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The Fram Strait is an area with a relatively low and irregular distribution of diatom microfossils in surface sediments, and thus microfossil records are scarce, rarely exceed the Holocene, and contain sparse information about past richness and taxonomic composition. These attributes make the Fram Strait an ideal study site to test the utility of sedimentary ancient DNA (sedaDNA) metabarcoding. Amplifying a short, partial rbcL marker from samples of sediment core MSM05/5-712-2 resulted in 95.7 % of our sequences being assigned to diatoms across 18 different families, with 38.6 % of them being resolved to species and 25.8 % to genus level. Independent replicates show a high similarity of PCR products, especially in the oldest samples. Diatom sedaDNA richness is highest in the Late Weichselian and lowest in Mid- and Late Holocene samples. Taxonomic composition is dominated by cold-water and sea-ice-associated diatoms and suggests several reorganisations – after the Last Glacial Maximum, after the Younger Dryas, and after the Early and after the Mid-Holocene. Different sequences assigned to, amongst others, Chaetoceros socialis indicate the detectability of intra-specific diversity using sedaDNA. We detect no clear pattern between our diatom sedaDNA record and the previously published IP25 record of this core, although proportions of pennate diatoms increase with higher IP25 concentrations and proportions of Nitzschia cf. frigida exceeding 2 % of the assemblage point towards past sea-ice presence.

Organic matter deposited in ancient, ice-rich permafrost sediments is vulnerable to climate change and may contribute to the future release of greenhouse gases; it is thus important to get a better characterization of the plant organic matter within such sediments. From a Late Quaternary permafrost sediment core from the Buor Khaya Peninsula, we analysed plant-derived sedimentary ancient DNA (sedaDNA) to identify the taxonomic composition of plant organic matter, and undertook palynological analysis to assess the environmental conditions during deposition. Using sedaDNA, we identified 154 taxa and from pollen and non-pollen palynomorphs we identified 83 taxa. In the deposits dated between 54 and 51 kyr BP, sedaDNA records a diverse low-centred polygon plant community including recurring aquatic pond vegetation while from the pollen record we infer terrestrial open-land vegetation with relatively dry environmental conditions at a regional scale. A fluctuating dominance of either terrestrial or swamp and aquatic taxa in both proxies allowed the local hydrological development of the polygon to be traced. In deposits dated between 11.4 and 9.7 kyr BP (13.4–11.1 cal kyr BP), sedaDNA shows a taxonomic turnover to moist shrub tundra and a lower taxonomic richness compared to the older samples. Pollen also records a shrub tundra community, mostly seen as changes in relative proportions of the most dominant taxa, while a decrease in taxonomic richness was less pronounced compared to sedaDNA. Our results show the advantages of using sedaDNA in combination with palynological analyses when macrofossils are rarely preserved. The high resolution of the sedaDNA record provides a detailed picture of the taxonomic composition of plant-derived organic matter throughout the core, and palynological analyses prove valuable by allowing for inferences of regional environmental conditions.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) represent a valuable tool for in vitro modeling of the cardiac niche and possess great potential in tissue engineering applications. However, conventional polystyrene-based cell culture substrates have adverse effects on cardiomyocytes in vitro due to the stress applied by a stiff substrate on contractile cells. Ultra-high viscosity alginates offer a unique versatility as tunable substrates for cardiac cell cultures due to their biocompatibility, flexible biofunctionalization, and stability. In this work, we analyzed the effect of alginate substrates on hPSC-CM maturity and functionality. Alginate substrates in high-throughput compatible culture formats fostered a more mature gene expression and enabled the simultaneous assessment of chronotropic and inotropic effects upon beta-adrenergic stimulation. Furthermore, we produced 3D-printed alginate scaffolds with differing mechanical properties and plated hPSC-CMs on the surface of these to create Heart Patches for tissue engineering applications. These exhibited synchronous macro-contractions in concert with more mature gene expression patterns and extensive intracellular alignment of sarcomeric structures. In conclusion, the combination of biofunctionalized alginates and human cardiomyocytes represents a valuable tool for both in vitro modeling and regenerative medicine, due to its beneficial effects on cardiomyocyte physiology, the possibility to analyze cardiac contractility, and its applicability as Heart Patches., (© 2023 Fraunhofer IBMT. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Proton-decoupled deuterium NMR spectra were obtained for an asymmetric liquid crystal dimer 1-(4-cyanobiphenyl-4'-yloxy)-6-(4-cyanobiphenyl-4'-yl)hexane (CB6OCB) containing a single -CD_{2}- group. The sample has two nematic liquid crystal phases: a twist-bend nematic, N_{TB}, at the lowest temperature followed by a uniaxial nematic, N_{U}, on increasing the temperature. Proton decoupling reduces the linewidths of the peaks in the deuterium spectrum from kHz to ∼100Hz, enabling quadrupolar splittings, Δν, to be obtained with enhanced precision as well as the dipolar coupling between deuterium nuclei within the CD_{2} group, hence enhancing the information content.

Background and Purpose: Meningiomas are intracranial tumors that usually carry a benign prognosis. Some meningiomas cause perifocal edema. Resting-state fMRI can be used to assess whole-brain functional connectivity, which can serve as a marker for disease severity. Here, we investigated whether the presence of perifocal edema in preoperative patients with meningiomas leads to impaired functional connectivity and if these changes are associated with cognitive function., Materials and Methods: Patients with suspected meningiomas were prospectively included, and resting-state fMRI scans were obtained. Impairment of functional connectivity was quantified on a whole-brain level using our recently published resting-state fMRI-based marker, called the dysconnectivity index. Using uni- and multivariate regression models, we investigated the association of the dysconnectivity index with edema and tumor volume as well as cognitive test scores., Results: Twenty-nine patients were included. In a multivariate regression analysis, there was a highly significant association of dysconnectivity index values and edema volume in the total sample and in a subsample of 14 patients with edema, when accounting for potential confounders like age and temporal SNR. There was no statistically significant association with tumor volume. Better neurocognitive performance was strongly associated with lower dysconnectivity index values., Conclusions: Resting-state fMRI showed a significant association between impaired functional connectivity and perifocal edema, but not tumor volume, in patients with meningiomas. We demonstrated that better neurocognitive function was associated with less impairment of functional connectivity. This result shows that our resting-state fMRI marker indicates a detrimental influence of peritumoral brain edema on global functional connectivity in patients with meningiomas., (© 2023 by American Journal of Neuroradiology.)

Background: Clinical onset of multiple sclerosis (MS postvacc ) and myelin-oligodendrocyte-glycoprotein-antibody-associated disease (MOGAD postvacc ) has been reported in association with SARS-CoV-2-vaccination. There is uncertainty as to whether this is causality (denovo disease) or temporal coincidence (manifestation of a preexisting, subclinical neuroinflammation)., Objectives: Comparing the clinical characteristics of MS postvacc -patients versus patients with MS (PwMS) whose clinical onset occurred independently of vaccination (MS reference )., Methods: Consecutive patients with clinical onset ≤30 days after SARS-CoV-2-vaccination were included. Clinical data, cerebrospinal fluid (CSF) parameters and magnetic resonance imaging (MRI) as well as optical coherence tomography (OCT) data were compared to an age- and sex-matched MS reference -cohort., Results: We identified 5 MS postvacc  and 1 MOGAD postvacc  patients who developed their clinical onset ≤ 30 days after SARS-CoV-2-vaccination. Clinical characteristics, CSF, MRI and OCT parameters from MS postvacc  patients were comparable to the MS reference  cohort and showed evidence of preexisting subclinical CNS disease. The single case with MOGAD postvacc  clearly differed from PwMS in higher CSF cell counts, remission of MRI lesions during follow-up, and absence of oligoclonal bands., Conclusions: Our case series indicates that MS postvacc  patients showed a rather typical initial manifestation in temporal association with SARS-CoV-2-vaccination and harbored preexisting subclinical neuroinflammation. This argues against the denovo development of MS in this cohort., Competing Interests: Declaration of Competing Interest JAG, HZ, EO, TC report no disclosures relevant to the manuscript. TK has received speaker honoraria and/or personal fees for advisory boards from Novartis Pharma, Roche Pharma, Alexion/Astra Zeneca and Biogen. The Institution she works for has received grant support for her research from Bayer-Schering AG, Novartis and Chugai Pharma in the past. JH has received grants for OCT research from the Friedrich-Baur-Stiftung and Merck, personal fees and non-financial support from Celgene, Merck, Alexion, Novartis, Janssen, Roche, Biogen and non-financial support of the Guthy-Jackson Charitable Foundation, all outside the submitted work. JH is partially funded by the German Federal Ministry of Education and Research ((DIFUTURE), Grant Numbers 01ZZ1603[A-D] and 01ZZ1804[A-H])., (Copyright © 2022. Published by Elsevier B.V.)

Post-transplant lymphoproliferative disease (PTLD) is a serious complication of solid organ transplantation. As early diagnosis remains challenging, we investigated the utility of serum-free light chain (FLC) and heavy chain/light chain pairs (HLC) as diagnostic biomarkers. Pre-treatment serum FLC and HLC levels were measured in 20 patients at their first diagnosis of B cell PTLD and in 14/20 patients during follow-up. Results were compared to serum FLC/HLC levels of 90 matched PTLD-free transplanted controls. Renal dysfunction was common in both cohorts, and combined FLC levels were often elevated above the conventional upper limit of normal (45.7 mg/L). Combined FLC levels were higher in patients with PTLD than in transplant controls (p = 0.013), and levels above the conventional ULN were associated with PTLD (OR 3.2, p = 0.05). Following adjustment to cystatin C as a marker of renal function an even stronger association was found for a (dimensionless) threshold value of 37.8 (OR 8.9, p < 0.001). In addition, monoclonal proliferation (abnormal FLC ratio, using an established renal range cutoff) was more common in PTLD than in controls (3/20 vs. 2/90, p = 0.04). Following therapy, at the time of protocolised restaging, patients experiencing subsequent sustained complete remission displayed lower FLC levels than those not experiencing such remission (p = 0.053). No relationship with HLC results was seen. Elevated polyclonal FLC levels (especially when adjusted for renal function) and monoclonal proliferation are a potential biomarker for PTLD diagnosis and disease surveillance. However, prospective validation is necessary before FLC measurement should be incorporated in follow-up of transplant recipients and PTLD management.

Atomic excitation in strong optical laser fields has been found to take place even at intensities exceeding saturation. The concomitant acceleration of the atom in the focused laser field has been considered a strong link to, if not proof of, the existence of the so-called Kramers-Henneberger (KH) atom, a bound atomic system in an intense laser field. Recent findings have moved the importance of the KH atom from being purely of theoretical interest toward real world applications; for instance, in the context of laser filamentation. Considering this increasing importance, we explore the limits of strong-field excitation in optical fields, which are basically imposed by ionization through the spatial field envelope and the field propagation.

Polycrystalline dimethyl sulfone is studied using central-transition oxygen-17 exchange NMR. The quadrupolar and chemical shift tensors are determined by combining quantum chemical calculations with line shape analyses of rigid-lattice spectra measured for stationary and rotating samples at several external magnetic fields. Quantum chemical computations predict that the largest principal axes of the chemical shift anisotropy and electrical field gradient tensors enclose an angle of about 73°. This prediction is successfully tested by comparison with absorption spectra recorded at three different external magnetic fields. The experimental one-dimensional motionally narrowed spectra and the two-dimensional exchange spectrum are compatible with model calculations involving jumps of the molecules about their two-fold symmetry axis. This motion is additionally investigated by means of two-time stimulated-echo spectroscopy which allows for a determination of motional correlation functions over a wider temperature range than previously reported using carbon and deuteron NMR. On the basis of suitable second-order quadrupolar frequency distributions, sin-sin stimulated-echo amplitudes are calculated for a two-site model in the limit of vanishing evolution time and compared with experimental findings. The present study thus establishes oxygen-17 NMR as a powerful method that will be particularly useful for the study of solids and liquids devoid of nuclei governed by first-order anisotropies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The ELISpot assay, as a sensitive and specific method, enables the detection of cytokines for immunological purposes and in vaccine development. Here we describe the successful transfer of the manual procedure to a commercially available automated liquid handling platform, based on the work described in Neubauer et al. (Cytotechnology 69:57-73, 2017). Different kinds of technical issues (dead volume reduction, instrumental handling limitations, liquid class improvement) have been solved and biological effects (reagents concentration, selectivity tests, dispensing way, etc.) have been controlled during the implementation process. At the end a maximum of 6% mean delta difference and a lower mean dispersion than the manual assay were reached as well as a turnaround time of four to six times higher than the manual process.

Neuromyelitis optica spectrum disorders (NMOSD) are mostly relapsing inflammatory conditions of the central nervous system (CNS). In 55% of the cases of NMOSD optic neuritis (ON) is the most frequent first manifestation and can cause severe damage to the afferent visual system and the retina with resultant severe visual impairment. In recent years, investigations of the retina as part of the CNS by optical coherence tomography (OCT) has been shown to be a valid and efficient method for diagnostics and evaluation of the disease course in NMOSD. In addition, OCT not only shows severe damage of the afferent visual system due to multiple bouts of ON but also reveals NMOSD-specific intraretinal pathologies. The latter could be just as important for future differential diagnostics as for the evaluation of potential therapeutic targets. This article briefly reviews the principles of the OCT technique and describes its relevance for the diagnostics and assessment of disease course in NMOSD.

The orientational order of the molecules in the bent mesogen CB6OCB has been studied throughout the range of temperature stability of both the N&#95;{U} and N&#95;{TB} liquid-crystal phases by ^{13}C NMR spectroscopy. These spectra provide local order parameters for the para axes of both of the nonequivalent cyanobiphenyl groups and show how they change on entering the twist-bend nematic phase. A key feature of the order parameters is a weak, but clear maximum in the temperature variation of the order parameter prior to the N&#95;{TB} phase. This suggests that the directors in both the N&#95;{U} and N&#95;{TB} phases are tilted with respect to the magnetic field of the spectrometer. Significantly the conformational states of the spacer are comparable in both phases, although the low temperature nematic is chiral but not that at high temperature. It is proposed that the higher temperature, tilted phase could be the splay-bend nematic phase.

Letermovir is a novel antiviral in clinical development for prophylaxis against human cytomegalovirus in immunocompromised transplant recipients. This two-part, single-center, randomized, double-blind, placebo-controlled trial evaluated the safety and pharmacokinetics of a hydroxypropyl β-cyclodextrin (HPβCD)-based intravenous formulation of letermovir in healthy women. Subjects received single, escalating doses (120, 240, 480, 720, and 960 mg; 6 letermovir, 2 placebo per cohort) or multiple, once-daily doses (240 mg; 8 letermovir, 4 placebo) of HPβCD-formulated letermovir and the associated pharmacokinetic profiles and adverse events were investigated. Single-dose and multiple-dose regimens were generally well tolerated. Single-dose escalation resulted in a slightly more-than-dose-proportional increase in the area under the letermovir plasma concentration-time curve (AUC), whereas increase in the maximal observed letermovir plasma concentration (C max ) was dose proportional. After once-daily dosing, accumulation ratios in AUC and C max were 1.22 and 1.03, respectively. The terminal half-life was 28.3 h, supporting once-daily dosing (EudraCT Number: 2012-001603-20)., (© 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The alpha-herpesviruses varicella zoster virus (VZV) and herpes simplex virus (HSV) share common features including lifelong persistence in sensory ganglia and the risk of recurrences. For both HSV and VZV, standard-of-care (SoC) is based on nucleoside analogs (NAs), which require specific activation in infected cells. These existing drugs exhibit substantial limitations, warranting the development of new and more effective drugs., (© 2017 American Society for Clinical Pharmacology and Therapeutics.)

The ELISpot assay is used for the detection of T cell responses in clinical trials and vaccine evaluations. Standardization and reproducibility are necessary to compare the results worldwide, inter- and intra-assay variability being critical factors. To assure operator safety as well as high-quality experiment performance, the ELISpot assay was implemented on an automated liquid handling platform, a Tecan Freedom EVO. After validation of the liquid handling, automated loading of plates with cells and reagents was investigated. With step by step implementation of the manual procedure and liquid dispensing optimization on the robot platform, a fully automated ELISpot assay was accomplished with plates remaining in the system from the plate blocking step to spot development. The mean delta difference amounted to a maximum of 6%, and the mean dispersion was smaller than in the manual assay. Taken together, we achieved with this system not only a lower personnel attendance but also higher throughput and a more precise and parallelized analysis. This platform has the potential to guarantee validated, safe, fast, reproducible and cost-efficient immunological and toxicological assays in the future.

Excitation and ionization in strong laser fields lies at the heart of such diverse research directions as high-harmonic generation and spectroscopy, laser-induced diffraction imaging, emission of femtosecond electron bunches from nanotips, self-guiding, filamentation and mirrorless lasing during propagation of light in atmospheres. While extensive quantum mechanical and semiclassical calculations on strong-field ionization are well backed by sophisticated experiments, the existing scattered theoretical work aiming at a full quantitative understanding of strong-field excitation lacks experimental confirmation. Here we present experiments on strong-field excitation in both the tunneling and multiphoton regimes and their rigorous interpretation by time dependent Schrödinger equation calculations, which finally consolidates the seemingly opposing strong-field regimes with their complementary pictures. Most strikingly, we observe an unprecedented enhancement of excitation yields, which opens new possibilities in ultrafast strong-field control of Rydberg wave packet excitation and laser intensity characterization.

Objective: To investigate different brain regions for grey (GM) and white matter (WM) damage in a well-defined cohort of neuromyelitis optica spectrum disorder (NMOSD) patients and compare advanced MRI techniques (VBM, Subcortical and cortical analyses (Freesurfer), and DTI) for their ability to detect damage in NMOSD., Methods: We analyzed 21 NMOSD patients and 21 age and gender matched control subjects. VBM (GW/WM) and DTI whole brain (TBSS) analyses were performed at different statistical thresholds to reflect different statistical approaches in previous studies. In an automated atlas-based approach, Freesurfer and DTI results were compared between NMOSD and controls., Results: DTI TBSS and DTI atlas based analysis demonstrated microstructural impairment only within the optic radiation or in regions associated with the optic radiation (posterior thalamic radiation p < 0.001, 6.9 % reduction of fractional anisotropy). VBM demonstrated widespread brain GM and WM reduction, but only at exploratory statistical thresholds, with no differences remaining after correction for multiple comparisons. Freesurfer analysis demonstrated no group differences., Conclusion: NMOSD specific parenchymal brain damage is predominantly located in the optic radiation, likely due to a secondary degeneration caused by ON. In comparison, DTI appears to be the most reliable and sensitive technique for brain damage detection in NMOSD., Key Points: • The hypothesis of a widespread brain damage in NMOSD is challenged. • The optic radiation (OR) is the most severely affected region. • OR-affection is likely due to secondary degeneration following optic neuritis. • DTI is currently the most sensitive technique for NMOSD-related brain-damage detection. • DTI is currently the most reliable technique for NMOSD-related brain-damage detection.

We report on sensitive detection of atmospheric methane employing quantum cascade laser based optical feedback cavity-enhanced absorption spectroscopy (OF-CEAS). An instrument has been built utilizing a continuous-wave distributed feedback quantum cascade laser (cw-QCL) with a V-shaped cavity, a common arrangement that reduces feedback to the laser from non-resonant reflections. The spectrometer has a noise equivalent absorption coefficient of 3.6 × 10 -9 cm -1 Hz -1 / 2 for a spectral scan of CH 4 at 7.39 μm. From an Allan-Werle analysis a detection limit of 39 parts per trillion of CH 4 at atmospheric pressure within 50 s acquisition time was found.

Currently methods to reduce radiation and contrast media application in endovascular repair of aortic aneurysms (EVAR) are investigated. First positive results for real-time contrast medium-enhanced ultrasonography (CEUS) guided endovascular aortic repair have been reported. A combination with image fusion of CEUS and preoperative multi-slice computed tomography (MS-CT) might offer added safety regarding stent-graft positioning and sealing of the landing zones.EVAR was performed in a patient with an asymptomatic infrarenal aortic aneurysm and a penetrating aortic ulcer in the neck region. The precise placement of the stent-graft was performed with CEUS using image fusion and native intraprocedural angiographic fluoroscopy and confirmed with digital subtraction angiography (DSA) using iondinated contrast media. At follow-up, CEUS was used to exclude endoleaks and stent-graft failure or malposition.The precise CEUS-guided placement of the stent-graft was technically successful. No artifacts due to electrical noise and metallic parts of the operating table and surgical instruments occurred. The amount of iodinated contrast media was reduced as intraoperative follow-up was performed using CEUS.CEUS with image fusion combined with intraprocedural angiographic fluoroscopy enables accurate stent-graft placement without use of any nephrotoxic contrast media. This allows EVAR in patients with renal insufficiency or allergic reactions to contrast media.

Purpose: To compare the value of a portable ultrasound system and a high end ultrasound system in detection of endoleaks after EVAR., Material and Methods: In this retrospective study, a cohort of 25 patients underwent both standard examination using a portable ultrasound system (Philips VISIQ) and a second examination using a high end ultrasound system (Philips EPIQ 7). The examination included B-mode and color Doppler in detection of endoleaks. Additional the maximum diameter of the aneurysm was measured in two planes (right-left and ventral-dorsal). The gold standard was contrast-enhanced ultrasound (CEUS) in detection of endoleaks., Results: 25 patients were included in the study. Patients were predominantly male (n = 23) with an average age of 73,30±7.82 years (range 54-85). Diameters of the treated aneurysms were in the right-left plane 5,32±1.88 cm and ventral-dorsal 4,99±1.78 cm using the high end system. Diameters of the treated aneurysms were in the right-left plane 5,30±1.82 cm and ventral-dorsal 4,87±1.74 cm using portable ultrasound system. In 80% of the cases CEUS could detect an endoleak. Whereas the high end system could detect in B-mode 40% and color Doppler 45% of the cases an endoleak. The portable system could detect in B-mode 30% and in color Doppler 35% of the cases an endoleak. On both systems in B-mode a false positive endoleak was found on the same patient. All high flow endoleaks, which needed intervention, could be detected on all systems., Conclusion: The high end ultrasound system does not seem to have an additional advantage in the measurement of the aneurysm diameter. Due to a higher resolution, more endoleaks could be detected in B-mode and color Doppler by using the high end system. The presence of small endoleaks could only be detected by using contrast enhanced ultrasound on an high end ultrasound system. High flow endoleaks could be reliable seen on both systems.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Two different speed optimized avalanche photodiodes (APDs) fabricated in a 0.35 μm standard high-voltage (HV) complementary metal-oxide-semiconductor (CMOS) process with a high unamplified responsivity (avalanche gain M=1) of 0.41 A/W at 670 nm are presented. These APDs differ regarding the effective doping of the deep p well (90% and 75%), using lateral well modulation doping. Compared to the -3  dB bandwidth of the unmodulated APD with 100% doping (850 MHz), this optimization leads to an improved bandwidth of 1.02 and 1.25 GHz for the 75% APD and 90% APD, respectively, both at a gain of M=50.

After edovascular repair of infrarenal aortic aneurysms (EVAR) endoleaks may occur necessitating further therapy. Therefore a reliable method for follow-up imaging after EVAR for detection and control of endoleaks is of high importance. Contrast-enhanced sonography (CEUS) does not require the application of nephrotoxid contrast media and does not stress the patient. CEUS is increasingly used and enables a quick, non-invasive follow-up examination for patient after EVAR. In addition, interventions as therapy for endoleaks may be executed using ultrasound. Initial experience with CEUS-guided aortic stenting shows that the amount of contrast media as well as X-ray time may be reduced., (Georg Thieme Verlag KG Stuttgart · New York.)

Electron microscopy is used in biological research to study the ultrastructure at high resolution to obtain information on specific cellular processes. Serial block face-scanning electron microscopy is a relatively novel electron microscopy imaging technique that allows three-dimensional characterization of the ultrastructure in both tissues and cells by measuring volumes of thousands of cubic micrometres yet at nanometre-scale resolution. In the scanning electron microscope, repeatedly an image is acquired followed by the removal of a thin layer resin embedded biological material by either a microtome or a focused ion beam. In this way, each recorded image contains novel structural information which can be used for three-dimensional analysis. Here, we explore focused ion beam facilitated serial block face-scanning electron microscopy to study the endothelial cell-specific storage organelles, the Weibel-Palade bodies, during their biogenesis at the Golgi apparatus. Weibel-Palade bodies predominantly contain the coagulation protein Von Willebrand factor which is secreted by the cell upon vascular damage. Using focused ion beam facilitated serial block face-scanning electron microscopy we show that the technique has the sensitivity to clearly reveal subcellular details like mitochondrial cristae and small vesicles with a diameter of about 50 nm. Also, we reveal numerous associations between Weibel-Palade bodies and Golgi stacks which became conceivable in large-scale three-dimensional data. We demonstrate that serial block face-scanning electron microscopy is a promising tool that offers an alternative for electron tomography to study subcellular organelle interactions in the context of a complete cell., (© 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.)

Objective: Tracheotomized patients often suffer from impairments in mucociliary clearance and limited capacities for active expectoration of secretions. We investigated the effects of a specific respiratory intervention method (bagging) for tracheotomized patients on respiratory parameters (pO2, pCO2, SpO2, respiratory rates), swallowing frequency, vigilance and secretion viscosity., Methods: The bagging method supports enforced mobilization and expectoration of secretions by application of a series of manual hyperinflations with a resuscitation bag during active inspiration and manual cough support on the chest. 30 tracheotomized neurological patients participated in a multiple-baseline study including a three-weeks intervention period and a follow-up measurement three weeks after termination of the treatment., Results: Most outcome parameters improved significantly during the intervention period: pO2 (p < .01), SpO2 (p < .01), respiratory rates (p < .01), swallowing rates (p < .01), and vigilance scores (p < .01). The quality of bronchial secretions improved in all participants. All effects were sustained up to the follow-up measurements., Conclusion: This preliminary data indicates positive effects for a respiratory intervention method (bagging) on respiratory function and additional respiration-related functions in tracheotomized neurological patients. This easy-to-learn and inexpensive method might expand the range of treatment options for tracheotomized and non-responsive patients., (© Georg Thieme Verlag KG Stuttgart · New York.)

Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel aquaporin-4 present in up to 80% of NMO patients enables distinction from MS. Optic neuritis may occur in either condition resulting in neuro-anatomical retinal changes. Optical coherence tomography (OCT) has become a useful tool for analyzing retinal damage both in MS and NMO. Numerous studies showed that optic neuritis in NMO typically results in more severe retinal nerve fiber layer (RNFL) and ganglion cell layer thinning and more frequent development of microcystic macular edema than in MS. Furthermore, while patients' RNFL thinning also occurs in the absence of optic neuritis in MS, subclinical damage seems to be rare in NMO. Thus, OCT might be useful in differentiating NMO from MS and serve as an outcome parameter in clinical studies., (© The Author(s), 2015.)

Using deuteron nuclear magnetic resonance, the molecular motions of specifically isotope-labeled ibuprofen were probed at the carboxylic group and at the methin group next to it. Spin relaxometry revealed slight differences between the molecular motions of the two isotopomers that are rationalized with reference to the hydrogen bonding of the COOH moiety. In the glassy state, a small-angle jump process among about four sites, related to the so-called γ-process, was identified using stimulated-echo spectroscopy. Indications for a Debye-like process, previously found to leave a weak signature in the dielectric loss, could not unambiguously be detected in magnetic resonance or shear mechanical experiments carried out for supercooled liquid ibuprofen.

Using field ionization combined with the direct detection of excited neutral atoms we measured the distribution of principal quantum number n of excited He Rydberg states after strong-field excitation at laser intensities well in the tunneling regime. Our results confirm theoretical predictions from semiclassical and quantum mechanical calculations and simultaneously underpin the validity of the semiclassical frustrated tunneling ionization model. Moreover, since our experimental detection scheme is spin sensitive in the case of He atoms, we show that strong-field excitation leads to strong population of triplet states. The origin of it lies in the fact that high angular momentum states are accessible in strong-field excitation. Thus, singlet-triplet transitions become possible due to the increased importance of spin-orbit interaction rather than due to direct laser induced spin-flip processes.

Telocyte (TC) is a newly identified type of cell in the cardiac interstitium (www.telocytes.com). TCs are described by classical transmission electron microscopy as cells with very thin and long telopodes (Tps; cellular prolongations) having podoms (dilations) and podomers (very thin segments). TCs' three-dimensional (3D) morphology is still unknown. Cardiac TCs seem to be particularly involved in long and short distance intercellular signalling and, therefore, their 3D architecture is important for understanding their spatial connections. Using focused ion beam scanning electron microscopy (FIB-SEM) we show, for the first time, the whole ultrastructural anatomy of cardiac TCs. 3D reconstruction of cardiac TCs by FIB-SEM tomography confirms that they have long, narrow but flattened (ribbon-like) telopodes, with humps generated by the podoms. FIB-SEM tomography also confirms the network made by TCs in the cardiac interstitium through adherens junctions. This study provides the first FIB-SEM tomography of a human cell type., (© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Laser induced strong-field phenomena in atoms and molecules on the femtosecond (fs) time scale have been almost exclusively investigated with traveling wave fields. In almost all cases, approximation of the strong electromagnetic field by an electric field purely oscillating in time suffices to describe experimental observations. Spatially dependent electromagnetic fields, as they occur in a standing light wave, allow for strong energy and momentum transfer and are expected to extend strong-field dynamics profoundly. Here we report a strong-field version of the Kapitza-Dirac effect for neutral atoms where we scatter neutral He atoms in an intense short pulse standing light wave with fs duration and intensities well in the strong-field tunneling regime. We observe substantial longitudinal momentum transfer concomitant with an unprecedented atomic photon scattering rate greater than 10(16)s(-1).

Purpose: To compare the value of high-resolution contrast-enhanced ultrasound in the detection and characterisation of endoleaks after EVAR., Material and Methods: In this retrospective study, a cohort of 80 patients underwent both standard examination using a curved array 5 MHz transducer and a second examination using a curved array 9 MHz transducer. The examination included B-mode, color Doppler and contrast-enhanced ultrasound using the Philips EPIQ 7 scanner., Results: 80 patients were included in the study. CEUS was used as the preferred examination in determining the presence of an endoleak. The sensitivity and specificity for the detection of endoleak using the 5 MHz transducer was: CEUS (96.8%, 100%), Color Doppler (47.6%, 94.1%), B-mode (15.8%, 94.1%), while for the 9 MHz transducer: CEUS (100%, 100%), Color Doppler (39.7%, 94.1%), B-mode (23.8%, 24.1%)., Conclusion: High resolution ultrasound (9 MHz) in detection and characterization of endoleaks after EVAR has some minor advantages in comparison to lower resolution ultrasound (5 MHz).

Background and Purpose: In recent years a possible non-motor involvement of the nervous system in amyotrophic lateral sclerosis (ALS) has come into the focus of research and has been investigated by numerous techniques. Optical coherence tomography (OCT) - with its potential to reveal neuroaxonal retinal damage - may be an appropriate tool to investigate whether the anterior visual pathway is involved. Our aim was to determine whether OCT-based measures of retinal nerve fiber layer, ganglion cell layer, inner nuclear layer and outer nuclear layer thickness are abnormal in ALS, or correlated with disease severity., Methods: Seventy-six ALS patients (144 eyes) and 54 healthy controls (108 eyes; HCs) were examined with OCT, including automated intraretinal macular segmentation. ALS disease severity was determined with the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised., Results: There was no significant difference between ALS patients and HCs in any of the examined OCT measures. Moreover, OCT parameters showed no correlation with clinical measures of disease severity., Conclusions: These findings indicate that involvement of the anterior visual pathway is not one of the non-motor manifestations of ALS., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

Human rabies is rare in Western Europe. It is not easily recognized in the absence of a history of exposure. We describe the clinical course, diagnosis and follow-up of an imported human rabies case in Switzerland. The patient, a U.S. citizen, presented at an outpatient clinic in Iraq with pain in his right shoulder on July 5, 2012. On July 8 he was transferred to a hospital in the United Arab Emirates, where he exhibited progressive encephalitis with coma. On July 29, he was transferred to a hospital in Switzerland, where he died on July 31, 2012. The autopsy showed severe encephalitis. Rabies was diagnosed by the rapid fluorescent focus inhibition test (RFFIT) and confirmed by fluorescence antibody testing (FAT) in brain smears and immunohistochemistry on paraffin-embedded brain sections. The viral strain was characterized by RT-PCR followed by sequencing and phylogenetic analysis as an American bat rabies strain associated with Tadarida brasiliensis. Close contacts and exposed health care workers received postexposure prophylaxis (PEP)., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Various cryoprotective agents (CPA) are added to cell media in order to avoid cell injury during cryo preservation. The resulting complex environment of the preserved cell, consisting of crystalline and liquid phases can however not be investigated non-invasively by established methods in cryobiology. This study shows how scanning confocal Raman microscopy can non-invasively extract information on chemical composition, phase domain and distribution at cryogenic temperatures. The formation of the salt hydrate, hydrohalite NaCl∙H2O, in solutions comprised of phosphate buffered saline (PBS) and dimethyl sulphoxide (DMSO) is studied in particular. Scanning confocal Raman microscopy can be used to unambiguously identify hydrohalite in a medium containing DMSO and saline. The confocal Raman microscopy imaging along with differential scanning calorimetric measurements further show that the hydrohalite is formed without eutectic formation. This method also allows for discrimination between closely packed hydrohalite crystals that are oriented differently.

Background: Pneumothoraces are a common injury pattern in emergency medicine. Rapid and safe identification can reduce morbidity and mortality. A new handheld, battery powered device, the Pneumoscan (CE 561036, PneumoSonics Inc., Cleveland, OH, USA), using micropower impulse radar (MIR) technology, has recently been introduced in Europe for the rapid and reliable detection of PTX. However, this technology has not yet been tested in trauma patients. This is the first quality control evaluation to report on emergency room performance of a new device used in the trauma setting., Material and Methods: This study was performed at a Level I trauma centre in Switzerland. All patients with thoracic trauma and undergoing chest X-ray and CT-scan were eligible for the study. Readings were performed before the chest X-ray and CT scan. The patients had eight lung fields tested (four on each side). All readings with the Pneumoscan were performed by two junior residents in our department who had previously received an instructional tutorial of 15min. The qualitative MIR results were blinded, and stored on the device. We then compared the results of the MIR to those of the clinical examination, chest X-ray and CT-scan., Results: 50 patients were included, with a mean age of 46 (SD 17) years. Seven patients presented with PTX diagnosed by CT; six of these were detected by Pneumoscan, leading to an overall sensitivity of 85.7 (95% confidence interval 42.1-99.6)%. Only two of seven PTX were found during clinical examination and on chest X-ray (sensitivity 28.6 (95% CI 3.7-71.0)%). Of the remaining 43 of 50 patients without PTX, one false-positive PTX was found by the Pneumoscan, resulting in a specificity of 97.7 (95% CI 87.7-99.9)%., Discussion: The Pneumoscan is an easy to use handheld technology with reliable results. In this series, the sensitivity to detect a PTX by the Pneumoscan was higher than by clinical examination and chest X-ray. Further studies with higher case numbers and a prospective study design are needed to confirm our findings., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Ritalin® (methylphenidate) is an amphetamine-like prescription stimulant commonly used in the treatment of attention deficit hyperactivity disorder in children and adults. Recently, the recreational use of Ritalin has increased, particularly among young adults. Well-known symptoms of intoxication include signs of sympathetic nervous stimulation, such as agitation, anxiety, tachycardia, hypertension, headache, tremor, and dizziness. This case report describes oral dyskinesia as a rare presentation of Ritalin intoxication, with the review of pathophysiology and some epidemiological data.

Several high-speed pnp phototransistors built in a standard 180 nm CMOS process are presented. The phototransistors were implemented in sizes of 40×40 μm 2 and 100×100 μm 2 . Different base and emitter areas lead to different characteristics of the phototransistors. As starting material a p + wafer with a p - epitaxial layer on top was used. The phototransistors were optically characterized at wavelengths of 410, 675 and 850 nm. Bandwidths up to 92 MHz and dynamic responsivities up to 2.95 A/W were achieved. Evaluating the results, we can say that the presented phototransistors are well suited for high speed photosensitive optical applications where inherent amplification is needed. Further on, the standard silicon CMOS implementation opens the possibility for cheap integration of integrated optoelectronic circuits. Possible applications for the presented phototransistors are low cost high speed image sensors, opto-couplers, etc.

We study the main (α-) and secondary (β-) relaxation in the plastically crystalline (PC) phase of cyanocyclohexane by various 2H nuclear magnetic resonance (NMR) methods (line-shape, spin-lattice relaxation, stimulated echo, and two-dimensional spectra) above and below the glass transition temperature T(g) = 134 K. Our results regarding the α-process demonstrate that molecular motion is not governed by the symmetry of the lattice. Rather it is similar to the one reported for structural glass formers and can be modeled by a reorientation proceeding via a distribution of small and large angular jumps. A solid-echo line-shape analysis regarding the β-process below T(g) yields again very similar results when compared to those of the structural glass formers ethanol and toluene. Hence we cannot confirm an intramolecular origin for the β-process in cyanocyclohexane. The fast β-process in the PC phase allows for the first time a detailed 2H NMR study of the process also at T > T(g): an additional minimum in the spin-lattice relaxation time reflecting the β-process is found. Furthermore the solid-echo spectra show a distinct deviation from the rigid limit Pake pattern, which allows a direct determination of the temperature dependent spatial restriction of the process. In Part II of this work, a quantitative analysis is carried out, where we demonstrate that within the model of a "wobbling in a cone" the mean cone angle increases above T(g) and the corresponding relaxation strength is compared to dielectric results.

Human embryonic stem cells (hESCs) play an important role in the fields of regenerative medicine, basic scientific research, tissue engineering and toxicology. Their unique morphology however makes them very sensitive to cryopreservation procedures. We recently introduced a surface dependent, enzyme- and serum-free method for the effective cryopreservation of bulk quantities of hESC colonies using direct immersion into liquid nitrogen (Beier et al., 2011 [5]). However, direct contact with liquid nitrogen risks contamination and cell infection and severely limits clinical application. This work introduces a modified method and a new combined cultivation and cryopreservation device to facilitate the surface dependent vitrification without contact with (possibly unsterile) liquid nitrogen. The technique allows the culture, cryopreservation, storage and post-thawing cultivation in the same device without detaching cell samples from the cultivation surface. Successful vitrification of bulk quantities of hESCs without direct liquid nitrogen contact is an important step towards automated cryopreservation processes for clinical applications of stem cells and other colony forming cell types., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Cord blood is regarded as a powerful source for adult stem cells. Cord blood transplants have been used successfully to treat children and adults in autologous and allogeneic settings. Nevertheless, in many cases, the clinically relevant cell number (CD34+ cells and total leukocytes) is a limiting factor. To enable standardized cell banking and future in vitro expansion of adult stem/progenitor cells, elimination of serum, which inevitably differs from lot to lot and donor to donor, is highly desirable. Here, we demonstrate the feasibility of a xeno-free, chemically defined cryopreservation procedure for cord blood-derived cells over a period of 1 year. Cell recoveries with respect to retrieval of clinically relevant CD34+ cells, colony-forming units, and in vitro cultures of erythroid progenitor cells under standardized conditions were analyzed after 1 week or 1 year of cryopreservation and found to be very high and similar to the samples before freezing. The established xeno-free procedure is an important step toward using the full potential of adult stem cells from cord blood, enabling the elimination of serum-derived factors negatively influencing proliferation, differentiation, and survival of hematopoietic stem cells.