Doppler Ultrasound Flow Reversal in the Superior Sagittal Sinus to Detect Cerebral Venous Congestion in Vein of Galen Malformation.

BACKGROUND AND PURPOSE: Vein of Galen malformation is a rare congenital cerebrovascular malformation. In affected patients, increased cerebral venous pressure constitutes an important etiologic factor for the development of brain parenchymal damage. The aim of this study was to investigate the potential of serial cerebral venous Doppler measurements to detect and monitor increased cerebral venous pressure. MATERIALS AND METHODS: This was a retrospective monocentric analysis of ultrasound examinations within the first 9 months of life in patients with vein of Galen malformation admitted at <28 days of life. Categorization of perfusion waveforms in the superficial cerebral sinus and veins into 6 patterns was based on antero- and retrograde flow components. We performed an analysis of flow profiles across time and correlation with disease severity, clinical interventions, and congestion damage on cerebral MR imaging. RESULTS: The study included 44 Doppler ultrasound examinations of the superior sagittal sinus and 36 examinations of the cortical veins from 7 patients. Doppler flow profiles before interventional therapy correlated with disease severity determined by the Bicêtre Neonatal Evaluation Score (Spearman ρ = -0.97, P = < .001). At this time, 4 of 7 patients (57.1%) showed a retrograde flow component in the superior sagittal sinus, whereas after embolization, none of the 6 treated patients presented with a retrograde flow component. Only patients with a high retrograde flow component (equal or more than one-third retrograde flow, n = 2) showed severe venous congestion damage on cerebral MR imaging. CONCLUSIONS: Flow profiles in the superficial cerebral sinus and veins appear to be a useful tool to noninvasively detect and monitor cerebral venous congestion in vein of Galen malformation.

Three-dimensional evaluation of condylar position after mandibular reconstruction with a fibula free flap-comparison of different surgical techniques.

Three-dimensional positional changes of the temporomandibular joint after mandible reconstruction using microvascular fibula flaps were investigated in 58 patients. The results of preoperative virtually planned surgery, intraoperative resection- and cutting-guided surgery, and non-guided surgery were compared. Pre- and postoperative computed tomography data of each patient were processed and superimposed digitally. The condyle deviations and rotations along the axes and planes of the skull, as well as Euclidean distances, were determined. Reliability analyses, descriptive statistics, and non-parametric tests were performed with the alpha level set at P = 0.05. Reliability proved to be excellent for all variables. The median Euclidean distance was 2.07 mm for the left condyle and 2.11 mm for the right condyle. Deviations of ≥ 10 mm occurred in nine (16%) cases. The maximum deviation occurred in the horizontal plane and the least deviation in the sagittal plane. Median rotation was ≤ 1.4° around all axes. The condylar displacements did not differ significantly between the different surgical techniques investigated. The three-dimensional measurement method applied is highly reliable for evaluating the three-dimensional condylar position after mandibular reconstruction.

Review: Bioavailability of trace elements in farm animals: definition and practical considerations for improved assessment of efficacy and safety.

Currently, the authorisation procedure of trace elements as feed additives in the European Union according to Regulation (EC) No. 1831/2003 does not consider the bioavailability of trace element sources. This manuscript provides framework conditions for in vivo experiments that aim to estimate differences in the relative bioavailability between supplements of essential trace elements. Framework conditions encompass necessary technical information on the test substance, the experimental design and diet composition as well as the suitability of status parameters that allow for relative comparisons of regression variables. This manuscript evolves recommendations for researchers to conduct solid and reliable experiments on the matter as well as decision makers to interpret the value of studies submitted with authorisation applications regarding a certain trace element supplement.

[Studies on Factors Influencing Influenza Vaccination Rates in Patients with Chronic Obstructive Pulmonary Disease]. / Untersuchungen zu Einflussfaktoren auf die Influenza-Impfraten bei Patienten mit chronisch obstruktiver Lungenerkrankung.

BACKGROUND : With low influenza vaccination rates among the chronically ill, approaches to increase these rates among risk patients with chronic obstructive pulmonary disease (COPD) are to be uncovered. METHODS : 120 COPD patients from Magdeburg filled out a questionnaire and were analyzed regarding the influenza vaccination status 2015/2016 or 2016/2017. Vaccinated and unvaccinated were compared in socio-epidemiological factors, the health belief model (HBM), self-efficacy (GESIS-ASKU), anxiety/depression (HADS-D) and disease processing (FKV-LIS). RESULTS : 62.5 % (n = 75) were vaccinated, 31.7 % (n = 38) unvaccinated, 5.8 % (n = 7) made no statement. In over or equal to 60-year-olds 76 % were vaccinated, in under 60-year-olds 42 % were vaccinated. 60 % (n = 72) knew to belong to a risk group. Unvaccinated indicated greater concern about side effects of the vaccination (p = .004) and drew a worse benefit-expense balance (p = .001). Unvaccinated were more often uncertain about the vaccination protection and the severity of influenza (p ≤ .001). Vaccinated were highly motivated to think about vaccination themselves and more often had a positive vaccination history (p = .001). COPD patients showed a lower self-efficacy than the reference group of the German general population (p = .000), vaccinated and unvaccinated did not differ (p = .418). No difference between vaccinated and unvaccinated was found in the processing of the disease and in depression and anxiety, but unvaccinated tended to give higher anxiety values. CONCLUSION : Measures should particularly target COPD patients under 60 years of age with a negative vaccination history and sensitize them as risk patients. Widespread uncertainties about the severity of influenza and vaccination protection should be addressed. It should be communicated that influenza vaccination does not lead to exacerbation. The vaccination recommendation should increasingly be made by pulmonologists.

Function Space Optimization: A Symbolic Regression Method for Estimating Parameter Transfer Functions for Hydrological Models.

Estimating parameters for distributed hydrological models is a challenging and long studied task. Parameter transfer functions, which define model parameters as functions of geophysical properties of a catchment, might improve the calibration procedure, increase process realism, and can enable prediction in ungauged areas. We present the function space optimization (FSO), a symbolic regression method for estimating parameter transfer functions for distributed hydrological models. FSO is based on the idea of transferring the search for mathematical expressions into a continuous vector space that can be used for optimization. This is accomplished by using a text generating neural network with a variational autoencoder architecture that can learn to compress the information of mathematical functions. To evaluate the performance of FSO, we conducted a case study using a parsimonious hydrological model and synthetic discharge data. The case study consisted of two FSO applications: single-criteria FSO, where only discharge was used for optimization, and multicriteria FSO, where additional spatiotemporal observations of model states were used for transfer function estimation. The results show that FSO is able to estimate transfer functions correctly or approximate them sufficiently. We observed a reduced fit of the parameter density functions resulting from the inferred transfer functions for less sensitive model parameters. For those it was sufficient to estimate functions resulting in parameter distributions with approximately the same mean parameter values as the real transfer functions. The results of the multicriteria FSO showed that using multiple spatiotemporal observations for optimization increased the quality of estimation considerably.

Application of the World Café method to discuss the efficiency of African swine fever control strategies in European wild boar (Sus scrofa) populations.

In the current epidemic of African swine fever (ASF) in Europe, the maintenance and spread of the disease among wild boar populations remains the most important epidemiological challenge. Affected and at-risk countries have addressed this situation using a diversity of wild boar management methods with varying levels of success. The methods applied range from conventional animal disease intervention measures (zoning, stakeholder awareness campaigns, increased surveillance and biosecurity measures) to measures aimed at reducing wild boar population movements (fencing and baiting/feeding) or population numbers (intensive hunting). To assess the perceived efficiency and acceptance of such measures in the context of a focal introduction of ASF, the authors organised a participatory workshop inviting experts from the fields of wildlife management, wild boar ecology, sociology, epidemiology and animal disease management to discuss the advantages and disadvantages of various control approaches. The discussions between professionals from different countries took place using the World Café method. This paper documents the World Café method as a tool for increasing the level of participation in multi-stakeholder group discussions, and describes the outputs of the workshop pertaining to the control measures. In summary, the World Café method was perceived as an efficient tool for quickly grasping comprehensive perspectives from the professionals involved in managing ASF and wild boar populations, while promoting engagement in multi-disciplinary discussions. The exercise achieved a good overview of the perceived efficiency and applicability of the different control methods and generated useful recommendations for ASF control in wild boar populations in Europe.

Pathogen-specific antibody profiles in patients with severe systemic infections.

Infections are often caused by pathobionts, endogenous bacteria that belong to the microbiota. Trauma and surgical intervention can allow bacteria to overcome host defences, ultimately leading to sepsis if left untreated. One of the main defence strategies of the immune system is the production of highly specific antibodies. In the present proof-of-concept study, plasma antibodies against 9 major pathogens were measured in sepsis patients, as an example of severe systemic infections. The binding of plasma antibodies to bacterial extracellular proteins was quantified using a semi-automated immunoblot assay. Comparison of the pathogen-specific antibody levels before and after infection showed an increase in plasma IgG in 20 out of 37 tested patients. This host-directed approach extended the results of pathogen-oriented microbiological and PCR diagnostics: a specific antibody response to additional bacteria was frequently observed, indicating unrecognised poly-microbial invasion. This might explain some cases of failed, seemingly targeted antibiotic treatment.

Backscattering design for a focusing grating coupler with fully etched slots for transverse magnetic modes.

Grating couplers are a fundamental building block of integrated optics as they allow light to be coupled from free-space to on-chip components and vice versa. A challenging task in designing any grating coupler is represented by the need for reducing back reflections at the waveguide-grating interface, which introduce additional losses and undesirable interference fringes. Here, we present a design approach for focusing TM grating couplers that minimizes these unwanted reflections by introducing a modified slot that fulfills an anti-reflection condition. We show that this antireflection condition can be met only for the Bloch mode of the grating that concentrates in the dielectric. As a consequence the light is scattered from the grating coupler with a negative angle, referred to as "backscattering design". Our analytic model shows that the anti-reflection condition is transferrable to grating couplers on different waveguide platforms and that it applies for both TE and TM polarizations. Our experimentally realized focusing grating coupler for TM-modes on the silicon photonics platform has a coupling loss of (3.95 ± 0.15) dB at a wavelength of 1.55 µm. It has feature sizes above 200 nm and fully etched slots. The reflectivity between the grating coupler and the connected waveguide is suppressed to below 0.16%.

Reciprocity approach for calculating the Purcell effect for emission into an open optical system.

Based on the reciprocity theorem, we present a formalism to calculate the power emitted by a dipole source into a particular propagating mode leaving an open optical system. The open system is completely arbitrary and the approach can be used in analytical calculations but may also be combined with numerical electromagnetic solvers to describe the emission of light sources into complex systems. We exemplify the use of the formalism in numerical simulations by analyzing the emission of a dipole that is placed inside a cavity with connected single mode exit waveguide. Additionally, we show at the example of a practical ring resonator system how the approach can be applied to systems that offer multiple electromagnetic energy decay channels. As a consequence of its inherent simplicity and broad applicability, the approach may serve as a powerful and practical tool for engineering light-matter-interaction in a variety of active optical systems.

Emission enhancement in dielectric nanocomposites.

We consider emitting nanoparticles in dielectric nanocomposites with varying refractive index contrast and geometry. For that we develop a simple and universal method to calculate the emission enhancement in nanocomposites that employs solely the calculation of the effective refractive index and electric field distributions from three quasistatic calculations with orthogonal polarizations. The method is exemplified for dilute nanocomposites without electromagnetic interaction between emitting particles as well as for dense nanocomposites with strong particle interaction. We show that the radiative decay in dielectric nanocomposites is greatly affected by the shape and arrangement of its constituents and give guidelines for larger enhancement.

A Simulation Model to Determine Sensitivity and Timeliness of Surveillance Strategies.

Animal surveillance systems need regular evaluation. We developed an easily applicable simulation model of the German wild boar population to investigate two evaluation attributes: the sensitivity and timeliness (i.e. the ability to detect a disease outbreak rapidly) of a surveillance system. Classical swine fever (CSF) was used as an example for the model. CSF is an infectious disease that may lead to massive economic losses. It can affect wild boar as well as domestic pigs, and CSF outbreaks in domestic pigs have been linked to infections in wild boar. Awareness of the CSF status in wild boar is therefore vital. Our non-epidemic simulation model is based on real data and evaluates the currently implemented German surveillance system for CSF in wild boar. The results show that active surveillance for CSF fulfils the requirements of detecting an outbreak with 95% confidence within one year after the introduction of CSF into the wild boar population. Nevertheless, there is room for improved performance and efficiency by more homogeneous (active and passive) sampling of wild boar over the year. Passive surveillance alone is not sufficient to meet the requirements for detecting the infection. Although CSF was used as example to develop the model, it may also be applied to the evaluation of other surveillance systems for viral diseases in wild boar. It is also possible to compare sensitivity and timeliness across hypothetical alternative or risk-based surveillance strategies.

Controlling the Spontaneous Emission Rate of Quantum Wells in Rolled-Up Hyperbolic Metamaterials.

We experimentally demonstrate the enhancement of the spontaneous emission rate of GaAs quantum wells embedded in rolled-up metamaterials. We fabricate microtubes whose walls consist of alternating Ag and (In)(Al)GaAs layers with incorporated active GaAs quantum-well structures. By variation of the layer thickness ratio of the Ag and (In)(Al)GaAs layers we control the effective permittivity tensor of the metamaterial according to an effective medium approach. Thereby, we can design samples with elliptic or hyperbolic dispersion. Time-resolved low temperature photoluminescence spectroscopy supported by finite-difference time-domain simulations reveal a decrease of the quantum well's spontaneous emission lifetime in our metamaterials as a signature of the crossover from elliptic to hyperbolic dispersion.

[Eye lens radiation exposure during ureteroscopy with and without a face protection shield: Investigations on a phantom model]. / Strahlenbelastung der Augenlinse bei ureterorenoskopischen Eingriffen ohne und mit Strahlenschutzvisier : Untersuchungen an einem Phantommodell.

BACKGROUND AND OBJECTIVES: Eye lens radiation exposure during radiologically-guided endoscopic procedures may result in radiation-induced cataracts; therefore, we investigated the ocular radiation exposure during ureteroscopy on a phantom model. MATERIALS AND METHODS: Using an Alderson phantom model and eye lens dosimeters, we measured the ocular radiation exposure depending on the number of X-ray images and on the duration of fluoroscopic imaging. The measurements were done with and without using a face protection shield. RESULTS: We could demonstrate that a significant ocular radiation exposure can occur, depending on the number of X-ray images and on the duration time of fluoroscopy. Eye lens doses up to 0.025 mSv were recorded even using modern digital X-ray systems. Using face protection shields this ocular radiation exposure can be reduced to a minimum. CONCLUSION: The International Commission on Radiological Protection (ICRP) recommendations of a mean eye lens dosage of 20 mSv/year may be exceeded during repeated ureteroscopy by a high volume surgeon. Using a face protection shield, the eye lens dose during ureteroscopy could be reduced to a minimum in a phantom model. Further investigations will show whether these results can be transferred to real life ureteroscopic procedures.

Isolation and functional characterization of the novel Clostridium botulinum neurotoxin A8 subtype.

Botulism is a severe neurological disease caused by the complex family of botulinum neurotoxins (BoNT). Based on the different serotypes known today, a classification of serotype variants termed subtypes has been proposed according to sequence diversity and immunological properties. However, the relevance of BoNT subtypes is currently not well understood. Here we describe the isolation of a novel Clostridium botulinum strain from a food-borne botulism outbreak near Chemnitz, Germany. Comparison of its botulinum neurotoxin gene sequence with published sequences identified it to be a novel subtype within the BoNT/A serotype designated BoNT/A8. The neurotoxin gene is located within an ha-orfX+ cluster and showed highest homology to BoNT/A1, A2, A5, and A6. Unexpectedly, we found an arginine insertion located in the HC domain of the heavy chain, which is unique compared to all other BoNT/A subtypes known so far. Functional characterization revealed that the binding characteristics to its main neuronal protein receptor SV2C seemed unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to BoNT/A1. Moreover, we found significantly lower enzymatic activity of the natural, full-length neurotoxin and the recombinant light chain of BoNT/A8 compared to BoNT/A1 in different endopeptidase assays. Both reduced ganglioside binding and enzymatic activity may contribute to the considerably lower biological activity of BoNT/A8 as measured in a mouse phrenic nerve hemidiaphragm assay. Despite its reduced activity the novel BoNT/A8 subtype caused severe botulism in a 63-year-old male. To our knowledge, this is the first description and a comprehensive characterization of a novel BoNT/A subtype which combines genetic information on the neurotoxin gene cluster with an in-depth functional analysis using different technical approaches. Our results show that subtyping of BoNT is highly relevant and that understanding of the detailed toxin function might pave the way for the development of novel therapeutics and tailor-made antitoxins.

Detection of 11 beta-hydroxysteroid dehydrogenase type 1, the glucocorticoid and mineralocorticoid receptor in various adipose tissue depots of dairy cows supplemented with conjugated linoleic acids.

Early lactating cows mobilize adipose tissue (AT) to provide energy for milk yield and maintenance and are susceptible to metabolic disorders and impaired immune response. Conjugated linoleic acids (CLA), mainly the trans-10, cis-12 isomer, reduce milk fat synthesis and may attenuate negative energy balance. Circulating glucocorticoids (GC) are increased during parturition in dairy cows and mediate differentiating and anti-inflammatory effects via glucocorticoid (GR) and mineralocorticoid receptors (MR) in the presence of the enzyme 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1). Activated GC are the main ligands for both receptors in AT; therefore, we hypothesized that tissue-specific GC metabolism is effected by varying amounts of GR, MR and 11ßHSD1 and/or their localization within AT depots. Furthermore, the lipolytic and antilipogenic effects of CLA might influence the GC/GR/MR system in AT. Therefore, we aimed to localize GR and MR as well as the expression pattern and activity of 11ßHSD1 in different AT depots during early lactation in dairy cows and to identify potential effects of CLA. Primiparous German Holstein cows were divided into a control (CON) and a CLA group. From day 1 post-partum (p.p.) until sample collection, the CLA group was fed with 100 g/d CLA (contains 10 g each of the cis-9, trans-11 and the trans-10, cis-12-CLA isomers). CON cows (n = 5 each) were slaughtered on day 1, 42 and 105 p.p., while CLA cows (n = 5 each) were slaughtered on day 42 and 105 p.p. Subcutaneous fat from tailhead, withers and sternum, and visceral fat from omental, mesenteric and retroperitoneal depots were sampled. The localization of GR and 11ßHSD1 in mature adipocytes - being already differentiated - indicates that GC promote other effects via GR than differentiation. Moreover, MR were observed in the stromal vascular cell fraction and positively related to the pre-adipocyte marker Pref-1. However, only marginal CLA effects were observed in this study.

Daily iTBS worsens hand motor training--a combined TMS, fMRI and mirror training study.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is used to increase regional excitability to improve motor function in combination with training after neurological diseases or events such as stroke. We investigated whether a daily application of intermittent theta burst stimulation (iTBS; a short-duration rTMS that increases regional excitability) improves the training effect compared with sham stimulation in association with a four-day hand training program using a mirror (mirror training, MT). The right dorsal premotor cortex (dPMC right) was chosen as the target region for iTBS because this region has recently been emphasized as a node within a network related to MT. METHODS: Healthy subjects were randomized into the iTBS group or sham group (control group CG). In the iTBS group, iTBS was applied daily over dPMC right, which was functionally determined in an initial fMRI session prior to starting MT. MT involved 20 min of hand training daily in a mirror over four days. The hand tests, the intracortical excitability and fMRI were evaluated prior to and at the end of MT. RESULTS: The results of the hand training tests of the iTBS group were surprisingly significantly poorer compared with those from the CG group. Both groups showed a different course of excitability in both M1 and a different course of fMRI activation within the supplementary motor area and M1 left. CONCLUSION: We suggest the inter-regional functional balance was affected by daily iTBS over dPMC right. Maybe an inter-regional connectivity within a network is differentially balanced. An excitability increase within an inhibitory-balanced network would therefore disturb the underlying network.

Family strain and its relation to psychosocial dysfunction in children and adolescents after liver transplantation.

Parental functioning is essential to children's development. Therefore, this cross-sectional single-center study examined the prevalence of family strain in 181 parents and its associations to psychosocial functioning in their children after LT. Median age at LT was one yr. Mean time elapsed since LT was 5.8 yr. The IFS, and the SDQ were applied to parents. Family strain in the present sample was comparable to that in the German normative group of families with a chronically ill or disabled child, but families of LT recipients showed a significantly higher financial impact, impact on coping, and impact on siblings (p < 0.001). Younger age of patients at survey, a more severe clinical course, child's restrictions, and financial losses following LT were determined as significant predictors of family strain (R(2)  = 0.42). Parents reported less family strain after living-related compared with deceased donation. Family strain was significantly correlated to psychosocial dysfunction in children post-LT. Present findings demonstrate a risk of maladjustment to the post-LT condition in families. They emphasize the importance of psychological assessment of parents and patients during transplant and follow-up to ensure the best achievable long-term outcome of patients.

[Overwhelming postsplenectomy infection syndrome]. / Fulminante Pneumokokkensepsis nach Splenektomie.

The overwhelming postsplenectomy infection syndrome (OPSI) is a fulminant sepsis that is mainly caused by Streptococcus pneumoniae and is characterized by a particular high mortality. Patients whose spleen was removed due to a hematological disease are at special risk. Even after the recommended immunization against Streptococcus pneumoniae 20-30 % of these patients do not develop an adequate level of antibody response. Therefore, this particular group of patients must be trained how to behave in case of fever and need to obtain immediate specific sepsis therapy with antibiotic prophylaxis.