Zeitschriftenaufsätze

Spectral analysis of repeatedly evoked potentials (EPs) is challenging since recordings contain a superposition of evoked signals and spontaneous activity. We developed a novel approach, N-interval Fourier Transform Analysis (N-FTA), which allows for reliable separation and simultaneous assessment of triggered and background spectral components. Median nerve stimulation data from a total of eleven volunteers recorded in two labs with different experimental settings were investigated. Consistently, short latency spectral components were mainly contained in the gamma and high gamma bands. In contrast, spontaneous activity displayed a 1/f spectral profile with distinct alpha and beta peaks. Spontaneous power spectral densities (PSDs) obtained for real and sham stimulation were highly comparable. The low frequency background PSD was more than two orders of magnitude above the spectral short latency peaks. Within the 30Hz to 90Hz band, the evoked peaks were -17dB to -4dB below the background suggesting that target band filtered short latency deflection might be extracted using less than 100 trials. SEPs following tibial nerve stimulation (3 subjects) displayed a narrower spectral band at about half the bandwidth as compared to median nerve stimulation. Evoked peaks were between 30Hz and 37Hz at PSD levels being -10dB to -4dB below the background activity. These spectral peaks were related to the short latency response of typical W-morphology. Cortical short latency responses are contained in distinct spectral target bands which are much narrower than the standard bandwidth recommendations for routine recordings. In particular, the high pass corner frequency may be selected about one order of magnitude above the current standard. This might render SEP recordings more robust since it eases the suppression of spontaneous activity and movement artifacts such as eye-blinks. Real-time zero-phase filters are required for translating these findings into improved recording systems.

Frequent complications arising from low anterior resections include urinary and fecal incontinence, as well as sexual disorders, which are commonly associated with damage to the pelvic autonomic nerves during surgery. To assist the surgeon in preserving pelvic autonomic nerves, a novel approach for intraoperative pelvic neuromonitoring was investigated that is based on impedance measurements of the innervated organs. The objective of this work was to develop an algorithm called AMINA to classify the bioimpedance signals, with the goal of facilitating signal interpretation for the surgeon. Thirty patients included in a clinical investigation underwent nerve-preserving robotic rectal surgery using intraoperative pelvic neuromonitoring. Contraction of the urinary bladder and/or rectum, triggered by direct stimulation of the innervating nerves, resulted in a change in tissue impedance signal, allowing the nerves to be identified and preserved. Impedance signal characteristics in the time domain and the time-frequency domain were calculated and classified to develop the AMINA. Stimulation-induced positive impedance changes were statistically significantly different from negative stimulation responses by the percent amplitude of impedance change Amax in the time domain. Positive impedance changes and artifacts were distinguished by classifying wavelet scales resulting from peak detection in the continuous wavelet transform scalogram, which allowed implementation of a decision tree underlying the AMINA. The sensitivity of the software-based signal evaluation by the AMINA was 96.3%, whereas its specificity was 91.2%. This approach streamlines and automates the interpretation of impedance signals during intraoperative pelvic neuromonitoring.

The fictitious surface charge method (FSCM) is used for the calculation of the induced electrical field in magnetic stimulation. The method was embedded and optimized in Python. It was designed to allow for the computation of large problems. An element-wise Jacobi method was combined with vectorized matrix operations to increase the parallelization capabilities and enable GPU computing. The induced fields are compared against an analytical solution for a homogeneous sphere and a FEM solution on a realistic head model. The results for both cases show that the normalized root mean square error of less than 0.5% can be achieved with the integral-free FSCM even on low-performance computer hardware.

Im Zuge der Fünften Fortschreibung der Richtlinie der Bundesärztekammer zur Feststellung des irreversiblen Hirnfunktionsausfalls, gültig seit September 2022, wurden die Empfehlungen der Deutschen Gesellschaft für Klinische Neurophysiologie und Funktionelle Bildgebung (DGKN) zu den ergänzenden elektrophysiologischen und Doppler-sonografischen Untersuchungen aktualisiert. Die hier präsentierten Empfehlungen der DGKN beinhalten die Indikationen, Voraussetzungen und die Durchführung dieser Zusatzverfahren bei Kindern und Erwachsenen.

Evaluations of new dry, high-density EEG caps have only been performed so far with serial measurements and not with simultaneous (parallel) measurements. For a first comparison of gel-based and dry electrode performance in simultaneous high-density EEG measurements, we developed a new EEG cap comprising 64 gel-based and 64 dry electrodes and performed simultaneous measurements on ten volunteers. We analyzed electrode-skin impedances, resting state EEG, triggered eye blinks, and visual evoked potentials (VEPs). To overcome the issue of different electrode positions in the comparison of simultaneous measurements, we performed spatial frequency analysis of the simultaneously measured EEGs using spatial harmonic analysis (SPHARA). The impedances were 516 ± 429 kOhm (mean ± std) for the dry electrodes and 14 ± 8 kOhm for the gel-based electrodes. For the dry EEG electrodes, we obtained a channel reliability of 77%. We observed no differences between dry and gel-based recordings for the alpha peak frequency and the alpha power amplitude, as well as for the VEP peak amplitudes and latencies. For the VEP, the RMSD and the correlation coefficient between the gel-based and dry recordings were 1.7 ± 0.7 μV and 0.97 ± 0.03, respectively. We observed no differences in the cumulative power distributions of the spatial frequency components for the N75 and P100 VEP peaks. The differences for the N145 VEP peak were attributed to the different noise characteristics of gel-based and dry recordings. In conclusion, we provide evidence for the equivalence of simultaneous dry and gel-based high-density EEG measurements.

This research addresses the long-term measurement of environmental data in geographically remote areas and an energy-optimized method of storing data on a storage medium. For this purpose, we have developed our measurement module ADL - Advanced Data Logger. In terms of connectivity, the module operates in 3 modes: offline - when measured data is primarily stored on the storage medium; IoT ready - measured data is stored on the storage medium and sent to the remote server in defined batches; online mode - when measured data is preferably sent to the remote server immediately after measurement. The design aims to minimize the module’s power consumption so that the autonomous operating time is close to one year. As part of the design, the simpleFS software module is designed for the role of a simple file system optimized to minimize I/O operations. Its other feature in data storage is the automatic normalization of the data transmitted from the attached sensors. The last part of the design is the AdlReader software solution, used to configure the hardware (HW) module and to retrieve the measured data files. We verified the correct operation of the ADL module along with nine sensors built in a vertical soil temperature profile probe in experimental installation and operation for two months. According to the requirements for our solution, the expected operation time of the ADL module is 9 - 12 months.

There is a variety of software packages, toolboxes, or libraries for the analysis and processing of neurophysiological data such as EEG and MEG. Many of these solutions provide algorithms for both, sensor-space analysis and sourcespace analysis. Especially with the solutions that run on Windows machines, it is noticeable that the step of the volume model generation is usually not included, since the state-ofthe- art software for this (FreeSurfer) is a Unix-based software and thus not available forWindows machines. Therefore, our goal was to develop a fully-integrated software solution for Windows machines, accessing all processing steps already implemented in an existing toolbox and using FreeSurfer in the same system. Due to its widespread use, we chose MNE Python as the basis for our fully integrated software solution. We used the Windows Subsystem for Linux to create a virtual Linux kernel for the FreeSurfer installation. To demonstrate the workflow, the libeep, and AutoReject libraries have been added. A 64-channel EEG recording during right-hand movement (ME) and imagination (MI) was used to test the implemented workflow. The developed framework consists of several modules within Python, mainly using existing scripts and functions. The library libeep was integrated to read the EEG data with the ‘.cnt’, eeprope format. AutoReject was used to automatically interpolate detected bad channels or to reject complete epochs. FreeSurfer was successfully integrated and customized Python scripts enabled the communication between MNE Python on a Windows machine and FreeSurfer on a virtual Linux kernel. With the above-mentioned EEG dataset, we performed source reconstruction and were able to show ERD/S patterns for both, ME and MI. Our new, fullyintegrated software framework can be used on Windows machines to perform a complete process of source reconstruction.

Temporal interference stimulation (TIS) aims at targeting deep brain areas during transcranial electrical alternating current stimulation (tACS) by generating interference fields at depth. Although its modulatory effects have been demonstrated in animal and human models and stimulation studies, direct experimental evidence is lacking for its utility in humans (in vivo). Herein, we directly test and compare three different structures: firstly, we perform peripheral nerve and muscle stimulation quantifying muscle twitches as readout, secondly, we stimulate peri-orbitally with phosphene perception as a surrogate marker, and thirdly, we attempt to modulate the mean power of alpha oscillations in the occipital area as measured with electroencephalography (EEG). We found strong evidence for stimulation efficacy on the modulated frequency in the PNS, but we found no evidence for its utility in the CNS. Possible reasons for failing to activate CNS targets could be comparatively higher activation thresholds here or inhibitory stimulation components to the carrier frequency interfering with the effects of the modulated signal.

Phase slips arise from state transitions of the coordinated activity of cortical neurons which can be extracted from the EEG data. The phase slip rates (PSRs) were studied from the high-density (256 channel) EEG data, sampled at 16.384 kHz, of five adult subjects during covert visual object naming tasks. Artifact-free data from 29 trials were averaged for each subject. The analysis was performed to look for phase slips in the theta (4-7 Hz), alpha (7-12 Hz), beta (12-30 Hz), and low gamma (30-49 Hz) bands. The phase was calculated with the Hilbert transform, then unwrapped and detrended to look for phase slip rates in a 1.0 ms wide stepping window with a step size of 0.06 ms. The spatiotemporal plots of the PSRs were made by using a montage layout of 256 equidistant electrode positions. The spatiotemporal profiles of EEG and PSRs during the stimulus and the first second of the post-stimulus period were examined in detail to study the visual evoked potentials and different stages of visual object recognition in the visual, language, and memory areas. It was found that the activity areas of PSRs were different as compared with EEG activity areas during the stimulus and post-stimulus periods. Different stages of the insight moments during the covert object naming tasks were examined from PSRs and it was found to be about 512 ± 21 ms for the ‘Eureka’ moment. Overall, these results indicate that information about the cortical phase transitions can be derived from the measured EEG data and can be used in a complementary fashion to study the cognitive behavior of the brain.

Dry electroencephalography (EEG) electrodes provide rapid, gel-free, and easy EEG preparation, but with limited wearing comfort. We propose a novel dry electrode comprising multiple tilted pins in a flower-like arrangement. The novel Flower electrode increases wearing comfort and contact area while maintaining ease of use. In a study with 20 volunteers, we compare the performance of a novel 64-channel dry Flower electrode cap to a commercial dry Multipin electrode cap in sitting and supine positions. The wearing comfort of the Flower cap was rated as significantly improved both in sitting and supine positions. The channel reliability and average impedances of both electrode systems were comparable. Averaged VEP components showed no considerable differences in global field power amplitude and latency, as well as in signal-to-noise ratio and topography. No considerable differences were found in the power spectral density of the resting state EEGs between 1 and 40 Hz. Overall, our findings provide evidence for equivalent channel reliability and signal characteristics of the compared cap systems in the sitting and supine positions. The reliability, signal quality, and significantly improved wearing comfort of the Flower electrode allow new fields of applications for dry EEG in long-term monitoring, sensitive populations, and recording in supine position.

Angiography is a very informative method for physicians such as cardiologists, neurologists and neuroscientists. The current modalities experience some shortages, e.g., ultrasound is very operator dependent. The computerized tomography (CT) and magnetic resonance (MR) angiography are very expensive and near infrared spectroscopy cannot capture the deep arteries. Microwave technology has the potential to address some of these issues while compromising between operator dependency, cost, speed, penetration depth and resolution. This paper studies the feasibility of microwave signals for monitoring of arteries. To this aim, a homogenous phantom mimicking body tissue is built. Four elastic tubes simulate arteries and a mechanical system creates pulsations in these arteries. A multiple input multiple output (MIMO) array of ultra-wideband (UWB) transmitters and receivers illuminates the phantom and captures the reflected signals over the desired observation time period. Since we are only interested in the imaging of dynamic parts, i.e., arteries, the static clutters can be suppressed easily by background subtraction method. To obtain a fast image of arteries, which are pulsating with the heartbeat rate, we calculate the Fourier transform of each channel of the MIMO system over the observation time and apply delay and sum (DAS) beamforming method on the heartbeat rate aligned spectral component. The results show that the lateral and longitudinal images and motion mode (M-mode) time series of different points of phantom have the potential to be used for diagnosis.

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

Electroencephalography (EEG) can detect changes in cerebral activity during spaceflight. This study evaluates the effect of spaceflight on brain networks through analysis of the Default Mode Network (DMN)'s alpha frequency band power and functional connectivity (FC), and the persistence of these changes. Five astronauts' resting state EEGs under three conditions were analyzed (pre-flight, in-flight, and post-flight). DMN’s alpha band power and FC were computed using eLORETA and phase-locking value. Eyes-opened (EO) and eyes-closed (EC) conditions were differentiated. We found a DMN alpha band power reduction during in-flight (EC: p < 0.001; EO: p < 0.05) and post-flight (EC: p < 0.001; EO: p < 0.01) when compared to pre-flight condition. FC strength decreased during in-flight (EC: p < 0.01; EO: p < 0.01) and post-flight (EC: ns; EO: p < 0.01) compared to pre-flight condition. The DMN alpha band power and FC strength reduction persisted until 20 days after landing. Spaceflight caused electrocerebral alterations that persisted after return to earth. Periodic assessment by EEG-derived DMN analysis has the potential to become a neurophysiologic marker of cerebral functional integrity during exploration missions to space.

Practicing mindfulness is associated with stress reduction and with positive effects in the context of learning and teaching. Although effects on student populations have been studied extensively, there are few studies implementing mindfulness exercises in university courses directly. For this reason, we aimed to investigate whether the use of a brief mindfulness exercise in regular university courses, guided by the lecturers, is feasible and has immediate effects on the students’ mental states. We conducted a preregistered multicenter study with one observational arm, following an ABAB design. In total, N = 325 students from 19 different university courses were included at baseline and n = 101 students at post measurement. Students were recruited by N = 14 lecturers located in six different universities in Germany. Lecturers started their courses either by guiding a brief mindfulness exercise (intervention condition) or as they regularly would, with no such exercise (control condition). In both conditions, the mental states of students and lecturers were assessed. Over the semester, n = 1193 weekly observations from students and n = 160 observations from lecturers were collected. Intervention effects were analyzed with linear mixed-effects models. The brief mindfulness exercise, compared to no such exercise, was associated with lower stress composite scores, higher presence composite scores, higher motivation for the courses, as well as better mood in students. Effects persisted throughout a respective course session. Lecturers also reported positive effects of instructing mindfulness. Implementing a brief mindfulness exercise in regular university teaching sessions is feasible and has positive effects on both students and lecturers.

Research over the past decades has revealed a variety of beneficial effects of meditation training. These beneficial effects span the levels of health and well-being, cognition, emotion, and social behavior. Around the same time, sociologists have shown that traits and outcomes on the individual level have the potential to spread in communities over three or more degrees. This means, for example, that changes can spread from one person to the next, and on to yet another person. Here, we propose that meditation-induced changes may likewise spread through the social networks of meditation practitioners. Such spreading may happen by positively influencing others through prosocial actions, improved cognitive functioning, and increased positive affect. Positive affective states and their underlying physiological correlates may also be shared in the literal sense. We argue that the spreading of positive meditation effects could provide the basis for collective responses to some of the urgent challenges we face in our current time and society and call for future meditation research to examine the phenomenon.

The cognitive performance of the crew has a major impact on mission safety and success in space flight. Monitoring of cognitive performance during long-duration space flight therefore is of paramount importance and can be performed using compact state-of-the-art mobile EEG. However, signal quality of EEG may be compromised due to the vicinity to various electronic devices and constant movements. We compare noise characteristics between in-flight extraterrestrial microgravity and ground-level terrestrial electroencephalography (EEG) recordings. EEG data recordings from either aboard International Space Station (ISS) or on earth’s surface, utilizing three EEG amplifiers and two electrode types, were compared. In-flight recordings showed noise level of an order of magnitude lower when compared to pre- and post-flight ground-level recordings with the same EEG system. Noise levels between ground-level recordings with actively shielded cables, and in-flight recordings without shielded cables, were similar. Furthermore, noise level characteristics of shielded ground-level EEG recordings, using wet and dry electrodes, and in-flight EEG recordings were similar. Actively shielded mobile dry EEG systems will support neuroscientific research and neurocognitive monitoring during spaceflight, especially during long-duration space missions.

Magnetic nanoparticles (MNPs) have been widely applied as magnetic resonance imaging (MRI) contrast agents. MNPs offer significant contrast improvements in MRI through their tunable relaxivities, but to apply them as clinical contrast agents effectively, they should exhibit a high saturation magnetization, good colloidal stability and sufficient biocompatibility. In this work, we present a detailed description of the synthesis and the characterizations of europium-substituted Mn-Zn ferrite (Mn0.6Zn0.4EuxFe2−xO4, x = 0.00, 0.02, 0.04, 0.06, 0.08, 0.10, and 0.15, herein named MZF for x = 0.00 and EuMZF for others). MNPs were synthesized by the coprecipitation method and subsequent hydrothermal treatment, coated with citric acid (CA) or pluronic F127 (PF-127) and finally characterized by X-ray Diffraction (XRD), Inductively Coupled Plasma (ICP), Vibrating Sample Magnetometry (VSM), Fourier-Transform Infrared (FTIR), Dynamic Light Scattering (DLS) and MRI Relaxometry at 3T methods. The XRD studies revealed that all main diffraction peaks are matched with the spinel structure very well, so they are nearly single phase. Furthermore, XRD study showed that, although there are no significant changes in lattice constants, crystallite sizes are affected by europium substitution significantly. Room-temperature magnetometry showed that, in addition to coercivity, both saturation and remnant magnetizations decrease with increasing europium substitution and coating with pluronic F127. FTIR study confirmed the presence of citric acid and poloxamer (pluronic F127) coatings on the surface of the nanoparticles. Relaxometry measurements illustrated that, although the europium-free sample is an excellent negative contrast agent with a high r2 relaxivity, it does not show a positive contrast enhancement as the concentration of nanoparticles increases. By increasing the europium to x = 0.15, r1 relaxivity increased significantly. On the contrary, europium substitution decreased r2 relaxivity due to a reduction in saturation magnetization. The ratio of r2/r1 decreased from 152 for the europium-free sample to 11.2 for x = 0.15, which indicates that Mn0.6Zn0.4Eu0.15Fe1.85O4 is a suitable candidate for dual-mode MRI contrast agent potentially. The samples with citric acid coating had higher r1 and lower r2 relaxivities than those of pluronic F127-coated samples.

The neocortex is organized around layered microcircuits consisting of a variety of excitatory and inhibitory neuronal types which perform rate- and oscillation-based computations. Using modeling, we show that both superficial and deep layers of the primary mouse visual cortex implement two ultrasensitive and bistable switches built on mutual inhibitory connectivity motives between somatostatin, parvalbumin, and vasoactive intestinal polypeptide cells. The switches toggle pyramidal neurons between high and low firing rate states that are synchronized across layers through translaminar connectivity. Moreover, inhibited and disinhibited states are characterized by low- and high-frequency oscillations, respectively, with layer-specific differences in frequency and power which show asymmetric changes during state transitions. These findings are consistent with a number of experimental observations and embed firing rate together with oscillatory changes within a switch interpretation of the microcircuit.

Background and Purpose: Malignant melanoma is a high-grade skin cancer with high feasibility to metastasize to both regional and distant sites when detected late. Therefore, it is crucial to diagnose this type of cancer at an early stage to ensure effective treatment. The identification of melanocytic lesions is a difficult issue, even for experienced experts. The current development of information technology, particularly related to image analysis and machine learning, is an opportunity to support the work of specialists and detect malignant melanoma more effectively. The aim of this work is to present a melanocytic skin lesion ontology (MLSO) structure, which serves as a basis for a melanoma diagnosis system and includes the formalization of the experts' and literature knowledge. Subjects and Methods: MLSO describes the most commonly used melanoma assessing strategies: Argenziano's (also known as the 7-point checklist), Menzies', and Stolz's (based on the ABCD rule) strategies as well as Chaos and Clues. Results: In this work, a case study was conducted on the description of a dermatoscopic digital image of a melanocytic skin nevus. The nevus was evaluated according to all of the strategies included in the MLSO, and inferences were made based on these strategies. The analyzed lesion was classified as a benign nevus since no malignancy was indicated by any of the applied strategies. Conclusion: Initial results indicate the usefulness of MLSO in diagnosing skin cancer. A significant advantage of MLSO is that it provides results obtained using four strategies. Therefore, the results are more objective and the possible errors may be avoided. The MLSO structure is still developing and will be implemented into an automated skin cancer diagnosis system.

The efficient estimation of an approximate model order is very important for real applications with multi-dimensional low-rank data that may be corrupted by additive noise. In this paper, we present a novel robust to noise method for model order estimation of noise-corrupted multi-dimensional low-rank data based on the LineAr Regression of Global Eigenvalues (LaRGE). The LaRGE method uses the multi-linear singular values obtained from the HOSVD of the measurement tensor to construct global eigenvalues. In contrast to the Modified Exponential Test (EFT) that also exploits the approximate exponential profile of the noise eigenvalues, LaRGE does not require the calculation of the probability of false alarm. Moreover, LaRGE achieves a significantly improved performance in comparison with popular state-of-the-art methods. It is well suited for the analysis of noisy multidimensional low-rank data including biomedical signals. The excellent performance of the LaRGE method is illustrated via simulations and results obtained from EEG recordings.

Fluorescence lifetime imaging ophthalmoscopy (FLIO) provides information on fluorescence lifetimes in two spectral channels as well as the peak emission wavelength (PEW) of the fluorescence. Here, we combine these measures in an integral three-dimensional lifetime-PEW metric vector and determine a normal range for this vector from measurements in young healthy subjects. While for these control subjects 97 (±8) % (median (interquartile range)) of all para-macular pixels were covered by this normal vector range, it was 67 (±55) % for the elderly healthy, 38 (±43) % for age-related macular degeneration (AMD)-suspect subjects, and only 6 (±4) % for AMD patients. The vectors were significantly different for retinal pigment epithelium (RPE) lesions in AMD patients from that of non-affected tissue (p < 0.001). Lifetime- PEW plots allowed to identify possibly pathologic fundus areas by fluorescence parameters outside a 95% quantile per subject. In a patient follow-up, changes in fluorescence parameters could be traced in the lifetime-PEW metric, showing their change over disease progression.

The performance of vacuum circuit breakers (VCBs) in the interruption and protection of an electric power system is highly dependent on the contact conditions; thus, the assessment of the contact conditions is essential. The field emission current has been recognized as an effective parameter with which to investigate the contact conditions both qualitatively and quantitatively. The traditional measurement method that uses the field emission current to determine the contact conditions is performed under ac voltage and requires the VCB to be dismantled, which limits the application of this method. The objective of this study is to develop a new measurement method for the contact conditions in a VCB with the field emission current during the closing operation under dc voltage. The new measurement method does not require the VCB to be dismantled and can simplify the processing of experimental data. Then, the new measurement method is applied to investigate the contact conditions during capacitive switching. The obtained result shows that the field enhancement factor $\beta $ of the contact surface oscillates up and down during the capacitive experiment, which can verify the conditioning and deconditioning effects of the inrush current on contact surfaces.

Insufficient binding selectivity of chemosensors often renders biorelevant metabolites indistinguishable by the widely used indicator displacement assay. Array-based chemosensing methods are a common workaround but require additional effort for synthesizing a chemosensor library and setting up a sensing array. Moreover, it can be very challenging to tune the inherent binding preference of macrocyclic systems such as cucurbit[n]urils (CBn) by synthetic means. Using a novel cucurbit[7]uril-dye conjugate that undergoes salt-induced adaptation, we now succeeded in distinguishing 14 bioorganic analytes from each other through the facile stepwise addition of salts. The salt-specific concentration-resolved emission provides additional information about the system at a low synthetic effort. We present a data-driven approach to translate the human-visible curve differences into intuitive pairwise difference measures. Ion mobility experiments combined with density functional theory calculations gave further insights into the binding mechanism and uncovered an unprecedented ternary complex geometry for CB7. TThis work introduces the non-selectively binding, salt-adaptive cucurbit[n]uril system for sensing applications in biofluids such as urine, saliva, and blood serum.

Background: Magnetorelaxometry imaging is an experimental imaging technique capable of reconstructing magnetic nanoparticle distributions inside a volume noninvasively and with high specificity. Thus, magnetorelaxometry imaging is a promising candidate for monitoring a number of therapeutical approaches that employ magnetic nanoparticles, such as magnetic drug targeting and magnetic hyperthermia, to guarantee their safety and efficacy. Prior to a potential clinical application of this imaging modality, it is necessary to optimize magnetorelaxometry imaging systems to produce reliable imaging results and to maximize the reconstruction accuracy of the magnetic nanoparticle distributions. Multiple optimization approaches were already applied throughout a number of simulation studies, all of which yielded increased imaging qualities compared to intuitively designed measurement setups. Purpose: None of these simulative approaches was conducted in practice such that it still remains unclear if the theoretical results are achievable in an experimental setting. In this study, we demonstrate the technical feasibility and the increased reconstruction accuracy of optimized coil configurations in two distinct magnetorelaxometry setups. Methods: The electromagnetic coil positions and radii of a cuboidal as well as a cylindrical magnetorelaxometry imaging setup are optimized by minimizing the system matrix condition numbers of their corresponding linear forward models. The optimized coil configurations are manufactured alongside with two regular coil grids. Magnetorelaxometry measurements of three cuboidal and four cylindrical magnetic nanoparticle phantoms are conducted, and the resulting reconstruction qualities of the optimized and the regular coil configurations are compared. Results: The computed condition numbers of the optimized coil configurations are approximately one order of magnitude lower compared to the regular coil grids. The reconstruction results show that for both setups, every phantom is recovered more accurately by the optimized coil configurations compared to the regular coil grids. Additionally, the optimized coil configurations yield better signal qualities. Conclusions: The presented experimental study provides a proof of the practicality and the efficacy of optimizing magnetorelaxometry imaging systems with respect to the condition numbers of their system matrices, previously only demonstrated in simulations. From the promising results of our study, we infer that the minimization of the system matrix condition number will also enable the practical optimization of other design parameters of magnetorelaxometry imaging setups (e.g., sensor configuration, coil currents, etc.) in order to improve the achievable reconstruction qualities even further, eventually paving the way towards clinical application of this imaging modality.

Purpose To investigate the spectral characteristics of fundus autofluorescence (FAF) in AMD patients and controls. Methods Fundus autofluorescence spectral characteristics was described by the peak emission wavelength (PEW) of the spectra. Peak emission wavelength (PEW) was derived from the ratio of FAF recordings in two spectral channels at 500-560 nm and 560-720 nm by fluorescence lifetime imaging ophthalmoscopy. The ratio of FAF intensity in both channels was related to PEW by a calibration procedure. Peak emission wavelength (PEW) measurements were done in 44 young (mean age: 24.0 ± 3.8 years) and 18 elderly (mean age: 67.5 ± 10.2 years) healthy subjects as well as 63 patients with AMD (mean age: 74.0 ± 7.3 years) in each pixel of a 30&ring; imaging field. The values were averaged over the central area, the inner and the outer ring of the ETDRS grid. Results There was no significant difference between PEW in young and elderly controls. However, PEW was significantly shorter in AMD patients (ETDRS grid centre: 571 ± 26 nm versus 599 ± 17 nm for elderly controls, inner ring: 596 ± 17 nm versus 611 ± 11 nm, outer ring: 602 ± 16 nm versus 614 ± 11 nm). After a mean follow-up time of 50.8 ± 10.8 months, the PEW in the patients decreased significantly by 9 ± 19 nm in the inner ring of the grid. Patients, showing progression to atrophic AMD in the follow up, had significantly (p ≤ 0.018) shorter PEW at baseline than non-progressing patients. Conclusions Peak emission wavelength (PEW) is related to AMD pathology and might be a diagnostic marker in AMD. Possibly, a short PEW can predict progression to retinal and/or pigment epithelium atrophy.

Zinc substituted spinel ferrite nanoparticles are appropriate for magnetic fluid hyperthermia. Stable suspensions of Zn2+ substituted magnetite (ZnxFe3-xO4, 0 ≤ x ≤ 0.20) nanoparticles in aqueous solutions (pH 5.5) were synthesized by means of co-precipitation approach, using citric acid (CA) and pluronic F127 as surfactants for hyperthermia application. The specimens were characterized by different methods. XRD patterns of the precipitates confirmed that all specimens have single phase cubic spinel structures and their lattice parameters increased as Zn2+ content increased. Mean crystallite sizes of the uncoated specimens were determined to be around 28 nm, using Scherrer's formula. By increasing the Zn2+ content, Curie temperature of the uncoated specimens reduced from 545 to 410 &ring;C monotonically caused by reduction in super-exchange interactions. Room temperature saturation magnetizations of the uncoated specimens increased to 98.8 emu/g for x = 0.10 initially, and then decreased to 79.6 emu/g for x = 0.20. It is attributed to the replacement of paramagnetic Fe3+ ions by diamagnetic Zn2+ ones and spin canting. FTIR spectra reconfirmed formation of pure magnetite and Zn2+ substituted magnetite nanoparticles and also proved the presence of ligands on the surface of the nanoparticles. TEM investigation showed that mean particle sizes of the coated nanoparticles were in the range of 35-40 nm. The obtained ferrofluids showed a good stability in aqueous medium (pH 5.5) and according to the room temperature magnetic measurements, heating efficiency is scarcely released due to relaxation processes. Maximum obtained specific loss power (SLP) was 539 W/g and that of intrinsic loss power (ILP) was 7.26 nHm2/kg for x = 0.05 (f = 290 kHz, H = 16 kA/m) with a nanoparticle concentration as low as 1.2 mg/ml, which is a promising candidate for magnetic hyperthermia applications potentially.

Magnetic hybrid materials are a promising group of substances. Their interaction with matrices is challenging with regard to the underlying physical and chemical mechanisms. But thinking matrices as biological membranes or even structured cell layers they become interesting with regard to potential biomedical applications. Therefore, we established in vitro blood-organ barrier models to study the interaction and processing of superparamagnetic iron oxide nanoparticles (SPIONs) with these cellular structures in the presence of a magnetic field gradient. A one-cell-type-based blood-brain barrier model was used to investigate the attachment and uptake mechanisms of differentially charged magnetic hybrid materials. Inhibition of clathrin-dependent endocytosis and F-actin depolymerization led to a dramatic reduction of cellular uptake. Furthermore, the subsequent transportation of SPIONs through the barrier and the ability to detect these particles was of interest. Negatively charged SPIONs could be detected behind the barrier as well as in a reporter cell line. These observations could be confirmed with a two-cell-type-based blood-placenta barrier model. While positively charged SPIONs heavily interact with the apical cell layer, neutrally charged SPIONs showed a retarded interaction behavior. Behind the blood-placenta barrier, negatively charged SPIONs could be clearly detected. Finally, the transfer of the in vitro blood-placenta model in a microfluidic biochip allows the integration of shear stress into the system. Even without particle accumulation in a magnetic field gradient, the negatively charged SPIONs were detectable behind the barrier. In conclusion, in vitro blood-organ barrier models allow the broad investigation of magnetic hybrid materials with regard to biocompatibility, cell interaction, and transfer through cell layers on their way to biomedical application.

Significance: Light-field fundus photography has the potential to be a new milestone in ophthalmology. Up-to-date publications show only unsatisfactory image quality, preventing the use of depth measurements. We show that good image quality and, consequently, reliable depth measurements are possible, and we investigate the current challenges of this novel technology. Aim: We investigated whether light field (LF) imaging of the retina provides depth information, on which structures the depth is estimated, which illumination wavelength should be used, whether deeper layers are measurable, and what kinds of artifacts occur. Approach: The technical setup, a mydriatic fundus camera with an LF imager, and depth estimation were validated by an eye model and in vivo measurements of three healthy subjects and three subjects with suspected glaucoma. Comparisons between subjects and the corresponding optical coherence tomography (OCT) measurements were used for verification of the depth estimation. Results: This LF setup allowed for three-dimensional one-shot imaging and depth estimation of the optic disc with green light. In addition, a linear relationship was found between the depth estimates of the OCT and those of the setup developed here. This result is supported by the eye model study. Deeper layers were not measurable. Conclusions: If image artifacts can be handled, LF technology has the potential to help diagnose and monitor glaucoma risk at an early stage through a rapid, cost-effective one-shot technology.

Transcranial magnetic stimulation (TMS) is a powerful tool to investigate causal structure-function relationships in the human brain. However, a precise delineation of the effectively stimulated neuronal populations is notoriously impeded by the widespread and complex distribution of the induced electric field. Here, we propose a method that allows rapid and feasible cortical localization at the individual subject level. The functional relationship between electric field and behavioral effect is quantified by combining experimental data with numerically modeled fields to identify the cortical origin of the modulated effect. Motor evoked potentials (MEPs) from three finger muscles were recorded for a set of random stimulations around the primary motor area. All induced electric fields were nonlinearly regressed against the elicited MEPs to identify their cortical origin. We could distinguish cortical muscle representation with high spatial resolution and localized them primarily on the crowns and rims of the precentral gyrus. A post-hoc analysis revealed exponential convergence of the method with the number of stimulations, yielding a minimum of about 180 random stimulations to obtain stable results. Establishing a functional link between the modulated effect and the underlying mode of action, the induced electric field, is a fundamental step to fully exploit the potential of TMS. In contrast to previous approaches, the presented protocol is particularly easy to implement, fast to apply, and very robust due to the random coil positioning and therefore is suitable for practical and clinical applications.

Microwave sensors have recently been introduced as high-temporal resolution sensors, which could be used in the contactless monitoring of artery pulsation and breathing. However, accurate and efficient signal processing methods are still required. In this paper, the matrix pencil method (MPM), as an efficient method with good frequency resolution, is applied to back-reflected microwave signals to extract vital signs. It is shown that decomposing of the signal to its damping exponentials fulfilled by MPM gives the opportunity to separate signals, e.g., breathing and heartbeat, with high precision. A publicly online dataset (GUARDIAN), obtained by a continuous wave microwave sensor, is applied to evaluate the performance of MPM. Two methods of bandpass filtering (BPF) and variational mode decomposition (VMD) are also implemented. In addition to the GUARDIAN dataset, these methods are also applied to signals acquired by an ultra-wideband (UWB) sensor. It is concluded that when the vital sign is sufficiently strong and pure, all methods, e.g., MPM, VMD, and BPF, are appropriate for vital sign monitoring. However, in noisy cases, MPM has better performance. Therefore, for non-contact microwave vital sign monitoring, which is usually subject to noisy situations, MPM is a powerful method.

The external pallidum (globus pallidus pars externa [GPe]) plays a central role for basal ganglia functions and dynamics and, consequently, has been included in most computational studies of the basal ganglia. These studies considered the GPe as a homogeneous neural population. However, experimental studies have shown that the GPe contains at least two distinct cell types (prototypical and arkypallidal cells). In this work, we provide in silico insight into how pallidal heterogeneity modulates dynamic regimes inside the GPe and how they affect the GPe response to oscillatory input. We derive a mean-field model of the GPe system from a microscopic spiking neural network of recurrently coupled prototypical and arkypallidal neurons. Using bifurcation analysis, we examine the influence of dopamine-dependent changes of intrapallidal connectivity on the GPe dynamics. We find that increased self-inhibition of prototypical cells can induce oscillations, whereas increased inhibition of prototypical cells by arkypallidal cells leads to the emergence of a bistable regime. Furthermore, we show that oscillatory input to the GPe, arriving from striatum, leads to characteristic patterns of cross-frequency coupling observed at the GPe. Based on these findings, we propose two different hypotheses of how dopamine depletion at the GPe may lead to phase-amplitude coupling between the parkinsonian beta rhythm and a GPe-intrinsic y rhythm. Finally, we show that these findings generalize to realistic spiking neural networks of sparsely coupled Type I excitable GPe neurons. - SIGNIFICANCE STATEMENT Our work provides (1) insight into the theoretical implications of a dichotomous globus pallidus pars externa (GPe) organization, and (2) an exact mean-field model that allows for future investigations of the relationship between GPe spiking activity and local field potential fluctuations. We identify the major phase transitions that the GPe can undergo when subject to static or periodic input and link these phase transitions to the emergence of synchronized oscillations and cross-frequency coupling in the basal ganglia. Because of the close links between our model and experimental findings on the structure and dynamics of prototypical and arkypallidal cells, our results can be used to guide both experimental and computational studies on the role of the GPe for basal ganglia dynamics in health and disease.

Retinal vessel phenotype is predictive for cardiovascular outcome. This cross-sectional population-based study aimed to quantify normative data and standard operating procedures for static and dynamic retinal vessel analysis. We analysed central retinal arteriolar (CRAE) and venular (CRVE) diameter equivalents, as well as retinal endothelial function, measured by flicker light‐induced maximal arteriolar (aFID) and venular (vFID) dilatation. Measurements were performed in 277 healthy individuals aged 20 to 82 years of the COmPLETE study. The mean range from the youngest compared to the oldest decade was 196 ± 13 to 166 ± 17 µm for CRAE, 220 ± 15 to 199 ± 16 µm for CRVE, 3.74 ± 2.17 to 3.79 ± 2.43% for aFID and 4.64 ± 1.85 to 3.86 ± 1.56% for vFID. Lower CRAE [estimate (95% CI): - 0.52 (- 0.61 to - 0.43)], CRVE [- 0.33 (- 0.43 to - 0.24)] and vFID [- 0.01 (- 0.26 to - 0.00)], but not aFID, were significantly associated with older age. Interestingly, higher blood pressure was associated with narrower CRAE [- 0.82 (- 1.00 to - 0.63)] but higher aFID [0.05 (0.03 to 0.07)]. Likewise, narrower CRAE were associated with a higher predicted aFID [- 0.02 (- 0.37 to - 0.01)]. We recommend use of defined standardized operating procedures and cardiovascular risk stratification based on normative data to allow for clinical implementation of retinal vessel analysis in a personalized medicine approach.

Assisting and automating software engineering tasks is a state-of-the-art way to support stakeholders of development projects. A common assistance function of IDEs is the auto-completion of source code. Assistance functions, such as auto-completion, are almost entirely missing in modeling tools though auto-completion in general gains continuously more importance in software development. We analyze a user’s performed editing operations in order to anticipate modeling activities and to recommend appropriate auto-completions for them. Editing operations are captured as events and modeling activities are defined as complex event patterns, facilitating the matching by complex-event-processing. The approach provides adapted auto-completions reactively upon each editing operation of the user. We implemented the RapMOD prototype as add-in for the modeling tool Sparx Enterprise Architect™ . A controlled user experiment with 37 participants performing modeling tasks demonstrated the approach's potential to reduce modeling effort significantly. Users having auto-completions available for a modeling scenario performed the task 27 percent faster, needed to perform 56 percent less actions, and perceived the task 29 percent less difficult.

Background - The surface of nanoparticles (NPs) is an important factor affecting the process of poly/peptides' amyloid aggregation. We have investigated the in vitro effect of trisodium citrate (TC), gum arabic (GA) and citric acid (CA) surface-modified magnetite nanoparticles (COAT-MNPs) on hen egg-white lysozyme (HEWL) amyloid fibrillization and mature HEWL fibrils. - Methods - Dynamic light scattering (DLS) was used to characterize the physico-chemical properties of studied COAT-MNPs and determine the adsorption potential of their surface towards HEWL. The anti-amyloid properties were studied using thioflavin T (ThT) and tryptophan (Trp) intrinsic fluorescence assays, and atomic force microscopy (AFM). The morphology of amyloid aggregates was analyzed using Gwyddion software. The cytotoxicity of COAT-MNPs was determined utilizing Trypan blue (TB) assay. - Results - Agents used for surface modification affect the COAT-MNPs physico-chemical properties and modulate their anti-amyloid potential. The results from ThT and intrinsic fluorescence showed that the inhibitory activities result from the more favorable interactions of COAT-MNPs with early pre-amyloid species, presumably reducing nuclei and oligomers formation necessary for amyloid fibrillization. COAT-MNPs also possess destroying potential, which is presumably caused by the interaction with hydrophobic residues of the fibrils, resulting in the interruption of an interface between [beta]-sheets stabilizing the amyloid fibrils. - Conclusion - COAT-MNPs were able to inhibit HEWL fibrillization and destroy mature fibrils with different efficacy depending on their properties, TC-MNPs being the most potent nanoparticles. - General significance - The study reports findings regarding the general impact of nanoparticles' surface modifications on the amyloid aggregation of proteins.

Hydroxyapatite- or calcium phosphate-coated iron oxide nanoparticles have a high potential for use in many biomedical applications. In this study, a co-precipitation method for the synthesis of hydroxyapatite-coated nanoparticles (SPIONHAp), was used. The produced nanoparticles have been characterized by dynamic light scattering, X-ray diffraction, vibrating sample magnetometry, Fourier transform infrared spectrometry, atomic emission spectroscopy, scanning electron microscopy, transmission electron microscopy, selected area diffraction, and energy-dispersive X-ray spectroscopy. The results showed a successful synthesis of 190 nm sized particles and their stable coating, resulting in SPIONHAp. Potential cytotoxic effects of SPIONHAp on EL4, THP-1, and Jurkat cells were tested, showing only a minor effect on cell viability at the highest tested concentration (400 [my]g Fe/mL). The results further showed that hydroxyapatite-coated SPIONs can induce minor TNF-α and IL-6 release by murine macrophages at a concentration of 100 [my]g Fe/mL. To investigate if and how such particles interact with other substances that modulate the immune response, SPIONHAp-treated macrophages were incubated with LPS (lipopolysaccharides) and dexamethasone. We found that cytokine release in response to these potent pro- and anti-inflammatory agents was modulated in the presence of SPIONHAp. Knowledge of this behavior is important for the management of inflammatory processes following in vivo applications of this type of SPIONs.

Surround View fisheye cameras are commonly deployed in automated driving for 360&ring; near-field sensing around the vehicle. This work presents a multi-task visual perception network on unrectified fisheye images to enable the vehicle to sense its surrounding environment. It consists of six primary tasks necessary for an autonomous driving system: depth estimation, visual odometry, semantic segmentation, motion segmentation, object detection, and lens soiling detection. We demonstrate that the jointly trained model performs better than the respective single task versions. Our multi-task model has a shared encoder providing a significant computational advantage and has synergized decoders where tasks support each other. We propose a novel camera geometry based adaptation mechanism to encode the fisheye distortion model both at training and inference. This was crucial to enable training on the WoodScape dataset, comprised of data from different parts of the world collected by 12 different cameras mounted on three different cars with different intrinsics and viewpoints. Given that bounding boxes is not a good representation for distorted fisheye images, we also extend object detection to use a polygon with non-uniformly sampled vertices. We additionally evaluate our model on standard automotive datasets, namely KITTI and Cityscapes. We obtain the state-of-the-art results on KITTI for depth estimation and pose estimation tasks and competitive performance on the other tasks. We perform extensive ablation studies on various architecture choices and task weighting methodologies. A short video at https://youtu.be/xbSjZ5OfPes provides qualitative results.

Purpose The localized heating of magnetic nanoparticles (MNPs) via the application of time-varying magnetic fields - a process known as magnetic field hyperthermia (MFH) - can greatly enhance existing options for cancer treatment; but for broad clinical uptake its optimization, reproducibility and safety must be comprehensively proven. As part of this effort, the quantification of MNP heating - characterized by the specific loss power (SLP), measured in W/g, or by the intrinsic loss power (ILP), in Hm2/kg - is frequently reported. However, in SLP/ILP measurements to date, the apparatus, the analysis techniques and the field conditions used by different researchers have varied greatly, leading to questions as to the reproducibility of the measurements.Materials and Methods An interlaboratory study (across N = 21 European sites) of calorimetry measurements that constitutes a snapshot of the current state-of-the-art within the MFH community has been undertaken. Identical samples of two stable nanoparticle systems were distributed to all participating laboratories. Raw measurement data as well as the results of in-house analysis techniques were collected along with details of the measurement apparatus used. Raw measurement data was further reanalyzed by universal application of the corrected-slope method to examine relative influences of apparatus and results processing.Results The data show that although there is very good intralaboratory repeatability, the overall interlaboratory measurement accuracy is poor, with the consolidated ILP data having standard deviations on the mean of ca. ± 30% to ± 40%. There is a strong systematic component to the uncertainties, and a clear rank correlation between the measuring laboratory and the ILP. Both of these are indications of a current lack of normalization in this field. A number of possible sources of systematic uncertainties are identified, and means determined to alleviate or minimize them. However, no single dominant factor was identified, and significant work remains to ascertain and remove the remaining uncertainty sources.Conclusion We conclude that the study reveals a current lack of harmonization in MFH characterization of MNPs, and highlights the growing need for standardized, quantitative characterization techniques for this emerging medical technology.

Wearable electronics and sensors are increasingly popular for personal health monitoring, including smart shirts containing electrocardiography (ECG) electrodes. Optimal electrode performance requires careful selection of the electrode position. On top of the electrophysiological aspects, practical aspects must be considered due to the dynamic recording environment. We propose a new method to obtain optimal electrode placement by considering multiple dimensions. The electrophysiological aspects were represented by P-, R-, and T-peak of ECG waveform, while the shirt-skin gap, shirt movement, and regional sweat rate represented the practical aspects. This study employed a secondary data set and simulations for the electrophysiological and practical aspects, respectively. Typically, there is no ideal solution that maximizes satisfaction degrees of multiple electrophysiological and practical aspects simultaneously; a compromise is the most appropriate approach. Instead of combining both aspects - which are independent of each other - into a single-objective optimization, we used multi-objective optimization to obtain a Pareto set, which contains predominant solutions. These solutions may facilitate the decision-makers to decide the preferred electrode locations based on application-specific criteria. Our proposed approach may aid manufacturers in making decisions regarding the placement of electrodes within smart shirts.

The transfer of substances via the blood-placenta barrier is tightly regulated and critical for the fetus and the expecting mother. In case of necessary medical interventions during pregnancy a comprehensive knowledge about the interaction of the drugs with this barrier is indispensable. Therefore well-engineered test systems are needed and valuable transport systems are helpful. We developed an in vitro microfluidic blood-placenta barrier system consisting of the human trophoblast cell line BeWo and human primary placental pericytes. The integrity and stability of the model was verified by a permeability assay and immunocytochemistry. As potential drug carriers magnetic nanoparticles with various coatings were applied and their ability to pass the barrier was quantified by magnetic particle spectroscopy. We could demonstrate that up to 4% of negatively charged nanoparticles pass the barrier in a time-dependent manner.

Pollen identification and quantification are crucial but challenging tasks in addressing a variety of evolutionary and ecological questions (pollination, paleobotany), but also for other fields of research (e.g. allergology, honey analysis or forensics). Researchers are exploring alternative methods to automate these tasks but, for several reasons, manual microscopy is still the gold standard. In this study, we present a new method for pollen analysis using multispectral imaging flow cytometry in combination with deep learning. We demonstrate that our method allows fast measurement while delivering high accuracy pollen identification. A dataset of 426 876 images depicting pollen from 35 plant species was used to train a convolutional neural network classifier. We found the best-performing classifier to yield a species-averaged accuracy of 96%. Even species that are difficult to differentiate using microscopy could be clearly separated. Our approach also allows a detailed determination of morphological pollen traits, such as size, symmetry or structure. Our phylogenetic analyses suggest phylogenetic conservatism in some of these traits. Given a comprehensive pollen reference database, we provide a powerful tool to be used in any pollen study with a need for rapid and accurate species identification, pollen grain quantification and trait extraction of recent pollen.

Assessments of source reconstruction procedures in electroencephalography and computations of transcranial electrical stimulation profiles require verification and validation with the help of ground truth configurations as implemented by physical head phantoms. For these phantoms, synthetic materials are needed, which are mechanically and electrochemically stable and possess conductivity values similar to the modeled human head tissues. Three-compartment head models comprise a scalp layer with a conductivity range of 0.137 S/m to 2.1 S/m, a skull layer with conductivity values between 0.066 S/m and 0.00275 S/m, and an intracranial volume with an often-used average conductivity value of 0.33 S/m. To establish a realistically shaped physical head phantom with a well-defined volume conduction configuration, we here characterize the electrical conductivity of synthetic materials for modeling head compartments. We analyzed agarose hydrogel, gypsum, and sodium chloride (NaCl) solution as surrogate materials for scalp, skull, and intracranial volume. We measured the impedance of all materials when immersed in NaCl solution using a four-electrode setup. The measured impedance values were used to calculate the electrical conductivity values of each material. Further, the conductivities in the longitudinal and transverse directions of reed sticks immersed in NaCl solution were measured to test their suitability for mimicking the anisotropic conductivity of white matter tracts.

Surface-functionalized gold-coated superparamagnetic iron oxide nanoparticles (Au-SPIONs) may be a useful tool in various biomedical applications. To obtain Au-SPIONs, gold salt was precipitated onto citrate-stabilized SPIONs (Cit-SPIONs) using a simple, aqueous one-pot technique inspired by the Turkevich method of gold nanoparticle synthesis. By the further stabilization of the Au-SPION surface with additional citrate (Cit-Au-SPIONs), controllable and reproducible Z-averages enhanced long-term dispersion stability and moderate dispersion pH values were achieved. The citrate concentration of the reaction solution and the gold/iron ratio was found to have a major influence on the particle characteristics. While the gold-coating reduced the saturation magnetization to 40.7% in comparison to pure Cit-SPIONs, the superparamagnetic behavior of Cit-Au-SPIONs was maintained. The formation of nanosized gold on the SPION surface was confirmed by X-ray diffraction measurements. Cit-Au-SPION concentrations of up to 100 [my]g Fe/mL for 48 h had no cytotoxic effect on Jurkat cells. At a particle concentration of 100 [my]g Fe/mL, Jurkat cells were found to take up Cit-Au-SPIONs after 24 h of incubation. A significantly higher attachment of thiol-containing L-cysteine to the particle surface was observed for Cit-Au-SPIONs (53%) in comparison to pure Cit-SPIONs (7%).

Spatial quantitative information about magnetic nanoparticle (MNP) distributions is a prerequisite for biomedical applications like magnetic hyperthermia and magnetic drug targeting. This information can be gathered by means of magnetorelaxometry (MRX) imaging, where the relaxation of previously aligned MNP's magnetic moments is measured by sensitive magnetometers and an inverse problem is solved. To remove or minimize the magnetic shielding in which MRX imaging is carried out today, the knowledge of the influence of background magnetic fields on the MNP's relaxation is a prerequisite. We show MRX measurements using an intensity-modulated optically pumped magnetometer (OPM) in background magnetic fields of up to 100 [my]T. We show that the relaxation parameters alter or may be intentionally altered significantly by applying static fields parallel or antiparallel to the MNPs alignment direction. Further, not only the relaxation process of the MNP's magnetic moments could be measured with OPM, but also their alignment due to the MRX excitation field.

This paper elucidates the feasibility of magnetic drug targeting to the eye by using magnetic nanoparticles (MNPs) to which pharmaceutical drugs can be linked. Numerical simulations revealed that a magnetic field gradient of 20 T m^-1 seems to be promising for dragging magnetic multicore nanoparticles of about 50 nm into the eye. Thus, a targeting magnet system made of superconducting magnets with a magnetic field gradient at the eye of about 20 T m^-1 was simulated. For the proof-of-concept tissue experiments presented here the required magnetic field gradient of 20 T m^-1 was realized by a permanent magnet array. MNPs with an optimized multicore structure were selected for this application by evaluating their stability against agglomeration of MNPs with different coatings in water for injections, physiological sodium chloride solution and biological media such as artificial tear fluid. From these investigations, starch turned out to be the most promising coating material because of its stability in saline fluids due to its steric stabilization mechanism. To evaluate the passage of MNPs through the sclera and cornea of the eye tissues of domestic pigs (Sus scrofa domesticus), a three-dimensionally printed setup consisting of two chambers (reservoir and target chamber) separated by the eye tissue was developed. With the permanent magnet array emulating the magnetic field gradient of the superconducting setup, experiments on magnetically driven transport of the MNPs from the reservoir chamber into the target chamber via the tissue were performed. The resulting concentration of MNPs in the target chamber was determined by means of quantitative magnetic particle spectroscopy. It was found that none of the tested particles passed the cornea, but starch-coated particles could pass the sclera at a rate of about 5 ng mm^-2 within 24 h. These results open the door for future magnetic drug targeting to the eye.

Uncertainty surrounding ohmic tissue conductivity impedes accurate calculation of the electric fields generated by non-invasive brain stimulation. We present an efficient and generic technique for uncertainty and sensitivity analyses, which quantifies the reliability of field estimates and identifies the most influential parameters. For this purpose, we employ a non-intrusive generalized polynomial chaos expansion to compactly approximate the multidimensional dependency of the field on the conductivities. We demonstrate that the proposed pipeline yields detailed insight into the uncertainty of field estimates for transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), identifies the most relevant tissue conductivities, and highlights characteristic differences between stimulation methods. Specifically, we test the influence of conductivity variations on (i) the magnitude of the electric field generated at each gray matter location, (ii) its normal component relative to the cortical sheet, (iii) its overall magnitude (indexed by the 98th percentile), and (iv) its overall spatial distribution. We show that TMS fields are generally less affected by conductivity variations than tDCS fields. For both TMS and tDCS, conductivity uncertainty causes much higher uncertainty in the magnitude as compared to the direction and overall spatial distribution of the electric field. Whereas the TMS fields were predominantly influenced by gray and white matter conductivity, the tDCS fields were additionally dependent on skull and scalp conductivities. Comprehensive uncertainty analyses of complex systems achieved by the proposed technique are not possible with classical methods, such as Monte Carlo sampling, without extreme computational effort. In addition, our method has the advantages of directly yielding interpretable and intuitive output metrics and of being easily adaptable to new problems.

This paper presents a scanning method for indoor mobile robot localization using the received signal strength indicator (RSSI) approach. The method eliminates the main drawback of the conventional fingerprint, whose database construction is time-consuming and which needs to be rebuilt every time a change in indoor environment occurs. It directly compares the column vectors of a kernel matrix and signal strength vector using the Euclidean distance as a metric. The highest resolution available in localization using a fingerprint is restricted by a resolution of a set of measurements performed prior to localization. In contrast, resolution using the scanning method can be easily changed using a denser grid of potential sources. Although slightly slower than the trilateration method, the scanning method outperforms it in terms of accuracy, and yields a reconstruction error of only 0. 08 m averaged over 1600 considered source points in a room with dimensions 9.7 m × 4.7 m × 3 m. Its localization time of 0. 39 s makes this method suitable for real-time localization and tracking.

Requirements traceability has long been recognized as an important quality of a well-engineered system. Among stakeholders, traceability is often unpopular due to the unclear benefits. In fact, little evidence exists regarding the expected traceability benefits. There is a need for empirical work that studies the effect of traceability. In this paper, we focus on the four main requirements implementation supporting activities that utilize traceability. For each activity, we propose generalized traceability completeness measures. In a defined process, we selected 24 medium to large-scale open-source projects. For each software project, we quantified the degree to which a studied development activity was enabled by existing traceability with the proposed measures. We analyzed that data in a multi-level Poisson regression analysis. We found that the degree of traceability completeness for three of the studied activities significantly affects software quality, which we quantified as defect rate. Our results provide for the first time empirical evidence that more complete traceability decreases the expected defect rate in the developed software. The strong impact of traceability completeness on the defect rate suggests that traceability is of great practical value for any kind of software development project, even if traceability is not mandated by a standard or regulation

Determination of the 3-D eddy current distribution inside a translatory moving conductor under a permanent magnet can accurately be done by using finite-element method (FEM). However, FEM calculations are very expensive, as they require discretization of the whole conductor volume. In this paper, we propose a new technique, to be called boundary element source method (BESM), where only boundary layers are discretized. The BESM is a modification of the hybrid boundary element method (HBEM). In the BESM, the concentrated point sources placed at the centers of boundary elements for the HBEM are replaced by distributed charge density over the area of the boundary element. This is especially useful in the regions, where neighboring boundary meshes significantly affect one another and when calculation point of eddy current is very close or belong to the surface of a boundary element. The method can handle arbitrary geometries of the specimen as well as the defect and arbitrary orientation of the magnetization vector. The accuracy of the proposed method is verified by comparing the results with the solutions obtained from a finite-element model. The proposed BESM approach is shown to be simple, robust, and computationally accurate.

Antenatal monitoring; cardiotocography; fetal electrocardiography; fetal heart rate variability; magnetocardiography; short-term variation

Objective: The source of somatosensory evoked high-frequency activity at about 600 Hz is still not completely clear. Hence, we aimed to study the influence of double stimulation on the human somatosensory system by analyzing both the low-frequency activity and the high-frequency oscillations (HFOs) at about 600 Hz. Methods: We used median nerve stimulation at seven interstimuli intervals (ISIs) with a high time resolution between 2.4 and 4.8 ms to investigate the N15, N20 and superimposed HFOs. Simultaneously, the electroencephalogram and the magnetoencephalogram of 12 healthy participants were recorded. Subsequently, the source analysis of precortical and cortical dipoles was performed. Results: The difference computations of precortical dipole activation curves showed in both the low- and high-frequency range a correlation between the ISI and the latency of the second stimulus response. The cortical low-frequency response showed a similar behavior. Contrarily, in the second response of cortical HFOs this latency shift could not be confirmed. We found amplitude fluctuations that were dependent on the ISI in the low-frequency activity and the HFOs. These nonlinear interactions occurred at ISIs, which differ by one full HFO period (1.6 ms). Conclusions: Low-frequency activity and HFOs originate from different generators. Precortical and cortical HFOs are independently generated. The amplitude fluctuations dependent on ISI indicate nonlinear interference between successive stimuli. Significance: Information processing in human somatosensory system includes nonlinearity.

AIM: To prove the hypothesis that patients with chronic pancreatitis would show increased theta activity during painful visceral stimulation. METHODS: Eight patients and 12 healthy controls underwent an experiment where the esophagus was electrically stimulated at the pain threshold using a nasal endoscope. The electroencephalogram (EEG) was recorded from 64 surface electrodes and "topographic matching pursuit" was used to extract the EEG information in the early brain activation after stimulation. RESULTS: A major difference between controls and patients were seen in delta and theta bands, whereas there were only minor differences in other frequency bands. In the theta band, the patients showed higher activity than controls persisting throughout the 450 ms of analysis with synchronous brain activation between the channels. The main theta components oscillated with 4.4 Hz in the patients and 5.5 Hz in the controls. The energy in the delta (0.5-3.5 Hz) band was higher in the controls, whereas the patients only showed scattered activity in this band. CONCLUSION: The differences in the theta band indicate that neuropathic pain mechanisms are involved in chronic pancreatitis. This has important implications for the understanding and treatment of pain in these patients, which should be directed against drugs with effects on neuropathic pain disorders.

Diese Beitragsfolge widmet sich Notwendigkeiten und Möglichkeiten einer didaktisch optimalen Erschließung der Querschnittsrekonstruktionsverfahren am Beispiel der Röntgencomputertomographie auf methodischer und experimenteller Ebene. Der vierte Teil behandelt die örtliche Dynamik als Teil des Signalübertragungsverhaltens des genutzten zeilenförmigen Röntgenstrahlendetektors.

Heart rate exhibits spontaneous fluctuations that are mainly modulated by control loops within the autonomic nervous system. Assessing the dynamics of heart rate fluctuations can provide valuable information about regulatory processes and patho-physiological behavior. In this paper heart rate fluctuations and its entropy are assessed using an algorithmic information theoretic concept applying a data compressor. First, the beat-to-beat fluctuations of heart rate are binary coded for decreases and increases, respectively. Subsequently, those symbol sequences are compressed using the LZ77 algorithm. The ratio of the length of the compressed sequences to the original length is used as an estimate of entropy. We investigated the compressibility of heart rate fluctuations in athletes before, during, and after a training camp. Heart rate time series were obtained from ECGs recorded over 30 minutes under supine resting conditions. We found a significant entropy reduction during the training camp, reflecting the effects of physical fatigue. In conclusion, the compression entropy seems to be a suitable approach to assess the complexity of heart rate fluctuations.

DIABCARE Q-Net is a European project with a consortium of partners in healthcare, industry, and research, which has the overall target of improvement in diabetes care by aggregation, evaluation, and feedback of anonymized patient data with the tools of modern telematics, resulting from the initiative of the St. Vincent-Declaration, St. Vincent, Italy. Based on standardized tools for quality improvement in diabetes care, i.e., the Basic Information Sheet (BIS) and recently developed data entry and feedback software (DIABCARE Data for Windows), DIABCARE Q-Net as a part of the Telematics Applications Program of the European Commission will improve diabetes care and disease management by the implementation of a quality network. Therefore, the project implements regional, national, and central nodes for processing of diabetes quality indicators. All participating centers (GP's and clinics in Europe) get feedback by standardized benchmarking. The pilot testing and the state of implementation of our network confirm the importance of improving the quality of life of diabetic patients in all participating countries.