On the uncertainty in numerical modeling of wireless communication devices operating at frequencies of 900 MHz, 1800 MHz, and 28 GHz.

Some of the difficulties in numerical modeling of wireless communication devices for dosimetric evaluations arise from, e.g. incomplete documentation available for the numerical model, such as missing information on dielectric materials or the antenna matching circuitry. This study investigates the impact of these difficulties on the dosimetric results, such as the peak spatial average specific absorption rate at 900 and 1800 MHz and the peak spatial average power density at 28 GHz. The impact of dielectric losses, detuning, and mesh resolution is quantified using different generic and Computer Aided Design (CAD) based models of wireless transmitters. The findings show that the uncertainties of the numerical results due to detuning and mesh resolution can be reduced by normalization to the antenna feedpoint power instead of the feedpoint current. Uncertainties due to variations in dielectric losses can largely be compensated by normalization to the radiated power.

A randomized, double-blind phase 1b study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of the NLRP3 inhibitor selnoflast in patients with moderate to severe active ulcerative colitis.

BACKGROUND: The NLRP3 inflammasome drives release of pro-inflammatory cytokines including interleukin (IL)-1ß and IL-18 and is a potential target for ulcerative colitis (UC). Selnoflast (RO7486967) is an orally active, potent, selective and reversible small molecule NLRP3 inhibitor. We conducted a randomized, placebo-controlled Phase 1b study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of selnoflast. METHODS: Nineteen adults with previous diagnosis of UC and current active moderate to severe disease were randomized 2:1 to selnoflast or placebo for 7 days. A dose of 450 mg QD (once daily) was selected to achieve 90% IL-1ß inhibition in plasma and colon tissue. Consecutive blood, sigmoid colon biopsies and stool samples were analyzed for a variety of PD markers. Safety and PK were also evaluated. RESULTS: Selnoflast was well-tolerated. Plasma concentrations increased rapidly after oral administration, reaching Tmax 1 h post-dose. Mean plasma concentrations stayed above the IL-1ß IC90 level throughout the dosing interval (mean Ctrough on Day 1 and Day 5: 2.55 µg/mL and 2.66 µg/mL, respectively). At steady state, post-dose selnoflast concentrations in sigmoid colon (5-20 µg/g) were above the IC90 . Production of IL-1ß was reduced in whole blood following ex vivo stimulation with lipopolysaccharide (LPS) (in the selnoflast arm). No changes were observed in plasma IL-18 levels. There were no meaningful differences in the expression of an IL-1-related gene signature in sigmoid colon tissue, and no differences in the expression of stool biomarkers. CONCLUSIONS: Selnoflast was safe and well-tolerated. Selnoflast 450 mg QD achieved plasma and tissue exposure predicted to maintain IL-1ß IC90 over the dosing interval. However, PD biomarker results showed no robust differences between treatment arms, suggesting no major therapeutic effects are to be expected in UC. The limitations of this study are its small sample size and indirect assessment of the effect on IL-1ß in tissue. TRIAL REGISTRATION: ISRCTN16847938.

Anisotropic coupling of individual vibrational modes to a Cu(110) substrate.

We present a study on the excitation of individual vibrational modes with ballistic charge carriers propagating along the Cu(110) surface. By means of the molecular nanoprobe technique, where the reversible switching of a molecule-in this case tautomerization of porphycene-is utilized to detect excitation events, we reveal anisotropic coupling of two distinct vibrational modes to the substrate. The N-H bending mode, excited below |E| ≈ 376 meV, exhibits maxima perpendicular to the rows of the Cu(110) substrate and minima along the rows. In contrast, the N-H stretching mode, excited above |E| ≈ 376 meV, displays maxima along the rows and is constant otherwise. This inversion of the anisotropy reflects the orthogonality between the N-H bending and stretching mode. Additionally, we observe an energy-dependent asymmetry in the propagation direction of charge carriers injected into the Cu(110) surface state. Hereby, the anisotropic band structure results in a correlation between the group velocity and the tunneling probability into electronic states of the substrate.

Real-space resolved surface reactions: deprotonation and metalation of phthalocyanine.

Upon deposition on a surface, molecules can undergo a plethora of changes, such as reactions with adsorbates and surface atoms and catalytic decomposition. Since different reaction pathways may coexist, spatially averaging techniques can be insufficient for the characterization and distinction of all on-surface products. Here, we present a study of single phthalocyanine molecules on a Cu(111) surface which was performed using high-resolution low-temperature STM. Upon deposition of metal-free H2Pc, we can identify three distinct molecular species. A thorough investigation reveals that temperature-driven on-surface reactions partially convert H2Pc into H0Pc and CuPc. The individual species are differentiated by their topographic appearance and can unambiguously be identified by their STM-induced rotational behavior. While H2Pc shows a switching between two orientations at low energies, a third orientation can be observed above E > 800 meV, which is induced by tautomerization. Around the Fermi level, the rotational behavior is asymmetric, owing to the excitation of vibrational modes in unoccupied states whereas resonant tunneling occurs in occupied states. A two-step deprotonation of H2Pc confirms that the second species is H0Pc. By comparison with CuPc evaporated on Cu(111), we unambiguously reveal that the third species is indeed CuPc, which exhibits an exceptionally low threshold for rotational switching accompanied by an asymmetric behavior around the Fermi level. Varying the post-annealing temperature, we found a sharp threshold for the H2Pc → CuPc on-surface metalation at around 100 °C. In contrast, the competing process of thermal decomposition from H2Pc to H0Pc only increases weakly.

Coverage factors for efficient demonstration of compliance of low-frequency magnetic near-field exposures with basic restrictions.

Objective. Regulators require that wireless power transfer (WPT) systems and other strong magnetic field sources are compliant with the basic restrictions (BR) defined as the limits of the fields induced in the human body, i.e. the induced electric field/current density/specific absorption rate limits. This can be achieved by demonstrating compliance with the reference levels (RL) defined in air without the human body, i.e. the incident electric/magnetic field limits. Local sources, such as WPT transmitters, generate non-uniform fields that can locally exceed the RL while the induced fields are still well below the BR. In these cases, robust compliance with BR can be demonstrated, generally requiring a large number of simulations. In this study, we proposed an efficient evaluation using a homogeneous phantom and applying a coverage factor to account for the local field enhancements caused by the dielectric contrasts of the highly inhomogeneous human tissues.Approach. The generally applicable coverage factors were derived from a statistical analysis of the field enhancements observed on four magnetic near-field sources placed at different separation distances (2-80 mm) and locations on the back of 12 anatomical models. The field enhancements were characterized by the ratios between the peak induced fields in the anatomical models and those in the homogeneous half-space phantom (ϵr= 55,σ= 0.75 S m-1,ρ= 1,000 kg m-3) at the same distance.Main results. The resulting 99th percentile coverage factors range from 1 and 9 depending on the dosimetric quantity.Significance. The use of these coverage factors reduces the compliance testing effort from hundreds of simulations to only one, and makes experimental testing feasible without the support of simulations. The study also demonstrates that running only a few use-case simulations with anatomical models may underestimate the exposure by more than 10 dB.

Controlled Formation of Porous 2D Lattices from C3 -symmetric Ph6 -Me-Tribenzotriquinacene-OAc3.

The on-surface self-assembly of molecules to form holey nanographenes is a promising approach to control the properties of the resulting 2D lattice. Usually, planar molecules are utilized to prepare flat, structurally confined molecular layers, with only a few recent examples of warped precursors. However, control of the superstructures is limited thus far. Herein, we report the temperature-controlled self-assembly of a bowl-shaped, acetylated C3 -symmetric hexaphenyltribenzotriquinacene derivative on Cu(111). Combining scanning tunneling microscopy (STM) and density functional theory (DFT) confirms the formation of highly differing arrangements starting with π-stacked bowl-to-bowl dimers at low coverage at room temperature via chiral honeycomb structures, an intermediate trigonal superstructure, followed by a fully carbon-based, flattened hexagonal superstructure formed by on-surface deacetylation, which is proposed as a precursor for holey graphene networks with unique defect structures.

Mechanism of Capacitive Coupling of Proximal Electromagnetic Sources With Biological Bodies.

This study investigates the absorption of the induced E-field in homogeneous biological tissue exposed to highly localized field sources in proximity of the body, such as the charged tips of antennas, where E-field coupling dominates. These conditions are relevant for compliance testing of modern mobile phones where exposure is evaluated at small separation between radiators and the body. We derive an approximation that characterizes the decay of the induced E-field in the tissue as a function of distance. The absorption is quantified in terms of the local specific absorption rate (SAR) at the tissue surface as a function of the charge at the antenna tip. The approximation is based on the analytical evaluation of the E-fields of a charged disk under quasi-static conditions. We validate this approximation using full-wave simulations of dipoles. We demonstrate that the coupling mechanism of the E-field is dominated by the perpendicular field component and that wave propagation need not be considered for the characterization of the exposure. The surface SAR decreases approximately with the fourth power of the distance and with the square of the ratio of the permittivities of the tissue and free-space. The approximation predicts the induced maximum E-field with an accuracy of better than 1.5 dB. © 2022 Bioelectromagnetics Society.

Capability of the TrueColor Sensor Array for Determining the Nitrogen Supply in Winter Barley (Hordeum vulgare L.).

In agriculture, efforts are being made to reduce pesticides and fertilizers because of the possible negative environmental impacts, high costs, political requirements, and declining social acceptance. With precision farming, significant savings can be achieved by the site-specific application of fertilizers. In contrast to currently available single sensors and camera-based systems, arrays or line sensors provide a suitable spatial resolution without requiring complex signal processing and promise significant potential regarding price and precision. Such systems comprise a cost-effective and compact unit that can be extended to any working width by cascading into arrays. In this study, experiments were performed to evaluate the applicability of a TrueColor sensor array in monitoring the nitrogen supply of winter barley during its growth. This sensor is based on recording the reflectance values in various channels of the CIELab color space: luminosity, green-red, and blue-yellow. The unique selling point of this sensor is the detection of luminosity because only the CIELab color space provides this opportunity. Strong correlations were found between the different reflection channels and the nitrogen level (R² = 0.959), plant coverage (R² = 0.907), and fresh mass yield (R² = 0.866). The fast signal processing allows this sensor to meet stringent demands for the operating speed, spatial resolution, and price structure.

Myocarditis and pericarditis in association with COVID-19 mRNA-vaccination: cases from a regional pharmacovigilance centre.

In this article we summarize suspected adverse events following immunization (AEFI) of pericarditis, myocarditis and perimyocarditis that were reported by our regional pharmacovigilance centre after COVID-19 mRNA-vaccination and discuss their association with these vaccines. Seventeen cases were reported between March and July 2021. Of these, nine had perimyocarditis, five myocarditis and three pericarditis. Twelve patients were male (71%). The median age was 38 years (range 17-88). The most commonly observed presenting symptom was acute chest pain (65%). While 47% of the patients were previously healthy, 53% had at least one pre-existing comorbidity, with hypertension being the most prevalent (24%). The European Society of Cardiology diagnostic criteria for the reported AEFIs were fulfilled in twelve cases (71%). The AEFIs occurred after the first vaccine dose in six cases (35%), after the second vaccine dose in ten cases (59%) and after both doses in one case (6%). The median latency of all AEFIs taken together was 14 days (range 1-28) after the first vaccination and 3 days (range 1-17) after the second one. All patients except one were hospitalized (94%) with a median length of stay of 7.5 days (range 3-13). The majority of patients (n = 11, 65%) did not experience any complications, and 13 (77%) of the patients had recovered or were recovering at the time of discharge. In 16 of the 17 cases (94%), the association between the AEFI and mRNA-vaccination was considered possible by the pharmacovigilance centre.

Reflection Properties of the Human Skin From 40 to 110 GHz: A Confirmation Study.

Several recent theoretical dosimetric studies above 6 GHz apply generic layered skin models. For this frequency range, new experimental phantoms for over-the-air performance of wireless devices were proposed that simulate the impedance matching effects of the stratum corneum layer (SCL) with a low-loss coating layer. The aim of this study was to verify the skin models by comparing their reflection coefficients S11 with measurements of 37 human volunteers (21 males, 16 females, 5-80 years) at 21 body locations (10 at palm, 11 at arm/face) with different SCL thicknesses, using waveguides covering frequencies from 40 to 110 GHz. Such measurements were also carried out with the phantom material. The statistical analysis showed strong evidence that S11 depends on the SCL thickness and no evidence that S11 depends on sex. The measured S11 values for thin and thick skin can be represented by SCL layers of 15 and 140 µm, respectively. These values correspond well to the assumptions of previous studies. (The cohort did not include volunteers doing heavy manual work.) The phantom material mimics the matching effect of the SCL with deviations from the waveguide measurements of less than 0.85 dB (22%), which confirms the suitability of layered phantoms to represent the electromagnetic reflection/absorption of human skin. © 2021 Bioelectromagnetics Society.

Compliance Assessment of the Epithelial or Absorbed Power Density Below 10 GHz Using SAR Measurement Systems.

The introduction of new dosimetric quantities, in particular, epithelial or absorbed power density for frequencies above 6 GHz, in exposure guidelines and safety standards requires the development of new experimental assessment procedures for compliance testing. In this study, we propose to approximate the peak spatial-average absorbed power density (psSab ) using the same measured data and algorithms that are used for determining the peak spatial-average specific absorption rate psSAR, which is currently limited to frequencies up to 10 GHz. The uncertainty component for the transformation of psSAR to psSab was evaluated as less than 0.55 dB (13.5%) for any source as close as 0.02 λ from the tissue simulating media. The approach is easy to implement and allows determining compliance with the basic restrictions of the latest safety guidelines. In the next project, we will expand dosimetric probes, phantoms, and procedures for frequencies above 10 GHz. © 2021 Bioelectromagnetics Society.

A case of intoxication with tea made from Digitalis purpurea.

We present the case of a 34-year-old woman with recurrent depressive disorder who ingested purple foxglove with suicidal intent. She bought a foxglove plant (Digitalis purpurea) over the internet and used all of its leaves to make a tea that she then drank over a period of a few hours. Seventeen hours later, she developed abdominal pain, emesis and bradycardia and was admitted via the emergency department to the intensive care unit for further treatment and monitoring. The plasma digoxin concentration measured 3.53 nmol/l (therapeutic reference range 0.77-1.50 nmol/l) 21 hours after ingestion of the tea. She remained heamodynamically and neurologically stable, was treated with antiemetics and simple analgesia and did not require digoxin-specific antibodies. Despite normal renal function, her plasma digoxin half-life was prolonged (estimated 76 h), reflecting the long half-life of the parent compound digitoxin which is the main cardiac glycoside in Digitalis purpurea. She was transferred to psychiatric care 48 h after admission. In this report, we compare this case to other similar cases, which to date have only been rarely reported in the literature.

Molecular Chains: Arranging and Programming Logic Gates.

One particularly fascinating vision for charge-operated devices is the controlled assembly of structures from single surface-deposited molecules. Here, we report on the assembly of linear clusters that consist of phthalocyanine (H2Pc) molecules on a Ag(111) surface. The molecules are imaged as well as manipulated with a low-temperature scanning tunneling microscope (STM). Upon deprotonation of every second H2Pc, the resulting HPc molecule exhibits an isomeric bistability which can be used as inputs in logic gates. Combining our STM measurements with density functional theory calculations we show that the HPc isomers exhibit a repulsive electrostatic interaction with adjacent H2Pc molecules which, due to the asymmetric charge distribution on HPc, results in a counterclockwise or clockwise molecule tilt of the latter, thereby defining the logic 0 and 1 of the output. It is shown that information can be relayed along molecule chains over distances equivalent to at least nine molecules.

TRANSMISSION COEFFICIENT OF POWER DENSITY INTO SKIN TISSUE BETWEEN 6 AND 300 GHZ.

The latest electromagnetic safety guidelines define transmitted or epithelial power density as the basic restriction above 6 GHz. In this note, we derive an approximation for a conservative transmission coefficient for quasi plane wave incidence as a function of the frequency for the normal component of the Poynting vector with respect to the evaluation plane or tissue surface |Sz inc| and for its modulus ||Sinc||. The maximum transmission coefficient for the normal component of the Poynting vector ${\boldsymbol{T}}_{\mathbf{z}}^{\mathbf{max}}$ is 1 independent of tissue composition and frequency. Approximations of ${\boldsymbol{T}}_{\mathbf{total}}^{\mathbf{max}}$ normalized to ||Sinc|| for thin and thick stratum corneum are provided allowing higher exposures. These approximations allow to conservatively demonstrate compliance with basic restrictions when quasi plane-wave conditions are locally satisfied and enhancement effects of standing waves between source and body can be neglected. The reported results are important to regulators and standardization bodies regarding revisions of compliance requirements and safety guidelines.

A hydraulic model of cardiovascular physiology and pathophysiology embedded into a computer-based teaching system for student training in laboratory courses.

Functional understanding of the different parts of the cardiovascular system is essential for an insight into pathomechanisms of numerous diseases. During training cardiovascular physiology, students and early-stage medical personnel should understand the role of different functional parameters for systolic and diastolic blood pressure, as well as for blood flow. The impact of isolated parameters can only be studied in models. Here physical hydraulic models are an advantage in which the students have a direct contact to the mechanical properties of the circulatory system. But these models are often difficult to handle. The aim of the present study was to develop a comprehensive model of the cardiovascular system, including a mechanical heart with valves, an elastic aorta, a more rigid peripheral artery system, a total peripheral resistance, and a venous reservoir representing the variable cardiac preload. This model allows one to vary systematically several functional parameters and to continuously record their impact on pressure and flow. This model is embedded into a computer-based teaching system (LabTutor) in which the students are guided through the handling of the model (as well as the systematic variation of parameters), and the measured data can be analyzed. This hybrid teaching system, which is routinely integrated in physiology laboratory courses of medical students, allows students to work with a complex hydraulic model of the cardiovascular system and to analyze systematically the impact of influencing variables (e.g., increased peripheral resistance or changed cardiac preload) as well as pathophysiological dysfunctions (e.g., reduced aortic compliance).

Limitations of Incident Power Density as a Proxy for Induced Electromagnetic Fields.

The most recent safety guidelines define basic restrictions for electromagnetic field exposure at frequencies more than 6 GHz in terms of spatial- and time-averaged transmitted power density inside the body. To enable easy-to-perform evaluations in situ, the reference levels for the incident power density were derived. In this study, we examined whether compliance with the reference levels always ensures compliance with basic restrictions. This was evaluated at several distances from different antennas (dipole, loop, slot, patch, and helix). Three power density definitions based on integration of the perpendicular real part of the Poynting vector, the real part of its three vector components, and its modulus were compared for averaging areas of λ2 /16, 4 cm2 (below 30 GHz) and 1 cm2 (30 GHz). In the reactive near-field (d < λ/(2π)), the transmitted power density can be underestimated if an antenna operates at the free space exposure limit. This underestimation may exceed 6 dB (4.0 times) and depends on the field source due to different coupling mechanisms. It is frequency-dependent for fixed-size averaging areas (4 and 1 cm2 ). At larger distances, transmission can be larger than the theoretical plane-wave transmission coefficient due to backscattering between the body and field source. Using the modulus of the incident Poynting vector yields the smallest underestimation. © 2020 Bioelectromagnetics Society.

RF-INDUCED TEMPERATURE INCREASE IN A STRATIFIED MODEL OF THE SKIN FOR PLANE-WAVE EXPOSURE AT 6-100 GHZ.

This study assesses the maximum temperature increase induced by exposure to electromagnetic fields between 6 and 100 GHz using a stratified model of the skin with four or five layers under plane wave incidence. The skin model distinguishes the stratum corneum (SC) and the viable epidermis as the outermost layers of the skin. The analysis identifies the tissue layer structures that minimize reflection and maximize the temperature increase induced by the electromagnetic field. The maximum observed temperature increase is 0.4°C for exposure at the present power density limit for the general population of 10 W m -2 . This result is more than twice as high as the findings reported in a previous study. The reasons for this difference are identified as impedance matching effects in the SC and less conservative thermal parameters. Modeling the skin as homogeneous dermis tissue can underestimate the induced temperature increase by more than a factor of three.

Paracrine crosstalk between intestinal L- and D-cells controls secretion of glucagon-like peptide-1 in mice.

DPP-4 inhibitors, used for treatment of type 2 diabetes, act by increasing the concentrations of intact glucagon-like peptide-1 (GLP-1), but at the same time, they inhibit secretion of GLP-1, perhaps by a negative feedback mechanism. We hypothesized that GLP-1 secretion is feedback regulated by somatostatin (SS) from neighboring D-cells, and blocking this feedback circuit results in increased GLP-1 secretion. We used a wide range of experimental techniques, including gene expression analysis, immunohistochemical approaches, and the perfused mouse intestine to characterize the paracrine circuit controlling GLP-1 and SS. We show that 1) antagonizing the SS receptor (SSTr) 2 and SSTr5 led to increased GLP-1 and SS secretion in the mouse, 2) SS exhibits strong tonic inhibition of GLP-1 secretion preferentially through SSTr5, and 3) the secretion of S was GLP-1 receptor dependent. We conclude that SS is a tonic inhibitor of GLP-1 secretion, and interventions in the somatostain-GLP-1 paracrine loop lead to increased GLP-1 secretion.

Theoretical and numerical assessment of maximally allowable power-density averaging area for conservative electromagnetic exposure assessment above 6 GHz.

The objective of this paper is to determine a maximum averaging area for power density (PD) that limits the maximum temperature increase to a given threshold for frequencies above 6 GHz. This maximum area should be conservative for any transmitter at any distance >2 mm from the primary transmitting antennas or secondary field-generating sources. To derive a generically valid maximum averaging area, an analytical approximation for the peak temperature increase caused by localized exposure was derived. The results for a threshold value of 1 K temperature rise were validated against simulations of a series of sources composed of electrical and magnetic elements (dipoles, slots, patches, and arrays) that represented the spectrum of relevant transmitters. The validation was successful for frequencies in which the power deposition occurred superficially (i.e., >10 GHz). In conclusion, the averaging area for a PD limit of 10 W/m2 that conservatively limits the temperature increase in the skin to less than 1 K at any distance >2 mm from the transmitters is frequency dependent, increases with distance, and ranges from 3 cm2 at <10 GHz to 1.9 cm2 at 100 GHz. In the far-field, the area depends additionally on distance and the antenna array aperture. The correlation was found to be worse at lower frequencies (<10 GHz) and very close to the source, the systematic evaluation of which is part of another study to investigate the effect of different coupling mechanisms in the reactive near-field on the ratio of temperature increase to incident power density. The presented model can be directly applied to any other PD and temperature thresholds. Bioelectromagnetics. 39:617-630, 2018. © 2018 Wiley Periodicals, Inc.

Proenkephalin for the early detection of acute kidney injury in hospitalized patients with chronic kidney disease.

BACKGROUND: The early detection of acute kidney injury (AKI) in patients with chronic kidney disease (CKD) is an unmet clinical need. Proenkephalin (PENK) might improve the early detection of AKI. METHODS: One hundred and eleven hospitalized CKD patients undergoing radiographic contrast procedures were enrolled. PENK was measured in a blinded fashion at baseline (before contrast media administration) and on day 1 (after contrast media administration). The potential of PENK levels to predict contrast-induced AKI was the primary endpoint. RESULTS: Baseline creatinine and baseline PENK were similar in AKI and no-AKI patients. In AKI patients, day 1 PENK (198 pmol/L vs 121 pmol/L, P < 0.01) was significantly higher compared to no-AKI patients. The area under the curve (AUC) for the prediction of AKI by day 1 PENK was 0.79, 95% CI: 0.70-0.87, similar to serum creatinine: 0.78, 95% CI: 0.61-0.95. Delta PENK was significantly higher in AKI compared to no-AKI patients (53 pmol/L vs 1 pmol/L, P < 0.01). The AUC for the prediction of AKI by delta PENK was high (0.92, 95%CI 0.82-1.00) and remained high for creatinine-blind AKI (0.94, 95% CI: 0.87-0.97). CONCLUSION: Delta PENK levels improve the early detection of contrast-induced AKI in CKD patients over serial creatinine sampling. Delta PENK accelerates the detection of creatinine-blind AKI by 24 hours.