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Purpose The German Arthroscopy Registry (DART) has been initiated in 2017 with the aim to collect real-life data of patients undergoing knee, shoulder, hip or ankle surgery. The purpose of this study was to present an overview of the current status and the collected data thus far. Methods Data entered between 11/2017 and 01/2022 were analyzed. The number of cases (each case is defined as a single operation with or without concomitant procedures) entered for each joint, follow-up rates and trends between different age groups (18–29 years, 30–44 years, 45–64 years, ≥ 65 years) and across genders, and quality of life improvement (pre- vs. 1 year postoperative EQ visual analogue scale [EQ-VAS]) for frequently performed procedures (medial meniscus repair [MMR] vs. rotator cuff repair [RCR] vs. microfracturing of the talus [MFX-T]) were investigated. Results Overall, 6651 cases were entered into DART, forming three distinct modules classified by joint (5370 knee, 1053 shoulder and 228 ankle cases). The most commonly entered procedures were: knee: partial medial meniscectomy (n = 2089), chondroplasty (n = 1389), anterior cruicate ligament reconstruction with hamstring autograft (n = 880); shoulder: sub acromial decompression (n = 631), bursectomy (n = 385), RCR (n = 359); ankle: partial synovectomy (n = 117), tibial osteophyte resection (n = 72), loose body removal (n = 48). In the knee and shoulder modules, middle-aged patients were the predominant age group, whereas in the ankle module, the youngest age group was the most frequent one. The two oldest age groups had the highest 1-year follow-up rates across all modules. In the knee and shoulder module, 1-year follow-up rates were higher in female patients, whereas follow-up rates were higher in male patients in the ankle module. From pre- to 1-year postoperative, MFX-T (EQ-VAS: 50.0 [25–75% interquartile range: 31.8–71.5] to 75.0 [54.3–84.3]; ∆ + 25.0) led to a comparably larger improvement in quality of life than did MMR (EQ-VAS: 70.0 [50.0–80.0] to 85.0 [70.0–94.0]; ∆ + 15.0) or RCR (EQ-VAS: 67.0 [50.0–80.0] to 85.0 [70.0–95.0]; ∆ + 18.0). Conclusion DART has been sufficiently established and collects high-quality patient-related data with satisfactory follow-up allowing for a comprehensive analysis of the collected data. The current focus lies on improving patient enrolment and follow-up rates as well as initiating the hip module.

Cartilage regeneration with cell-free matrices has developed from matrix-associated autologous cartilage cell transplantation (MACT) over ten years ago. Adjustments to the legal framework and higher hurdles for cell therapy have led to the procedures being established as an independent alternative to MACT. These procedures, which can be classified as matrix-induced autologous cartilage regeneration (MACR), all rely on the chemotactic stimulus of a cross-linked matrix, which mostly consists of collagens. Given the example of a commercially available type I collagen hydrogel, the physicochemical properties of such a matrix are explained and the available experimental data highlighted in more detail. The interaction between different cell types and the chemotactic properties of the collagen has been investigated extensively and, from a clinical point of view, today offers various reference points for a smart modification of the described method to further improve clinical outcomes. Since the origin of the cells in the ultimately formed repair tissue is still unrevealed, further investigations to clarify the exact mechanism are crucially needed.Die Knorpelregeneration mit zellfreien Matrices hat sich vor mittlerweile über 10 Jahren aus der matrixassoziierten autologen Knorpelzelltransplantation (MACT) entwickelt. Anpassungen der rechtlichen Rahmenbedingungen und höhere Hürden für die Zelltherapie haben dazu geführt, dass sich die Verfahren als eigenständige Alternative zur MACT etabliert haben. Die als matrixinduzierte autologe Knorpelregeneration (MACR) einzuordnenden Verfahren setzen sämtlich auf den chemotaktischen Reiz einer vernetzten Matrix, die zumeist aus Kollagenen besteht. Am Beispiel eines marktüblichen Kollagen-Typ-I-Hydrogels werden die physikochemischen Eigenschaften einer solchen Matrix erläutert und die hierzu vorliegenden experimentellen Daten näher beleuchtet. Das Zusammenspiel zwischen verschiedenen Zelltypen und den chemotaktischen Eigenschaften des Kollagens wurde umfangreich untersucht und bietet aus klinischer Sicht heute unterschiedliche Anknüpfungspunkte zur sinnvollen Modifikation des Verfahrens zur Verbesserung des klinischen Outcomes. Da der Ursprung der Zellen im letztlich gebildeten Regeneratgewebe nach wie vor ungeklärt ist, sind weitere Untersuchungen zur Aufklärung des genauen Wirkmechanismus jedoch zwingend erforderlich.

Summary Background Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT). Methods In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22. Findings Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided de-escalation group and in 118 patients (9%) in the control group (p non-inferiority =0·0004; hazard ratio [HR] 0·81 [95% CI 0·62–1·06], p superiority =0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; p non-inferiority =0·0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%) in the control group (HR 0·82 [95% CI 0·59–1·13]; p=0·23). Interpretation Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI. Funding Klinikum der Universitat Munchen, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

Manual assembly needs to be able to react fast and flexible on product modifications at an increasing number of product variants. Cognitive assistance systems and smart devices can increase the efficiency and quality of this product assembly. However, both need to be validated for shop floor application in order to secure the operator’s acceptance. Moreover, available assistance systems force operators to a predefined assembly path and do not support dynamic deviations. Hence, the present paper focuses on the evaluation of smart devices for assembly workstations and the development of a cognitive assistance system for dynamic repair processes. In a comparative study, a smartwatch, a wristband with gesture control and a voice control are compared with an IR remote control and evaluated using defined criteria. Furthermore, different smart devices are connected to an assistance system, which reacts flexibly to a specific error and acts situationally to deviations using a precedence graph.

The crystallization of 11BaO-25CaO-64SiO2 mol% glass powders and related effects of glass powder milling have been studied by X-ray diffraction (XRD), light and scanning electron microscopy (SEM) and differential thermal analysis (DTA). Glass powders were made by ZrO2 crushing with subsequent sieving or sedimentation or alternatively made by milling with agate, corundum and tungsten carbide. Although surface crystallization was detectable during late sintering, all powders fully sintered. Wollastonite was found as primary crystal phase followed by cristobalite and sanbornite precipitation. The latter crystallization steps caused a second DTA-peak for fine powders. DTA-peak temperatures shifted to lower temperature with decreasing particle size in any case. No significant effects of milling materials on DTA-peak temperatures were evident. As an exception, however, milling in agate caused strongly decreased temperatures of the second DTA-peak. This observation can be explained by the progressive mechanical damaging, which results from the required prolonged milling time with agate due to its small materials density, and the fact that diamond made scratches did promote surface crystallization of cristobalite. The present study thus shows that even for glass powders with excellent sinterability, milling can affect microstructure evolution.

In this study, the domain structure, bimodality of domains and wedge-shape formation of domain tips are investigated in tetragonal Pb[Zr0.375Ti0.625]O3 and Pb[Zr0.45Ti0.55]O3 ferroelectrics by transmission electron microscopy (TEM). Finite element method (FEM) calculations predicted the stability of the experimentally observed domain configuration for different boundary conditions concerning electrical as well as mechanical state. Detailed TEM studies of a specific bimodal domain configuration, composed of four different domains, revealed the presence of a domain wall with alternating tiny head-to-side and tail-to-side arrays and broad head-to-tail areas. The experimentally observed existence of both, wedge-shaped domain tips and bimodality, could be rationalized either by the presence of charges or by shear stress as evidenced by FEM calculations.

Prediction of transmembrane spans and secondary structure from the protein sequence is generally the first step in the structural characterization of (membrane) proteins. Preference of a stretch of amino acids in a protein to form secondary structure and being placed in the membrane are correlated. Nevertheless, current methods predict either secondary structure or individual transmembrane states. We introduce a method that simultaneously predicts the secondary structure and transmembrane spans from the protein sequence. This approach not only eliminates the necessity to create a consensus prediction from possibly contradicting outputs of several predictors but bears the potential to predict conformational switches, i.e., sequence regions that have a high probability to change for example from a coil conformation in solution to an α-helical transmembrane state. An artificial neural network was trained on databases of 177 membrane proteins and 6048 soluble proteins. The output is a 3 × 3 dimensional probability matrix for each residue in the sequence that combines three secondary structure types (helix, strand, coil) and three environment types (membrane core, interface, solution). The prediction accuracies are 70.3% for nine possible states, 73.2% for three-state secondary structure prediction, and 94.8% for three-state transmembrane span prediction. These accuracies are comparable to state-of-the-art predictors of secondary structure (e.g., Psipred) or transmembrane placement (e.g., OCTOPUS). The method is available as web server and for download at www.meilerlab.org.

In particle finite element simulations, a continuous body is represented by a set of particles that carry all physical information of the body, such as the deformation. In order to form this body, the boundary of the particle set needs to be determined. This is accomplished by the α-shape method, where the crucial parameter α controls the level of detail of the detected shape. However, in solid mechanics, it can be observed that α has an influence on the structural integrity as well. In this paper, we study a single boundary segment of a body during a deformation and it is shown that α can be interpreted as the maximum stretch of this segment. On the continuum level, a relation between α and the eigenvalues of the right Cauchy–Green tensor is presented.

Activation of metabotropic glutamate receptor subtype 4 has been shown to be efficacious in rodent models of Parkinson's disease. Artificial neural networks were trained based on a recently reported high throughput screen which identified 434 positive allosteric modulators of metabotropic glutamate receptor subtype 4 out of a set of approximately 155,000 compounds. A jury system containing three artificial neural networks achieved a theoretical enrichment of 15.4 when selecting the top 2 % compounds of an independent test dataset. The model was used to screen an external commercial database of approximately 450,000 drug-like compounds. 1,100 predicted active small molecules were tested experimentally using two distinct assays of mGlu(4) activity. This experiment yielded 67 positive allosteric modulators of metabotropic glutamate receptor subtype 4 that confirmed in both experimental systems. Compared to the 0.3 % active compounds in the primary screen, this constituted an enrichment of 22 fold.

OBJECTIVES: The feasibility of transcatheter aortic valve implantation (TAVI) in patients with a failing surgical aortic bioprosthesis has been reported from single centres. We present results from a multi-centre feasibility study in such patients followed for 1 year after TAVI. METHODS: This study evaluated 18 patients undergoing implantation with the 18-Fr CoreValve TAVI prosthesis in a failing surgical aortic bioprosthesis at three centres in Germany. Subject inclusion requirements included ≥75 years old and either surgical risk with logistic European System for Cardiac Operative Risk Evaluation ≥15% or ≥1 high-risk co-morbidity. RESULTS: Implanted subjects were 79 ± 4 years old, 67% males, 78% NYHA Class III/IV, with logistic EuroSCORE 34 ± 14, and had failed surgical bioprostheses from six manufacturers. The procedure was considered technically successful in 94% (17/18) of cases. One subject was converted to surgery during the procedure. Mortality at 30 days and 1 year was 11% (2/18) and 28% (5/18), respectively. Two cardiac deaths occurred, including 1 within 30 days. Two subjects had strokes, both within 30 days. After 30 days and 1 year, respectively, 86 and 73% of subjects improved at least 1 NYHA class and the remainder had no change. No aortic regurgitation was reported beyond mild (Grade 1) at 6- and 12-month follow-up. CONCLUSIONS: Most patients with a failing aortic surgical bioprosthesis were successfully implanted with a TAVI prosthesis in this multi-centre feasibility study. Outcomes at 30 days were within expectations for this very high-risk subgroup and improvements were sustained through 12 months.

Glutamate, the major excitatory neurotransmitter, functions in the brain via activation of ligand gated cation channels and also the eight subtypes of Class C G protein-coupled metabotropic glutamate receptors (mGlus).[1] Selective allosteric modulation of mGlu5 has been shown to have potential for treatment of a variety of neurological disorders[2,3] including anxiety disorders[4,5], Parkinson’s disease[6–8], Fragile X syndrome[9] and schizophrenia.[10–14] The majority of mGlu5 negative allosteric modulators (NAMs) developed to date either contain an alkyne moiety 1–4 or employ the alkyne topology as basis for ligand design,[15] as in 5–8 (Figure 1). Only recently have mGlu5 NAM chemotypes been identified, through high-throughput screening (HTS) campaigns, that are structurally unrelated to the classical acetylenic derivatives, such as 9–12 (Figure 1).[16] Due to the prevalence of ‘molecular switch‘phenomenon in MPEP related scaffolds, our interest focused on the discovery and development of novel mGlu5 NAM chemotypes, by both HTS and Artificial Neural Network (ANN) virtual screens.

Crystallization behavior in different atmospheres (air, Ar, and 7% H2/Ar) of lithium iron phosphate glass (33Li2O–33Fe2O3–1Nb2O5–33P2O5 (LFNP)) powders with different sizes of 2–1000 μm was examined. The crystallization peak temperature (Tp) in Ar and 7% H2/Ar decreased with decreasing the particle size of glass powders, but the value of Tp in air was independent of particle size. The crystallized glass obtained by heating to Tp showed the formation of the α-Li3Fe2(PO4)3 and LiFePO4 crystalline phases. Fe2O3 crystals were formed only in the inside of crystallized glass plates in the heating in air. The crystallization of LiFePO4 was largely enhanced in the particle size of

The structural evolution of misfit dislocation networks at γ/γ′ phase interfaces in Ni-based single crystal superalloys under tensile loading and temperatures is simulated by molecular dynamics. From the simulation, we find that, with increasing load or temperature, the patterns of dislocation networks on the (100), (110) and (111) phase interfaces change from regular to irregular or disappear. Under the same load and temperature, the dislocation networks of the different phase interfaces show different degrees and patterns of damage. The density and stability of the dislocation networks decrease with increasing temperature. When the interfacial dislocation networks become more regular, the γ/γ′ interfaces become more stable. The simulated results are supported by related experimental findings. Moreover, based on MD simulations, the averaged stress–strain responses for different phase interfaces under loading are presented. The results indicate that the combined influences of temperature and load play an ...

Aim of this study isto propose, to develop, to validate and to applyin intensive simulations an efficient non-hypersingular traction boundary integral equation method (BIEM) for the solution of anti-plane dynamic problems of piezoelectric solids with cracks or/and holes. The modelling approach is in the frame of continuum mechanics, wave propagation and linear fracture mechanics. The simulations reveal the dependenceof the stress concentration factor(SCF) and the stress intensity factor (SIF) ontheelectromechanical coupling,onthe type and characteristics of the dynamic load, onthematerialparameters and on the geometry of the defects.

Objectives The purpose of this study was to evaluate the safety, device performance, and clinical outcome up to 2 years for patients undergoing transcatheter aortic valve implantation (TAVI). Background The role of TAVI in the treatment of calcific aortic stenosis evolves rapidly, but mid-and long-term results are scarce. Methods We conducted a prospective, multicenter, single-arm study with symptomatic patients undergoing TAVI for treatment of severe aortic valve stenosis using the 18-F Medtronic CoreValve (Medtronic, Minneapolis, Minnesota) prosthesis. Results In all, 126 patients (mean age 82 years, 42.9% male, mean logistic European System for Cardiac Operative Risk Evaluation score 23.4%) with severe aortic valve stenosis (mean gradient 46.8 mm Hg) underwent the TAVI procedure. Access was transfemoral in all but 2 cases with subclavian access. Retrospective risk stratification classified 54 patients as moderate surgical risk, 51 patients as high-risk operable, and 21 patients as high-risk inoperable. The overall technical success rate was 83.1%. Thirty-day all-cause mortality was 15.2%, without significant differences in the subgroups. At 2 years, all-cause mortality was 38.1%, with a significant difference between the moderate-risk group and the combined high-risk groups (27.8% vs. 45.8%, p = 0.04). This difference was mainly attributable to an increased risk of noncardiac mortality among patients constituting the high-risk groups. Hemodynamic results remained unchanged during follow-up (mean gradient: 8.5 +/- 2.5 mm Hg at 30 days and 9.0 +/- 3.4 mm Hg at 2 years). Functional class improved in 80% of patients and remained stable over time. There was no incidence of structural valve deterioration. Conclusions The TAVI procedure provides sustained clinical and hemodynamic benefits for as long as 2 years for patients with symptomatic severe aortic stenosis at increased risk for surgery. (J Am Coll Cardiol 2011;57:1650-7) (C) 2011 by the American College of Cardiology Foundation

This work addresses the evaluation of the stress and electric field concentrations around a circular hole in a functionally graded piezoelectric plane subjected to anti-plane elastic SH-wave and in-plane time-harmonic electric load. All material parameters vary exponentially along a line of arbitrary orientation in the plane of the piezoelectric material under consideration. The computational tool is a non-hypersingular traction based boundary integral equation method (BIEM). The kernel functions used in the BIEM are exact fundamental solutions that have been derived in previous work by the authors. Numerical solutions for the stress and electric field concentration factors (SCF and EFCF, respectively) around the perimeter of the hole are obtained. The simulation demonstrates the efficiency of the computational approach and its potential to reveal in an adequate way the dynamic stress and electric field distribution around the hole. Presented are results showing their dependence on various system parameters as e.g. the electro-mechanical coupling, the type of the dynamic load and its characteristics, the wave-hole and wave-material interaction and the magnitude and direction of the material inhomogeneity.

The ultrasonic welding technology is an innovative method to produce hybrid joints for multi-material components. In this contribution, the behaviour of an interface layer of metal/fibre-reinforced polymer single overlap tensile specimens is considered. The investigations are carried out using the ultrasonic metal welding technique (UMW) for joining carbon fibre reinforced thermoplastic composites (CFRP) with aluminium alloys. An interfacial traction-separation-law based on elastoplasticity with Lemaitre-type damage is applied. The finite element method is used for the analysis of damage evolution. Two-dimensional interface elements are employed for modelling the solid interface in a 3-D problem. Numerical simulations are carried out for three different interface geometries: square, elongated rectangle and cross rectangle. It is shown that damage develops slower in the specimen with square interface than in the specimen with rectangle interface. The damage parameter reaches the maximum value in every loadstep in the specimen with cross-rectangle interface. Comparison with experimental data shows that the damage process and the fractured zone are identical to simulated results for the specimen with square interface.