Bayesian inference of spatially resolved Zeff profiles from line integrated bremsstrahlung spectra.

In nuclear fusion research, the effective ion charge Zeff, which characterizes the overall content of impurities, can be experimentally derived from the plasma electron-ion bremsstrahlung, given the electron density ne and temperature Te. At Wendelstein 7-X, a multichannel near-infrared spectrometer is installed to collect the plasma bremsstrahlung along 27 lines of sight covering more than half the plasma cross section, which provides information on Zeff over the entire plasma radius. To infer spatially resolved Zeff profiles, a Bayesian model is developed in the Minerva framework. Zeff, ne, and Te profiles are modeled as Gaussian processes, whose smoothness is determined by hyperparameters. These profiles are transformed to fields in Cartesian coordinates, given the poloidal magnetic flux surfaces calculated by the variational moments equilibrium code. Given all these physical quantities, the model predicts line-of-sight integrals of near-infrared bremsstrahlung spectra. The model includes the predictive (forward) models of the interferometer, Thomson scattering system, and visible and near-infrared spectrometers. Given the observations of all these diagnostics, the posterior probability distribution of Zeff profiles is calculated and shown as an inference solution. The smoothness (gradient) of the profiles is optimally chosen by Bayesian Occam's razor. Furthermore, wall reflections can significantly pollute the measurements of the plasma bremsstrahlung, which leads to over-estimation of Zeff values in the edge region. In the first results presented in this work, this problem does not appear, and the posterior samples of Zeff profiles are overall plausible and consistent with Zeff values inferred, given the data from the single-channel visible spectrometer.

Rift Valley fever virus detection in susceptible hosts with special emphasis in insects.

Rift Valley fever phlebovirus (RVFV, Phenuiviridae) is an emerging arbovirus that can cause potentially fatal disease in many host species including ruminants and humans. Thus, tools to detect this pathogen within tissue samples from routine diagnostic investigations or for research purposes are of major interest. This study compares the immunohistological usefulness of several mono- and polyclonal antibodies against RVFV epitopes in tissue samples derived from natural hosts of epidemiologic importance (sheep), potentially virus transmitting insect species (Culex quinquefasciatus, Aedes aegypti) as well as scientific infection models (mouse, Drosophila melanogaster, C6/36 cell pellet). While the nucleoprotein was the epitope most prominently detected in mammal and mosquito tissue samples, fruit fly tissues showed expression of glycoproteins only. Antibodies against non-structural proteins exhibited single cell reactions in salivary glands of mosquitoes and the C6/36 cell pellet. However, as single antibodies exhibited a cross reactivity of varying degree in non-infected specimens, a careful interpretation of positive reactions and consideration of adequate controls remains of critical importance. The results suggest that primary antibodies directed against viral nucleoproteins and glycoproteins can facilitate RVFV detection in mammals and insects, respectively, and therefore will allow RVFV detection for diagnostic and research purposes.

[Impact of prematurity on the optic nerve]. / Impact de la prématurité sur l'aspect morphologique et tomographique du nerf optique.

INTRODUCTION: Thanks to the progress made in the past few years in pediatric intensive care as well as the increased survival of preterm infants, the consequences of premature birth are increasingly well documented. With regard to ophthalmologic complications, retinopathy of prematurity is well described, but the optic nerve may also be affected. The goal of this study is to compare the optic nerves of preterm infants as a function of their gestational period with a control group of the same age. MATERIALS AND METHODS: We conducted a case-control study pairing a full-term infant with each preterm infant. Inclusion criteria were: any child from 5- to 10-years-old, separated into three sub-groups according to their degree of prematurity. Variables were: cup/disc ratio, ocular biometry, intraocular pressure and RNFL thickness. RESULTS: Thirty-seven preterm infants and 37 controls were included in the study. The mean age at the time of inclusion was 7.05 years for the preterm group and 7.19 years for the control group. No significant difference was observed in axial length or spherical equivalent (P=0.31 and P=0.98, respectively). No significant difference was observed in pachymetry or intraocular pressure (P=0.28 and P=0.22, respectively). We observed a significant increase of 0.1 in the cup/disc ratio of the preterm group compared to the control group (P<0.05). The preterm group cup/disc ratio was 0.36 versus 0.27 for the control group. No significant difference was observed in the 7 quadrants of RNFL between the two groups. However, when comparing infants born before 28 weeks gestation with the control group, we observed a mean decrease of 14.5 microns in the superior temporal sector (P=0.04), a 9 micron decrease in the global thickness G (P=0.03) and a 12.7 micron decrease in the nasal sector (P=0.01). CONCLUSIONS: In the case of the studied children (aged 5 to 10), the reduced RNFL fiber thickness is a phenomenon dependent essentially on the stage of prematurity. It would be useful to follow these preterm populations over the long term and to compare them to a matched control group to be able to obtain functional results.

Factors contributing to delayed decannulation of temporary tracheostomies following free tissue reconstructive surgery for head and neck cancer.

Temporary tracheostomies (TT) are performed to secure the airway perioperatively and postoperatively in head and neck cancer patients undergoing tumour resection and free tissue reconstructive surgery. Patients report that having a TT is unpleasant and they appreciate its removal at the earliest opportunity. Early removal not only improves patient satisfaction but should allow for a more rapid recovery. The aim of this prospective study was to assess factors that contribute to delays in decannulation following TT and hence to provide an insight into the factors that will support earlier decannulation when it is safe to do so. Consecutive patients who had TT over a six-month period were included. Delayed decannulation was defined as that after day seven postoperatively. There were 42 patients with a median (IQR) age of 70 (60-74) years, 26 of whom were men. The tracheostomy was surgical in 29 and percutaneous in 13. The median (IQR) time to decannulation was 4 (3-5) days (range 1-11 days). Seven patients had delayed removal (7-11 days), the reasons being hospital-acquired pneumonia (HAP) (n=4), prolonged stay in the high dependency unit (HDU) following postoperative myocardial infarction and cardiac arrest (n=1), failure to tolerate TT occlusion (n=1), and not stated (n=1). There were early postoperative complications in 14 patients but despite this seven decannulations were still performed within two and six days. Additional multiprofessional assessment over weekends is likely to facilitate earlier decannulation. As some TTs are removed after a few days there is a need for better selection to avoid their use in certain patients.

First Observation of a Stable Highly Dissipative Divertor Plasma Regime on the Wendelstein 7-X Stellarator.

For the first time, the optimized stellarator Wendelstein 7-X has operated with an island divertor. An operation regime in hydrogen was found in which the total plasma radiation approached the absorbed heating power without noticeable loss of stored energy. The divertor thermography recorded simultaneously a strong reduction of the heat load on all divertor targets, indicating almost complete power detachment. This operation regime was stably sustained over several energy confinement times until the preprogrammed end of the discharge. The plasma radiation is mainly due to oxygen and is located at the plasma edge. This plasma scenario is reproducible and robust at various heating powers, plasma densities, and gas fueling locations. These experimental results show that the island divertor concept actually works and displays good power dissipation potential, producing a promising exhaust concept for the stellarator reactor line.

Accurate IVIM model-based liver lesion characterisation can be achieved with only three b-value DWI.

OBJECTIVE: The objective of this study was to evaluate a simplified intravoxel incoherent motion (IVIM) approach of diffusion-weighted imaging (DWI) with four b-values for liver lesion characterisation at 1.5 T. METHODS: DWI data from a respiratory-gated MRI sequence with b = 0, 50, 250, 800 s/mm2 were retrospectively analysed in 173 lesions and 40 healthy livers. The apparent diffusion coefficient ADC = ADC(0,800) and IVIM-based parameters D1' = ADC(50,800), D2' =ADC(250,800), f1', f2', D*', ADClow = ADC(0,50), and ADCdiff=ADClow-D2' were calculated voxel-wise without fitting procedures. Differences between lesion groups were investigated. RESULTS: Focal nodular hyperplasias were best discriminated from all other lesions by f1' with an area under the curve (AUC) of 0.989. Haemangiomas were best discriminated by D1' (AUC of 0.994). For discrimination between malignant and benign lesions, ADC(0,800) and D1' were best suited (AUC of 0.915 and 0.858, respectively). Discriminatory power was further increased by using a combination of D1' and f1'. CONCLUSION: IVIM parameters D and f approximated from three b-values provided more discriminatory power between liver lesions than ADC determined from two b-values. The use of b = 0, 50, 800 s/mm2 was superior to that of b = 0, 250, 800 s/mm2. The acquisition of four instead of three b-values has no further benefit for lesion characterisation. KEY POINTS: • Diffusion and perfusion characteristics are assessable with only three b-values. • Association of b = 0, 50, 800 s/mm2is superior to b = 0, 250, 800 s/mm2. • A fourth acquired b-value has no benefit for differential diagnosis. • For liver lesion characterisation, simplified IVIM analysis is superior to ADC determination. • Simplified IVIM approach guarantees numerically stable, voxel-wise results and short acquisition times.

First results of the multi-purpose real-time processing video camera system on the Wendelstein 7-X stellarator and implications for future devices.

A special video camera has been developed for the 10-camera overview video system of the Wendelstein 7-X (W7-X) stellarator considering multiple application needs and limitations resulting from this complex long-pulse superconducting stellarator experiment. The event detection intelligent camera (EDICAM) uses a special 1.3 Mpixel CMOS sensor with non-destructive read capability which enables fast monitoring of smaller Regions of Interest (ROIs) even during long exposures. The camera can perform simple data evaluation algorithms (minimum/maximum, mean comparison to levels) on the ROI data which can dynamically change the readout process and generate output signals. Multiple EDICAM cameras were operated in the first campaign of W7-X and capabilities were explored in the real environment. Data prove that the camera can be used for taking long exposure (10-100 ms) overview images of the plasma while sub-ms monitoring and even multi-camera correlated edge plasma turbulence measurements of smaller areas can be done in parallel. These latter revealed that filamentary turbulence structures extend between neighboring modules of the stellarator. Considerations emerging for future upgrades of this system and similar setups on future long-pulse fusion experiments such as ITER are discussed.

[Differential diagnosis of dissociative seizures]. / Differenzialdiagnose dissoziativer Anfälle.

Patient history taking and semiology provide seminal clues to the diagnosis of dissociative seizures. Openness and alertness of the treating physician are essential. Video-electroencephalogram(EEG)-based analyses of the events are crucial to establish the correct diagnosis, particularly in complex cases. The patient-doctor relationship is of particular importance in order to successfully motivate the patient for psychotherapeutic treatment. Coexisting psychiatric morbidity as well as other functional somatic symptoms must be actively explored. Current changes in the established diagnostic manuals, including ICD-11, reflect the ongoing vivid interest and controversial discussions in the field of dissociative disorders.

Synthetic plasma edge diagnostics for EMC3-EIRENE, highlighted for Wendelstein 7-X.

Interpretation of spectroscopic measurements in the edge region of high-temperature plasmas can be a challenge since line of sight integration effects make direct interpretation in terms of quantitative, local emission strengths often impossible. The EMC3-EIRENE code-a 3D fluid edge plasma and kinetic neutral gas transport code-is a suitable tool for full 3D reconstruction of such signals. A versatile synthetic diagnostic module has been developed recently which allows the realistic 3D setup of various plasma edge diagnostics to be captured. We highlight these capabilities with two examples for Wendelstein 7-X (W7-X): a visible camera for the analysis of recycling, and a coherent-imaging system for velocity measurements.

Feasibility of line-ratio spectroscopy on helium and neon as edge diagnostic tool for Wendelstein 7-X.

A beam emission spectroscopy system on thermal helium (He) and neon (Ne) has been set up at Wendelstein 7-X to measure edge electron temperature and density profiles utilizing the line-ratio technique or its extension by the analysis of absolutely calibrated line emissions. The setup for a first systematic test of these techniques of quantitative atomic spectroscopy in the limiter startup phase (OP1.1) is reported together with first measured profiles. This setup and the first results are an important test for developing the technique for the upcoming high density, low temperature island divertor regime.

Spectroscopic imaging of limiter heat and particle fluxes and the resulting impurity sources during Wendelstein 7-X startup plasmas.

A combined IR and visible camera system [G. A. Wurden et al., "A high resolution IR/visible imaging system for the W7-X limiter," Rev. Sci. Instrum. (these proceedings)] and a filterscope system [R. J. Colchin et al., Rev. Sci. Instrum. 74, 2068 (2003)] were implemented together to obtain spectroscopic data of limiter and first wall recycling and impurity sources during Wendelstein 7-X startup plasmas. Both systems together provided excellent temporal and spatial spectroscopic resolution of limiter 3. Narrowband interference filters in front of the camera yielded C-III and Hα photon flux, and the filterscope system provided Hα, Hß, He-I, He-II, C-II, and visible bremsstrahlung data. The filterscopes made additional measurements of several points on the W7-X vacuum vessel to yield wall recycling fluxes. The resulting photon flux from both the visible camera and filterscopes can then be compared to an EMC3-EIRENE synthetic diagnostic [H. Frerichs et al., "Synthetic plasma edge diagnostics for EMC3-EIRENE, highlighted for Wendelstein 7-X," Rev. Sci. Instrum. (these proceedings)] to infer both a limiter particle flux and wall particle flux, both of which will ultimately be used to infer the complete particle balance and particle confinement time τP.

Overview of diagnostic performance and results for the first operation phase in Wendelstein 7-X (invited).

Wendelstein 7-X, a superconducting optimized stellarator built in Greifswald/Germany, started its first plasmas with the last closed flux surface (LCFS) defined by 5 uncooled graphite limiters in December 2015. At the end of the 10 weeks long experimental campaign (OP1.1) more than 20 independent diagnostic systems were in operation, allowing detailed studies of many interesting plasma phenomena. For example, fast neutral gas manometers supported by video cameras (including one fast-frame camera with frame rates of tens of kHz) as well as visible cameras with different interference filters, with field of views covering all ten half-modules of the stellarator, discovered a MARFE-like radiation zone on the inboard side of machine module 4. This structure is presumably triggered by an inadvertent plasma-wall interaction in module 4 resulting in a high impurity influx that terminates some discharges by radiation cooling. The main plasma parameters achieved in OP1.1 exceeded predicted values in discharges of a length reaching 6 s. Although OP1.1 is characterized by short pulses, many of the diagnostics are already designed for quasi-steady state operation of 30 min discharges heated at 10 MW of ECRH. An overview of diagnostic performance for OP1.1 is given, including some highlights from the physics campaigns.

Tumor suppression in mice lacking GABARAP, an Atg8/LC3 family member implicated in autophagy, is associated with alterations in cytokine secretion and cell death.

GABARAP belongs to an evolutionary highly conserved gene family that has a fundamental role in autophagy. There is ample evidence for a crosstalk between autophagy and apoptosis as well as the immune response. However, the molecular details for these interactions are not fully characterized. Here, we report that the ablation of murine GABARAP, a member of the Atg8/LC3 family that is central to autophagosome formation, suppresses the incidence of tumor formation mediated by the carcinogen DMBA and results in an enhancement of the immune response through increased secretion of IL-1ß, IL-6, IL-2 and IFN-γ from stimulated macrophages and lymphocytes. In contrast, TGF-ß1 was significantly reduced in the serum of these knockout mice. Further, DMBA treatment of these GABARAP knockout mice reduced the cellularity of the spleen and the growth of mammary glands through the induction of apoptosis. Gene expression profiling of mammary glands revealed significantly elevated levels of Xaf1, an apoptotic inducer and tumor-suppressor gene, in knockout mice. Furthermore, DMBA treatment triggered the upregulation of pro-apoptotic (Bid, Apaf1, Bax), cell death (Tnfrsf10b, Ripk1) and cell cycle inhibitor (Cdkn1a, Cdkn2c) genes in the mammary glands. Finally, tumor growth of B16 melanoma cells after subcutaneous inoculation was inhibited in GABARAP-deficient mice. Together, these data provide strong evidence for the involvement of GABARAP in tumorigenesis in vivo by delaying cell death and its associated immune-related response.

Detecting divertor damage during steady state operation of Wendelstein 7-X from thermographic measurements.

Wendelstein 7-X (W7-X) aims to demonstrate the reactor capability of the stellarator concept, by creating plasmas with pulse lengths of up to 30 min at a heating power of up to 10 MW. The divertor plasma facing components will see convective steady state heat flux densities of up to 10 MW/m(2). These high heat flux target elements are actively cooled and are covered with carbon fibre reinforced carbon (CFC) as plasma facing material. The CFC is bonded to the CuCrZr cooling structure. Over the life time of the experiment this interface may weaken and cracks can occur, greatly reducing the heat conduction between the CFC tile and the cooling structure. Therefore, there is not only the need to monitor the divertor to prevent damage by overheating but also the need to detect these fatigue failures of the interface. A method is presented for an early detection of fatigue failures of the interface layer, solely by using the information delivered by the IR-cameras monitoring the divertor. This was developed and validated through experiments made with high heat flux target elements prior to installation in W7-X.

Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: toward recommendation for molecular testing and management.

SHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had four or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included intrauterine growth restriction (IUGR) <10th percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended.

[Do we still need clinical studies in rheumatology?]. / Brauchen wir noch klinische Studien in der Rheumatologie?

Despite a large number of approved therapies demonstrating efficacy in the treatment of rheumatic diseases, only 60-85 % of patients with the indications for rheumatoid arthritis are adequately treated in Germany. Additionally, approved therapies for other immune-mediated diseases are often entirely lacking, indicating the great medical need for the development of new innovative therapies in this specialized field. The development of new drugs is expensive due to the high costs of conducting clinical trials in all phases of development up to obtaining approval; therefore, pharmaceutical companies are looking for ways to save costs in the particular developmental stages. Although the classical regions for drug development (i.e. western Europe, the USA and Japan) offer both a high level of data quality and a good infrastructure to conduct clinical trials due to high standards of education and quality, clinical trials are expensive in these regions. Beside high costs, the comparatively low recruitment rates in these regions are one of the main reasons for the shifting of drug developmental stages from classical regions to eastern European, Latin American and Asian countries, which provide services for drug development and high recruitment rates for comparatively less money. However, there are many strong arguments for the participation of regions in western Europe, especially German sites in clinical trials. In this article these arguments are discussed and possible solutions and strategies for conducting and compensation of study centers in Germany for clinical trials in the field of rheumatology are provided.

Optimisation of a sol-gel synthesis route for the preparation of MgF2 particles for a large scale coating process.

A synthesis route for the preparation of optically transparent magnesium fluoride sols using magnesium acetate tetrahydrate as precursor is described. The obtained magnesium fluoride sols are stable for several months and can be applied for antireflective coatings on glass substrates. Reaction parameters in the course of sol synthesis are described in detail. Thus, properties of the precursor materials play a crucial role in the formation of the desired magnesium fluoride nanoparticles, this is drying the precursor has to be performed under defined mild conditions, re-solvation of the dried precursor has to be avoided and addition of water to the final sol-system has to be controlled strictly. Important properties of the magnesium fluoride sols like viscosity, particle size distribution, and structural information are presented as well.

Iatrogenic lesions of peripheral nerves.

Iatrogenic nerve lesions (INLs) are an integral part of peripheral neurology and require dedicated neurologists to manage them. INLs of peripheral nerves are most frequently caused by surgery, immobilization, injections, radiation, or drugs. Early recognition and diagnosis is important not to delay appropriate therapeutic measures and to improve the outcome. Treatment can be causative or symptomatic, conservative, or surgical. Rehabilitative measures play a key role in the conservative treatment, but the point at which an INL requires surgical intervention should not be missed or delayed. This is why INLs require close multiprofessional monitoring and continuous re-evaluation of the therapeutic effect. With increasing number of surgical interventions and increasing number of drugs applied, it is quite likely that the prevalence of INLs will further increase. To provide an optimal management, more studies about the frequency of the various INLs and studies evaluating therapies need to be conducted. Management of INLs can be particularly improved if those confronted with INLs get state-of-the-art education and advanced training about INLs. Management and outcome of INLs can be further improved if the multiprofessional interplay is optimized and adapted to the needs of the patient, the healthcare system, and those responsible for sustaining medical infrastructure.

Status of the diagnostics development for the first operation phase of the stellarator Wendelstein 7-X.

An overview of the diagnostics which are essential for the first operational phase of Wendelstein 7-X and the set of diagnostics expected to be ready for operation at this time are presented. The ongoing investigations of how to cope with high levels of stray Electron Cyclotron Resonance Heating (ECRH) radiation in the ultraviolet (UV)/visible/infrared (IR) optical diagnostics are described.