Search

This document provides an overview of the motivation and objectives of REALHOLO in combination with desired specifications and corresponding challenges. An outlook beyond REALHOLO is given with focus on opportunities arising from future availability of the new component and potential further steps to proper commercialization.

We report on the synthesis of the II‐IV‐N2 semiconductors ZnSiN2, MnSiN2, and the Zn1–xMnxSiN2 solid solutions by a one‐step solid‐state metathesis reaction. The successful syntheses were carried out by reacting the corresponding metal halides with stoichiometric amounts of silicon nitride and lithium azide in sealed tantalum ampoules. After washing out the reaction byproduct LiCl, powder X‐ray diffraction patterns were indexed with orthorhombic space group Pna21. Single phase products were obtained without applying external pressure and at a moderate reaction temperature of 700 °C. The resulting ZnSiN2 was found to consist of nano‐sized grains and needle‐shaped nano‐crystals. With increasing manganese content in the Zn1–xMnxSiN2 solid solution, we found the reaction product to be increasingly crystalline. Both the cell parameters and the bandgap values across the different compositions of the solid solutions change linearly. The sample Zn0.95Mn0.05SiN2 synthesized by means of solid‐state metathesis reaction is an intense red emitter with a broad emission maximum at λmax ≈ 619 nm when excited with ultraviolet light after annealing the sample at a pressure of 6 GPa and a temperature of 1200 °C.

Conflicts in the management of renewable natural resources are situations in which actors have diverging opinions on issues of natural resource use. In the literature, among the causal factors for ...

In Deutschland werden die Facharztprufungen im Auftrag der Gesundheitsministerien der Bundeslander durch ein Gremium von Fachvertretern von den Landesarztekammern durchgefuhrt. Es handelt sich dabei um ein mundliches „kollegiales Gesprach“, das wenigstens 30 min dauern soll, in der Praxis aber 45–60 min in der Regel nicht ubersteigt. Der Artikel geht auf Qualitatskriterien ein, die Prufungen ganz allgemein zugrunde liegen sollten, und beschreibt die haufigsten Fehler, die bei der Durchfuhrung mundlicher Examina im Besonderen drohen. Es wird auf Moglichkeiten hingewiesen, wie auch in mundlichen Prufungen ein hohes Mas an Standardisierung, Objektivitat, Transparenz und juristischer Handhabbarkeit durch den Einsatz von „guided questions“ (GQ) implementiert werden kann. Der Ablauf eines Examens unter Verwendung von GQ wird beschrieben, und es werden die bisher in Brandenburg und Thuringen gesammelten Erfahrungen mit der Nutzung dieses Prufungsformats dargelegt.

The use of standardized outcome parameters is essential for the comparability of clinical studies. Pure-tone audiometry and speech audiometry are widely used, but there is no systematic evaluation of the outcome parameters in clinical application. Nevertheless, there is presumably a great heterogeneity especially in the field of speech audiometry. This study presents a snapshot of the current situation of documentation and usage of outcome parameters in otologic research. Retrospective study of existing literature analyzing common speech audiometric test material and procedure Intervention Studies from 2012 to 2016 concerning hearing ability were eligible for evaluation. Studies were analyzed with regard to study design, pathology and intervention, speech audiometric parameters, pure-tone audiometry, implementation of reporting standards and journal related data. 279 studies were included. Over 50% of the analyzed studies lacked proper documentation. In the remaining studies, there was a broad variance concerning the documented speech audiometric parameters, most often with a fixed presentation level of 65 dB SPL. The lack of generally used standards for reporting hearing outcomes makes it difficult to compare results of different clinical studies. An adequate description of the methods would be a first and important step in improving reports on audiological outcomes.

The lanthanum oxonitridophosphate La21 P40 O46 N57 was synthesized by high-pressure metathesis from partially hydrolysed LiPN2 and LaCl3 at 750-950 °C and 7-9 GPa. The combination of transmission electron microscopy (TEM) and diffraction using microfocused synchrotron radiation revealed a monoclinic crystal structure (space group P21 /n, a=14.042(4), b=7.084(3), c=41.404(10) A, β=97.73(3)° and Z=2), which is characterized by loop-branched 21 member single chains of P(O,N)4 tetrahedra that extend along [2 0 1]. These chains are related to the loop-branched dreier single chains with dreier-ring loops in stillwellite (CeBSiO5 ). In La21 P40 O46 N57 , these chains are characterized by a complex long-periodic conformation and exhibit disorder that involves La/N and P split positions. This is an extraordinarily long periodicity with respect to branched single chains of tetrahedra. La21 P40 O46 N57 constitutes the first rare-earth oxonitridophosphate exhibiting a chain structure. Single-crystal data are consistent with electron and powder X-ray diffraction.

Derzeit findet ein umfassender gesellschaftlicher Veranderungsprozess statt, der auch die Medizin vereinnahmt. Die „digitale Transformation“ leitet aktuell einen fundamentalen Umwandlungsprozess des uns bislang vertrauten Gesundheitssystems ein, auch des Medizinstudiums. Der Masterplan 2020 sieht zwar eine Veranderung der Studienstruktur und von Ausbildungsinhalten vor, doch bedauerlicherweise limitiert sich der Fokus auf die Ausbildung von Kompetenzen in der Kommunikation und auf das wissenschaftliche Arbeiten, nicht jedoch auf die Ausbildung digitaler Kompetenzen. Die alltaglichen arztlichen Rahmenbedingungen machen aber gerade diese Kompetenzen in zunehmendem Mase unentbehrlich. Im Rahmen der Studierendenausbildung an der HNO(Hals-Nasen-Ohren)-Klinik der Medizinischen Fakultat Freiburg wurde das Seminar „Digitalisierung in der HNO-Heilkunde“ als Pilotprojekt erstmalig implementiert: 141 Studierende absolvierten und evaluierten dieses Seminar im Rahmen des 2‑wochigen Blockpraktikums „HNO-Heilkunde“ im Wintersemester 2017/2018. Inhalt des Seminars war die Vermittlung digitaler Kompetenzen anhand praktischer Beispiele. Die Evaluation ergab ein hohes Interesse der Studierenden an der Thematik im Allgemeinen, aber auch an detaillierteren Unterpunkten zum Thema Digitalisierung. Grundsatzlich waren die Studierenden sehr aufgeschlossen, aber auch kritisch der Thematik gegenuber. Die Akzeptanz des neuen Lehrangebots fiel deutlich positiv aus. Positiv zu werten ist zudem, dass das Lehrkonzept auf andere Fachdisziplinen ubertragbar ist. Folgerichtig ist im Allgemeinen die Berucksichtigung der Ausbildung von „digitalen Kompetenzen“ bei der Umsetzung des Masterplan 2020 dringlich zu empfehlen.

Background GATA3 is a dual-zinc finger transcription factor that regulates gene expression in many developing tissues. In the kidney, GATA3 is essential for ureteric bud branching, and mice without it fail to develop kidneys. In humans, autosomal dominant GATA3 mutations can cause renal aplasia as part of the hypoparathyroidism, renal dysplasia, deafness (HDR) syndrome that includes mesangioproliferative GN. This suggests that GATA3 may have a previously unrecognized role in glomerular development or injury. Methods To determine GATA3's role in glomerular development or injury, we assessed GATA3 expression in developing and mature kidneys from Gata3 heterozygous (+/-) knockout mice, as well as injured human and rodent kidneys. Results We show that GATA3 is expressed by FOXD1 lineage stromal progenitor cells, and a subset of these cells mature into mesangial cells (MCs) that continue to express GATA3 in adult kidneys. In mice, we uncover that GATA3 is essential for normal glomerular development, and mice with haploinsufficiency of Gata3 have too few MC precursors and glomerular abnormalities. Expression of GATA3 is maintained in MCs of adult kidneys and is markedly increased in rodent models of mesangioproliferative GN and in IgA nephropathy, suggesting that GATA3 plays a critical role in the maintenance of glomerular homeostasis. Conclusions These results provide new insights on the role GATA3 plays in MC development and response to injury. It also shows that GATA3 may be a novel and robust nuclear marker for identifying MCs in tissue sections.

We propose a novel system based on the Floating Mass Transducer (FMT) to be used as the active component of a fully implantable, Vibrant Soundbridge-like middle ear implant. The new system replaces the external microphone used in the currently available design with an implantable piezoelectric sensor that is inserted into the incudostapedial joint and picks up the vibrations transmitted to the long process of the incus. The FMT is coupled to the round window of the cochlea. We characterize the system by measuring the gain in intracochlear sound pressure using laser Doppler vibrometry at a surgically installed “third window” into the cochlea of six temporal bones. Closed-loop feedback oscillations limit the system's available output. We show that using an adaptive control algorithm, a mean functional gain of up to 40 dB is achieved, which is similar to Soundbridge functional gain. The concept matches the FMT's one-point fixation philosophy and offers several advantages over other designs, namely an easy and time-efficient surgery, reversibility of implantation, and natural hearing for the prospective patient.

Dynamic pressure at the tympanic membrane is transformed and subsequently transferred through the ossicular chain in the form of forces and moments. The forces are primarily transferred to the inner ear. They are transferred partly to the stapedial annular ligament which exhibits non-linear behavior and stiffens for larger static forces. In unventilated middle ears, static pressure is additionally transferred to the ossicles. The purpose of this study was to measure the force inside the ossicular chain as a physiological parameter. We determined the forces which act for dynamic sound transmission and for static load on the ossicular chain. The study is the first one which introduces these forces. The static forces have direct impact on clinically relevant questions for middle ear reconstructions with passive or active prosthesis. The dynamic forces have an impact on the development of middle ear sensors. Quasi-static forces in the incudostapedial joint (ISJ) gap were measured with two different sensor types in 17 temporal bones. The sensing elements, a single crystal piezo and a strain gauge element for validation, were bonded to a thin flexible titanium plate and encapsulated in a titanium housing to allow the acquisition of the applied force signal inside the ossicular chain. Dynamic forces were measured in 11 temporal bones with the piezo sensor. We measured a static force of 23 mN in the ISJ after sensor insertion. The mean force for dynamic physiological acoustic excitation from 250 Hz to 6 kHz was 26 μN/Pa. If the tympanic membrane is loaded with a static pressure, the static force in the ISJ increases up to 1 N for a maximum static pressure load scenario of 30 kPa.

Background and Aims Sporadic hepatitis E is an emerging indigenous disease in Europe induced by genotype 3 of the virus. While the disease takes an acute self‐limited course in immunocompetent individuals, under immunocompromised conditions chronic hepatitis E might develop. The histology of chronic hepatitis E has not been described in detail systematically. Methods Liver biopsies from 19 immunosuppressed patients with chronic hepatitis E were collected: 17 were organ transplant recipients, one had a CD4‐deficiency and one had received steroid therapy because of ulcerative colitis. Biopsies were processed with standard stains. Evaluation of histologic activity and fibrosis was performed according to Ishak. Additionally, immunohistochemistry with antibodies directed against open reading frame 2 and 3 of the virus was performed and liver biopsies were tested for hepatitis E virus RNA. Results Biochemical data showed an increase in alanine transaminase, aspartate transaminase, gamma‐glutamyl transferase and total bilirubin. Histopathology displayed typical features of chronic hepatitis with mild to moderate activity. The number of polymorphonuclear leucocytes was considerably increased and all patients had a florid cholangitis that presented as a destructive form in five of them. Hepatocytes and bile duct epithelia stained positive for hepatitis E virus by immunohistochemistry. Conclusions Chronic hepatitis E in immunocompromised individuals runs a similar course as hepatitis B and C and shows similar histopathology. However, the presence of destructive cholangitis in some cases accompanied by an increased number of polymorphonuclear leucocytes is markedly different. Immunohistochemically the virus is present in bile duct epithelia, seemingly the cause for cholangitis.

Current research into neuropeptides is bringing to light many remarkable functions of these endocrine/neurocrine/paracrine factors, such as their roles in modulating immune responses. Galanin is a neuropeptide expressed in both neural and non‐neural tissues and exerts its effects through three G protein–coupled receptors, GAL1,2,3‐R. It has been demonstrated that galanin has modulatory effects on immune cells, including neutrophils and natural killer cells. Because monocytes express GAL2‐R, and therefore are expected to be a target of galanin, we analyzed the effect of galanin on the expression of cytokines and chemokines by monocytes. Galanin increased the expression of IL‐1β up to 1.5‐fold, TNF‐α, IL‐10, IL‐18, and CCL3 up to twofold, and CXCL8 up to fourfold in nonactivated monocytes, but had no major effect on activated monocytes. A cross‐correlation analysis of cytokine expression profiles, irrespective of the activation status of the monocytes, revealed that galanin changed the cross‐correlation of the expression of certain cytokines. Galanin abolished several significant correlations in IFN‐γ–stimulated monocytes. For example, treatment with 10 nM galanin changed the Spearman's rank coefficient of IL‐18 and CXCL8 from 0.622 (P ≤ 0.01) to 0.126. These results further emphasize the importance of neuroregulatory peptides, such as galanin and their therapeutic potential to treat inflammatory diseases., Neuropeptides have various functions, including modulating immune responses. Because monocytes express one of the receptors for the neuropeptide galanin, the authors analyzed the effect of galanin on the expression of cytokines and chemokines by monocytes. Their data indicate that galanin modulates the immune responses of monocytes by regulating cytokine expression networks and that it exerts different functions in naive and inflammation‐induced cells.

HYPOTHESIS Bone dust (BD) harvested during operation may be suitable as an autologous obliteration material for noncritical size defects. Bioactive glass (BA) can be an alternative. BACKGROUND To treat noncritical size defects, BD and BA are commonly used for obliteration techniques. However, the optimal harvesting method and parameters for BD have not been examined. In this study, we analyzed the osseoregenerative potential of both materials. METHODS Thirteen female merino sheep (7-yr old) underwent surgery on the frontal calvaria. Three defects were inserted. The first defect was considered a reference and remained unfilled, the second defect was filled with BD from the calvaria bone, and the third defect was filled with BA S53P4. The animals were sacrificed after 3 weeks. To evaluate bone regeneration, we used digital volume tomography, bone density measurement, fluorochrome sequence labeling, and histological analysis. RESULTS All analyses showed quantitative and qualitative bone regeneration 3 weeks after operation. The control blank defect showed significantly less new bone growth than the BD-filled defect. Moreover, bone regeneration occurred from the surrounding bone and showed only a defect bridge in the BD-filled defect. The BA completely filled the defect and had the highest density although the same amount of new mineralized bone generated as in the reference. CONCLUSION BD and BA seemed to be suitable bone replacement materials for obliteration techniques because they completely filled the defects. Thus, BD harvested under standardized conditions provided a higher level of osteoreparation potential for the generation of woven bone and establishment of defect bridges.

The human tympanic membrane (TM) captures sound waves from the environment and transforms them into mechanical motion. The successful transmission of these acoustic vibrations is attributed to the unique architecture of the TM. However, a limited knowledge is available on the contribution of its discrete anatomical features, which is important for fabricating functional TM replacements. This work synergizes theoretical and experimental approaches toward understanding the significance of geometry in tissue-engineered TM scaffolds. Three test designs along with a plain control are chosen to decouple some of the dominant structural elements, such as the radial and circumferential alignment of the collagen fibrils. In silico models suggest a geometrical dependency of their mechanical and acoustical responses, where the presence of radially aligned fibers is observed to have a more prominent effect compared to their circumferential counterparts. Following which, a hybrid fabrication strategy combining electrospinning and additive manufacturing has been optimized to manufacture biomimetic scaffolds within the dimensions of the native TM. The experimental characterizations conducted using macroindentation and laser Doppler vibrometry corroborate the computational findings. Finally, biological studies with human dermal fibroblasts and human mesenchymal stromal cells reveal a favorable influence of scaffold hierarchy on cellular alignment and subsequent collagen deposition.