Modulus (126 kHz), Phase angle (40 kHz) and the Delta of the phase angle (between 126 and 158 kHz). These variables were combined in a Compound variable C. The area under the curve in a receiver operating characteristic was consecutively increased for the Modulus (78 %), Phase angle (86 %), Delta of the phase angle (94 %), and the Compound variable C (97 %), indicating highest specificity and sensitivity for C. An algorithm based on C was implemented in a real-time feasibility test and used in an additional test animal to demonstrate our new method. Discrimination between nerve tissue and other tissue types was improved by combining several impedance variables at multiple measurement frequencies.Electrical impedance measurements have been used to detect intraneural needle placement, but there is still a lack of precision with this method. The purpose of the study was to develop a method for the discrimination of nerve tissue from other tissue types based on multiple frequency impedance measurements. Impedance measurements with 25 different frequencies between 1.26 and 398 kHz were obtained in eight pigs while placing the tip of a stimulation needle within the sciatic nerve and in other tissues. Various impedance variables and measurement frequencies were tested for tissue discrimination. Best tissue discrimination was obtained by using three different impedance parameters with optimal measurement frequencies: The online version of this article (doi:10.1007/s10877-015-9698-3) contains supplementary material, which is available to authorized users. Nerve injuries related to peripheral nerve blocks can be caused by toxicity of the injected solution or by mechanical nerve damage. In the worst cases, nerve damage can lead to persistent motor or sensory impairment and debilitating neuropathic pain , 2. ThusModulus and the Phase Angle, unlike resistance in a DC circuit that has only a magnitude which is expressed by a single value [Modulus is the ratio of the voltage amplitude to the current amplitude and is given in ohms. The Modulus defines the length of a vector in the complex impedance plane. The Phase Angle reflects the phase shift by which the current delays behind the applied voltage and is given in degrees. The Phase angle defines the direction of the vector in the impedance plane. All biological impedance variables depend on the frequency of the applied measurement signal.Impedance is a measure of the opposition of the flow of alternating current (AC) similar to the resistance of a conductor to direct current (DC). Impedance is given as a complex number that can be described as a vector in a complex plane defined by the le value . The ModElectrical bioimpedance in a needle-electrode circuit has been measured in an animal model and in clinical studies to detect placement of the block needle within a nerve , 14. TheIn the present study, bioimpedance measurements were made with multiple frequencies as described in a previous publication . The comAfter institutional animal care committee approval (ID 5143) nine pigs were supplied for this study by the Center for Comparative Medicine . General anesthesia with endotracheal intubation was administered with fentanyl and isoflurane after premedication with ketamin, azaperone, and atropin.® A; B. Braun, Melsungen, Germany) was used without fluid priming. The needle was advanced from anterolateral to posteromedial under in-plane ultrasound guidance until the needle-tip was positioned within the epineurium of the sciatic nerve.We used an ATL HDI 5000 ultrasound unit with a L12-5 transducer  to visualize the left sciatic nerve in an oblique axis below the biceps femoris muscle. The unilateral setup was due to a consecutive study that was scheduled for the same test animals after bioimpedance measurements were performed. A 100 mm, 21-gauge insulated needle with a 30° bevel  was connected to the needle and a gel reference electrode  on the skin. The current threshold needed to obtain a neuromuscular response was established starting at 0 mA and gradually increasing the current . The nerve stimulator was removed and a Solartron complex impedance measurement system  was connected for 3-electrode impedance measurements. The needle was connected as the measuring electrode and two skin electrodes were attached to the skin of the lower abdomen for use as indifferent electrodes. A 50 mV excitation signal was driven by the Solartron 1294 between the needle and one of the skin electrodes, and the resultant potential was measured between the needle and the other skin electrode. This 3-electrode setup, and the large differences in electrode area between the needle and the skin electrodes, ensured a unipolar impedance measurement totally dominated by the needle and the tissue adjacent to its tip [A nerve stimulator  were plotted graphically for visual interpretation to assemble characteristic properties from the measured data set for defined frequency ranges. Descriptive statistics including principal component analysis (PCA) were used to illustrate variances and compare the measurements in order to identify tissue specific differences.All the statistical analyses were conducted in R (Team 2010) for MAC . The impDelta of the phase angle was defined as the difference in measured phase angles between two consecutive measurement frequencies; The Compound variable C was derived by manual identification of tissue specific patterns in the PCA plots. One-Way ANOVA was used to evaluate the mean differences between tissue types versus intraneural .The information in the PCA plots was used to derive two new variables: The Modulus, Phase angle, and Delta we defined the mean value in intraneural tissue as the starting point with zero positive classification . The cut off range was then extended by moving the upper and lower cut off values in steps of 5 %, until all the values in the total data set were included at 100 %. C was normalized to zero at the intraneural mean value. Hence, zero was used as the starting point for C. The cut of range for C was extended by increasing the value by adding 5 %.A receiver operating characteristic curve (ROC) was a final test and comparison of the tissue discrimination variables, where the area under the curve (AUC) was used as an indicator of how well a variable can distinguish between nerve tissue and other tissue types. For the To demonstrate the feasibility of the method in a real-time clinical device an algorithm based on the best variables was used in a generic impedance measurement . The feasibility test was performed in the ninth test animal.The sciatic nerve and surrounding anatomy was identified unilaterally in eight 3 months old pigs . Current thresholds for a distal muscle response ranged from 0.04 to 0.28 mA when the needle was placed within the sciatic nerve. 128 datasets from bioimpedance measurements in a frequency range from 1.26 to 398 kHz were obtained when the needle-tips were either placed intraepineurally, paraneurally, within muscle tissue, or in subcutaneous fat. 17 of these datasets were excluded as missing data because of contact failure in the needle connection lead or disturbance of the measurement setup.Figures Delta phase angle (defined as the difference in measured phase angles between two consecutive measurement frequencies) best results were obtained between 126 and 158 kHz  in a Compound variable C, according to the following equation:Modulus and P is the Phase angle at the frequencies given by the subscripts , Phase angle (86 %), Delta (94 %), and C (97 %). This indicates highest specificity and sensitivity for C.The four variables used to discriminate intraneural needle placement from other tissue types were plotted in a ROC curve Fig. . The AUCCompound variable was below a predefined cutoff value of C = 1. Based on the ROC . The setup was programmed with an indicator colour panel that turned from green to red when the ROC Fig.  this shoCompound variable C to optimise tissue discrimination.A novel algorithm for bioimpedance measurements to detect nerve tissue, and discriminate it from surrounding tissue types, was developed by analysing a complex impedance dataset based on multiple measurement frequencies. Several impedance variables were combined in the Modulus at a measurement frequency of 126 kHz, for the Phase angle at 40 kHz, and for the Delta of the phase angle between 126 kHz and 158 kHz. Compared with the Modulus, discrimination was improved with the Phase angle, and even better when using Delta .The specific curve shapes obtained by plotting the impedance variables as a function of the frequencies  werModulus and Phase angle measured at a single frequency are highly dependent on the measurement setup and the electrodes used [Delta is mainly based on the specific curve shape and is less vulnerable to inconstancies. Combining these measurements in the variable C made the discrimination even more robust.The absolute values for the des used . The DelOur study has several limitations. First, our measurements were obtained in an exploratory animal study and refer only to the sciatic nerve in pigs. Comparisons by Gabriel (28) shows that the impedance properties of animal tissues are comparable to human tissues, and that the variations within a species may well exceed variations between species. The differences they found between human and animal species were not systematic. At the present time, comparable data for peripheral nerves are not available.Different peripheral nerves might have different conductive properties. It must be emphasised that the sciatic nerve is formed by to independent nerve structures, a tibial and a peroneal component that are surrounded by a distinct connective tissue layer . Marked The stimulation needle was placed in multiple positions within the sciatic nerve. Repeated needle advancements might change the conductive properties of the nerve. This was not the case in our study. No statistical correlation for repeated measurements was found in our data.® A needles, most of the electrical contact between tissue and the needle is obtained on the bevel surface. When the needle is filled with conductive solutions the distal part of the needle cavity will contribute to current conduction. However, body fluids will also pass into the needle during block procedures. This can alter the impedance in the cavity for both primed and unprimed needles. Ideally, block needles could be optimized for impedance measurements by isolating its cavity surface (in addition to the outer surface) to reduce variations in the electrode area caused by different fluid contents.In our study the needles were not primed with fluid. For the StimuplexUltrasound is known as an observer-dependent method; the identification of anatomical structures and estimation of the position of the needle-tip have a subjective component. To insure true intraneural needle positions we chose a large nerve that was easy to identify and to access. With an in-plane needle approach we aimed for a central position of the needle-tip in the middle of the nerve. When placing the needle in the paraneural tissue, indentation of the nerve wall was avoided. Intraneural injections to confirm needle positions by a typical spread of the injectate  were notEven though highly clinically relevant, we could not specify whether the needle was placed within the neural fascicles or in the surrounding perineurium. Neither did we investigate needle positions in transition from the extra- to the intra-epineural space. To identify needle position within smaller structures or compartments in our porcine model, nerves might have to be surgically exposed. However, we don’t expect reliable and representative bioimpedance patterns after removing the paraneural tissue from the nerve as the current path and the electrical field would be changed or impeded . The lacOur measurements show distinct patterns for subcutaneous fat, muscle, and intraneural tissue. The results obtained from the paraneural needle positions were almost identical to the measurements in muscle, as can be seen in Figs. Temperature and fluid status in the tissue can be confounding variables in bioimpedance measurements. Temperature coefficients for body tissues are unlikely to exceed 1–2 % per °C, and are most significant at low frequencies . Fluid cIn the present study, a controlled potential of 50 mV was used to ensure a low current density. This should give a linear relationship between current and potential. High current density, on the other hand, could lead to a nonlinear behaviour of the measurement setup and irreproducible results , 26.Whereas our measurements were based on defined sine wave frequencies, others have used a square pulse signal  for bioimpedance measurements. Tsui et al.  performeAccording to Fourier’s theory, a square pulse represents multiple frequencies. , 28 ImpuC was implemented in a generic impedance measurement device and used in an additional animal test to confirm our findings .The method seems feasible for use in clinical practice to perform continuous bioimpedance monitoring during peripheral nerve block performance. An algorithm based on We anticipate that our method for tissue discrimination might be implemented in a nerve stimulator. Multiple frequency bioimpedance measurements could be made in the pauses between stimulation pulses. Previous studies have shown specific bioimpedance patterns for a variety of organs and tissue types . BioimpeElectrical impedance measurements are used in numerous clinical devices . The meaWe have developed a novel algorithm based on complex impedance measurements at multiple frequencies, and defined sine wave excitation, which is able to discriminate needle positions in nerve tissue from other tissue types. Clinical studies in humans are needed to confirm our results.Video 1Compound variable was below a predefined cutoff value of C = 1. This should give a sensitivity of 80% and a specificity of 96% for the discrimination for intraneural tissue (MP4 9577 kb)Real-time feasibility test to discriminate intraneural needle placement from other tissue types: The setup was programmed with an indicator colour panel that turned from green to red when the


Non-negative linear combinations of elementary flux modes (EMs) describe all feasible reaction flux distributions for a given metabolic network under the quasi steady state assumption. However, only a small subset of EMs contribute to the physiological state of a given cell.Pichia pastoris and experimental fluxome data of Saccharomyces cerevisiae. The proposed method is benchmarked against principal component analysis (PCA), commonly used to study the structure of metabolic flux data sets.In this paper, a method is proposed that identifies the subset of EMs that best explain the physiological state captured in reaction flux data, referred to as principal EMs (PEMs), given a pre-specified universe of EM candidates. The method avoids the evaluation of all possible combinations of EMs by using a branch and bound approach which is computationally very efficient. The performance of the method is assessed using simulated and experimental data of The overall results show that the proposed method is computationally very effective in identifying the subset of PEMs within a large set of EM candidates (cases with ~100 and ~1000 EMs were studied). In contrast to the principal components in PCA, the identified PEMs have a biological meaning enabling identification of the key active pathways in a cell as well as the conditions under which the pathways are activated. This method clearly outperforms PCA in the interpretability of flux data providing additional insights into the underlying regulatory mechanisms.The online version of this article (doi:10.1186/s12859-016-1063-0) contains supplementary material, which is available to authorized users. An elementary flux mode (EM) represents a unique and non-decomposable sub network of metabolic reactions that works coherently in steady state . ElementS the metabolic network stoichiometric matrix (dim(S) = nc × nv) and v a vector of reaction fluxes (dim(v) = nv). A set of i = 1, …, nd flux distributions V = {vi}(dim(V) = nv × nd) obeying to eq.   data wasX, such that for each latent variable a maximum of variance in the data can be captured Saccharomnabolism , 29. A bnabolism  replacinnabolism .nFac-1 EMs (1–3 factors) to a second selection of the same EMs for four to six factors . The conversion of glucose to lactate and succinate, e48, can be observed to be predominantly active in experiments one and three, which both have a low specific biomass growth rate. Lactate and succinate formation were assumed to be zero for experiments five to seven and at the same time e48 is hardly active. This EM is the only one which transforms glucose to lactate and succinate and it is interesting to note that the flux goes through the pentose phosphate pathway. It was described in [Energy generation is described by ribed in  that dure685, which due to the involvement in both processes has a length of 15 and such is longer than EMs that only describe glucose conversion. This EM is majorly active in experiments six and seven, in agreement with the observed higher glycerol formation. The e31 was repeatedly selected by PEMA across different numbers of factors and it describes the formation of citrate and malate from glucose. The flux goes through the pentose phosphate pathway, thus it is longer (length 23) than the shortest option (length 21). In experiments five to seven citrate and malate formation was assumed to be zero and consequently this EM is not active for those experiments.The conversion of glucose to glycerol and the generation of energy are described by e501. This EM is particularly active in experiments three and four, the experiments with the high SAM producing strain Kyokai 6. The increased activity of the TCA cycle observed in these experiments [e501, in that malate is produced via the TCA cycle.The production of S-adenosyl-L-methionine (SAM), malate and glycerol is described by eriments , is part24 . Thus, in this case the combinations are evaluated about 2 times faster (1.57 × 10−6/7.94 × 10−7). The reason for this improvement in performance is the way the algorithm can be implemented, using vector and matrix multiplications. Only two operations are required to evaluate m − iFac EMs, i.e.: computing the results for eqs.  modes (EM) has been proposed. The method avoids the evaluation of all possible combinations of EMs by using a branch and bound approach. It was shown that PEMA identifies the principal elementary modes (PEMs), which are those combinations of EMs that account for most of the variance in the flux data, and that PEMs are a faithful representation of active pathways. From studies in which 2 and 10 % Gaussian noise was added to the data, it can be concluded that the performance did not deteriorate for the correct identification of the PEMs. Also the performance in terms of explained variance did not decrease significantly for increasing levels of noise. In comparison to PCA it was observed that PCA can explain more variance in the data with fewer latent variables, but in contrast to PCA latent structures, the PEMs have a biological meaning. It also appears to be easier to choose the number of PEMs than the number of principal components in PCA. In addition, it was shown that the analysis of the PEMs might reveal insights into the regulation of the pathways. The set of PEMs is not exhaustive as only those PEMs can be identified that have a traceable footprint in the flux data, whereas other EMs might be active that do not contribute to the footprint significantly and thus are probably of minor interest.Not applicable.Not applicable.All data are publically available, either from the additional files or the original articles, which are cited in this article.


One of the more commonly reported variations in musculocutaneous and median nerves is a communication between the two. Such communications have been noted in the literature for well over a century, and numerous studies have attempted to quantify their rate of incidence and classify their different patterns. Most communications occur close to the brachial plexus in the proximal arm; communications distal to the musculocutaneous nerve perforation of the coracobrachialis have been reported with less frequency, and several rare and unique communication patterns have been reported as case studies. This paper describes a case of a communicating branch between the musculocutaneous and median nerves, distal to the origin of the brachialis muscle. This communication was found during a routine educational dissection and is closer to the level of the elbow than previously documented communications that are distal to the musculocutaneous perforation of the coracobrachialis. Identification and documentation of the variety of musculocutaneous and median nerve communications is relevant to clinical diagnosis of peripheral nerve pathologies, as well as for planning surgical approaches and procedures. Variations in anatomic patterns of both the musculocutaneous (MC) and median nerves have been described in the literature for well over a century . One of Such variations have been found to occur in 10%–43% of cadaver upper limbs . ClassifA unilateral communication between the MC and median nerves was observed during a cadaveric study of the brachial plexus, examining anatomic variants. The brachial plexus and associated peripheral nerves were carefully dissected and identified in order to assess their anatomical relationships. The variation was recorded and documented by neurosurgeons. The communication was found in the left arm, branching off from the MC after piercing the CB muscle, distal to both the insertion of the CB and the origin of the brachialis muscle. The branch continued medially and distally to join the median nerve as shown in Figure The communication was six inches from the coracoid and four inches from the elbow flexion crease. No other abnormalities of the brachial plexus, median nerve, MC nerve, or other peripheral nerves were found and no communication was present in the right arm.Communications between the MC and median nerves are more often found proximal to the MC perforation of the CB, closer to the brachial plexus . CommuniCommunicating branches between the MC and median nerves are thought to be a result of fibers that normally run through the lateral root of the median nerve and instead join it distally via the MC nerve. This phenomenon is described here as more distally located than typically reported and should be considered in relevant clinical settings such as biceps tendon repairs, given the high incidence (up to 43%) of similar communications.This classification indicates a more rare variation, as the majority of communications have been found to occur proximal to the CB and at the level of the brachial plexus -8. CommuThe Guerri-Guttenberg and Ingolotti classification system does leave some gray area within this 1A to 1D category of variation. Communications in this classification have a proximal boundary—the perforation of the CB—but no distal boundary, making it difficult to categorize the location of the communication. Other classification systems for MC variations have generally been less robust and also do not specify the level of a communicating branch that is distal to the CB.Although several studies have described a communication distal to the MC perforation of the CB, none have described a communication distal to the CB insertion or distal to the origin of the brachialis muscle. Representations of a communication distal to the MC perforation of the CB have typically been shown to be proximal to the insertion of the CB -2, 5. ThTraditionally with an upper plexus injury, elbow flexion is restored with an Oberlin transfer, which involves transfer from the ulnar nerve to the biceps motor nerve. MacKinnon felt that this transfer was not robust enough to provide functional improvement and suggested transferring median nerve branches to the brachialis motor branch of the MC nerve in addition to the Oberlin transfer . BecauseCommunicating branches between the MC and median nerves are thought to be related to embryologic development and a result of fibers that normally run through the lateral root of the median nerve and instead join it distally via the MC nerve .This is the first report of a specific anatomical variant of a far distal MC and median nerve communication. This variant was documented in a controlled anatomic cadaveric study. This finding has implications for surgeons dealing with the local anatomy, including orthopedic surgeons performing biceps tendon repairs and neurosurgeons performing Oberlin nerve transfers.


Formulas for variances of plane parameters fitted with Nonlinear Least Squares to point clouds acquired by 3D imaging systems  are derived. Two different error objective functions used in minimization are discussed: the orthogonal and the directional functions. Comparisons of corresponding formulas suggest the two functions can yield different results when applied to the same dataset. I, where I denotes the distance from an instrument to a point on a surface of the object and ϑ and φ are the elevation and the azimuth angles to that point. Usually a point cloud in a Cartesian coordinate system associated with the instrument is derived from the range image. Current 3D imaging systems may collect point clouds containing hundreds of thousands of points within a few seconds , a gradient of the function has to be zero. This implies that the original 3D search space may be reduced to a 2D space and the error function may be re-written asE being located atWhen the error function ϑ*) and var(φ*) may be calculated following the same general approach developed for fitting a sphere to range data [Pj can be expressed asjr is a range measured at bearings  and ||Pj|| = jr. In this approximation the bearings are treated as noise-free control variables and a unit vector pj is defined asThe variances of the fitted plane parameters var ajr and kr is negligible for any j ≠ k. When both assumptions are valid, the variances of the fitted plane parameters may be estimated by applying to Note that for other types of instruments, for example Coordinate Measuring Machines (CMM), the above assumption may not be valid and the formulas for variances of fitted plane parameters developed in this paper may not be applicable. In addition, it is assumed that the correlation in the measured ranges D* may be calculated from the uncertainty propagation formula [D defined in D are calculated at .The variance of the third parameter  formula  applied j the following 2 × 2 system of linear equationsSj and Vj are defined asThe individual sensitivities H is the Hessian of the error function EThe matrix OE and the directional error function DE.These general formulas are now applied to two specific error functions: the orthogonal error function Oj corresponding to the experimental point Pj is defined as the orthogonal projection of Pj on a plane. Thus, For the orthogonal plane fitting see  the theoP0 here is the centroid of all experimental points P{N}. This condition states that the plane fitted with the orthogonal error function has to contain the centroid, P0. Defining a scalar product jd of two vectors w and pj given by D when using jr is a measured range. In this notation, ϑ, φ) can be written asApplying condition OE defined in H defined in Then, the elements of the gradient of the error function ∇Vj defined in jr the elements of the gradient ∇OE given by Uj given by P0 of all points Pj as well the dependence of Pj on jr given by Vj can be evaluated asFinally, the elements of vector j,kδ is the Kronecker delta, and pk is the unit vector defined in w, defined in H and vectors Vj are known, the sensitivity vectors Sj can be calculated for every j by solving the 2 × 2 system of linear ϑ*) and var(φ*) and the covariance cov can then be determined from D*, defined in Eqs.  can be written asIn this notation, DEH defined in Using the following auxiliary functionsVj defined in j,kδ is the Kronecker delta. Once the matrix H and vectors Vj are known, the sensitivity vectors Sj can be calculated for every j by solving a 2 × 2 system of linear ϑ*) and var(φ*) and the covariance cov can then be determined from Eqs.  is decreasing, even when the uncertainty of the measured ranges jr is large. The optimal value of the error function is usually interpreted as a gauge of noise level in experimental data (assuming that a right model is fitted to the data). For 3D imaging systems, due to a divergence of a laser beam, range measurements collected for large AOI have large uncertainty. Thus, the behavior of OE is in a sharp contrast with the common experimental observation. The directional fitting is free of this flaw and a residual value of the directional error function DE correctly estimates a level of noise in the acquired experimental dataset P{N} for any AOI. When OE is minimized, the sensitivities of the fitted angles OE and DE is diminishing and both error functions are expected to provide correct estimates for the variances of fitted parameters.Sj of fitted angles are calculated from Vj on the right hand side of this equation behaves differently for the orthogonal and the directional error function, see Eqs.  of plane parameters fitted to a dataset acquired with 3D imaging systems. Two error functions were investigated: the orthogonal and the directional error function. Comparison of corresponding formulas suggests the two functions may yield different results when applied to the same range data. However, in order to quantify the anticipated difference, laboratory experiments and computer simulations are needed.


The phenomenon of social exclusion can be investigated by using a virtual ball-tossing game called Cyberball. In neuroimaging studies, structures have been identified which are activated during social exclusion. But to date the underlying mechanisms are not fully disclosed. In previous electrophysiological studies it was shown that the P3 complex is sensitive to exclusion manipulations in the Cyberball paradigm and that there is a correlation between P3 amplitude and self-reported social pain. Since this posterior event-related potential (ERP) was widely investigated using the oddball paradigm, we directly compared the ERP effects elicited by the target  and non-target  events in both paradigms. Analyses mainly focused on the effect of altered stimulus probabilities of the target and non-target events between two consecutive blocks of the tasks. In the first block, the probability of the target and non-target event was 33% , in the second block target probability was reduced to 17%, and accordingly, non-target probability was increased to 66% . Our results indicate that ERP amplitude differences between inclusion and exclusion are comparable to ERP amplitude effects in a visual oddball task. We therefore suggest that ERP effects–especially in the P3 range–in the Oddball and Cyberball paradigm rely on similar mechanisms, namely the probability of target and non-target events. Since the simulation of social exclusion  did not trigger a unique ERP response, the idea of an exclusion-specific neural alarm system is not supported. The limitations of an ERP-based approach will be discussed. Social exclusion is a topic which got particular attention in recent years in both social psychology and neuroscience. The seminal model of Williams and colleagues e.g. , 2) stat stat2]) per se )target event is varied systematically. Following this approach, we used a partial exclusion condition in our previous studies allowing a separate analysis of ERP responses to the event “self”  during inclusion and exclusion. In line with an early Cyberball study ) On the contrary, the results of the visual Oddball task show that by eliminating the social context reduced target probability–which was clearly noticed by the participants–did not lead to a feeling of social exclusion. Although there is evidence that the credibility of the cover story or the source of exclusion have minimal influence on the induction of social need threat during Cyberball , 31, theThe reduction of target probabilities was noticed in both groups. However, the Cyberball group was more sensitive with respect to the perceived difference in target probability. This task effect could be due to discrepancies in the instructions and experimental procedure: in the Cyberball task, participants were asked to imagine themselves in two different situations of a ball-tossing game (in the meadow and on a beach), so that it would be easier for them to differentiate between blocks while retrospectively filling out the questionnaires after the second block of the game. In contrast, participants in the Oddball group were told that they took part in a simple reaction task, and an additional imaging task was not required. This might have diminished the differentiation between blocks. However, this modulation by the factor “task” did not lead to a different processing of the target events on the level of ERPs which will be discussed in detail in the following.A direct comparison of ERP results obtained in the Cyberball and Oddball task showed that the processing of target events  did not differ: two components were elicited by the presentation of this event–a parietal N2, and a P3 complex constituted by a centro-parietal P3a and a parietal P3b.Since the N2 component was not affected by the reduction of target probability, we suggest that this component reflects task relevance or target detection: it was shown previously that targets compared to non-targets and ball receptions compared to non-ball receptions elicited a posterior N2 , 27, 33.r and p values for both experimental groups). Both observations question the relation of the ERP effects to need threat, since the effects in the P3 range are not necessarily associated with the experience of social exclusion. The P3 effect rather corresponds to the estimation of target probability and the subjective expectancy for target appearance [The effects of target probability on the P3 complex in the visual oddball task were similar to the effects obtained during Cyberball. The P3 complex in our previous study was divided into a more central P3a and a parietal P3b  which wepearance , 35, whipearance .Non-target events elicited two distinct components in the Cyberball and Oddball task which were affected by the factor “block”: an early N2 component and a P3 complex with a fronto-central P3a and a following–more widespread–P3b.The N2 elicited by non-targets was more pronounced in the second block of both tasks. This effect was restricted to the N2 recorded at Cz, but it was not modulated by the factor “task”. It is probably related to differentially pronounced response preparation processes between blocks , but thiThe P3 complex elicited by non-targets had a more anterior topography as compared to the target P3s. This is in line with a recent Cyberball study  where anIn a previous Cyberball study the P3b triggered by the event “other” was more pronounced during inclusion as compared to exclusion . AccordiIn the Cyberball studies mentioned above the P3 effect was correlated with an increase in social pain , or an dDespite the striking similarities between the ERP effects obtained in the Cyberball and Oddball task–especially for the processing of target events–we have to consider that the topography of effects on P3a amplitudes elicited by non-targets slightly differs between tasks. This shift in topography towards frontal leads in the Cyberball task has to be confirmed by multi-electrode recordings to explore if different neural networks are involved. Although this shift is the only significant difference of ERP effects between tasks, grand averages–with respect to the P3b –suggest that the effect of probability was more pronounced in the Oddball task as compared to the Cyberball task see . Even thIn a previous ERP Cyberball study late (> 400 ms after stimulus appearance) frontal components were related to perceived distress . We haveAnother important point is if our findings are specifically related to the Cyberball paradigm. Although we conclude that expectancy violations account for the effects obtained in this paradigm–on the level of probability sensitive ERP components and also on the level of questionnaire data –we cannoS1 Table(DOCX)Click here for additional data file.


The method of using Global Positioning System-leveling data to obtain orthometricheights has been well studied. A simple formulation for the weighted least squares problem has been presented in an earlier work. This formulation allows one directly employing the errors-in-variables models which completely descript the covariance matrices of the observables. However, an important question that what accuracy level can be achieved has not yet to be satisfactorily solved by this traditional formulation. One of the main reasons for this is the incorrectness of the stochastic models in the adjustment, which in turn allows improving the stochastic models of measurement noises. Therefore the issue of determining the stochastic modeling of observables in the combined adjustment with heterogeneous height types will be a main focus point in this paper. Firstly, the well-known method of variance component estimation is employed to calibrate the errors of heterogeneous height data in a combined least square adjustment of ellipsoidal, orthometric and gravimetric geoid. Specifically, the iterative algorithms of minimum norm quadratic unbiased estimation are used to estimate the variance components for each of heterogeneous observations. Secondly, two different statistical models are presented to illustrate the theory. The first method directly uses the errors-in-variables as a priori covariance matrices and the second method analyzes the biases of variance components and then proposes bias-corrected variance component estimators. Several numerical test results show the capability and effectiveness of the variance components estimation procedure in combined adjustment for calibrating geoid error model. Based on this inherent appeal of the relationship between ellipsoidal, orthometric heights and gravimetric geoid data, if any two of the heights are given, the third can be derived with Eq.  observations and leveling data have been adopted to evaluate gravimetric geoid, and many studies have been carried out by comparing the interpolated values of the gravimetric geoid at the GPS benchmarks with the corresponding GPS-leveling heights  is employed to the combined least-squares (LS) adjustment in Eq.  Teuniss. There aA is the m × t matrix of known coefficients depends on the parametric model , x is t × 1 vector of the unknown parameters depending on the parametric model, Qv is the m × m CV symmetric cofactor matrix of the observables, σ is the variance or CV components, and the observations vector l consists of the height ‘misclosure’ at the GPS-leveling benchmark as follows,To establish the LS variance component estimation, a combined adjustment is carried though using the following functional model with orthometric, ellipsoidal heights and gravimetric geoid data. Considering the Gauss–Markov model, the system of observation equation and the solution can be expressed as,A corresponding to the parametric model the model of Multi-surface function fit is being used,φ and λ are latitude, longitude respectively, and ai are the coefficients.Here, for the design matrix m × 1) vector of unobservable random error with zero mean, for each of heterogeneous height data types are given by,B is the block-structured matrix I is an m × m unit matrix.C is a positive-definite symmetric matrix. Here we assume that there are no correlations between the heterogeneous height types. Q(⋅) are known positive cofactor matrices for ellipsoidal, orthometric heights and gravimetric geoid data, and The corresponding CV matrix is described in Eq. , which cP associated with the observations take the forms,P(⋅) is assumed diagonal with elements which is the reciprocal of the error variances. According to LS adjustment, the unknown parameters and adjusted residuals of observations can be easily solved. The unknown parameters is given as follows,The vector of unknown parameters is computed by using LS minimization principle,The adjusted residuals of the GPS, leveling and gravimetric geoid height observations can be obtained byAnd the mean square error and the accuracy of parameters estimations are given as follow,According to this combined LS adjustment approach, the solution can be achieved depending on two issues, one is the appropriateness of the parametric models, which refers to the correction for the data inconsistencies and the systematic errors, and another is the residuals of the height data types which allow for the calibration of data covariance matrices. Since the former problem has been well studied, the main work of next section focus on a description of the implement of VCE schemes to the combined LS height adjustment.There are many methods available to implement VCE within the LS adjustment Helmert . The firS is denoted bySij in the matrix is derived bytr(·) is the trace operator, Q(·) is the cofactor matrix for observables. Considering the matrix S may not be of full rank, the algorithm of pseudo-inverse should be used to solve Eq.  gravity anomalies used for geoid computation are consisted of 4,574 ground data irregularly distributed in the test area and are referred to GRS80, and the data set of FA gravity anomalies is referred to the NAD83. All data have been removed the duplicate points and validated Least squares collocation (LSC). The error ratio used in this method is about 8 % and the remaining points are used for test  technique for the purpose of making the gravity anomalous small and easy to be gridded  (Haagmans et al. The GPS-leveling heights are employed to estimate the absolute and relative accuracies of gravimetric geoid. A total number of 170 GPS-leveling benchmarks distributed throughout the test area were used. Figure Fully populated initial CV matrices are computed for ellipsoidal, orthometric heights and gravimetric geoid data. The CV matrix for the ellipsoidal heights is obtained from the results of the GPS post-processing software package being used. These are the direct results without considering the spatial, temporal and physical correlations between GPS phase observables. Similarly, the CV matrix for the orthometric height are obtained from the rigorous adjustment of leveling measurements and the CV matrix for the gravimetric geoid heights at the GPS benchmarks are derived in a straightforward manner by applying the law of error propagation to the geoid solution. Table When estimating variance components, convergence depends on the given initial values of weight of the measurements. Here we will study an algorithm to improve the convergence speed and behavior of estimating variance components.jth step Considering the availability of fully populated CV matrices is a luxury, the iterative application of MINQUE is used to estimate the variance components in practice. First of all, suppose that by using a conventional technique of variance component estimation, we have the three estimates at the The iterative procedures are given in Fig. In order to study the correlations among observations, numerical tests are performed with diagonal CV matrices. Figure N, with ellipsoidal height h from GPS measurement and orthometric height H from leveling measurement N denote an evaluation for the accuracy of gravimetric geoid. In order to estimate the accuracy of gravimetric geoid, the different between gravimetric geoid solutions are compared with 165 GPS-leveling heights.A popular approach is to compute the difference between the gravimetrical geoidal undulation Each of the height data types refers to different reference surfaces which results in that biases are introduced into the geoid model. In order to absorb the errors due to the datum inconsistencies between the gravimetric geoid and GPS-leveling heights, a parametric model has been used. In general, the process of choosing the parametric model suffers from a high degree of arbitrariness. In order to evaluate the availability of parametric models, the semi-automated assessment procedure combined with F-significance test is used. Figure Since the main idea of this paper is to discuss the influence of a priori CV matrices on the final computed variance components, two numerical examples are conducted to assess the gravimetric geoid accuracy in this section. In the scheme of case study II, combined height adjustment is conducted by using the a priori CV matrices as given in Table Such a scheme selects the best GPS benchmarks to evaluate the accuracy of geoid with minimum range and standard deviation criteria. The selected GPS benchmarks are used to fit geoid using the multi-surface function fit technique. 150 GPS benchmarks are selected to fit geoid models in this paper. The residual values at the all the rest GPS benchmarks denote the relative accuracy of the geoid. The statistical results of the residuals at the 15 GPS benchmarks are shown in Table The main focus point of this study is to give a procedure of geoid determined with available high precise gravimetric geoid and GPS and leveling heights and to improve the accuracy of geoid. In the context, a precise formula for the geoid computation is derived, and the relationship between ellipsoidal, orthometric heights and gravimetric geoid data is conducted. And a detailed algorithm uses the complete description of the CV matrices of the observation vector and of the coefficient matrix, possibly with unknown components of each. In the practice of this context, the iterative application of MINQUE is employed to test the variance components matrices for heterogeneous height data. Numerical case studies shows that the best results were obtained combined with the variance components estimation, with an outside precision of 1.91 cm and an inside precision of 0.29 cm, while the classical method with a-prior CV matrix is a bit worse, with an outside precision of 4.70 cm and an inside precision of 1.25 cm. The results of numerical examples show the capability and effectiveness of variance components estimation procedure in combined adjustment for calibrating geoid error model.


This arrangement limits the number of communication tracks to three, while ensuring maximum testing versatility by providing independent access to all 12 electrodes in any configuration. Laser-patterned platinum-iridium foil forms the implant’s conductive tracks and electrodes. Double rivet bonds were employed for the dice microassembly. The active electrode array can deliver current pulses  and supports interleaved stimulation with independent control of the stimulus parameters for each pulse. The stimulation timing and pulse duration are very versatile. The array was electrically characterized through impedance spectroscopy and voltage transient recordings. A prototype was tested for long term mechanical reliability when subjected to continuous bending. The results revealed no track or bond failure. To the best of the authors’ knowledge, this is the first time that flexible active electrode arrays with embedded electronics suitable for implantation inside the rat’s spinal canal have been proposed, developed and tested in vitro.Epidural spinal cord electrical stimulation (ESCS) has been used as a means to facilitate locomotor recovery in spinal cord injured humans. Electrode arrays, instead of conventional pairs of electrodes, are necessary to investigate the effect of ESCS at different sites. These usually require a large number of implanted wires, which could lead to infections. This paper presents the design, fabrication and evaluation of a novel flexible active array for ESCS in rats. Three small (1.7 mm Recently epidural spinal cord electrical stimulation (ESCS) has been shown to restore supra-sacral control of muscles paralysed by spinal cord injury (SCI). Harkema et al.  reportedvan den Brand et al.  conducteThe development of epidural electrode arrays for chronic testing in rats presents special challenges compared to other parts of the body. The main issues relate to the limited cross-sectional area at the implantation site [3 mm wide, 300 μm thick  electrode arrays for ESCS in rats have been recently reported  can be exploited by assembling the custom designed silicon microchips on the passive electrode arrays . Depending on the ASIC’s functionality, the active microimplants could potentially lead to devices free from external equipment, suitable for testing in freely moving animals.This paper presents the design, fabrication and characterization of active flexible epidural electrode arrays for ESCS in rats. The implants are made of polydimethylsiloxane (PDMS) substrates and feature 12 platinum-iridium (PtIr) electrodes which can be independently selected in any possible configuration. Embedded ASICs minimize the required power supply and control signal connections to only three, while featuring rapid parameter adjustment and ultralow power consumption. To the best of the authors’ knowledge, this is the first time that active electrode arrays with microelectronics suitable for implantation inside the rat’s spinal canal have been developed and tested. The rest of this paper is organized as follows. The following subsection discusses the specifications posed by the implantation site and presents the proposed implant design. Section The concept of integrating electronic circuits close to their respective electrodes is not new and active electrode arrays have been previously reported for a variety of applications. Lithographically patterned probes and arrays on silicon substrates, where custom circuits for processing are included were reported  was selected to form the conductive parts of the implant. It was preferred to previously reported pure Pt   with 10–30 % iridium (Ir) have similar CSC to pure Pt . This is enabled by an on-chip storage capacitor. The third line delivers the stimulus current, up to 1 mA, with one or two pulses to give monophasic or biphasic electrode currents respectively. This is externally generated to keep the silicon area small, and most importantly, to reduce the power consumption (and hence heat dissipation) close to the spinal cord. The on-chip analog circuits have been designed for minimum power dissipation. An asynchronously controlled digital unit provides maximum versatility on the control of the stimulation timing, while its design also ensures minimum unwanted power consumption by avoiding on-chip clocks. As a result a maximum of only 114 μW is consumed by the whole 3-ASIC-system during a full biphasic stimulus cycle. The ASICs have an output voltage compliance of up to 25 V, to accommodate for high impedance loads or high currents. A block level diagram showing the components of the circuit is presented in Fig. 2 with a square layout. They include large  custom designed pads to facilitate manual microassembly on the flexible array. The prototype chips were fabricated using XFAB XP018, a 0.18 μm high-voltage CMOS technology.All three ASICs have different layouts and work together as one system able to drive 13 electrodes (12 on the array and one extra subcutaneous electrode) independently, in any possible configuration. Interleaved stimulation is also supported, allowing more pulses of different characteristics, all delivered from a single current source, at repetition rates of up to 100 pulses per second (pps). Each ASIC can be used independently of the others if needed . All ASICs receive and store the same information from the external control unit, however each ASIC only services specific electrodes (defined by a unique electrode ID). Their footprint is only 1.75 mmThe dice received from the foundry were approximately 1 mm thick. To satisfy the restrictions for the total implant volume, a dice thinning target of 100 μm was set. ASICs of this thickness are already thin enough for this application, and are, at the same time, strong enough to handle.2). The method is based exclusively on mechanical polishing. This ensures that no special care needs to be taken to avoid damaging the active die area due to chemicals – this could be especially complicated for such small areas.The thinning of silicon chips is usually done at wafer level, and processes such as mechanical grinding followed by a chemical stress-relief step are commonly employed  pads was evaluated and a parameter optimization study was conducted  were employed for each bond, one above and one below the 150 × 150 μm PtIr pad  The parameters used for the rivet bonding are those in Table Fabrication of the electrode interconnects (top-layer-first approach):Formation and shaping of the top PDMS layer.Lamination of metal and shaping of the conductive lines, pads and electrodes.Formation and shaping of the bottom PDMS layer.Microassembly of the ASICs:Bumping of the thin dice.ASICs and flexible array alignment and assembly.Final encapsulation:Bottom layer.Top layer.The proposed fabrication method of the active array comprises three main processes: (I) fabrication of the electrode interconnects, (II) microassembly of the ASICs, and (III) final encapsulation. Each process comprises several different steps. The flow of the basic processes is summarized below:Figure In Fig. In [Fig. The second  layer of PDMS is then spun initially uniformly along the surface of the device, but post processed to keep the top surface of the Kapton tape free [Fig. After the second layer has been formed, the device is released from the substrate and the PDMS that was present where the ASICs are to be placed is removed [Fig. The integration of the ASICs on the rest of the device [Fig. To align the parts, a dedicated stage has been designed Fig. . The strDuring the bonding process, the ASICs are securely attached  on the alignment stage [Fig. Next, the array is aligned on top of the ASICs so that the holes on the metal tracks are placed directly on top of the first gold stud [Fig. To complete the fabrication process the ASICs need to be encapsulated in PDMS. The encapsulation ensures that the conductive parts are isolated and are not in contact with the tissue, and it also provides mechanical support to the bonds, resulting in a more reliable device.To keep the thickness of the device within the desired limits and to ensure no air bubbles are formed during the encapsulation stage (this would compromise the lifetime of the implant) a custom-made mould was used in this part of the process Fig. . This coIn the final step, the electrodes are covered with Kapton tape for protection, and some extra PDMS is deposited [so that the top layer of Fig. For the connection of the array to the stimulation control unit, stainless steel wires  are soldered on the pads . This is interfaced via stainless steel wires to a PCB where the ASICs are mounted, and through which the desired sites become accessible. Of course, small deviations from the measurements are expected for the active implant, but they should not be significant.SS line of one of the ASICs. We subjected the device to continuous bending for 14 days, during which we applied electrical stimulation  for a total of 21 h. No failures were observed after the end of the test (over 1.2 M bending cycles), either at any of the – initially good – bonds, or at any of the tracks. The good continuity was also verified electrically. In addition, examination under the microscope revealed that the metal of the electrode contacts and tracks had not degraded in any visible way.The tested prototype had nine functional electrodes out of the 13. This was due to a failed connection during fabrication on the VFigure Figure p of Fig. a is close to 2 V for 1 mA).When a PtIr electrode is immersed in an electrolyte containing chloride, the maximum voltage swing before oxygen and hydrogen evolution is about 2.15 V , for example, for a closed-loop system as it reduces noise introduced by long tracks on the recorded signal.The limitation of the current implant layout is the fact that all ASICs are connected together serially. As a result if a failure occurs in one of the input lines of the first-in-the-series ASIC, the failure will affect all the following ASICs. Due to the limited area available for this application, this type of connection was selected as a trade-off for a smaller implant width. If that was not of such concern one could modify the track design to make sure that all chips’ input lines are connected in parallel, thus isolating the failures only to the ASIC in which they occurred.Regarding the fabrication of the active arrays, one of the most challenging stages was the temporary fixing of the small dice on the wire bonder during the assembly process. The bonding of the ASICs requires that the dice are very well attached on the substrate during the procedure [Fig. in vitro electrical and mechanical evaluation of the implant’s performance has been presented. The electrical evaluation indicated that safe stimulation is possible; the low power operation of the ASICs ensures that the dissipated heat will not cause tissue damage [by respecting the limit for implantable devices of a maximum of 400 μW/mm2 chronic heat flux  is high enough to accommodate for these impedance changes, the correct charge will always be delivered to the load.The voltage waveform in Fig. A novel design and fabrication process for flexible active stimulating epidural electrode arrays for rats has been proposed. The 12-electrode PDMS-based array includes three small, thin ASICs that are suitable for implantation inside the rat’s spinal canal. Thanks to the ASICs, using only three communication wires independent access can be provided to all 12 PtIr electrodes in any possible configuration. Chronic bending tests with a custom setup on one prototype revealed no bond or track failure. The electrical evaluation of the devices suggests safe stimulation. The active arrays can be electronically programmed via a GUI that communicates with an external control unit connected to the implant. Stimulation parameter adjustment is rapid, and can be done several times during a gait cycle. This feature, together with interleaved stimulation supported by the hardware, ensure full testing protocol versatility.


Most injuries to young children happen in the home. Therefore, this study aimed to investigate if extended individual information to mothers’ related to injury to children in the home and possible preventative actions has any effect on their awareness of the problem and if Sense of Coherence has an influence.This was a quasi-experimental designed intervention study with a comparison group. Extended individual information with empowerment as the approach was used.Ninety-nine mothers of children under the age of 7 months participate. A questionnaire with sociodemographic data and questions regarding awareness towards prevention was used. Mothers who took part in the intervention significantly increased their awareness of the fact that child injuries take place at home when compared with the mothers in the comparison group, . However, no significant improvement of awareness towards prevention was noted, neither any association to the mothers’ SOC-scores.This study showed that the intervention had a positive effect on mothers’ awareness towards the fact that child injuries are taking place at home, but it did not increase the mothers’ awareness towards prevention of child injury. From an international perspective, incidents of child injuries and child mortality in Sweden are low . Accordi1 and 14 years old and most injuries to young children [0–3 years old] take place in the home. Most frequently it is boys of 1–2 years of age who suffer scald and burn injuries . The injTengland  stressedA human being’s inner strength is influenced by self-empowerment. Antonovsky , p. 19 dSeveral reports have found that effective community-based interventional programmes potentially reduce the risk for a child being injured in their home, although few reviews gave any proof of effectiveness , 18. LowThis quasi-experimental designed intervention study with a comparison group took place in two different areas in a city in southern Sweden and focused on families with a low education level. Due to the possibility of a Hawthorn effect  in a ranThe decision was made to create a sample of 100 mothers using a power calculation. The sample decreased to 99 since one mother answered the questionnaire twice. All mothers gave their written consent to participate. Fifty of the mothers were registered at one CHC (IG) and the other 49 mothers were registered at the other CHC (CG). The choice of which CHC was to be the IG respectively the CG was decided by lot. The mothers were identified through their children’s journals and were selected consecutively at the CHC by the first author. All the mothers with babies aged 4–7 months attending the CHC during a 6-month period were included and received a written invitation to participate in the study (n = 184). Three reminders were sent out. The CHC’s offered all the families standard information concerning prevention focusing on child injuries at home. This information aimed to prevent burns, fall injuries, poisonings and choking hazard.A pilot study with face validity, which included nine mothers, was performed in order to test the questionnaire. The questionnaire contained background questions such as, the mother’s awareness about child injuries and questions about awareness of child injury prevention at home. No changes in the questionnaire were necessary. The analysis of the current study did not involve the data from the pilot test.Five questions concerned sociodemographic i.e. educational level, Swedish by origin, less than 4 years in Sweden, two children or more, and experience of historical injuries to children.Furthermore, three statements focusing on child injury and the mothers’ awareness towards prevention at home (scores from 0–10/disagree-agree) were made  were kept out of reach for the children. The mothers then answered the baseline questionnaire once again.2 method was used to assess dichotomized answers and for comparison between the groups, before and after the intervention. The Statistical Package for the Social Sciences programme (SPSS version 16.0) was used. A non-response analysis showed no significant differences in the background characteristics between the mothers in the IG and those in the CG. This study was approved by the Regional Ethics Board of Lund, Sweden (LU: 30/2008).The independent variable consisted of the extended individual information whereas the dependent variable was the mother’s awareness of child injury at home and preventions. The Mann–Whitney and χp < 0.001).The participating mothers came from 25 different countries, most were from Iraq, Lebanon and former Yugoslavia. Background variables were collected and concordance was found between the mothers in both groups regarding (i) educational level, (ii) Swedish by origin, (iii) less than 4 years in Sweden, (iv) two children or more. A significant difference was noted between the groups regarding experience of historical injury to children. The children of the mothers in the intervention group had a significantly higher number of historical injuries (n = 17) than those in the comparison group (n = 3), , received their injuries from scald and burn accidents, whereas 30 % (n = 6) had fallen from furniture, and 20 % (n = 4) had suffered from eye or head injury, or medicine poisoning.No significant difference was found in a comparison between mothers’ awareness towards child injuries and injury prevention in the home at baseline, or regarding mothers with or without experience of historical child injuries in the family Table .When comparing the effect of SOC-scores assessed at baseline concerning awareness, no influence was found in a comparison between groups at follow-ups. The association of a high/low SOC-score with the mothers’ awareness towards child injuries and injury prevention at home was not proven in the baseline-assessed awareness or in the comparison between the IG and the CG of mothers at follow-ups Table .Table 2Bp < 0.025). A comparison between those who took part in the IG and those of the CG indicated that the IG mothers had increased their awareness to a greater extent . The IG was statistically used as the reference group [OR 1.0], (Table However, concerning the subject; ‘many injuries to young children occur at home’ the awareness in the IG had improved significantly after intervention compared to baseline (This study showed that an intervention with extended individual information and home visits concerning the prevention of child injury at home had a significant positive effect on mothers’ awareness towards child injury. Since research has shown that approximately 30 % of all unintentional injuries among children can be prevented  studies A review study has shown that parental intervention seems to be effective  and therAfter the study questionnaire was developed, a pilot test with face validity was performed and any obstacles preventing a full understanding of the questions due to language were decreased after the questionnaire was presented in English, Albanian and Arabic.In all, 29 % of the mothers were missing in the follow-up but in a comparison of the mothers who completed the study and the non-responders, little variation and no significant difference was found. This study showed that the mothers’ awareness towards child injuries and injury prevention was not influenced by their SOC-scores but there is a likelihood that the sample size in the current study was too small to enable associations to be made.The baseline characteristics of the mothers in the IG and the CG respectively were similar except for the historical injuries that had happened to a greater number of the children in the IG. This might have been a reason why the IG, after the intervention, had an increased awareness concerning the fact that many young children are injured at home. Yet the intervention showed no significant effect on awareness of prevention among the IG. This is in line with the results from Vladutin et al. , which sFurthermore, there might also be a limitation of the study by the fact that mothers with a history of experiences concerning injury among their children could have been more inclined to have increased awareness, compared to mothers lacking such experiences. The high median scores reached in questions concerning mothers’ sufficient knowledge and the taking of sufficient precautions was found in both the IG and the CG. It might be explained as an effect of the mothers’ reading the questionnaire and therefore reflecting on child accident prevention. Reflection upon awareness toward the prevention of child injury at home could possibly have influenced the mothers’ to become more aware. Furthermore, the reflection might be more pertinent in relation to the mothers’ awareness of the possible risk for injury at home. Perhaps the answer alternatives ‘sufficient’ and ‘good’ were not optimal and hence misled the mothers. Another explanation for why the two questions above did not show significant improvement of the mothers’ awareness might be that they were already high at baseline. Some mothers also stated that their knowledge had been insufficient before receiving the extended individual information. One explanation for this may be that after the intervention mothers became aware of what they did not know prior to the intervention.Furthermore, the workshop might have increased the mother’s understanding about their own knowledge, which led to their awareness that they overvalued their knowledge at baseline.The intervention consisted of home-visits offering empowerment and extended individual information based on the individual person attending. To overcome some of the risk for bias, the first author made all the interventions.This study cannot verify which part of the intervention it was that increased the mothers’ awareness of the fact that child injuries occur at home. WHO and UNICEF recommend home visits in the baby’s first week of life . There aThis study showed that the intervention had a positive effect on mothers’ awareness towards the fact that child injuries are taking place at home, but it did not increase the mothers’ awareness towards prevention of child injury. The clinical implications are that Child Health Care Services has a huge challenge in developing interventions in order to prevent child injuries and to make the mothers’ aware of the importance of prevention.


Energy-dependent patterns in the arrival directions of cosmic rays are searched for using data of the Pierre Auger Observatory. We investigate local regions around the highest-energy cosmic rays with  The long-standing question about the origin and nature of the ultra-high energy cosmic rays (UHECRs) is yet unanswered. Presumably, UHECRs are charged nuclei of extragalactic origin. They are deflected in extragalactic magnetic fields and the magnetic field of the Milky Way such that their arrival directions may not point back to their sources . The strThe Pierre Auger Observatory , 7 is cuc matter  yielded mentclasspt{minimac matter .Nevertheless, if the highest-energy cosmic rays with In this report, we investigate the local regions around cosmic rays with We use two methods to characterize the energy distributions inside the local regions. In one method we study energy-energy correlations between pairs of cosmic rays depending on their angular separation from the center of the region. With this measurement we search for signal patterns expected from particle deflection in turbulent magnetic fields. In the second method we decompose the directional energy distribution of the cosmic rays along its principal axes. This general decomposition method imposes no requirement on the sign of the cosmic-ray charge, or the charge itself. Beyond measuring the strength of collimation along principal axes, the axis directions of the individual regions around the highest-energy cosmic rays potentially reveal local deflection patterns due to magnetic fields.Both methods were originally studied in particle physics, and were referred to as energy-energy correlations and thrust observables, respectively , 15. SimThis paper is structured as follows. The observables of the energy-energy correlations and the principal-axis analysis are defined in Sect. In this section we introduce the main components used for the measurement. We first define the local regions in which we analyze the cosmic-ray energies and arrival directions. We then explain the energy-energy correlation observable and its angular dependence. Finally, we present the method of calculating the principal axes of the energy distribution which results in the three values to characterize the strength of collimation along each axis, and the directions of the axes themselves.The observables used here are calculated from the events detected in a bounded region in the sky, here denoted as ‘region of interest’ (ROI). To minimize the statistical penalty from multiple tries, we do not scan the entire sky but investigate a limited number of ROIs located around events with an energy above 60 EeV. This energy cut is motivated by the limitation of the propagation distance by, e.g., the GZK effect , 19 and i, j within a ROI usingi with the angular separation Energy-energy correlations (EECs) are used to obtain information on the turbulent part of galactic and extragalactic magnetic fields . The conThe cosmic rays in a ROI can be separated into a signal fraction, whose arrival direction is correlated with the energy, and an isotropic background fraction. The values of We present the angular distribution of the EEC as the average distribution of all ROIs. Each value i. The values of To further characterize energy-dependent patterns within each individual ROI, we calculate the three principal axes of the energy distribution which we denote as detector  in the dllisions , 24.For entclass1pt{minimaentclass1pt{minimai. The thrust axis is thus the radial unit vector In arbitrarily defined spherical coordinates  the ROI .The thrust-major and thrust-minor axes can consequently be written asentclass1pt{minimaNote that in a perfect isotropic scenario, the energy distribution within the plane defined by analysis . HoweverFor obtaining a general understanding of the energy-energy correlations and the thrust observables, we use simple scenarios of cosmic-ray deflections in magnetic fields to demonstrate resulting distributions. First we describe the procedure for simulating mock data representing cosmic-ray deflection in turbulent and coherent magnetic fields. For different quantitative mixtures of these field types we then present the distributions of the energy-energy correlations and finally discuss the resulting thrust distributions.To demonstrate the sensitivity of the observables to deflections expected from magnetic fields, we simulate a ROI with UHECRs in a simplified scenario. The deflection in cosmic magnetic fields is supposed to result in two different kinds of patterns in the arrival direction of the UHECRs. First, if the UHECR’s trajectory resembles a directed random walk, a symmetric blurring of the source is expected. Second, if the particles are deflected in large-scale coherent fields, e.g. in the Milky Way, an energy ordering of the UHECRs in threadlike multiplets is expected.Here we model the distribution of UHECRs in a region around the source as a superposition of both effects. Events in this region of interest are generated in three steps as sketched in Fig. c fields , 27 thisSecond, a simple model for the deflection in coherent magnetic fields is added on top of the model for turbulent magnetic fields used above. Here the individual cosmic rays are deflected in one direction by an angle mentclass2pt{minimThird, particles deflected outside the region of interest are added as a background to keep the number of particles in this setup constant cf. Fig. c. The enspectrum .The EEC distributions resulting from simulated scenarios using the three values for the turbulent deflection strength entclass1pt{minimaentclass1pt{minimaIn Fig. All three observables are sensitive to a symmetric blurring of the source. For increasing V derived in the specialized statistics for directional data . Th. ThV derV from the n observations R is defined asR in Eq.  to observe a cosmic ray for discrete directions and energies using parameterizations for energy losses and energy-dependent deflections. In the calculations, energy losses of the UHECRs from interaction with extragalactic-photon backgrounds, effects from the expansion of the universe and deflection in extragalactic magnetic fields are accounted for using parameterizations. To account for deflections in the galactic magnetic field, the calculated pdf is transformed using matrices derived from backtracked UHECRs using the CRT software .As model for the galactic magnetic field, we use here the model proposed by Jansson and Farrar , 35. Forx layout . The eneD of the source. We scanned the parameter range We simulated scenarios with unstructured point sources with density Since the sources of the UHECRs are randomly distributed and have a maximum injection energy ly (e.g. ) and is Q directly, but the modified likelihood ratioQ larger than the observed value are obtained in simulations of the alternative hypothesis and Limits on the strength of the deflection and the density of point sources in the simulation are set using the S method , 39. HerA combination of the limits is not attempted here as it depends on scenario-specific correlations between the observables. If the cosmic rays are not protons but heavier nuclei the limits are reduced accordingly. For the extreme case that all cosmic rays are iron nuclei with Previously, we derived from two-point correlations of UHECRs with an energy mentclasspt{minimaWith the current analysis we obtain for the lowest EGMF considered a limit of In this work, we characterized the distribution of UHECRs with Within the simulated scenario, we estimate that the strength of the deflection in the extragalactic magnetic field has to be larger than


However, the copper columns tended to be cone-shape when the initial gap between electrodes became larger (35 μm or above). The number of voids inside the copper column and the average deposition rate both decreased with the increase of the initial gap. Moreover, the process of LECD under varied electric field has also been simulated using COMSOL software, and the formation of cylindrical and conical copper columns was further explained based on the electric field distribution at the cathode.Micrometer copper columns were fabricated via a technology named localized electrochemical deposition (LECD). This paper studies the effects of applied potential and the initial gap between electrodes on the LECD process. The surface and cross sectional morphologies, as well as the average deposition rate were investigated to evaluate the quality of the deposited copper columns. Results demonstrated that the copper columns tended to be cylinder-shape with few voids inside at lower potential (<2.4 V). Whereas,the copper columns tended to be dendriform-shape with lots of voids inside at larger potential (>2.8 V). The average deposition rate increased with the raise of potential. In addition, the copper columns tended to be cylinder-shape with the initial gap between electrodes to be 10  They proposed a qualitative interpretation for the interplay between metal-ion diffusion and migration in the deposition process. El-Giar et al.et al.et al.et al.In order to investigate the mechanism of localized electrochemical deposition, Seol In this paper, the potential and the initial gap between electrodes were adjusted during the LECD process to investigate the structural changes of the micrometer copper columns. In addition, the process of LECD has also been simulated using COMSOL Multiphysics (COMSOL for short) software and the electric field distribution was analyzed to explain the mechanism towards the different surface morphologies of micrometer copper columns.μm/s. An exponential function that fits the relationship between potential and average deposition rate is expressed asAverage deposition rate is calculated by dividing the total height of copper column by the deposition time. Dr represents the average deposition rate, p represents the applied potential. Thus, the average deposition rate increases exponentially when potential is in the range of 2.2 V to 3.2 V. This fitted model could be employed to predict the average deposition rate under other applied potential. In addition, as shown in where μm, 15 μm and 35 μm, respectively, are shown in μm, the copper column tends to be cylinder-shape and there are some voids inside the cross section. When the initial gap between electrodes increases to 15 μm, the copper column is still cylinder-shape, but the number of voids inside the cross section decreases apparently. When the initial gap is set as 35 μm, the copper column tends to be cone-shape with diameter decreasing from the bottom to the top and there are nearly no voids inside the cross section.The SEM images of the surface and the corresponding cross sectional (the position of a copper column marked by a line) morphologies of the copper column deposited with the initial gaps as 5 Dk, the average column diameter h to the height of nh is defined as the nth stage of electroplating. The electric field distribution around the surface of cathode at the initial time (0 s) in the first stage of electroplating under different initial gaps is simulated as shown in 4 V/m, and the corresponding width at the cathode is about 150 μm which is close to the bottom diameter of the copper column deposited at the potential of 2.4 V in the experiment. Therefore, there could be a critical electric field intensity4 V/m. When the electric field intensity is lower than this threshold, the deposition will not happen.Since the micro-anode moves upward intermittently in the experiment, the process of electroplating is corresponding intermittent. The process of deposits growing from the Ag substrate to the height of μm, the copper column tends to be a cone. While the initial gap is less than 15 μm, the copper column tends to be a cylinder. To understand the relationship between electric field and the shape of copper column, the variation of electric field distribution on the surface of cathode during the process of LECD is obtained through the simulation. When the initial gap between electrodes is 35 μm, the distribution map of the electric field strength of the whole electroplating domain and the electric field distribution on the surface of cathode at the initial time (0 s) from the first to the fourth stage of electroplating in the simulation is shown in 4 V/m) continuously narrows down, which indicates that the diameter of copper column deposited at the cathode will become smaller and smaller during the process of electroplating. Hence, this may explain the formation of conical copper columns in the experiment. When the initial gap between electrodes decreases to 5 μm, the distribution map of the electric field strength of the whole electroplating domain and the electric field distribution on the surface of cathode at the initial time (0 s) from the first to the fourth stage of electroplating in the simulation are shown in 4 V/m) nearly keeps the same, which means that the diameter of the copper column deposited at the cathode will not change during the process of electroplating. Hence, this may explain the formation of cylindrical copper columns in the experiment.As shown in The effects of the applied potential and the initial gap between electrodes on the surface morphology and deposition rate for the deposited copper column are investigated in this paper. It demonstrates that copper columns with regular shape and compact structures are fabricated at low potential. When potential becomes higher, the copper column tends to be dendriform-shape. The average deposition rate increases with the raise of potential. The copper columns tend to be cylinders when the initial gap between electrodes is small, whereas the copper columns tend to be cone-shape when the initial gap becomes larger. The average deposition rate decreases with the raise of the initial gap between electrodes.4 V/m) narrows down continuously. When the initial gap between electrodes is small, the width with electric field intensity over the threshold (4 × 104 V/m) nearly keeps the same. Based on the difference of electric field distributions at the cathode, the formation of cylindrical and conical copper columns in the experiment could be explained.According to the simulation by COMSOL, we found that the diameter of copper column is affected by electric field distribution at the cathode. When the initial gap between electrodes is quite large, the width with electric field intensity over the threshold (4 × 10μm in diameter) insulated in a capillary glass tube filled with epoxy resin was used as the anode. The cathode was made of an Ag-coated Cu substrate (6 mm × 4.5 mm × 0.1 mm) mounted with epoxy resin. The front surface of the cathode plate was ground by a sequence of emery papers and wetly polished to reveal a mirror surface4·5H2O) at room temperature.A platinum wire  (TESCAN MIRA3 LMU) was used to examine the surface morphology and microstructure of the micrometer copper columns. To observe the cross section of the copper column, the column was embedded into an epoxy resin and then polished to a mirror-like surface using a series of emery papers and the slurries of fine alumina.How to cite this article: Wang, F. et al. Effects of applied potential and the initial gap between electrodes on localized electrochemical deposition of micrometer copper columns. Sci. Rep.6, 26270; doi: 10.1038/srep26270 (2016).