Results from a synthetic model of the ITER XRCS-Core diagnostic based on high-fidelity x-ray ray tracing.

A high-fidelity synthetic diagnostic has been developed for the ITER core x-ray crystal spectrometer diagnostic based on x-ray ray tracing. This synthetic diagnostic has been used to model expected performance of the diagnostic, to aid in diagnostic design, and to develop engineering tolerances. The synthetic model is based on x-ray ray tracing using the recently developed xicsrt ray tracing code and includes a fully three-dimensional representation of the diagnostic based on the computer aided design. The modeled components are: plasma geometry and emission profiles, highly oriented pyrolytic graphite pre-reflectors, spherically bent crystals, and pixelated x-ray detectors. Plasma emission profiles have been calculated for Xe44+, Xe47+, and Xe51+, based on an ITER operational scenario available through the Integrated Modelling & Analysis Suite database, and modeled within the ray tracing code as a volumetric x-ray source; the shape of the plasma source is determined by equilibrium geometry and an appropriate wavelength distribution to match the expected ion temperature profile. All individual components of the x-ray optical system have been modeled with high-fidelity producing a synthetic detector image that is expected to closely match what will be seen in the final as-built system. Particular care is taken to maintain preservation of photon statistics throughout the ray tracing allowing for quantitative estimates of diagnostic performance.

On the origin of low-valent uranium oxidation state.

The significant interest in actinide bonding has recently focused on novel compounds with exotic oxidation states. However, the difficulty in obtaining relevant high-quality experimental data, particularly for low-valent actinide compounds, prevents a deeper understanding of 5f systems. Here we show X-ray absorption near-edge structure (XANES) measurements in the high-energy resolution fluorescence detection (HERFD) mode at the uranium M4 edge for the UIII and UIV halides, namely UX3 and UX4 (X = F, Cl, Br, I). The spectral shapes of these two series exhibit clear differences, which we explain using electronic structure calculations of the 3d-4f resonant inelastic X-ray scattering (RIXS) process. To understand the changes observed, we implemented crystal field models with ab initio derived parameters and investigated the effect of reducing different contributions to the electron-electron interactions involved in the RIXS process. Our analysis shows that the electron-electron interactions weaken as the ligand changes from I to F, indicative of a decrease in ionicity both along and between the UX3 and UX4 halide series.

Filamentation of a relativistic proton bunch in plasma.

We show in experiments that a long, underdense, relativistic proton bunch propagating in plasma undergoes the oblique instability, which we observe as filamentation. We determine a threshold value for the ratio between the bunch transverse size and plasma skin depth for the instability to occur. At the threshold, the outcome of the experiment alternates between filamentation and self-modulation instability (evidenced by longitudinal modulation into microbunches). Time-resolved images of the bunch density distribution reveal that filamentation grows to an observable level late along the bunch, confirming the spatiotemporal nature of the instability. We provide a rough estimate of the amplitude of the magnetic field generated in the plasma by the instability and show that the associated magnetic energy increases with plasma density.

Hosing of a Long Relativistic Particle Bunch in Plasma.

Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma-based accelerators and represent the first characterization of hosing.

Smoking is associated with increased eryptosis, suicidal erythrocyte death, in a large population-based cohort.

Smoking has multiple detrimental effects on health, and is a major preventable cause of premature death and chronic disease. Despite the well-described effect of inhaled substances from tobacco smoke on cell toxicity, the association between smoking and suicidal erythrocyte death, termed eryptosis, is virtually unknown. Therefore, the blood samples of 2023 participants of the German National Cohort Study (NAKO) were analyzed using flow cytometry analysis to determine eryptosis from fluorescent annexin V-FITC-binding to phosphatidylserine-exposing erythrocytes. Blood analyses were complemented by the measurement of hematologic parameters including red blood cell count, hematocrit, hemoglobin, mean corpuscular cell volume (MCV) and mean corpuscular hemoglobin (MCH). Eryptosis was higher in smokers than in non- and ex-smokers, and positively associated with the number of cigarettes smoked daily (r = 0.08, 95% CI [0.03, 0.12]). Interestingly, despite increased eryptosis, smokers had higher red blood cell indices than non-smokers. To conclude, smokers were characterized by higher eryptosis than non-smokers, without showing any obvious detrimental effect on classic hematological parameters.

Characterization and prognostic impact of ACTBL2-positive tumor-infiltrating leukocytes in epithelial ovarian cancer.

Actin beta-like 2 (ACTBL2) was recently identified as a new mediator of migration in ovarian cancer cells. Yet, its impact on tumor-infiltrating and thus migrating leukocytes (TILs) remains to date unknown. This study characterizes the subset of ACTBL2-expressing TILs in epithelial ovarian cancer (EOC) and elucidates their prognostic influence on the overall survival of EOC patients with special regard to different histological subtypes. Comprehensive immunohistochemical analyses of Tissue-Microarrays of 156 ovarian cancer patients revealed, that a tumor infiltration by ACTBL2-positive leukocytes was significantly associated with an improved overall survival (OS) (61.2 vs. 34.4 months; p = 0.006) and was identified as an independent prognostic factor (HR = 0.556; p = 0.038). This significant survival benefit was particularly evident in patients with low-grade serous carcinoma (OS: median not reached vs. 15.6 months, p < 0.001; HR = 0.058, p = 0.018). In the present cohort, ACTBL2-positive TILs were mainly composed of CD44-positive cytotoxic T-cells (CD8+) and macrophages (CD68+), as depicted by double-immunofluorescence and various immunohistochemical serial staining. Our results provide significant evidence of the prognostic impact and cellular composition of ACTBL2-expressing TILs in EOC. Complementary studies are required to analyze the underlying molecular mechanisms of ACTBL2 as a marker for activated migrating leukocytes and to further characterize its immunological impact on ovarian carcinogenesis.

Middle-ear effusion in children with cleft palate: congenital or acquired?

OBJECTIVE: Cleft palates are one of the most common congenital malformations. Because of the loss of Eustachian tube function, middle-ear ventilation is reduced. The aim of this study was to determine if middle-ear effusions were present at birth or at the three-month audiological evaluation. METHOD: A total of 53 children with a cleft palate were included. Data review included the results of newborn hearing screening, microscopic findings, a tympanometry, a free field audiometry and intra-operative findings. RESULTS: A total of 58.4 per cent of patients had a median, 26.4 per cent had a bilateral, 11.3 per cent had a unilateral and 3.8 per cent had a limited soft palate cleft. Newborn hearing screening showed a pass in 83.1 per cent of newborns bilaterally. The first ear microscopy showed a bilateral middle-ear effusion in 90.6 per cent of cases. During cleft surgery, bilateral paracentesis was performed in all cases, and in 90.6 per cent middle-ear effusion was sucked out. CONCLUSION: The majority of children with a cleft palate do not present with middle-ear effusion at birth. It develops within several days or weeks of life.

Transition between Instability and Seeded Self-Modulation of a Relativistic Particle Bunch in Plasma.

We use a relativistic ionization front to provide various initial transverse wakefield amplitudes for the self-modulation of a long proton bunch in plasma. We show experimentally that, with sufficient initial amplitude [≥(4.1±0.4) MV/m], the phase of the modulation along the bunch is reproducible from event to event, with 3%-7% (of 2π) rms variations all along the bunch. The phase is not reproducible for lower initial amplitudes. We observe the transition between these two regimes. Phase reproducibility is essential for deterministic external injection of particles to be accelerated.

Proton-driven plasma wakefield acceleration in AWAKE.

In this article, we briefly summarize the experiments performed during the first run of the Advanced Wakefield Experiment, AWAKE, at CERN (European Organization for Nuclear Research). The final goal of AWAKE Run 1 (2013-2018) was to demonstrate that 10-20 MeV electrons can be accelerated to GeV energies in a plasma wakefield driven by a highly relativistic self-modulated proton bunch. We describe the experiment, outline the measurement concept and present first results. Last, we outline our plans for the future. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

[Functional rehabilitation of severe laryngopharyngeal injuries after near-lethal suicide attempt by hanging]. / Funktionelle Rehabilitation schwerer laryngopharyngealer Verletzungen nach Suizidversuch durch Erhängen.

BACKGROUND: Hanging is a common method of suicide with an estimated mortality rate of about 70%. Survival of patients with severe laryngopharyngeal injuries after strangulation is not common. However, clinical findings of patients reaching the hospital alive may be minimal. A rapid onset of multidisciplinary diagnostic and therapeutic management is mandatory, followed by psychiatric treatment and functional rehabilitation. CASE PRESENTATION AND RESULTS: Two uncommon cases after severe laryngopharyngeal injury due to near-lethal suicide attempt by hanging demonstrate the emergency management and reconstructive surgery. Subsequent tracheal cannula management and swallowing therapy to full recovery are described. In addition, a proposal for an interdisciplinary treatment algorithm for those patients is presented. CONCLUSION: Minimal external clinical findings after near-lethal suicide attempts by hanging do not exclude severe internal injuries of the upper aerodigestive tract structures. After reconstructive surgery an appropriate tracheal cannula management and an early and intensive swallowing therapy parallel to the psychiatric treatment is mandatory to restore voice, airway and deglutition.

Acceleration of electrons in the plasma wakefield of a proton bunch.

High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration1-5, in which the electrons in a plasma are excited, leading to strong electric fields (so called 'wakefields'), is one such promising acceleration technique. Experiments have shown that an intense laser pulse6-9 or electron bunch10,11 traversing a plasma can drive electric fields of tens of gigavolts per metre and above-well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies5,12. The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage13. Long, thin proton bunches can be used because they undergo a process called self-modulation14-16, a particle-plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN17-19 uses high-intensity proton bunches-in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules-to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage20 means that our results are an important step towards the development of future high-energy particle accelerators21,22.

Pilot-RCT of an integrative group therapy for patients with refractory irritable bowel syndrome (ISRCTN02977330).

OBJECTIVE: Different forms of psychotherapeutic treatments have been proven effective in irritable bowel syndrome (IBS), but disorder-oriented and integrative concepts are still rare. Therefore, we implemented and evaluated an integrative group therapeutic concept within an interdisciplinary tertiary care clinic for functional gastrointestinal disorders (FGIDs). AIMS: present our integrative group concept, assess feasibility issues, and evaluate efficacy. METHODS: A pilot-RCT with a randomized controlled wait-listed group design was conducted. The treatment concept was a disorder-oriented multicomponent group therapy (12 90-min weekly sessions) integrating interactive psychoeducation, gut-directed hypnotherapy, and open group phases. All patients received enhanced medical care and completed a short online diary as an active wait-listed control condition. INCLUSION CRITERIA: refractory IBS diagnosed as somatoform autonomic dysfunction of the lower gastrointestinal tract (SAD). PRIMARY OUTCOME: IBS symptom severity (IBS-SSS). RESULTS: Of 294 patients, 220 had IBS (ROME III), 144 were diagnosed as SAD (ICD-10), 51 were eligible regarding inclusion/exclusion criteria, and 30 consented to participate (group intervention: n=16, wait-listed control condition: n=14). Only 1 patient dropped out. Intention-to-treat-analysis with repeated-measures mixed ANOVA showed that the group intervention was not significantly superior to the wait-listed control condition. Nevertheless, the calculated effect size for the between-group difference in IBS-SSS at the end of treatment (post) was moderate (d=0.539). CONCLUSION: Our disorder-oriented integrative group intervention for IBS proved to be acceptable and feasible in an interdisciplinary tertiary care setting. There is promise in this intervention, but a larger RCT may be needed to investigate efficacy.

[UCl4(HCN)4] - a hydrogen cyanide complex of uranium tetrachloride.

The reaction of uranium tetrachloride with anhydrous liquid hydrogen cyanide yields a turquoise microcrystalline powder of tetrachloridotetraformonitrileuranium(iv), [UCl4(HCN)4]. We determined the crystal structure of this compound by powder neutron diffraction. The compound was further characterized by IR spectroscopy and thermogravimetric analysis as well as by magnetic measurements. The paramagnetic compound crystallizes in the tetragonal space group type I4[combining macron]. To the best of our knowledge this compound represents the first structurally elucidated uranium(iv) complex with HCN as a ligand.

Characterization and Validation of the LT-SYS Copper Assay on a Roche Cobas 8000 c502 Analyzer.

OBJECTIVE: Validation of the LT-SYS quantitative in vitro copper assay on a Roche Cobas 8000 c502 analyzer and comparison with a BIOMED assay on a Roche Cobas Mira analyzer. METHODS: Imprecision and bias were quantified at different concentration levels (serum and plasma) over a 20-day period. Linearity was assessed covering a range from 4.08 µmol/L to 33.8 µmol/L. Limit of blank (LoB) and limit of detection (LoD) were established based on a total of 120 blank and low-level samples. The method comparison was based on 58 plasma samples. RESULTS: Within-run imprecision ranged from 0.7% to 1.2% and within-laboratory imprecision from 1.4% to 3.3%. Relative bias for the 2 serum pools with known target values was less than 2.5%. The assay did not deviate from linearity over the tested measuring range. LoB and LoD were 0.12 µmol/L and 0.23 µmol/L, respectively. The method comparison revealed an average deviation of 11.5% (2.016 µmol/L), and the linear regression fit was y = 1.464 + 0.795x. CONCLUSIONS: The LT-SYS copper assay characterized in this study showed a fully acceptable performance with good degrees of imprecision and bias, no deviation from linearity in the relevant measuring rangem, and very low LoB and LoD.

Br2F7- and Br3F10-: peculiar anions showing µ2- and µ3-bridging F-atoms.

RbCl and CsCl react with BrF3 yielding the corresponding decafluoridotribromates(iii), MBr3F10 (M = Rb, Cs), which were structurally characterized for the first time. The Br3F10- anion is surprisingly not linear but contains a µ3-bridging fluorine atom and seems to be the first example of µ3-F bridging of Br atoms. The compounds are highly reactive and cannot be handled in glassware. As for the tetrafluoridobromates themselves, they are powerful oxidizers and thus suitable for the dry-chemical recycling of precious metals and additionally feature a significantly higher BrF3 content.

Perilymph pharmacokinetics of locally-applied gentamicin in the guinea pig.

Intratympanic gentamicin therapy is widely used clinically to suppress the vestibular symptoms of Meniere's disease. Dosing in humans was empirically established and we still know remarkably little about where gentamicin enters the inner ear, where it reaches in the inner ear and what time course it follows after local applications. In this study, gentamicin was applied to the round window niche as a 20 µL bolus of 40 mg/ml solution. Ten 2 µL samples of perilymph were collected sequentially from the lateral semi-circular canal (LSCC) at times from 1 to 4 h after application. Gentamicin concentration was typically highest in samples originating from the vestibule and was lower in samples originating from scala tympani. To interpret these results, perilymph elimination kinetics for gentamicin was quantified by loading the entire perilymph space by injection at the LSCC with a 500 µg/ml gentamicin solution followed by sequential perilymph sampling from the LSCC after different delay times. This allowed concentration decline in perilymph to be followed with time. Gentamicin was retained well in scala vestibuli and the vestibule but declined rapidly at the base of scala tympani, dominated by interactions of perilymph with CSF, as reported for other substances. Quantitative analysis, taking into account perilymph kinetics for gentamicin, showed that more gentamicin entered at the round window membrane (57%) than at the stapes (35%) but the lower concentrations found in scala tympani were due to greater losses there. The gentamicin levels found in perilymph of the vestibule, which are higher than would be expected from round window entry alone, undoubtedly contribute to the vestibulotoxic effects of the drug. Furthermore, calculations of gentamicin distribution following targeted applications to the RW or stapes are more consistent with cochleotoxicity depending on the gentamicin concentration in scala vestibuli rather than that in scala tympani.

[Patient Satisfaction after Pitch Elevation and Development of a Therapy Algorithm]. / Zufriedenheit nach Stimmerhöhung bei Transsexualität ­ Entwicklung eines Therapiealgorithmus.

Objective: Voice feminization is an important step in the therapy of male-to-female transsexualism. Approaches are conservative voice therapy and surgical interventions. The most powerful parameter of gender perception is the fundamental frequency. Besides the vocal pitch, there are other parameters influencing gender perception of a voice, e. g. intonation, prosody or formant frequencies. Material and methods: In 21 male to female transgender persons after surgical elevation of the vocal pitch the Voice Handicap Index (VHI), the Life Satisfaction Questionnaire (FLZ) and a new addendum were used. A new algorithm for voice feminization in male-to-female transsexualism was deduced. Results: After elevation of the vocal pitch, the self-confidence of the male-to-female transgender persons has increased. Despite of an elevated pitch some persons were not satisfied with their voice. Conclusion: Surgical intervention changes only the pitch of a voice. To change other parameters, conservative voice therapy is necessary. If the transgender persons are able to reach a satisfying female voice with conservative voice therapy alone, surgical intervention is not indicated.

[Direct Drive Simulation - Sound-Simulation of the Vibrant Soundbridge®]. / Direct Drive Simulation - Klangsimulation des Vibrant Soundbridge®-Hörens.

BACKGROUND: The Direct-Drive-Simulation (DDS) tends to simulate the sound quality of hearing with the active middle ear implant Vibrant Soundbridge(®) (VSB). Up to now a scientific evaluation of the validity is missing. Furthermore, the test procedure has not been described yet. Aim of this study was to evaluate the test validity and to describe the test realization in detail. MATERIAL AND METHODS: 10 patients evaluated their sound impression on scales from 1 to 10 concerning sound quality during DDS, postoperative free field testing at least 3 month after the first fitting of the VSB and in the everyday life situation. 3 patients were implanted bilaterally. Together, 36 data sets could be analyzed. RESULTS: Coupling of the Floating Mass Transducer (FMT), which was placed inside of a silicone probe during DDS was successful in all cases. In 11 out of 13 cases the coupling quality was judged as "good" an only in 2 cases as "medium". None of the patients needed local anesthesia. Comparing the evaluation of the sound impression during DDS preoperatively, and with the implanted VSB in free field testing and in everyday life no significant differences were found. CONCLUSION: The DDS offers the possibility of a realistic preoperative sound simulation of the "VSB-hearing" in case of sensorineural hearing loss. Thus, the test is supposed to facilitate the patient's decision towards possible treatment options. The specialist gets additional information regarding the indication especially when audiologic indication criteria are critical. The DDS should be a basic part of the preoperative diagnostic prior to VSB-implantation.