Cytokines in alphavirus induced arthritis as possible targets for novel treatments

This study highlighted the involvement of macrophages, muscle cells and adipocytes in the pathogenesis of RRV disease and investigated the release of various cytokines from these cells during infection, such as TNFα, MIF, NO, HMGB proteins, IL-6, IL-18, IL-33, IL-10 and others. Several known cytokine inhibitors were tested for their anti-inflammatory properties in RRV infected cell lines as possible future treatment options. These inhibitors included erythromycin, clarithromycin, roxithromycin, ethyl pyruvate, pentoxifylline and resveratrol

Wettbewerbsvorteile durch ökologische Produkte

Durch das Auffinden von Umweltschwachstellen und das konkrete Gestalten von Produkten mit Ecodesign können erfolgreich ökointelligente Produkte entwickelt werden. Die Erfahrungen aus verschiedenen Fallbeispielen liefern konkrete Hinweise für die Umsetzung in Produktion und Vermarktung

FORCE AND MOMENT MEASUREMENTS DURING ALPINE SKIING DEPENDING ON HEIGHT POSITION

INTRODUCTION: When a ski is set on edge a lever arm is produced by the force FS, which is applied through the skier’s leg and boot midline, and the ground reaction force FR, which acts on the ski edge. A moment is necessary to keep the ski in its position (see figure and compare with Lind). It is hypothesized that the magnitude of this moment is mainly determined by the width-height proportion of ski and binding. In order to adjust this moment, the skier has to rotate his knee inwards or angle his hip in the lateral direction (Lind, Howe). The objective of this study was to clarify whether the height of the binding plate has any influence on the generated moment. METHODS: A professional ski racer (A-Kader DSV) descended a giant slalom course (at 25° steepness) nine times consecutively. For every run the equipment was identical (skis: ATOMIC ARC RS, binding: ESS 10.28) except for the adjusted height of the binding plate. Three different height positions were used. System A was comprised without a plate between ski and binding, system B with a plate of 1 cm height and system C with a plate of 2 cm height. Using a previously described measuring boot (Wimmer), the ground reaction forces were determined at four distinct locations underneath the boot soles. The specific set-up of the force sensors (two at every edge of the skis) allowed us to calculate the generated moments by known lever-arms. RESULTS: Out of nine runs, seven runs differed in elapsed time by less than 0.3 sec, and the average duration was 20 sec. For this reason a good comparability can be derived. The three fastest runs were made with the 2 cm binding plate, the three slowest runs without the binding plate. The magnitude of ground reaction force ranged from 2000 to 3500 N. The calculated moment was approx. 40-70 Nm and was independent of height position at all turns. Indeed, the moment variation was more affected by the specific turns of the course than by height position. However, the force readings during turns (and thus the moments) were smoother when a higher plate was used. CONCLUSIONS: Because no moment differences could be assigned to the different height positions, the varying width-height-proportions of the three systems may have resulted in three different edging angles. For system C a smaller edging angle would be necessary than for system B, whereas system A would need the largest edging angle. This might be important for the skier, since a smaller body angle in the lateral direction would be necessary to maintain equilibrium using a binding plate

Towards Additively Manufactured Metamaterials with Powder Inclusions for Controllable Dissipation: The Critical Influence of Packing Density

Particle dampers represent a simple yet effective means to reduce unwanted oscillations when attached to structural components. Powder bed fusion additive manufacturing of metals allows to integrate particle inclusions of arbitrary shape, size and spatial distribution directly into bulk material, giving rise to novel metamaterials with controllable dissipation without the need for additional external damping devices. At present, however, it is not well understood how the degree of dissipation is influenced by the properties of the enclosed powder packing. In the present work, a two-way coupled discrete element - finite element model is proposed allowing for the first time to consistently describe the interaction between oscillating deformable structures and enclosed powder packings. As fundamental test case, the free oscillations of a hollow cantilever beam filled with various powder packings differing in packing density, particle size, and surface properties are considered to systematically study these factors of influence. Critically, it is found that the damping characteristics strongly depend on the packing density of the enclosed powder and that an optimal packing density exists at which the dissipation is maximized. Moreover, it is found that the influence of (absolute) particle size on dissipation is rather small. First-order analytical models for different deformation modes of such powder cavities are derived to shed light on this observation

Development and Evaluation of a Web-Based Paediatric Drug Information System for Germany

Background: Off-label use is frequent in paediatrics but that does not necessarily mean that the risk-benefit ratio is negative. Nevertheless, evidence-based data is essential for safe drug therapy. In Germany, there is no publicly available compendium providing transparent, evidence-based information for paediatric pharmacotherapy to date. This work describes the development of a web-based paediatric drug information system (PDIS) for Germany and its evaluation by health care professionals (HCP). Methods: Since 2012, a PDIS is being developed by the authors and is supported by the Federal Ministry of Health since 2016. Dosing recommendations were established based on systematic literature reviews and subsequent evaluation by clinical experts. The prototype was evaluated by HCP. Based on the results, the further development was concluded. Results: 92% of HCP believed that the PDIS could improve the quality of prescribing, as currently available information is deficient. Besides the license and formulations, dosing recommendations were the most relevant modules. A dosage calculator was the most wanted improvement. To facilitate sustainability of future development, a collaboration with the Dutch Kinderformularium was established. As of 2021, the database will be available to German HCP. Conclusion: The fundamentals for a German PDIS were established, and vital steps were taken towards successful continuation

Finiteness and children with specific language impairment: an exploratory study

Children with specific language impairment (SLI) are well known for their difficulties in mastering the inflectional paradigms; in the case of learning German they also have problems with the appropriate verb position, in particular with the verb in second position. This paper explores the possibilities of applying a broader concept of finiteness to data from children with SLI in order to put their deficits, or rather their skills, into a wider perspective. The concept, as developed by Klein (1998, 2000), suggests that finiteness is tied to the assertion that a certain state of affairs is valid with regard to some topic time; that is, finiteness relates the propositional content to the topic component. Its realization involves the interaction of various grammatical devices and, possibly, lexical means like temporal adverbs. Furthermore, in the acquisition of finiteness it has been found that scope particles play a major role in both first- and second-language learning. The purpose of this paper is to analyze to what extent three German-learning children with SLI have mastered these grammatical and lexical means and to pinpoint the phase in the development of finiteness they have reached. The data to be examined are mostly narrative and taken from conversations and experiments. It will be shown that each child chooses a different developmental path to come to grips with the interaction of these devices

Gauge Theory on Fuzzy S^2 x S^2 and Regularization on Noncommutative R^4

We define U(n) gauge theory on fuzzy S^2_N x S^2_N as a multi-matrix model, which reduces to ordinary Yang-Mills theory on S^2 x S^2 in the commutative limit N -> infinity. The model can be used as a regularization of gauge theory on noncommutative R^4_\theta in a particular scaling limit, which is studied in detail. We also find topologically non-trivial U(1) solutions, which reduce to the known "fluxon" solutions in the limit of R^4_\theta, reproducing their full moduli space. Other solutions which can be interpreted as 2-dimensional branes are also found. The quantization of the model is defined non-perturbatively in terms of a path integral which is finite. A gauge-fixed BRST-invariant action is given as well. Fermions in the fundamental representation of the gauge group are included using a formulation based on SO(6), by defining a fuzzy Dirac operator which reduces to the standard Dirac operator on S^2 x S^2 in the commutative limit. The chirality operator and Weyl spinors are also introduced.Comment: 39 pages. V2-4: References added, typos fixe

European multidisciplinary consensus statement on the use and monitoring of metal-on-metal bearings for total hip replacement and hip resurfacing.

Summary Introduction There is an ongoing debate about the optimal use of metal-on-metal (MoM) bearings in total hip replacement, since there are uncertainties about local and systemic adverse effects due to wear and corrosion of these bearings. Despite various national recommendations, efforts to achieve international harmonization of specific evidence-based recommendations for best practice are still lacking. Hypothesis An international consensus study group should be able to develop recommendations on the use and monitoring of MoM bearings, preferably at the European level, through a multidisciplinary approach, by integrating the perspectives of various stakeholders. Materials and methods Twenty-one experts representing three stakeholder groups and eight countries participated in this European consensus study, which consisted of a consensus meeting, subsequent structured discussion, and consensus voting. Results The current statement defines first of all benefits, local and systemic risks, as well as uncertain issues related to MoM bearings. Safety assessment after implantation of MoM comprises all patients. A closer follow-up is recommended for large head MoM (≥ 36 mm) and resurfacing. In these implants basic follow-up should consist of x-rays and metal ion measurement of cobalt in whole blood, performed with GF-AAS or ICP-MS. Clinical and/or radiographic abnormality as well as elevated ion levels needs additional imaging (ultrasound, CT-scan and/or MARS-MRI). Cobalt values less than 2 μg/L are probably devoid of clinical concern, the threshold value for clinical concern is expected to be within the range of 2–7 μg/L. Discussion This is the first multinational, interdisciplinary, and multiprofessional approach for developing a recommendation for the use and monitoring of MoM bearings in total hip replacement. The current recommendations are in partial agreement with previous statements regarding the extent of follow-up and imaging techniques. They however differ from previous communications regarding measurement of metal ions and especially the investigated medium, technique, and eventual threshold levels. Level of evidence Level V, expert opinion/agreement conference