3 periodic array of gold nano-spheres in vacuum, 50 nm in radius, with a gap of 10 nm between the particles. As shown in fmn and gmn related to magnetic and electric multipolar contributions to the total radiation respectively. With such an expansion, it is possible to consider the whole structure as a unique scattering object virtually bounded by the smallest sphere enclosing the structure. Here, we use the term multipole to refer to the different n orders of the expansion, e.g. n = 1 dipolar, n = 2 quadrupolar, etc. The scattering coefficients are computed in order to identify the nature of the different optical resonances sustained by the structure and particularly those at the origin of the Fano resonance. In the following, we consider the contribution of these different multipoles to the total extinction.By expanding the total field scattered by the whole structure in a multipolar basis (see Methods), we access the oligomer’s scattering coefficients m = 0 for the dipolar magnetic (DM), m = ±1 for the quadrupolar magnetic (QM), m = ±1 for the dipolar electric (DE) and m = ±2 for the quadrupolar electric (QE) multipole . In this sense, the QE and DM modes (at grazing incidence) are both only coupled to the driving excitation without mutual coupling, since they present a Lorentzian shaped resonance centered at independent wavelengths . In turna1 and a2 of two mutually coupled resonance modes upon a driving excitation f0 can be described using the coupled equations30According to the CMT, the temporal amplitudes κi is the coupling coefficient of the ith mode with the driving excitation, ωi its complex valued angular eigenfrequency, κ12 and κ21 are the mutual coupling coefficients. It has to be noted here that the real part of a complex valued angular frequency corresponds to the associated resonance position while its imaginary part corresponds to its half-width at half-maximum (HWHM) and is related to the mode losses. Considering the amplitudes in ω, we can rewrite them as ai(t) = ãi(t)exp(−jωt) and where i(ω) of the ith mode is then formally expressed as a sum of two singular functions of the angular frequency, that are characterized by their complex poles (ω+ and ω−) and amplitude constants (ω+ and ω−) contributing to the spectral response of the two mutually coupled modes.The frequency domain resonance amplitude ãIn order to demonstrate the hybridization of the DE and QM multipolar contributions to the total extinction of the structure, we apply the CMT to the resonant behavior observed in the complex valued extinction of the electric (ã2(ω)) satisfy Anticipating the coupling between DE and QM multipolar contributions, their complex extinction should be mainly described by the sum of two singular functions resonant at the same frequencies as described in Finally, the Fano-like resonance of the structure results from the spectral overlapping of the DE and QM multipoles. If the Fano-like resonance line profile can be fully interpreted in terms of spectral overlapping of resonant modes, the asymmetry of the latter can be described as mostly originating from coupling (hybridization) processes in the structure. In general, the nanoparticle size and spatial arrangement as well as the illumination conditions affect both the direct excitation and the mutual coupling between resonant modes, which in turn fixes the overall optical response of the plasmonic structure. As an example, when scaling down the oligomer’s size  under normal incidence, the characteristic Fano dip of the total extinction spectrum gradually vanishes  and tranChanging the illumination conditions also significantly affects the structure’s optical response. Considering the initial structure, the Fano dip obtained at normal incidence progressively vanishes from the total extinction  when incAn interesting feature of such a system is the local magnetic field enhancement that occurs in the spectral range of the Fano dip (around 600 nm) . At thisThe tunability of hot-spot localization with the wavelength has been pointed out in the case of metallic nanoparticle chains4647The spectral behavior of such plasmonic oligomers has been experimentally characterized using arrays of gold cylinders. These structures, fabricated using electron beam lithography, consist of a series of 3 × 3 arrays of gold/chromium bi-metallic disks (the chromium acting as an adhesive layer). The disks have a diameter of 100 nm and a height of 5 nm (chromium) + 25 nm (gold) and have been deposited on a quartz substrate. The particular structure considered here is slightly different from the theoretical case which has been previously thoroughly studied. The differences concern the presence of a plane interface (the substrate), the geometry of particles (cylinders rather than spheres) and finally changes in the gaps between particles. For the external lines, the gap between particles is 20 nm, whereas it is 10 nm in the central line . CompareThe spectral behavior of samples shown in Having shown previously that a minimal oligomer size is required for the emergence of a Fano-like resonance, we explore here how the structure optical properties evolve when scaling up its dimensions. When keeping the radius to gap ratio constant and equal to 5, the increase in the particle size results in a redshift and a broadening of the Fano dip in the total extinction spectra . The conInterestingly, the interplay between electric and magnetic modes also explains the formation of Fano-like resonances in other plasmonic oligomers. As an example, the widely studied heptamers49We characterized the Fano-like resonance of a 3 × 3 array of gold nanoparticles illuminated at normal incidence, as resulting from the coupling between the dipolar electric and quadrupolar magnetic multipolar contributions to the total extinction of the structure.On the basis of the coupled mode theory, the asymmetric Fano line shape was analyzed by using an analytical representation of the structure and by expressing the complex optical extinction as a sum of singular functions of the angular frequency. This analysis brings a clear evidence of hybridization of the electric and magnetic multipolar contributions. The unusual phase behavior of the two hybrid modes formed by the coupling process explains the non-Lorentzian resonance profiles and the characteristic Fano dip results from their spectral interferences.As theoretically highlighted, the structure supports a local enhancement of the magnetic field, but also the special feature to confine the electric near-field intensity in different lines depending on the illumination wavelength relative to the Fano dip under normal incidence. This interesting property was assumed to result from constructive or destructive contributions of electric and magnetic multipoles to the total near-field on the different lines of the array. An experimental characterization of the Fano-type resonance has been performed through the optical extinction measurement of gold nano-disk arrays. In accordance to simulations, the Fano dip vanishes when increasing the incidence angle from the normal.Based on the fully analytical Mie theory, the methodology presented in this work can be applied to the analysis of the resonance behavior of arbitrary structures composed of nano-spheres. The results obtained here are retrieved in other plasmonic oligomers. We pointed out that the Fano-type resonance observed in heptamers also results from electric and magnetic mode interplay. This could extend the application range of this kind of structures, particularly for the possibility to generate artificial magnetism at optical frequencies.All simulations are performed using the Mie theory generalized to interacting particles, that allows for solving rigorously the multiple scattering problem41420 is the damping constant of bulk gold (0 = 70.9 meV), ωP is the plasma angular frequency of gold (ωp = 9.02 eV). εib is the contribution of interband transitions computed by using Kramers-Kronig relations on the experimentally obtained refractive indexwhere ΓOnce the scattering problem is solved, the total electric field scattered by the structure is represented in terms of vector wave function decomposition:fmn and gmn respectively. The superscript “3” on these wave functions corresponds to the use of spherical Hankel functions of the first kind as radial functions, that ensures the Silver-Müller radiation condition for the scattered fieldwhere k1 the wavenumber in the surrounding medium, E0 the incident electric field, amn and bmn the incident field expansion coefficients. The representation (4) directly provides the contribution of the multipolar electric and magnetic modes. Then the terms n = 1 correspond to the dipolar magnetic (DM) contribution to the total scattering, with n = 2 to the quadrupolar magnetic (QM) contribution, and so on. Moreover, the terms n = 1 correspond to the dipolar electric contribution, n = 2 to the quadrupolar electric one. The contribution of all these modes to the total extinction cross-section can then be computed through their expansion coefficients:with These expressions are used to plot the different mode extinctions in ek of the incident plane wave given by the spherical angles , and is practically computed using the expansion coefficients:The complex valued extinction with As in the case of the extinction cross-section, the contribution of all magnetic and electric modes to the total complex extinction is computed by using the related expansion terms:The complex valued extinction of the dipolar electric and the quadrupolar magnetic modes are used in the singular analysis to characterize their coupling.2 and up) to form the desired patterns. The substrate is then dipped in water for 30 s to dissolve the Aquasave coating. The PMMA film is developed using a cold process by soaking the substrate in an isopropanol:water (7:3) solution at 5 °C, for 100 s, and under ultrasonication. This cold development process is non-standard, extra high contrast and gives the higher resolution of the structures. Finally both chromium (5 nm) and gold (25 nm) are deposited (using a Semicore evaporator) on the substrate before performing a lift-off of the PMMA film using dichloromethane.The gold nanostructures are fabricated using electron beam lithography. Poly-methyl methacrylate  polymer is spin coated at 1000 rpm on the glass substrate to form a 60 nm in thickness layer and baked 5 min at 180 °C. An Aquasave conductive polymer is then spun at 2000 rpm and baked at 100 °C. This film dissipates the charges while exposing the sample to an electron beam . The other end of the multimode fiber is fixed to a movable board. The light out-coupled from the fiber is collimated with a lens (L2). Then, it is linearly polarized using a linear polarizer (LP). Now, to know the angular position θ of the movable board, the latter is mounted on top of a goniometer. The alignment of the platform is done with respect to the normal direction of a sample holder, which is chosen to be the 0° of the goniometer. The sample holder is moved with a 3D nano-positioning system , which is attached to three 1D translation stages. The substrate containing the 3 × 3 arrays is glued onto the sample holder. Then, the linearly polarized beam is shone onto the sample. The scattering of the arrays, as well as the direct illumination, are collected with a microscope objective . Since the sample is placed on the focal plane of the MO, the signal is collimated after MO. Then, a tube lens (L3) having a focal distance of 150 mm focuses the light down to a multimode fiber, which acts as a confocal filter. Finally, the fiber is then plugged into a spectrometer , where the extinction spectra of the different measurements are retrieved. The confocal detection area is about 700 nm in diameter that allows measurements on single structures.The spectral behavior of the samples shown in b). This background measurement takes into account the lamp spectrum, as well as the effect of all the other elements present in the set-up. Then, a measurement of the 3 × 3 structure in consideration is done (I). The extinction measurement is obtained using the following relation:Then, in order to measure the extinction of a nanoarray, a double measurement is done. Keeping the same illumination always, two confocal measurements are done. Firstly, a background spectrum is recorded .


It is argued that they incorrectly extracted the extracellular impedance because of an inaccurate representation of the large confounding impedance of the neuronal membrane. In conclusion, no compelling evidence has been provided to undermine the well-established and physically plausible consensus that the brain extracellular impedance is low and approximately resistive.Numerous measurements in the brain of the impedance between two extracellular electrodes have shown that it is approximately resistive in the range of biological interest, <10 kHz, and has a value close to that expected from the conductivity of physiological saline and the extracellular volume fraction in brain tissue. Recent work from Gomes et al. has claimed that the impedance of the extracellular space is some three orders of magnitude greater than these values and also displays a  This analysis will focus on the most recent article by Gomes et al. .−1 (−1) and the volume fraction (0.2) of brain tissue . As drawn, any current circulating in the recording electrode must also traverse the reference electrode, so it would not be “passive”. Moreover, Gomes et al. state that “variations on the extracellular electrode did not exceed 1% of the variations of the intracellular potential”. However, no circuit is shown or described that is able to measure the extracellular voltage independently.r = 5 μm. The resistance of the extracellular space from the spherical surface to infinity is given byIt is useful to quantify the expected extracellular impedance. Assume the soma of a neurone is a sphere of radius The potential difficulty of accurately extracting the extracellular impedance from the series combination with the much higher electrode and neuronal impendances is apparent. Departing temporarily from the nomenclature of Gomes et al., they measure a global impedance asTo extract Gomes et al. represent the impedance of the neuron’s dendritic tree using an approximation they call the “generalized cable formalism”. The impedance of the dendritic tree is expected to dominate the global impedance measured, so the failure of the generalized cable formalism to account entirely for the measured impedance potentially arises from a limitation of the model representation or a fitting problem (see below). However, instead of adjusting their dendrite model, Gomes et al. obtain a better fit by the ad hoc inclusion of a series impedance element with a sistance , 10.A and B were obtained by fitting and are given in the legend of their Fig. 2 as A = 99 MThe extracellular Warburg impedance proposed by Gomes et al. is given by their equation 2 and, at low frequencies, approaches the limit of There are possible problems with the authors’ inclusion of this Warburg impedance. Normally the mechanism of the Warburg impedance requires depletion/accumulation of charges that contribute to electrode reactions, but there is no oxidation or reduction occurring at the membrane. Gomes et al. do not establish an equivalence with ions that do cross the membrane, presumably mostly potassium ions, although this may be their implicit assumption. There is no attempt to model the changes of potassium ion concentrations and the resulting change of extracellular conductivity. In any case, for sufficiently small currents, the effects of this mechanism would disappear because the concentration changes would become small relative to the resting ionic concentrations. Instead of constraining their model Warburg impedance with available information, Gomes et al. introduce it with three free parameters, enabling it to attain unrealistically high impedances during the fitting procedure.A further problem is that ionic currents only account for a significant fraction of the membrane current at low frequencies. Thus, above ∼10 Hz, a majority of the membrane current is capacitive, and that fraction increases further with frequency. Because capacitive currents only involve displacement of ions relative to the membrane, no ionic transfer and no electrode reaction are required; this weakens the authors’ argument that there is a special property of the membrane-solution interface that has not been accurately captured in previous measurements.The model fitting appears to have been difficult. According to the methods, “traditional fitting methods” did not work, so the parameter space was probed by a Monte Carlo method. However, the density of sampling seems to have been rather low: at most, 5000 samples from “very large” domains. Some of the models had six parameters, so this amounts to an effective grid of little more than four (sixth root of 5000) random values per dimension. In turn, imprecision of fitting might undermine the model evaluation.In their most recent preprint, Gomes et al. suggest that previous measurements of the extracellular space might have been affected by tissue damage from the electrode . It is uInsertion of an electrode will have two opposing effects on the tissue resistance . If tisshttps://www.ncbi.nlm.nih.gov/pubmed/26745426.In conclusion, the observations attributed by Gomes et al. to the extracellular impedance may instead arise from an incorrect representation of the membrane impedance of the complex dendritic tree, which confounds extraction of the extracellular impedance from an extremely difficult measurement configuration. This, in turn, would imply that there is no evidence calling into question the previous determinations of a low and largely resistive extracellular impedance in brain tissue. Similar arguments may be relevant to other publications on this subject by the same group , 13. Rea


Conventional colonoscopy requires a high degree of operator skill and is often painful for the patient. We present a preliminary feasibility study of an alternative approach where a self-propelled colonoscope is hydraulically driven through the colon.A hydraulic colonoscope which could be controlled manually or automatically was developed and assessed in a test bed modelled on the anatomy of the human colon. A conventional colonoscope was used by an experienced colonoscopist in the same test bed for comparison. Pressures and forces on the colon were measured during the test.The hydraulic colonoscope was able to successfully advance through the test bed in a comparable time to the conventional colonoscope. The hydraulic colonoscope reduces measured loads on artificial mesenteries, but increases intraluminal pressure compared to the colonoscope. Both manual and automatically controlled modes were able to successfully advance the hydraulic colonoscope through the colon. However, the automatic controller mode required lower pressures than manual control, but took longer to reach the caecum.The hydraulic colonoscope appears to be a viable device for further development as forces and pressures observed during use are comparable to those used in current clinical practice. Colonoscopy is the only commonly used method for screening the colon which allows for full endoscopic examination of the colon and for polypectomies and biopsies to be carried out as required. It is recognised as the gold standard for establishing the diagnosis of colorectal cancers, and in excess of ten million colonoscopies are carried out each year .However, the procedure has some limitations. It utilises a conventional colonoscope (CC), which is a flexible endoscope equipped with a steerable tip. Even in expert hands, the passage of the colonoscope up to the caecum can cause pain and discomfort to the patient. For this reason, the procedure is usually carried out under sedation. Concern about pain and discomfort also reduces patient compliance . AdvanciVarious alternatives to the CC have been trialled with the aim of overcoming its limitations . These rIn this paper, we describe the “Hydraulic Colonoscope” (HC), a colonic propulsion system, which aims to reduce patient discomfort and the amount of skill required by the operator to advance the colonoscope to the caecum. The system may reduce discomfort in two ways. Firstly, it is a self-propelled device obviating the need for external pushing; a self-propelled device should reduce forces on the colon and thus patient pain, an outcome which has previously been demonstrated in a clinical study . Secondl2; however, the system described in the present report uses water as the pressurised driving fluid. A prototype of the device was constructed and tested in a test bed constructed from porcine colon, reconfigured to simulate human colonic anatomy including flexures and mesenteric attachments. The paper reports on the design of the system and its performance compared to a conventional colonoscope.The propulsion principle of the HC is for a flexible seal to be formed in the lumen of the colon which is then driven through the colon by pressurised fluid. This principle was used in the Aer-O-Scope , which wThe HC system comprises a colonic vehicle (CV), which is linked to a supporting extra-corporeal system of pumps and valves via a tether. It is controlled and monitored by a control system running on a connected PC.The body of the CV is surrounded by a balloon, which is able to form a seal within the colonic lumen, blocking fluid flow past the CV. The balloon is flexible and may be inflated or deflated so that it conforms to the varying dimensions of the colonic lumen while maintaining a seal. It is capable of sliding through the lumen because of the low-friction characteristics of the colonic mucosal surface. As the sealing balloon fills the lumen of the colon, the walls of the colon passively guide the CV, and thus the CV will follow the lumen of the colon without an active guidance system. The balloon is linked to an extra-corporeal pressure control system by a 1.8 m long PVC tube, with 6 mm outer diameter. This tube passes through the colon and also acts as a tether, allowing for easy withdrawal of the CV. The tether also passes through a PTFE seal in the anal port, thereby allowing the tether to slide while preventing water leakage from the colon. The mean friction of the tether passing through this seal was measured as 0.35 N (max 0.8 N).An extra-corporeal pump system is used to pump water into the colon behind the CV so that a pressure differential is created across the CV. This forces the CV forward through the colon, until it ultimately reaches the caecum. The subsystems for inflating/deflating both the sealing balloon and the colon are similar. Each consists of a pressurised water supply for inflation, a pump for deflation, a solenoid valve for control and a pressure sensor for feedback. A schematic of the elements of the system can be seen in Fig. Piezoelectric pressure transducers monitor the pressures in the colon in front of and behind the device. Currently, these sensors are attached to the test bed at each end of the colon, but they could be built into the CV and anal port. If excessive water builds up in front of the CV, the balloon is deflated and the entire colon is drained of water.The CV contains a magnetic tracker  to allow monitoring of its position and orientation. As the current study is focused on the propulsion system, a camera is not included in the CV; however, a dummy rigid body (Ø 11 mm × 25 mm long) is included at the distal tip to simulate the effects of carrying a camera in the device.The ultimate goal of the control system is to autonomously drive the HC to the caecum, while keeping pressures within the safe physiological range. The control is non-deterministic as the colon’s mechanical properties, constraints and shape vary greatly between individuals and in different sections of a single colon , 18.To achieve this goal, the controller has been designed to integrate two mutually dependent parallel finite state machines (FSMs) in a closed loop. State machines are the oldest known formal model for sequential behaviour , where tThe first FSM controls the inflation of the balloons and has three possible states: hold, deflate and inflate see Fig. A. The seThe controller allows for either fully automatic or manual control of the HC. During manual control, the operator has access to the information gathered from the sensors via the interface, as well as being able to directly observe the HC and colon. The user interface can be seen in Fig. The controller has been designed to ensure patient safety by limiting pressures to safe values. These safety measures are included in the system as high-priority interruptions in the different modes of operation. If the pressures being monitored  exceed safe values an override mode is entered where an action is taken to reduce pressure. For example, if the maximum admissible pressure in the colon has been exceeded, then the balloon and colon are deflated fully before the FSM system retakes control.The HC system was evaluated by measuring selected parameters to assess the interaction of the device with the colon. Testing was carried out in a porcine colon arranged within a rigid polymer cast of a cadaveric human abdominal cavity and orientated to simulate a patient in the supine position. One end of the colon was attached to a fixed anal port, through which the CV or a CC could be inserted. The other  end of the colon was attached to a fixed plug. Each end of the colon was attached to a separate pressure sensor. See Fig. The colon was held in place by the surrounding abdominal cavity and was attached directly to the walls of the cavity along the ascending and descending colons. It was also constrained by artificial mesenteries placed at the sigmoid, splenic and hepatic flexures. These artificial mesenteries consisted of inelastic cords sutured onto the colon. Each cord passed through a guide and was attached to a load cell fixed on the underside of the test bed see Fig. . This enTesting was carried out in two porcine colons which had been frozen for storage, then thawed to room temperature and cleaned before use. The porcine colons were approximately 120 cm long, with a diameter of 26–35 mm.Before each test replicate, the CV was lubricated with mineral oil; the efficacy of oil as a lubricant in colonoscopy has been demonstrated in previous clinical trials .Three colonoscopic systems were tested: (1) the HC with automatic control, (2) the HC with manual control and (3) the CC, operated by an experienced colonoscopist (as control). Testing involved advancing the device through the colon in the test bed from the anus to the caecum, the time required to achieve this is described as “insertion time”. Withdrawal of the device and examination of the colon were not included. For each device, we carried out three replicate experiments in each of the two colons tested, for a total of six experiments per device. Reported pressures have been adjusted to represent gauge pressure at the lowest point in the colon, which in our test bed was the anus. This corresponds to the maximum pressure in the colon as pressures at higher points will be reduced due to hydrostatic pressure variation. Forces measured by the load cells were filtered to remove high-frequency noise. Maximum force represents the highest force measured by any of the three load cells.The experiments confirmed that it was possible to successfully navigate through the test bed as far as the caecum using the HC. The CC was also successfully inserted.F = 6.92, p = 0.02, r = 0.55; F = 9.99, p < 0.01, r = 0.62].As the two porcine colons used were not identical, an analysis of covariance (ANCOVA) with planned contrasts was carried out to account for colon-related effects. This colon covariate had a significant effect on the maximum force and the insertion time of the procedures . No other significant differences were identified. See Table The results revealed that the CC applied a significantly higher maximum force to the colon than the HC . However, it also generated significantly lower mean pressures at the anus  and in the sealing balloon . No other significant differences were identified. See Table The comparison of manual and automatic control modes for the HC showed that the automatic controller had a significantly longer insertion time than the manual control mode [The greatest forces observed at any point during testing were 4.3 and 1.6 N for the CC and HC, respectively. The greatest intraluminal pressures observed during testing were 2.3 and 7.8 kPa for the CC and HC, respectively.Figure Although the shape of the colon was considered to be reasonably realistic, it is not representative of the full range of human colons because of the large natural variation of colonic anatomy in vivo.The artificial mesentery constraints were placed in anatomically realistic positions, but were unrealistic in that they were discrete rather than a continuous membrane. The forces measured by the load cells were reduced by the friction of the colon on the base and of the cord on the guide. A large fraction of the forces acting on the devices came from the fixed walls of the simulated abdominal cavity, where they could not be measured. For these reasons, we acknowledge that the results may not accurately reflect loads on real mesenteries. Nonetheless, they should allow a reasonable comparison between devices.p = 0.2). The insufflation pressures used during CC insertion (mean 1.52 kPa) were also low, but within the reported range of clinical values of 1.1–7.6 kPa (mean 3.0 kPa) [Our CC insertion time of 4.9 ± 3.3 min was somewhat shorter, but not significantly different from reported mean clinical times of 6.9 ± 4.2 min  (p = 0.23.0 kPa) . The lacThe colon used was an ex vivo porcine colon. Porcine colon is considered to be morphologically and physiologically similar to human colon , but it The number of test replicates was low . This was due to the complexity of setting up the test bed and experimental apparatus with fresh colon tissue. Additionally, it was only possible to have a limited number of replicates in each colon due to the fact that the porcine colons tended to deteriorate or ultimately rupture after prolonged testing, limiting their effective lifetimes. We accounted for the low number of colon specimens in our statistical analysis by including the colon as a covariate in an analysis of covariance. While this testing was sufficient for an initial feasibility study, further testing would be required to reliably prove the safety and efficacy of the device.The cause of pain during colonoscopy is excessive strain in the colon and mesocolon; contact with the bowel wall cannot be directly perceived due to the lack of sensory receptors  and so iPatients’ post-procedure perception of pain during colonoscopy has been reported to more closely correlate with the instantaneous maximum pain experienced than the time-averaged pain ; therefoThe average burst pressure of a cadaveric human colon is reported to be approximately 15 kPa, and the observable trauma due to pressure occurs at ≥6.9 kPa . Burst o2 [The insertion times were comparable between the CC and HC, and differences were not statistically significant. Mesentery loading was significantly less with the HC, this may be explained by the fact that the HC is designed to be flexible and has approximately one hundred times less flexural rigidity than a CC (roughly 2 vs 200 N cm2 ).The HC is currently a simple device, with reduced capabilities compared to a CC; it does not have a steerable tip, and in its present form, it does not possess capability for biopsy. However, its simplicity has advantages in that it is easy to produce, control and automate.Although the current prototype contains a rigid cylinder to simulate carrying an on-board camera, no camera has been installed. As a result, we are not able to assess the quality of imaging acquired. As the tip is not actively steerable, the ability to closely examine a given anatomical feature is limited. However, with a wide-angle lens, it should be possible to inspect the colon. It was observed that the tip of the CV passively tends to point along the lumen of the colon; however, it may touch the colonic wall in tight flexures, potentially causing “red-out” as happens in routine manual colonoscopy.2 and is of proven clinical viability. Both fluids have merits. CO2 is around 100 times less viscous than water, which can allow for a smaller, more flexible device to be constructed. Additionally, it is easier to remove fluid from in front of the CV; if a tube of reasonable diameter is provided gas should flow out naturally, whereas water requires a suction pump to drain the colon. A second advantage of using a gas is that hydrostatic pressure differentials become negligible; this will reduce the maximum pressure acting on the colon for a given mean diving pressure.The experiments have confirmed that water is a viable driving fluid, in contrast to the Aer-O-Scope which uses COIn contrast, use of warm water helps to relax the patient’s bowel, improving patient comfort , 30. As We have demonstrated the ability of a HC to navigate an in vitro test bed, which was modelled on a human colon. A comparison to a standard colonoscope showed that the HC caused reduced loading on the artificial mesenteries, but caused increased intraluminal pressures in the lower colon. The data indicate that based on strain applied to the colon and mesocolon, the device could reduce patient discomfort.While it has previously been demonstrated  that a pFinally, we have also shown that the HC can be used under automatic or manual control. A finite state machine-based automatic controller was developed which was able to successfully navigate the test bed based on feedback from pressure and movement sensors. The automatic controller was able to successfully navigate the colon with lower mean pressures in the lower colon and sealing balloon than used by a human controller. However, the automatic controller was has a significantly longer insertion time than manual control. As the HC can be driven by an automatic controller, it has the potential to reduce the amount of skill required by the operator to advance the device to the caecum.


In a fire investigation the rapid detection of the presence of ignitable liquids like gasoline is of great importance as it allows appropriate treatment of the remains, the identification of prevention methods and detects the possible presence of an arsonist. In some cases, analysts cannot access the fire scene in the first few hours due to the dangers involved in the situation and, as a consequence, phenomena such as weathering start. Ignitable liquid weathering is an evaporation process that results in an increase in the abundance of non-volatile compounds relative to volatile compounds, and this process changes the chemical composition. In the present work, the weathering of samples of gasoline at different times (from 0 h to a month) has been studied using an electronic nose (eNose). The influence of the volume used (40 µL and 80 µL) and the type of support  has been studied. Chemometric tools have been used with the aim of ascertaining the weathering time for which the developed method is capable of detecting the presence of gasoline. The eNose was able to discriminate samples of weathered gasoline. The support used for the samples did not seem to have an influence on the detection and the system. Fires (mainly forest fires) around the world and the consequent material and human damage are becoming a significant problem in our society, particularly given that human activity  is responsible for most cases. For this reason it is necessary to continue to study the capacity of new analytical tools and methodologies that can help investigators to determine the origin and cause of a fire, which is the ultimate goal of any fire investigation . The most common ignitable liquids used as accelerants in arson attacks are gasoline, diesel and kerosene; especially the former due to it is ready availability and its more rapid combustion when compared to ignitable liquids ,3,4.After a fire is extinguished, analysis of the evidence remaining at the scene is a crucial step that can provide very valuable information on how the fire occurred. For instance, the detection of unexplained ignitable liquids, for example neat ignitable liquid (IL) adsorbed to different surfaces or recovered from the fire debris, can be crucial in determining whether the fire was deliberately started or not, that is, whether an act of arson is suspected ,6.Fire debris analysis is usually complicated due to the destructive nature of the fire, the high temperatures reached at the scene and the firefighting efforts. In addition, fire debris is usually subjected to different additional degradation processes such as evaporation or weathering, pyrolysis or microbial degradation. All of these phenomena can modify the chemical composition of the liquid and therefore its analysis, thus making it more difficult to identify the IL. In order to carry out a reliable interpretation of the results, the behavior of the different liquids under these processes must be studied. In particular, weathering is a degradation phenomenon in which the most volatile compounds of a mixture evaporate more quickly than non-volatile compounds, thus modifying the composition on the solid support ,8. In thWhen an IL is used to start a fire, traces of the liquid may remain at the scene adhered to different materials . These rA large number of research and review articles have covered the different methods used for the determination and discrimination of ignitable liquids ,17. DiffRecently, the total ion spectrum (TIS) combined with chemometric methods has become a good alternative to TIC for identification and classification purposes ,30,31,32m/z) acts as a “sensor” and its abundance is equivalent to the sensor signal. The resulting mass spectra (MS) can be mathematically treated as an equivalent to the TIS and it is characteristic of each sample. As a consequence, suitable chemometric treatment of that signal can be easily developed as a fingerprint for each sample and used for rapid identification or characterization purposes. The eNose has been successfully optimized and validated for the analysis of ignitable liquids in fire debris and has provided characteristic fingerprints [The development of non-separative techniques such as the electronic nose (eNose) has recently appeared as a promising alternative to chromatographic techniques, since in some cases it is sufficient to obtain a signal profile or fingerprint of the sample formed by all the components for identification purposes . There aerprints ,38, for erprints , for theerprints ,40, and erprints . HoweverThe objective of the work described here was to study the evolution/modification of the eNose gasoline fingerprint after an evaporation weathering process for different times (from 0 h to 1 month) using different volumes and substrates of different natures in order to check the capacity of the eNose in the identification of weathered IL samples.In order to assess the effect of the volume and the materials in a weathering process, a total of 72 samples were prepared by adding two different volumes of gasoline (40 µL and 80 µL) to four different substrates . The substrates used were square pieces of substrate with a width of 0.5 cm.All samples were placed in 10 mL open vials  inside the laboratory hood with accurate control of temperature (25 °C) and the flow of the laboratory hood was zero with the purpose of simulating natural conditions for the evaporation/weathering process.Each support was placed in the middle of the base of the vial and the volume of gasoline was added to it. At different times  the vials with both volumes of gasoline for each type of substrate were closed and then analyzed. All samples were prepared in duplicate.The samples were denoted as W when the support used was wood, C for cork, P for paper and S for cotton sheet. The volume and the time were also noted for each sample. For example, the first experiment with 40 µL in wood for 15 days was named “W_40 µL_15d_1”. The gasoline and the substrates used were purchased in local Spanish gas stations and stores, respectively. Analysis of the weathered samples was performed on an Alpha Moss eNose system  composed of an HS 100 static headspace autosampler and a Kronos quadrupole mass spectrometer. Closed vials were placed in the autosampler oven to be heated at a temperature of 145 °C and agitated at 500 rpm in order to generate the headspace during 10 min. Headspace was extracted using a 5 mL gas syringe and injected into the mass spectrometer. The injection volume selected was 4.5 mL and the injection speed was 75 µL/s. The gas syringe was heated above the sample temperature (150 °C) to avoid condensation phenomena. Between each sample injection, the gas syringe was flushed with carrier gas (nitrogen) during 120 s at a fill speed of 100 µL/s to avoid cross-contamination. These conditions were previously optimized . The totm/z 45–200. Instrument control was achieved using RGA  and Alpha Soft 7.01 software .The components in the headspace of the vials were passed directly to the mass detector without any chromatographic separation or sample pre-treatment. In this way, for any given measurement, the resulting mass spectra (MS) give a fingerprint of the sample. Ion electron impact spectra were recorded in the range Mass spectra data were analyzed by hierarchical cluster analysis (HCA) and linear discriminant analysis (LDA). All these chemometric analyses were carried out using the statistical computer package SPSS 17.0 .Firstly, a weathering study of gasoline supported on cotton sheet was carried out. These samples cover the two different volumes used for the gasoline (40 µL and 80 µL). Analyses of these samples were carried out over a period of four weeks. In order to remove noisy signals in the eNose system, any signal below 10% of the highest one at 0 h was not used in the study. The remaining signals were represented in mass spectra (MS), from which differences in the recorded signals during the study could be observed.m/z) meaning that weathering process strongly starts during the first hours (m/z (57/105) is below 1 in the case of 6 h but above 1 in the case of 12 h. Moreover, from 6 to 12 h, the intensity of m/z 57 decreases around 25%, while m/z 105 falls near 80%.In the MS obtained on samples with 40 µL of gasoline, a modification in the intensities and their ratio can be observed according to the weathering time. This change was very significant between 0 and 6 h with a dramatic decrease in the intensities and the ratios of the signals (st hours . HoweverIn the case of samples with 80 µL gasoline the gap between 0 and 6 h remains but the remaining intensities from samples after more than 6 h of weathering are higher than in the case of 40 µL. m/z) from samples with 40 µL of gasoline supported on cotton sheet as variable for forming groups. The method selected for this analysis was Ward’s method with a squared Euclidean distance. The results of the HCA are graphically represented in a dendrogram in The evolution of the weathering process on gasoline samples was evaluated by carrying out a hierarchical cluster analysis (HCA). Signals  was run with the aim of studying the grouping properties of the samples. Based on the HCA results, two groups were selected. The first group covers samples from 6 h to 12 h of weathering  and the second group includes samples from 24 h to one month of weathering .The results of the LDA show a classification of 100% confirming that two main groups can be found in the samples. The first group contains the samples at 6 and 12 h of weathering (four samples) while the second group covers samples after 24 h of weathering (12 samples). It was determined that after 24 h the signals from the remaining gasoline from the samples were so similar that differences could not be found. This means, a similar behavior for all signals from the samples was obtained after 24 h of weathering. Additionally, those signals differed from the resulting ones for less than 24 h of weathering.m/z selected in the LDA as being significant were considered for each support and volume, and correlations between all of these m/z values were studied in order to identify the next m/z values for the development of intensity with time: 56, 57, 91, 106.With the aim of studying the weathering process in more detail, the m/z values were normalized to the base peak at 100%. Two different fingerprints were obtained. It can be seen that in the first few hours (group 0) the signals at m/z 57 and 91 show the higher relative values and after 24 h, when the presence of a second pattern was detected, m/z 57 continued to show high levels, however m/z 56 and 106 became more significant. The selected signals were used to generate a spider chart that allowed a fingerprint to be obtained for each kind of sample . The m/zBased on these results, two different patterns could be identified in real samples—the first corresponding to the samples at the beginning of weathering and the second due to gasoline samples after an intense weathering process.Volume was considered as a potentially influential variable. In order to evaluate the effect on the signal when double the initial volume was used, similar experiments were carried out using 80 µL of gasoline on all of the supports. The results are shown in The same procedures and analyses carried out on the 40 µL gasoline samples on cotton sheet were then carried out with 80 µL of gasoline. The initial intensity obtained on using a volume of 80 µL was markedly higher than that obtained on using 40 µL. Furthermore, the remaining signal was still similar to the initial signal after 24 h of weathering in the case of 80 µL samples. For the 40 µL, it must be noted that similar signals were obtained only up to 24 h, later moving to a different pattern. Therefore, the time taken to remove samples when attempting to detect gasoline on a supporting material is strongly dependent on the volume of gasoline in the material, because different signal patterns will be obtained depending on the time that elapses after gasoline was added to the solid material.In order to study the influence of the surface of the support in conjunction with gasoline, three additional supports other than cotton sheet were selected . m/z from the LDA results. A similar study than the previously described for cotton sheet, that is, first an HCA, later an LDA was applied for each supporting material. Finally, two different groups were obtained based on the specific resulting pattern obtained using the selected m/z values highlighted as being important in the LDA were selected and normalized by assigning one unit to the m/z with the maximum intensity.In order to analyze the influence that weathering time has on the final results from the analysis in the eNose system a kinetic study was carried out. In this respect, the m/z values were added and plotted against the analysis time  lead to a slow process of differentiation of signals from the initial case, and this requires longer analysis times to identify the presence of gasoline. Finally, the eNose system was able to discriminate samples of weathered gasoline regardless of the support used.


We study the ground motion simulations based on three finite-source models for the 2007 Mw6.6 Niigata Chuetsu-oki, Japan, earthquake in order to discuss the performance of the input ground motion estimations for the near-field seismic hazard analysis. The three models include a kinematic source inverted from the regional accelerations, a dynamic source on a planar fault with three asperities inferred from the very-near-field ground motion particle motions, and another dynamic source model with conjugate fault segments. The ground motions are calculated for an available 3D geological model using a finite-difference method. For the comparison, we apply a goodness-of-fit score to the ground motion parameters at different stations, including the nearest one that is almost directly above the ruptured fault segments. The dynamic rupture models show good performance. We find that seismologically inferred earthquake asperities on a single fault plane can be expressed with two conjugate segments. The rupture transfer from one segment to another can generate a significant radiation; this could be interpreted as an asperity projected onto a single fault plane. This example illustrates the importance of the fault geometry that has to be taken into account when estimating the very-near-field ground motion. Predicting the ground motions for any given scenario of an earthquake is an important seismological task for seismic hazard evaluation  was the subject of a major debate about the reliability of seismic hazard estimation  × 120 km (NS) × 30 km (UD). The ground surface is approximated as flat, and the Sea of Japan is not taken into account. The maximum reliable frequency is estimated as fmax = Vmin/(5 ⋅ Δs) = 400/(5 ⋅ 80) = 1.0 Hz. The time step is 0.004 s; the calculation is run for a duration of 60 s. The simulation procedure for generating ground motion is basically the same for both the kinematic and dynamic source models, as in Aochi and Dupros . However, in the forward direction in the southwest area (NIG024 and NIG025), we find that the characteristic waveforms are better simulated by the dynamic model (AK) than by the kinematic model (K). This is an important feature. The kinematic model is based on an inversion that might have missed or underestimated significant behavior of the rupture process due to a priori constraints or smoothing of the inversion. Therefore, the source model might underestimate the strong ground motions that are closely related to the source process. The dynamic models AD and AK produce similar waveforms, in particular at NIG024, NIG025, NIG004, and NIG019, and seem to be closer to the observations than model K. The similarity of the resultant ground motions for the two models, AD and AK, indicates that the asperities inferred on a single fault plane can be represented by the geometrical irregularities of the fault system.In Fig. This paper does not aim to improve the model parameters, but tries to show the performance of different earthquake models in generating the ground motion, in particular the performance of the two dynamic rupture models. Although inversion of dynamic rupture parameters has been done for a decade , FS , DUR, and ENER for the synthetics with respect to the observed seismograms filtered between 0.1 and 1.0 Hz, as already shown in Figs. Kristekova et al.  proposedThe aim of this paper was to examine the performance of the dynamically simulated earthquake ruptures in computing ground motion for the purpose of quantitative seismic hazard analysis. For the 2007 Mw6.6 Chuetsu-oki, Japan, earthquake, we compute ground motion in a 3D geological model using a kinematic source model and two dynamic source models. To quantify the performance of the models, we apply a GOF criterion to the simulated ground motions. From the comparisons, we find that the kinematic model does not always have the best performance in reproducing the characteristics of the strong ground motion. In particular, it does not work well in the very near field and in the forward direction of the rupture propagation. This is probably because an abrupt change in the rupture process (rupture onset and changes in rupture velocity) may not be well simulated by the kinematic description. Two dynamic rupture models produce a similar ground motion radiation. However, the model with the asperities distributed on a single fault plane might be a projection of the rupture process on conjugate fault segments. The rupture process changes the wave radiation naturally due to the geometrical irregularities. From this perspective, the dynamic rupture model on a complex fault geometry produces a reasonable rupture scenario and wave radiation for practical applications.For the 2007 Chuetsu-oki earthquake, the conjugate segments might be a reasonable causal source model, as inferred from the geodetic analyses (Nishimura et al. There remains a scientific debate on the different aspects of the dynamic rupture process because the dynamics are technically difficult to solve and the frictional component of the faulting is difficult to study. However, progress over the last two decades helps us to understand various aspects of the dynamics of the earthquake mechanism. Dynamic rupture scenarios have been used to compute the ground motions for high-seismic-hazard areas such as California (e.g., Olsen et al.


The article provides information about a new device, AlgaTox developed in the R&D project sponsored by the Technology Agency (n.TA02030179) and patented in Czech Republic (CZ 305687). Its functionality is based on the use of biosensor, and its main advantage is fast response rate. The toxicity detection is achieved through precise measurement of green algae oxygen production dynamics after their exposure to light of wavelength of 680 nm. Clark sensor with a resolution of 0.05% of the equilibrium oxygen concentrations and stability at a constant pressure and temperature of 0.1% of the equilibrium oxygen concentration at the 24-h measurement is used for the oxygen detection. Laboratory testing of the device has been made using silver nitrate, substance with known inhibitory effect on algae. Real samples of aqueous soil extracts and waste sample from old dried-up industrial tailing pond enriched with insecticide have been also tested. The values of oxygen production inhibition or stimulation determined with the new device in the evaluation of real samples were up to six times higher in comparison with the corresponding values of inhibition (stimulation) of growth rates determined by standard procedure. The environmental pollution is currently at such level that the systematic control is almost impossible. Nevertheless, it is necessary to secure the quality of the environment for future generations. The monitoring of the environment is done using the classic chemical analyses and eco-toxicological testing. The advantage of biological tests is that they can determine the toxic effects of the sample on the sensitive organism. Its reaction allows a complete detection of the effects of chemical substances on the environment, and it is even possible to determine the toxic effects of those harmful substances, whose classic analysis has not been methodically done yet. The fact that the biological testing can detect mutual interaction of toxic substances in their mixture is an important advantage . These phenomena can be observed by classic analyses only with great difficulties. Plants and animals of various trophic levels are used for testing, and they have been chosen due to their sensitivity to chemical compounds and environmental pollution. The main disadvantage of these tests is that they are very time-consuming. They require several days for cultivation of organisms with toxic substance or environment sample. The information about the toxicity of the given sample is obtained after a longer period, and it does not provide a possibility for timely intervention in the case of positive toxicity test. These measurements can be simplified and accelerated with the use of biosensors. Biosensors are analytical instruments which use biochemically sensitive material for obtaining chemical information without the need for a complete processing of the sample. A suitable converter converts the output signal from the biosensor to quantitatively measurable signal. The most frequent output signals are current and voltage  immobilized in matrix, which prevents from its leaching without reduction in cell stability and activity  has been used for detection of heavy metals  and pesticides  or on tracking the development of photosynthetic oxygen (amperometric)  of toxic substances presence. The oxygen electrode is the Clark type electrode. It is composed of the electrode body, in which the glass body of the cathode is mounted; the cathode is made of platinum (Pt). The reference electrode made of silver (Ag) is placed on the glass body. Teflon membrane, which allows transfer of oxygen and some other gases (nitrogen), is placed on the active surface of the working electrode. The electrode cover with the Teflon membrane is screwed on the electrode body and filled with electrolyte (1 M KCl). The optimum distance between the stirrer and the electrode is 0.5–1 mm. The oxygen electrode is optimized in such a way, that its long-term stability (24 h) at a constant atmospheric pressure and constant temperature is better than 0.1% of equilibrium oxygen concentration in water at given conditions. The resolution of this oxygen measurement is better than 0.05% of the equilibrium oxygen concentration in water at given conditions. These parameters allow the device to accurately determine even small changes in the life cycle of algae. Thus, the high sensitivity of the toxicity determination is achieved.The reaction vessel detail is shown in Fig. Scenedesmus quadricauda, strain GREIFSWALD/15, from the Culture Collection of Autotrophic Organisms of the Institute of Botany of the Czech Academy of Science . The algae intended for the measurements have been pre-cultivated in ½ Simmer-Šetlík medium .The −1 have been used. The ½ Simmer-Šetlík medium  have been tested in the AlgaTox device. The algae S. quadricauda has been chosen based on the process of measurement conditions optimization. These algae have showed the highest stability of the measured signal and at the same time have given a signal strong enough for a further processing in comparison with other tested species of algae that showed significantly smaller signal and high noise values on the contrary.The algae oxygen production has been measured and recorded in the AlgaTox device for all test samples and the control sample. The algae are very sensitive to the environmental pollution, they are of suitable size, and their life cycle is well-known. They are used in the test described in the EN ISO 8692  standardISO 8692  standardUnlike in the standard algae test . For the concentration of 0.6 mg L−1, the oxygen production decreased for approximately 20%. For concentrations higher than 0.7 mg L−1, a significant decrease in the oxygen production occurred within the first hour of the measurement. The EC50 value for silver nitrate has been determined by the standard algae test according to the EN ISO 8692 .The results of 12-hour measurement for the individual concentrations of the aqueous waste extract using the AlgaTox device are shown in Fig. act Fig. . The EC5ISO 8692  standardλ = 1.59 × 10−2 h−1 (4.42 × 10−6 s−1).The decrease area of 0–100% corresponds to the direct inhibition of the photosystem II. For these concentrations, a full inhibition of the growth rate in the standard algae test can be expected. Relevant comparison of tests according to EN ISO 8692  standard50 values specified in the standard procedure .The device and its methodology have a much wider scope of application than just the detection of toxic substances in the environmental samples. The device can be used in chemical productions, resp. chemical substances evaluation in correspondence with the REACH legislation, where the producer can test the impact of chemicals on the living organisms. The device can be used for more than just the evaluation of the impact on algae but for accurate measurement of biochemical oxygen consumption, for accurate measurement of chemical oxygen consumption, for cell growth tests of tissues, small animal who consume or produce oxygen (respirometry), for sterility tests based on tracking of the growth of microorganisms or for the measurement of slow reaction rates with changing concentration of oxygen .


Orogastric tube placement is a common procedure routinely used in clinical anesthesiology and intensive care medicine. Nevertheless high failure rates and severe complications have been reported. We conducted this study to evaluate if the usage of the new gastric tube guide would speed up the placement of orogastric tubes and ease the procedure.Thirty one professionals were given a hands-on-training in orogastric tube placement in a simulation manikin without and with the gastric tube guide. Afterwards they performed both methods in randomized order. We recorded the placement time, counted the required attempts and asked the participants to rate their experience with both methods.The median placement time using the gastric tube guide was 14 s compared to 25 s without the device. In addition all participants were able to place the orogastric tube when using the gastric tube guide compared to 26/31 (84%) without it. Furthermore 26/31 (84%) users preferred the gastric tube guide over the standard method.Our results show that using the gastric tube guide to place orogastric tubes in a manikin led to a significant shorter placement time and a higher overall success rate. Insertion of an orogastric tube is a common procedure in clinical anesthesiology to achieve gastric decompression and to reduce gastric contents. The procedure is usually performed after induction of general anaesthesia and tracheal intubation. As the patient is unable to swallow and cannot follow further instructions placement of nasogastric and orogastric tubes can be difficult. This leads to a high failure rate of nearly 50% for the first attempt . As the Based on the concept of slit endotracheal tubes the new gastric tube guide  was designed to facilitate the insertion of orogastric tubes. The device is made of polyvinyl chloride, is 33 cm in length, has an outer diameter of 10.3 mm and an inner diameter of 7.5 mm which allows the placement of gastric tubes up to 6.0 mm (18 Fr). According to the manufacturer the gastric tube guide is fitted with an insertion funnel on proximal end to ease the placement of gastric tubes and an atraumatic tip to decrease the risk of mucosal bleeding during the placement of orogastric tubes. It has a precurved shape p = 0.0253). The median time required for orogastric intubation was 25  seconds without and 14  seconds with usage of the gastric tube guide, ranging from 4 to 123 s among those who successfully placed the gastric tube without the device and 6 to 20 s with the guide  but a significant treatment effect . Table Twenty six participants (84%) were able to place the orogastric tube within 180 s without using the gastric tube guide. All participants (100%) were able to place the tube within 180 s when using the gastric tube guide p = 0.025. The medp = 0.0293). All participants were able to remove the gastric tube guide without removing the orogastric tube. There was no malpositioning of the orogastric tube in the trachea in both groups. When rating the two methods, 26 (84%) of the participants preferred the gastric tube guide to the standard method, whereas only one (3%) preferred the standard method to the gastric tube guide and four (13%) rated both methods in the same category (p = 0.0499). Table Of the participants, 22 (71%) needed only one attempt to place the gastric tube without the device, five (16%) made two attempts, four of which were successful and four (13%) made three attempts – all without success. In contrast, 30 (97%) of the participant were successful at the first attempt with the guide and only one participant (3%) needed a second attempt to successfully place the gastric tube  seconds without to 14  seconds with the gastric tube guide. Although the reduction of 11 s may not be relevant in clinical routine we suppose that this effect will be greater in the clinical setting as the placement time in general was short during our study. Another important finding was the reduction of attempts until an orogastric tube could be inserted when using the gastric tube guide as every attempt increases the risk of complications especially for mucosal bleeding and laryngeal injuries.A limitation of our study may be the applied time limit of 180 s. This was done for two reasons: First, we wanted to reduce the effect of personal motivation on the attempts performed, especially on when to stop the procedure in case of several failed attempts. Second, as the placement of orogastric tubes can be time consuming we wanted a defined cut-off. Indeed no participant was able to place an orogastric tube after 123 s which might be due to reduced stiffness of the tube after warming up [Manikin studies in general have been proven to be a reliable surrogate for clinical scenarios. On one hand the setting cannot simulate the precise conditions in a real patient in this context especially the warming to body temperature and the presence of various body fluids, on the other hand the use of manikins allows a strict standardization of study conditions. For that reason further clinical studies are necessary to determine the benefits and risks when using the gastric tube guide to place orogastric tubes.Our study showed that the usage of the gastric tube guide to place orogastric tubes in a simulation manikin leads to a higher success rate and a faster placement time and may therefore also be beneficial in clinical routine to reduce complications associated with the placement of orogastric tubes.


Certain diseases affect brain areas that control the movements of the patients’ body, thereby limiting their autonomy and communication capacity. Research in the field of Brain-Computer Interfaces aims to provide patients with an alternative communication channel not based on muscular activity, but on the processing of brain signals. Through these systems, subjects can control external devices such as spellers to communicate, robotic prostheses to restore limb movements, or domotic systems. The present work focus on the non-muscular control of a robotic wheelchair.A proposal to control a wheelchair through a Brain–Computer Interface based on the discrimination of only two mental tasks is presented in this study. The wheelchair displacement is performed with discrete movements. The control signals used are sensorimotor rhythms modulated through a right-hand motor imagery task or mental idle state. The peculiarity of the control system is that it is based on a serial auditory interface that provides the user with four navigation commands. The use of two mental tasks to select commands may facilitate control and reduce error rates compared to other endogenous control systems for wheelchairs.Seventeen subjects initially participated in the study; nine of them completed the three sessions of the proposed protocol. After the first calibration session, seven subjects were discarded due to a low control of their electroencephalographic signals; nine out of ten subjects controlled a virtual wheelchair during the second session; these same nine subjects achieved a medium accuracy level above 0.83 on the real wheelchair control session.The results suggest that more extensive training with the proposed control system can be an effective and safe option that will allow the displacement of a wheelchair in a controlled environment for potential users suffering from some types of motor neuron diseases. There are certain diseases that could prevent the patient’s communication with his or her surroundings to the point of not even having control over such seemingly simple actions as precise control of the eyes or breathing (e.g. advanced states of locked-in syndrome ). HoweveThe interest in controlling a mobile device through a BCI system has been growing since the publication of Millán et al., wherein the control of a mobile robot was presented . Tanaka Although there are some BCWs that are controlled by potential P300 e.g. , 11) or  or 11]) We can divide the systems most commonly used in BCW navigation to date into two groups: i) those with high-level navigation, in which the user just needs to select the destination and the BCW performs the navigation of the path, choosing the necessary commands e.g. , 17) and and17]) Another important feature is the type of movement that the BCW makes. The control can be performed through continuous movements e.g. , 20) or  or 20]) To summarize, the research carried out in relation to the control of a wheelchair through brain activity is limited. From existing systems, those based on the discrimination of mental tasks offer more autonomy to subjects. All the studies related to those systems are included in Table In order to provide several navigation commands without worsening the performance of the BCI system, the BCI group of the University of Málaga (UMA-BCI) has been working on a paradigm based on the discrimination of only two mental tasks , allowing the selection of four different navigation commands. This paradigm uses a serial auditory interface, so that subjects hear the available commands and they use one task to select the command, or the other task to let it go. The paradigm has been validated to navigate in virtual environments (VEs) , 25 and The main objective of this work is to study whether the proposed paradigm is an effective option to control a BCW in all directions . The coThe study initially involved 17 participants , identified as A1–A12 and B13–B17 here. With the exception of subject A1, none of them had previous experience of BCI systems. Subjects B13 to B17 participated in the preliminary study in . SubjectThe EEG was recorded at a sample rate of 200Hz from two large Laplacian channels (for details see ) placed a) The reactive frequency band of each participant was automatically selected from all possible frequency intervals between 5 and 17 Hz (with a minimum bandwidth of 2 Hz). The search for the optimal frequency band was limited to the μ band. Although in some cases it is possible to find subjects whose reactive band belongs to the β band, for simplicity we finally selected the 5–17 Hz band. For each tested frequency interval, feature extraction and classification were carried out, giving a frequency band-dependant error rate as a result. The band that led to the lowest classification error rate was regarded as the subject’s reactive frequency band.b) The feature extraction consisted of estimating the average power of the signal from the two EEG channels in the specific frequency interval for each trial. This average was calculated by i) digitally band-pass filtering the EEG using a fifth-order Butterworth filter, ii) squaring each sample, and iii) averaging over several consecutive past samples. A total of 100 samples were averaged, giving an estimation of the band power for several intervals of 500 ms.c) The features from both channels for all trials were used to compute the error rate time course of a linear discriminant analysis (LDA) classifier  by meansd) Feedback generation: the previously selected frequency band and the obtained features were used to set up the LDA whose classification results determined the feedback ‘L’, which was used in the next sessions. This feedback was computed online every 31.25 ms. All data processing was carried out in MATLAB.As mentioned above, subjects participated in an initial training session  for calibration purposes. In this session, we recorded the EEG of each subject performing two mental tasks . With this data, an automatic process calculated, for each subject, a reactive frequency band and a classification error rate (detailed below). After processing it, we selected those subjects with classification error rates under 30% and obtained the subject-dependent parameters for the next sessions with feedback. Data processing and feedback generation were based on the procedure detailed in ).Compared with other BCWs, the control strategy proposed in this study seems to allow efficient control of the wheelchair without requiring long training or large mental effort. Besides, because the system is achieved by discriminating only two mental tasks, misclassification is minimized, which is very important in order to guarantee the usability of the system and the user’s safety.Future work will focus on training users with low initial performance over several sessions until they achieve good control of the wheelchair. Another important objective will be to evaluate the performance of the system with continuous movement.Thanks to the metrics displayed in the confusion matrix about the performance of the user controlling a BCW, new ways of adjusting the user parameters of our control interface (i.e. the facility to extend the bar or the time needed to maintain the bar above the selection threshold) have been identified in order to make the BCW an efficient proposal with dynamic and efficient management.


The measurements were made with the machines set at various gantry angles with and without the scattering phantom, and with the collimators set at the maximum and the minimum field sizes. Neutron dose equivalent measurements were made for five other accelerator vaults. Empirical equations were used to fit the dose data at points along the center of the maze, at 1 m above floor level, with the primary radiation beam pointing downward. It is reported here that both the capture gamma and the neutron dose attenuations along the maze are in agreement with the literature. The neutron dose is dependent on the square root of the ratio of the cross‐sectional areas of the inner maze entrance and the maze. The tenth value distance PACS number(s): 87.52.Ga A frequently used design of a high energy linear accelerator vault includes a main treatment room with a maze leading to the vault entrance. In addition to the maze wall shielding the direct neutron flux, the maze length allows the use of a much lighter door for the maze entrance. Methods used in estimating the neutron dose equivalent at the external maze entrance of medical accelerator vaults are available in the literature.The first set of measurements was made along the maze centerline of a recently constructed vault for a medical linear accelerator .10 cm×10 cm field has a percent depth dose value of 76.4%. The ionization ratio is 0.76 according to the TG21 protocol,m−3. The layout of the vault is shown to scale in The manufacturer stated photon energies of the dual energy machine are 6 and 15 MV. Only the results for the 15 MV modality are presented in this work. The 100 cm SSD The photon measurements were made using an ion chamber type survey meter, Inovision/Victoreen model 450P . The survey meter was calibrated, and the factor traceable to NIST by K & S Associates  within one year prior to and after the work. The neutron response of a survey meter of the same model has been shown to be negligible by McGinley and Miner.BF3 proportional counter operating at 1150 V. The active length is 5.08 cm. The gamma and x‐ray rejection was tested in fields of 137Cs and 0.5 MeV scatter up to 5 Sv−h−1. The neutron meter was calibrated by the manufacturer before and after this work. At calibration, the meter was oriented with the specific side of the long axis perpendicular to the general direction of the neutron source. The calibration certificate stated, “Verification of this instrument has been performed using Ra‐Be fast neutrons. The radiation rate measured from the Ra‐Be neutron source was calibrated by using a transfer standard calibrated to a NIST traceable Cf‐252 neutron source. The expanded uncertainty of the calibration is 23%. This value was determined using NIST Technical Note 1297 and the ISO Guide to the Expression of Uncertainty in Measurement (1993).”The neutron dose equivalent measurements were made using an Inovision Model 190N meter. The neutron meter is based upon the standard Anderson and Braun design, with a The neutron meter showed a significant variation in the isotropy test, in which the meter was rotated horizontally at 45° intervals and readings were taken. Data reported in this work obtained with the axis of the meter perpendicular to the general direction of neutrons as at calibration are denoted as nominal, or as measured at “nominal” angle.Vault‐2 measurements were made around the same time using the same instruments described above. The two vaults are adjacent to each other, and are very similar in layout and construction. The accelerator (Varian Clinac 1800) has photon energies of 6 and 15 MV Only the data for 15 MV are presented here. The TG21 NAP is the same as the machine in Vault‐1.The second set of measurements was made for five medical linear accelerators of energies 15 to 25 MV, housed by five different vaults with similar maze design but with different maze lengths, maze cross‐sectional areas, and inner maze entrance areas. Only neutron dose measurements are presented here. The measurements were made using a neutron survey meter made byBF3 tube in the center. The meter has a current NIST traceable calibration.Eberline . The model of the reader was ESP‐1, and the moderator was the NRD neutron REM detector, a 23 cm diameter polyethylene sphere with a The two neutron meters were intercompared and the result showed agreements well within the calibration uncertainty quoted above. Some readings presented in this work were obtained using both sets of meters. The differences are well within 10%.10 cm×10 cm field. The isocenter dose was calibrated to water according to the TG51 protocol3−5 Gy−min‐1.All measurements were made with the meter placed on top of a wood stand at 1 m above the floor. The door at the maze entrance was kept opened during the measurements. The photon and neutron dose data were normalized to isocenter dose (Gy) for A for all seven vaults. Point A is the point at 1 m above floor, on the centerline of the maze, just visible from the isocenter. . The measurements were repeated with the survey meter rotated horizontally at different orientation angles at several points along the maze to evaluate the anisotropy properties. The readings taken with the meter set at the same angle as at calibration are displayed in A. It was determined that data taken at nominal angle and at meter rotation angle of 180° . Using the straight line portion of the plots, these tenth value lengths were determined for all seven vaults. Attempts were made to correlate the TN with the inner maze entrance cross‐sectional area S0, maze cross‐sectional area S1, and room surface area S for all seven vaults. The study produced a simple equation as follows:TN is the tenth value length in S1 is the cross‐sectional area of the maze in m2.The semilog plots of the measured data show that near the inner maze entrance, the neutron dose equivalent decreases with a tenth value length of 1.9 m. This component has been reported by McGinley,Similar observations have been reported for thermal neutron attenuation through mazes and ducts .TN determined as above, the neutron dose data were further analyzed. Attempts were made to correlate the data for all seven vaults with the ratio (S0/S1), simple exponents of the ratio, as well as S0 and S1 separately. Kersey(S0/S1). However, these data do not support such a relationship. Using semilog graphical plots, with more weight given to the data for Vault‐1 and Vault‐2, it was found that the square root of the ratio would give better agreements.With the values of 2.4×10−15 is in units of Sv‐md2 =2 m for Vault‐1 and Vault‐2, using the parameters tabulated in The coefficient 40×40×40 cm3 solid phantom placed at the isocenter at 100 cm source‐surface distance. The neutron dose in the maze was found to be lower when the collimators were set to larger field sizes. This observation has been reported by McGinley and Huffman.0×0 cm2 field size with no phantom, the 40×40 cm2 data are about 10% lower for the accelerator and vault configuration used in this study. However, at or near the inner maze entrance, the effect of collimator setting is reversed. The neutron dose increases with the increase in field size. The 40×40 cm2 value is about 23% higher than that of 0×0 cm2 field size for Vault‐1 at 1 m from point A. These observations are best illustrated by Neutron dose data were obtained at several points along the centerline of the maze of Vault‐1, with the collimator settings varied. The radiation beam was set pointing downward, with a B to C in C towards B direction shown in d2=0.5, 3, and 6 m), as shown in The effect of gantry angle on neutron dose in the maze was studied using the 15 MV photon beam of the accelerator in Vault‐1. Measurements were made with the neutron meter oriented at the nominal angle described above, at three chosen locations along the centerline of the maze. As shown in the following figure, when the gantry was rotated to 90° (radiation beam pointing from (d2) from point A, with a tenth value length of 6.2 m, according to d2 as the sum of two components. The first component has a tenth value length of 1.9 m, and the second component has a tenth value length of TN. The value of TN is proportional to the square root of the cross‐sectional area of the maze, as given by S0 values at both ends of the range. Caution should be given when applying the equations for vaults of significantly different designs. The effect of smaller S0 on the reduction of maze neutron dose merits the extra effort of vault designers to find ways to minimize the area of the inner maze entrance. Specifically, the height of the entrance should not be more than necessary, such as for the rigging in of the accelerator. Furthermore, the neutron source strengths used in the equations were measured for recent model accelerators. Older models are known to have higher Q values.,In this work the neutron and photon dose equivalents have been measured at various points along the centerlines of the mazes for several accelerator vaults with a design similar to that shown in