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BACKGROUND: Thrombosis remains a critical complication during venovenous extracorporeal membrane oxygenation (VV ECMO). The involvement of neutrophil extracellular traps (NETs) in thrombogenesis has to be discussed. The aim was to verify NETs in the form of cell-free DNA (cfDNA) in the plasma of patients during ECMO.
METHODS: A fluorescent DNA-binding dye (QuantifFluor®, Promega) was used to detect cell-free DNA in plasma samples. cfDNA concentrations from volunteers (n = 21) and patients (n = 9) were compared and correlated with clinical/technical data before/during support, ECMO end and time of a system exchange.
RESULTS: Before ECMO, patients with a median (IQR) age of 59 (51/63) years, SOFA score of 11 (10/15), and ECMO run time of 9.0 (7.0/19.5) days presented significantly higher levels of cfDNA compared to volunteers (6.4 (5.8/7.9) ng/μL vs. 5.9 (5.4/6.3) ng/μL; p = 0.044). Within 2 days after ECMO start, cfDNA, inflammatory, and hemolysis parameters remained unchanged, while platelets decreased (p = 0.005). After ECMO removal at the end of therapy, cfDNA, inflammation, and coagulation data (except antithrombin III) remained unchanged. The renewal of a system resulted in known alterations in fibrinogen, d-dimers, and platelets, while cfDNA remained unchanged.
CONCLUSION: Detection of cfDNA in plasma of ECMO patients was not an indicator of acute and circuit-induced thrombogenesis.
Theoretical considerations on a 2D compliant tensegrity joint in context of a biomedical application
(2023)
In this paper, a two-dimensional compliant tensegrity joint was investigated for potential biomedical applications such as orthotics or exoskeletons. The structure consists of two compressed members connected by five compliant tensioned members. The concept is based on the tensegrity principle, which allows the realization of dynamic orthoses without conventional hinge joints. Another advantage is the adaptability to the individual needs of the patient through a suitable design of the structure and the careful selection of the characteristics of the elements. Using geometric nonlinear analysis, the mechanical behavior of the structure was investigated, focusing on mechanical compliance. The main objective was to determine the influence of the initial length and stiffness of the tensioned members and the influence of the magnitude of external forces on the overall stiffness of the movable member of the structure. The results highlight the significant impact of member parameters on the structure's stiffness and movability under varying load magnitudes. The research laid the foundation for future development of dynamic orthoses based on this structure.
In diesem Beitrag erfolgt die theoretische Untersuchung einer zweidimensionalen nachgiebigen Tensegrity-Struktur in Hinsicht auf ihre potenzielle Eignung als Basisstruktur für eine dynamische Handorthese. Translatorische und rotatorische relative Bewegungsmöglichkeiten zwischen den Drucksegmenten der Struktur sind möglich, da diese Segmente durch nachgiebige Zugsegmente miteinander verbunden sind. Die Form der Struktur und ihre Vorspannung in einer statisch stabilen Gleichgewichtskonfiguration werden mit Hilfe der Minimierung des Kräfte- und Momentenungleichgewichts, der Betrachtung der potentiellen Energie der Struktur und einem Ansatz mittels statischer Finite-Elemente-Methode (FEM) in Abhängigkeit der Segmentparameter untersucht.
Aufgrund der steigenden Lebenserwartung und dem damit einhergehenden demographischen Wandel wird der Bedarf an Rehabilitations-Behandlungen in absehbarer Zukunft stark ansteigen. Ein Beispiel für diesen Trend ist die physiotherapeutische Behandlung nach Erhalt einer Knie-Totalendoprothese (Knie-TEP). So gehen Modellrechnungen basierend auf dem Bevölkerungswachstum und der bisherigen Prävalenz von Knie-TEPs davon aus, dass die Anzahl an durchgeführten Eingriffen in einkommensstarken Ländern wie Deutschland weiter zunehmen wird. Weiterhin stoßen traditionelle Rehabilitationsverfahren, gerade in strukturschwachen Regionen, schon heute an ihre Grenzen. Deutlich zu sehen war das während den Hochphasen der aktuellen Covid-19-Pandemie, als der Kontakt zwischen Therapeut*in und Patient*in flächendeckend eingeschränkt war. Eine erhöhte Nachfrage nach neuartigen Reha-Angeboten ist die logische Konsequenz. Innovative Konzepte sind daher dringend notwendig, um die daraus resultierenden technischen, sozialen und ökonomischen Herausforderungen zu bewältigen.
BACKGROUND:
Tracheobronchial mucus plays a crucial role in pulmonary function by providing protection against inhaled pathogens. Due to its composition of water, mucins, and other biomolecules, it has a complex viscoelastic rheological behavior. This interplay of both viscous and elastic properties has not been fully described yet. In this study, we characterize the rheology of human mucus using oscillatory and transient tests. Based on the transient tests, we describe the material behavior of mucus under stress and strain loading by mathematical models.
METHODS:
Mucus samples were collected from clinically used endotracheal tubes. For rheological characterization, oscillatory amplitude-sweep and frequency-sweep tests, and transient creep-recovery and stress-relaxation tests were performed. The results of the transient test were approximated using the Burgers model, the Weibull distribution, and the six-element Maxwell model. The three-dimensional microstructure of the tracheobronchial mucus was visualized using scanning electron microscope imaging.
RESULTS:
Amplitude-sweep tests showed storage moduli ranging from 0.1 Pa to 10000 Pa and a median critical strain of 4 %. In frequency-sweep tests, storage and loss moduli increased with frequency, with the median of the storage modulus ranging from 10 Pa to 30 Pa, and the median of the loss modulus from 5 Pa to 14 Pa. The Burgers model approximates the viscoelastic behavior of tracheobronchial mucus during a constant load of stress appropriately (R2 of 0.99), and the Weibull distribution is suitable to predict the recovery of the sample after the removal of this stress (R2 of 0.99). The approximation of the stress-relaxation test data by a six-element Maxwell model shows a larger fit error (R2 of 0.91).
CONCLUSIONS:
This study provides a detailed description of all process steps of characterizing the rheology of tracheobronchial mucus, including sample collection, microstructure visualization, and rheological investigation. Based on this characterization, we provide mathematical models of the rheological behavior of tracheobronchial mucus. These can now be used to simulate mucus flow in the respiratory system through numerical approaches.
Für Fußballer:innen stellen muskuläre Verletzungen der unteren Extremitäten ein großes Problem dar. Ein Beispiel hierfür liefert die Nationalmannschaftsstürmerin Alexandra Popp, die aufgrund muskulärer Probleme das EM-Finale 2022 in Wembley kurzfristig verpasste. Oftmals stehen gerade hohe Anspannungssituationen in zeitlichem Zusammenhang mit Verletzungen, der Einfluss der psychischen Beanspruchung auf die biomechanischen Belastungen wird jedoch meist nur wenig beachtet.
To avoid dislocation of the shoulder joint after reverse total shoulder arthroplasty, it is important to achieve sufficient shoulder stability when placing the implant components during surgery. One parameter for assessing shoulder stability can be shoulder stiffness. The aim of this research was to develop a temporary reverse shoulder implant prototype that would allow intraoperative measurement of shoulder stiffness while varying the position of the implant components. Joint angle and torque measurement techniques were developed to determine shoulder stiffness. Hall sensors were used to measure the joint angles by converting the magnetic flux densities into angles. The accuracy of the joint angle measurements was tested using a test bench. Torques were determined by using thin-film pressure sensors. Various mechanical mechanisms for variable positioning of the implant components were integrated into the prototype. The results of the joint angle measurements showed measurement errors of less than 5° in a deflection range of ±15° adduction/abduction combined with ±45° flexion/extension. The proposed design provides a first approach for intra-operative assessment of shoulder stiffness. The findings can be used as a technological basis for further developments.
In Vitro Analysis of Human Cartilage Infiltrated by Hydrogels and Hydrogel-Encapsulated Chondrocytes
(2023)
Osteoarthritis (OA) is a degenerative joint disease causing loss of articular cartilage and structural damage in all joint tissues. Given the limited regenerative capacity of articular cartilage, methods to support the native structural properties of articular cartilage are highly anticipated. The aim of this study was to infiltrate zwitterionic monomer solutions into human OA-cartilage explants to replace lost proteoglycans. The study included polymerization and deposition of methacryloyloxyethyl-phosphorylcholine- and a novel sulfobetaine-methacrylate-based monomer solution within ex vivo human OA-cartilage explants and the encapsulation of isolated chondrocytes within hydrogels and the corresponding effects on chondrocyte viability. The results demonstrated that zwitterionic cartilage–hydrogel networks are formed by infiltration. In general, cytotoxic effects of the monomer solutions were observed, as was a time-dependent infiltration behavior into the tissue accompanied by increasing cell death and penetration depth. The successful deposition of zwitterionic hydrogels within OA cartilage identifies the infiltration method as a potential future therapeutic option for the repair/replacement of OA-cartilage extracellular suprastructure. Due to the toxic effects of the monomer solutions, the focus should be on sealing the OA-cartilage surface, instead of complete infiltration. An alternative treatment option for focal cartilage defects could be the usage of monomer solutions, especially the novel generated sulfobetaine-methacrylate-based monomer solution, as bionic for cell-based 3D bioprintable hydrogels.
It is generally known that project-based learning is a very important part of engineering education to connect theoretical knowledge with practical work. Students learn to apply their knowledge to real-world challenges as it is the case in their later professional life. If students are not used to project work or the scientific topic is new and relatively complex, they may be overwhelmed. The consequence is that students achieve poor results, are frustrated, and therefore learning success is low. Semi-structured projects are introduced that combine the advantages of structured experiments with projects. The project work is structured into several parts with detailed descriptions of the tasks. In the end, students get similar results to doing a free project, but the success rate is higher due to higher guidance. Therefore, these semi-structured projects are seen to be an appropriate method to guide students to learn how to do project work. The feedback from most students is very positive. Some students with no previous lab experience complained about the project work and wished for more guidance to become familiar with lab work. In sum, the student feedback is encouraging to develop semi-structured projects further.
In the treatment of hand injuries in the context of orthopedic care, movable hand orthoses are used in many cases. Early motion therapy is in most cases advantageous for adequate, rapid, and successful long-term healing of the hand. Conventional mobile hand orthoses can only be used for movement therapy to a limited extent since they represent the wrist as a simple rotating joint and neglect the complexity of the movement possibilities of the hand. In this paper, a novel concept for movable hand orthoses based on prestressed compliant structures is presented. The advantage with this concept is that it replicates the multiaxial motion capabilities without the need for conventional joints. Besides the derivation and description of the concept, a first three-dimensional CAD design is shown. Additionally, the next planned steps in the development of such a novel dynamic hand orthosis are described.
In the treatment of hand injuries in the context of orthopedic care, movable wrist hand orthoses are used in numerous instances. Early motion therapy is in most cases advantageous for adequate, rapid and successful long-term healing of the hand. Conventional dynamic wrist hand orthoses can only be used for movement therapy to a limited extent since they represent the wrist as a simple rotating joint and neglect the complexity of the hand movement possibilities. In this paper, a preliminary concept for dynamic wrist hand orthoses based on prestressed compliant structures is presented. The distinctive feature of this concept lies in the enabling of multiaxial motion capabilities of the human hand without applying conventional joints. According to the concept the wrist region is surrounded by a prestressed compliant structure. Besides the derivation and description of the concept, a first three-dimensional computer-aided design is shown. Additionally, the necessary steps in the development of such a novel dynamic wrist orthosis are discussed.
Surgical Smoke is generated during the cauterization of tissue with high-frequency (HF) devices and consists of 95% water vapor and 5% cellular debris. When the coagulation tweezers, which are supplied with HF voltage by the HF device, touch tissue, the electric circuit is closed, and smoke is generated by the heat. In-vivo investigations are performed during tracheotomies where surgical smoke is produced during coagulation of tissue. Furthermore, in-vitro parametric studies to investigate the particle number and size distribution and the spatial distribution of surgical smoke with laser light sheet technique are conducted. With higher power of the HF device, the particles generated are larger in size and the total number of particles generated is also higher. Adding artificial saliva to the tissue shows even higher particle counts. The study by laser light sheet also confirms this. The resulting characteristic size distribution, which may include viruses and bacterial components, confirms considering the risk arising from surgical smoke. Furthermore, the experiments will provide the database for further numerical investigations.
High Spatial Resolution Tomo-PIV of the Trachea Focussing on the Physiological Breathing Cycle
(2023)
Investigations of complex patient-specific flow in the nasopharynx requires high resolution numerical calculations validated by reliable experiments. When building the validation base and the benchmark of computational fluid dynamics, an experimental setup of the nasal airways was developed. The applied optical measurement technique of tomo-PIV supplies information on the governing flow field in three dimensions.
This paper presents tomo-PIV measurements of the highly complex patient-specific geometry of the human trachea. A computertomographic scan of a person’s head builds the basis of the experimental silicone model of the nasal airways. An optimised approach for precise refractive index matching avoids optical distortions even in highly complex non-free-of-sight 3D geometries. A linear-motor-driven pump generates breathing scenarios, based on measured breathing cycles. Adjusting of the CCD cameras‘ double-frame-rate PIV-Δt enables the detailed analysis of flow structures during different cycle phases. Merging regions of interest enables high spatial resolution acquisition of the flow field.
Introduction
Shear induced multimerisation of von-Willebrand-factor (vWF) is supposed to play an important role in coagulation inside extracorporeal membrane oxygenators. However, there is no proof that links observed vWF structures to computed or measured flow conditions.
Methods
The structures of multimeric vWF fibers, observed in clinically used membrane oxygenators is examined using immunofluorescence microscopy (IFM) using Carstairs’ staining method (positive ethics committee vote). The flow around the membrane fibres inside the oxygenator is investigated in terms of shear rate, wall shear velocity and streamlines by using CFD (RANS, Carreau-Yasuda viscosity, geometry remodelled after high-resolution µCT-scans). By interpreting the histological and numerical results in this common context, indications for shear induced coagulation mechanisms can be identified.
Results
The fibre structures of multimeric vWF build regular but not exactly symmetric formations around the contact face (CF) between the crosswise stacked oxygenator fibres (OF), see fig.1B, vWF marked red. Annular around the CF arranged, cells are likely to be found, see fig.1B, nuclei marked blue.
The computed streamlines around the OF show attached flow around the circular fibres. However, the irregular arrangement of real OF produce considerable cross flow between the interconnected neighbouring channels, in contrast to previous 2D-simulations. Thus, the CF are washed around closely by blood, also from neighbouring channels. The wall shear velocity streamlines form regular, slightly asymmetric shapes around the contact faces. The occurring maximum shear rates are in the range of 1,000 1/s.
Discussion
The shapes of vWF structures found in clinically used oxygenators match the computational results in terms of wall shear velocity and streamlines well. The accumulation of cells close to the CF can also be explained by fluid mechanics, as there are small shear gradients and slow velocities. However, occurring shear rates between OFs are too low to trigger multimerisation of vWF. That raises the question where in the circuit the actual activation of vWF is started and how, at least partly chained, vWF multimeres are attracted towards the OF surface. A next step will be the investigation of the actual shear rate triggered (or mediated) multimerisation of vWF. Towards this end, microfluidic experiments with shear triggered coagulation will be performed. Also of big interest is the computation of the flow situation in the oxygenator in proximity to chaining threads, which have been ignored in computations so far. However, first a realistic representation of the effective viscosity in computations is needed, which is not available yet.
Für Mutter und Kind konnte das Risiko der Geburt durch die Weiterentwicklung der Medizin drastisch reduziert werden. Doch wie ist es um das Wohl derer bestellt, die die Gebärende unterstützen? Eine Studie der Ostbayerischen Technischen Hochschule Regensburg hat sich mit den muskuloskelettalen Beschwerden von Geburtshelfer:innen auseinandergesetzt
Osteoporosis is a common disease of old age. However, in many cases, it can be very well prevented and counteracted with physical activity, especially high-impact exercises. Wearables have the potential to provide data that can help with continuous monitoring of patients during therapy phases or preventive exercise programs in everyday life. This study aimed to determine the accuracy and reliability of measured acceleration data at different body positions compared to accelerations at the pelvis during different jumping exercises. Accelerations at the hips have been investigated in previous studies with regard to osteoporosis prevention. Data were collected using an IMU-based motion capture system (Xsens) consisting of 17 sensors. Forty-nine subjects were included in this study. The analysis shows the correlation between impacts and the corresponding drop height, which are dependent on the respective exercise. Very high correlations (0.83–0.94) were found between accelerations at the pelvis and the other measured segments at the upper body. The foot sensors provided very weak correlations (0.20–0.27). Accelerations measured at the pelvis during jumping exercises can be tracked very well on the upper body and upper extremities, including locations where smart devices are typically worn, which gives possibilities for remote and continuous monitoring of programs.
Influence of CFD Strategy on WSS and OSI Determination for Intracranial Aneurysm Rupture Assessment
(2019)
Feasibility of detecting thrombotic deposits in membrane oxygenators using micro computed tomography
(2019)
Coagulative disorders, especially clotting during extracorporeal membrane oxygenation, are frequent complications. Direct visualization and analysis of deposits in membrane oxygenators using computed tomography (CT) may provide an insight into the underlying mechanisms causing thrombotic events. However, the already established multidetector CT1 (MDCT) method shows major limitations. Here, we demonstrate the feasibility of applying industrial micro-CT (μCT) to circumvent these restrictions. Three clinically used membrane oxygenators were investigated applying both MDCT and μCT.
The scans were analyzed in terms of clot volume and local clot distribution. As validation, the clot volume was also determined from the fluid volume, which could be filled into the respective used oxygenator compared to a new device. In addition, cross-sectional CT images were compared with crosscut oxygenators. Based on the μCT findings, a morphological measure (sphericity) for assessing clot structures in membrane oxygenators is introduced. Furthermore, by comparing MDCT and μCT results, an augmentation of the MDCT method is proposed, which allows for improved clot volume determination in a clinical setting.
Clot formation within membrane oxygenators (MOs) remains a critical problem during extracorporeal membrane oxygenation (ECMO). The composition of the clots—in particular, the presence of von Willebrand factor (vWF)—may be an indicator for prevalent nonphysiological flow conditions, foreign body reactions, or coagulation abnormalities in critically ill patients. Mats of interwoven gas exchange fibers from randomly collected MOs (PLS, Maquet, Rastatt, Germany) of 21 patients were stained with antibodies (anti‐vWF and anti‐P‐selectin) and counterstained with 4′,6‐diamidino‐2‐phenylindole. The extent of vWF‐loading was correlated with patient and technical data. While 12 MOs showed low vWF‐loadings, 9 MOs showed high vWF‐loading with highest accumulations close to crossing points of adjacent gas fibers. The presence and the extent of vWF‐fibers/“cobwebs,” leukocytes, platelet–leukocyte aggregates (PLAs), and P‐selectin‐positive platelet aggregates were independent of the extent of vWF‐loading. However, the highly loaded MOs were obtained from patients with a significantly elevated SOFA score, severe thrombocytopenia, and persistent liver dysfunction. The coagulation abnormalities of these critically ill patients may cause an accumulation of the highly thrombogenic and elongated high‐molecular‐weight vWF multimers in the plasma which will be trapped in the MOs during the ECMO therapy.
The special wing geometry of dragonflies consisting of veins and a membrane forming a corrugated profile leads to special aerodynamic characteristics. To capture the governing flow regimes of a dragonfly wing in detail, a realistic wing model has to be investigated. Therefore, this study aimed to analyze the aerodynamic characteristics of a 3D dragonfly wing reconstructed from a high-resolution micro-CT scan. Afterwards, a spatially high discretized mesh was generated using the mesh generator CENTAUR™ 14.5.0.2 (CentaurSoft, Austin, TX, US) to finally conduct Computational Fluid Dynamics (CFD) investigations in Fluent® 2020 R2 (ANSYS, Inc., Canonsburg, PA, US). Due to the small dimensions of the wing membrane, only the vein structure of a Camacinia Gigantea was captured at a micro-CT voxel size of 7 microns. The membrane was adapted and connected to the vein structure using a Boolean union operation. Occurring nconsistencies after combining the veins and the membrane were corrected using an adapted pymesh script [1]. As an initial study, only one quarter of the wing (outer wing section) was investigated to reduce the required computational effort. The resulting hybrid mesh consisting of 10 pseudo-structured prism layers along the wing surface and tetrahedra in the farfield area has 43 mio. nodes. The flow around the wing was considered to be incompressible and laminar using transient calculations. When the flow passes the vein structures, steady vortices occur in the corrugation valleys leading to recirculation zones. Therefore, the dragonfly wing resembles the profile of an airfoil. This leads to comparable lift coefficients of dragonfly wings and airfoil profiles at significantly reduced structural weight. The reconstructed geometry also included naturally occurring triangular prismlike serrated structures at the leading edge of the wing, which have comparable effects to micro vortex generators and might stabilize the recirculation zones. Further work aims to investigate the aerodynamic properties of a complete dragonfly wing during wing flapping.
Air leakage past High-Volume-Low-Pressure (HVLP) endotracheal tube (ETT) cuffs creates a potential infection risk for health care professionals during ventilation of patients suffering from contagious airborne diseases. However, unlike silent aspiration, a phenomenon where fluids enter the airways of intubated patients, the aspect of aerosol emergence through cuff folds -what we called accordingly “silent breathing” (SB)- has not been investigated in detail so far.
This study investigates air leakage past HVLP cuffs with varying cuff pressures under realistic artificial breathing scenarios experimentally and in addition numerically. The focus was laid on the parametric investigation of the occurrence and furthermore on different influencing factors of silent breathing. The morphology of the folds responsible for the leakage was captured using high-resolution 3D microcomputed tomography (μCT). For the numerical investigations (Com-putational Fluid Dynamics - CFD), the commercial CFD Software package FLUENT 2021 R2 (ANSYS, Inc., Canonsburg, PA, US), as well as the DLR in-house research code THETA has been used.
High Spatial Resolution Tomo-PIV of the Nasopharynx Focussing on the Physiological Breathing Cycle
(2022)
Investigations of complex patient-specific flow in the nasopharynx requires high resolution numerical calculations validated by reliable experiments. When building the validation base and the benchmark
of computational fluid dynamics, an experimental setup of the nasal airways was developed. The applied optical measurement technique of tomo-PIV supplies information on the governing flow field in three dimensions. This paper presents tomo-PIV measurements of the highly complex patient-specific geometry of the human trachea. A computertomographic scan of a person’s head builds the basis of the experimental silicone model of the nasal airways. An optimised approach for precise refractive index matching avoids optical distortions even in highly complex non-free-of-sight 3D geometries. A linear-motor-driven pump generates breathing scenarios, based on measured breathing cycles. Adjusting of the CCD cameras‘ double-frame-rate PIV-Δt enables the detailed analysis of flow structures during different cycle phases. Merging regions of interest enables high spatial resolution acquisition of the flow field.
Surgical smoke has been a little discussed topic in the context of the current pandemic. Surgical smoke is generated during the cauterization of tissue with heat-generating devices and consists of 95% water
vapor and 5% cellular debris in the form of particulate matter. In-vivo investigations are performed during tracheotomies where surgical smoke is produced during tissue electrocautery. Furthermore, in-vitro parametric studies to investigate the particle number and size distribution and the spatial distribution of surgical smoke with laser light sheet technique are conducted. The higher the power of the high-frequency-device the larger the particles in size and the higher the resulting particle counts. The images taken show the densest smoke at 40W with artificial saliva. The resulting characteristic size distribution, which may include viruses and bacterial components, confirms that the risk arising from surgical smoke should be considered. Furthermore, the experiments will provide the database for further numerical investigations.
Clot formation within membrane oxygenators (MOs) remains a critical problem during extracorporeal membrane oxygenation (ECMO). The composition of the clots-in particular, the presence of von Willebrand factor (vWF)-may be an indicator for prevalent nonphysiological flow conditions, foreign body reactions, or coagulation abnormalities in critically ill patients. Mats of interwoven gas exchange fibers from randomly collected MOs (PLS, Maquet, Rastatt, Germany) of 21 patients were stained with antibodies (anti-vWF and anti-P-selectin) and counterstained with 4 ',6-diamidino-2-phenylindole. The extent of vWF-loading was correlated with patient and technical data. While 12 MOs showed low vWF-loadings, 9 MOs showed high vWF-loading with highest accumulations close to crossing points of adjacent gas fibers. The presence and the extent of vWF-fibers/"cobwebs," leukocytes, platelet-leukocyte aggregates (PLAs), and P-selectin-positive platelet aggregates were independent of the extent of vWF-loading. However, the highly loaded MOs were obtained from patients with a significantly elevated SOFA score, severe thrombocytopenia, and persistent liver dysfunction. The coagulation abnormalities of these critically ill patients may cause an accumulation of the highly thrombogenic and elongated high-molecular-weight vWF multimers in the plasma which will be trapped in the MOs during the ECMO therapy.
Modelling blood flow an shear induced coagulation in membraene oxygenators (MO) is challenging. The relevant geometry of oxygenator fibers (OF) and chaining threads is complex and spans several length scales. In relevant scales and regimes blood shows several significant non-Newtonian effects. Existing models are only capable of accounting for some, but not all relevant effects. Additionally, coagulation processes are influencing fluid properties and geometry significantly. Due to the enormous size of the discretised geometries highly detailed viscosity and coagulation properties of blodd flow in MOs. First step is to find a gemoetry dependent viscosity representation on basis of parametric micro channel experiments with anti-coagulated blood. Next step is a statistic coagulation model, based on micro channel experiments with human (re-calcified citrated) whole blood an evaluation of clinically used osygenators. Since shear rate dependent (i.e. viscosity dependet) coagulation in return influences the viscosity, a combined model with suitable implementation in a RANS framework is necessary. Towards this end, micro channel experiments with new and used single OFs triggering coagulation are performed. Structures of multimeric von Willebrand fibers (vWF), as indicator for shear induced coagulation, are compared to computed and measured flow conditions, using immunofluorescence microscopy, RANS-computations and µPIV, respectively. Preliminary examinations in clinically used MOs show good agreement between occurring structures of vWF, cell depositions and computed flow patterns (geometry form µCT-Scans). However, computed shear rates might be to low to actually trigger activation of vWF. The complex geometry of MOs results in huge meshes, which makes RANS with statistical modelling of viscosity and coagulation a reasonable approach. Towards this end, experimental data on micro channel level with evaluation on real application level is crucial. Especially regarding clotting processes, micro fluidic experiments are powerful research tool.
BACKGROUND:
Shear-induced conformational changes of von Willebrand factor (vWF) may be responsible for coagulation disorder and clot formation inside membrane oxygenators (MOs) during extracorporeal membrane oxygenation (ECMO) therapy.
OBJECTIVE:
The aim was to identify vWF structures inside clinically used MOs and employ computational fluid dynamics to verify the corresponding flow conditions.
METHODS:
Samples from gas exchange membranes (GEM) from MOs were analysed for accumulations of vWF and P-selectin-positive platelets using immunofluorescence techniques. Streamlines and shear rates of the flow around GEMs were computed using a laminar steady Reynolds-Averaged-Navier-Stokes approach.
RESULTS:
Most samples were colonized with equally distributed leukocytes, integrated in thin cobweb-like vWF-structures. Only 25 % of the samples showed extended accumulations of vWF. Computed streamlines showed considerable cross flow between interconnected neighbouring channels. Stagnation points were non-symmetric and contact faces were washed around closely. The occurring maximum shear rates ranged from 2,500 to 3,000 1/s.
CONCLUSIONS:
If pronounced vWF structures are present, shape and extent match the flow computations well. Computed shear rates bear a critical degree of uncertainty due to the improper viscosity model. If flow conditions inside the MO were sufficient to affect vWF, a more consistent distribution of vWF across the samples should be present.
BACKGROUND:
Construct stiffness affects healing of bones fixed with locking plates. However, variable construct stiffness reported in the literature may be attributable to differing test configurations and direct comparisons may clarify these differences.
QUESTIONS/PURPOSES:
We therefore asked whether different distal femur locking plate systems and constructs will lead to different (1) axial and rotational stiffness and (2) fatigue under cyclic loading.
METHODS:
We investigated four plate systems for distal femur fixation (AxSOS, LCP, PERI-LOC, POLYAX) of differing designs and materials using bone substitutes in a distal femur fracture model (OTA/AO 33-A3). We created six constructs of each of the four plating systems. Stiffness under static and cyclic loading and fatigue under cyclic loading were measured.
RESULTS:
Mean construct stiffness under axial loading was highest for AxSOS (100.8 N/mm) followed by PERI-LOC (80.8 N/mm) and LCP (62.6 N/mm). POLYAX construct stiffness testing showed the lowest stiffness (51.7 N/mm) with 50% stiffness of AxSOS construct testing. Mean construct stiffness under torsional loading was similar in the group of AxSOS and PERI-LOC (3.40 Nm/degree versus 3.15 Nm/degree) and in the group of LCP and POLYAX (2.63 Nm/degree versus 2.56 Nm/degree). The fourth load level of > 75,000 cycles was reached by three of six AxSOS, three of six POLYAX, and two of six PERI-LOC constructs. All others including all LCP constructs failed earlier.
CONCLUSIONS:
Implant design and material of new-generation distal femur locking plate systems leads to a wide range of differences in construct stiffness.
CLINICAL RELEVANCE:
Assuming construct stiffness affects fracture healing, these data may influence surgical decision-making in choosing an implant system.
Patients with age-related macular degeneration (AMD) or hereditary macular dystrophies (JMD) rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT) at their preferred retinal locus (PRL) used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later) took part in three functional magnetic resonance imaging (fMRI) sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p = 0.001) in the stimulus onset asynchrony (SOA) between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p = 0.014). The following trends were observed: (i) improvement in Vernier acuity for an eccentric line-bisection task; (ii) positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r = 0.531); (iii) positive correlation between the increase in task performance and initial fixation stability (r = 0.730). The first two trends were non-significant, whereas the third trend was significant at p = 0.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex.
Hereditary and age-related forms of macular dystrophy (MD) are characterized by loss of cone function in the fovea, leading to central scotomata and eccentric fixation at the so-called preferred retinal locus (PRL). We investigated whether perceptual learning enhances visual abilities at the PRL. We also determined the neural correlates (3-Tesla fMRI) of learning success. Twelve MD patients (eight with age-related macular dystrophy, four with hereditary macular dystrophies) were trained on a texture discrimination task (TDT) over six days. Patients underwent three fMRI sessions (before, during and after training) while performing the TDT (target at PRL or opposite PRL). Reading speed, visual acuity (Vernier task) and contrast sensitivity were also assessed before and after training. With one exception, all patients showed improved performance (i.e. significant decrease in stimulus onset asynchronies and reaction times, significant increase in hit rates) on the TDT. Eight patients also showed moderate increases in reading speed, six patients showed improved thresholds in contrast sensitivity and nine patients showed improved thresholds in a vernier visual acuity task after TDT training. We found an increase in BOLD response in the projections zone of the PRL in the primary visual cortex in nine of twelve patients after training. The change in fMRI signal correlated (r = .8; p = .02) with the patients’ performance enhancements when the target was in the PRL. The results suggest that perceptual learning can enhance eccentric vision and cortical processing in MD patients.
Computational Fluid Dynamics (CFD) and experimental investigations on a generic model of the trachea have been carried out focusing on the impact of an endotracheal tube (ETT) on the resulting flow regime. It could be shown that detailed modelling of the airway management devices is essential for proper flow prediction, but secondary details as Murphy Eyes can be neglected. Models with bending and connector promote the formation of stronger secondary flows and disturbances which persist for a longer time.
Hereditary and age-related forms of macular dystrophy (MD) are characterized by loss of cone function in the fovea, leading to central scotomata and eccentric fixation at the so-called preferred retinal locus (PRL). We investigated whether perceptual learning enhances visual abilities at the PRL. We also determined the neural correlates (3-Tesla fMRI) of learning success. Twelve MD patients (eight with age-related macular dystrophy, four with hereditary macular dystrophies) were trained on a texture discrimination task (TDT) over six days. Patients underwent three fMRI sessions (before, during and after training) while performing the TDT (target at PRL or opposite PRL). Reading speed, visual acuity (Vernier task) and contrast sensitivity were also assessed before and after training. With one exception, all patients showed improved performance (i.e. significant decrease in stimulus onset asynchronies and reaction times, significant increase in hit rates) on the TDT. Eight patients also showed moderate increases in reading speed, six patients showed improved thresholds in contrast sensitivity and nine patients showed improved thresholds in a vernier visual acuity task after TDT training. We found an increase in BOLD response in the projections zone of the PRL in the primary visual cortex in nine of twelve patients after training. The change in fMRI signal correlated (r = .8; p = .02) with the patients’ performance enhancements when the target was in the PRL. The results suggest that perceptual learning can enhance eccentric vision and cortical processing in MD patients.
We investigated the role of informative feedback on the neural correlates of perceptual learning in a coherent-motion detection paradigm. Stimulus displays consisted of four patches of moving dots briefly (500 ms) presented simultaneously, one patch in each visual quadrant. The coherence level was varied in the target patch from near threshold to high, while the other three patches contained only noise. The participants judged whether coherent motion was present or absent in the target patch. To guarantee central fixation, a secondary RSVP digit-detection task was performed at fixation. Over six training sessions subjects learned to detect coherent motion in a predefined quadrant (i.e., the learned location). Half of our subjects were randomly assigned to the feedback group, where they received informative feedback after each response during training, whereas the other group received non-informative feedback during training that a response button was pressed. We investigated whether the presence of informative feedback during training had an influence on the learning success and on the resulting BOLD response. Behavioral data of 24 subjects showed improved performance with increasing practice. Informative feedback promoted learning for motion displays with high coherence levels, whereas it had little effect on learning for displays with near-threshold coherence levels. Learning enhanced fMRI responses in early visual cortex and motion-sensitive area MT+ and these changes were most pronounced for high coherence levels. Activation in the insular and cingulate cortex was mainly influenced by coherence level and trained location. We conclude that feedback modulates behavioral performance and, to a lesser extent, brain activation in areas responsible for monitoring perceptual learning.
Patients with juvenile retinal dystrophy often report that they are unaware of their central scotoma, suggesting the presence of perceptual filling-in. We used functional Magnetic Resonance Imaging (fMRI) to determine possible neural correlates of perceptual filling-in in patients with retinal distrophy and clinically established central scotoma in both eyes. The data of 5 patients (Stargardt disease, cone-rod dystrophy; mean age 45 yrs; scotoma diameter 10-20°) and of 5 normally sighted controls were analyzed. Fixation behaviour and perimetry were measured with a Nidek microperimeter. Magnetic resonance imaging was performed using a Siemens 3T Allegra scanner. We stimulated the central visual field (30 deg) with a vertically oriented, low spatial frequency (1 c/deg) high-contrast sinewave grating that was either a) continuous, or b) was interrupted by a central grey disk. The disk was either slightly larger than the scotoma (detectable on 75% of trials) or slightly smaller (detectable on 25% of trials). To control for attention, an eccentric fixation task was performed during scanning. Data were analyzed using SPM8 (GLM with ROI analysis to obtain percent signal change for foveal projection zone). Results: for all patients, the BOLD signal in the foveal projection area was significantly higher for the small disk (i.e., condition leading to complete filling-in) than for the large disk (i.e., no filling-in). This effect was absent in the control subjects. Our findings support the existence of an active neural process that leads to filling-in in patients with central visual field scotomata.
Exoskeletons were invented over 100 years ago but have only become popular in the last two decades, especially in the working industry as they can decrease work-related loads significantly. The most often used exoskeletons are for the lower back and shoulder since these are commonly affected body regions. All devices have in common that their purpose is to reduce internal loads of vulnerable body regions. Nevertheless, there is still little understanding on how biomechanical loading in the human body changes when exoskeletons are used. Therefore, further analyses are needed. A promising candidate for these are musculoskeletal models, which are based on an inverse dynamics approach and can calculate external parameters such as ground reaction forces or other interaction forces as well as internal parameters such as joint reaction forces or muscle activities. The various examples in the literature show that these models are increasingly used for assessing the biomechanical effects of exoskeletons on the human body. Furthermore, musculoskeletal models can calculate biomechanical loadings of humans with and without exoskeletons for all kinds of applications and allow an evaluation of their purpose.
Practical Relevance: This article highlights the possibilities of musculoskeletal models for assessing the design and efficiency of occupational exoskeletons. Several practical use cases are described along with distinct descriptions of common implications of musculoskeletal and exoskeleton modeling.
Innovationsmanagement
(2011)
Das Management in der Medizinprodukteindustrie steht vor vielfältigen Herausforderungen. So sinken einerseits die Produktpreise, anderseits wird auch für die kommenden Jahre in vielen Segmenten ein Mengenwachstum erwartet. Dies stellt die internen Prozesse, vom Customer Service bis hin zur Forschung & Entwicklung, auf den Prüfstand. Die Entscheidungsträger auf Kundenseite verändern sich, weg vom Produktanwender hin zu professionellen Einkaufsgemeinschaften mit immer größerer Verhandlungsmacht. Der hohe Internationalisierungsgrad der Unternehmen führt zu einer steigenden Komplexität bei der Implementierung von Marketing-, Vertriebs- und Produktentwicklungsstrategien auf Länderebene. Darüber hinaus werden zunehmend neue Geschäftsmodelle mit hohem Dienstleistungsanteil entwickelt, die mit der traditionellen Lieferantenrolle wenig zu tun haben und von Managern eine neue Fähigkeiten für die Umsetzung erfordern. Die Autoren des Sammelbands greifen die genannten Herausforderungen auf und bieten mit ihren Beiträgen Lösungsansätze, die sowohl für Manager im Medizinprodukteunternehmen als auch für Wissenschaftler und Studierende relevant sind.
In the structure of musculoskeletal injuries, calcaneal fractures account for up to 4 % of all skeletal fractures and up to 60 % of hindfoot fractures. The effect of the displacement of the peripheral fragment of the calcaneus on the calf muscles’s reaction forces at the time of the adoption of the simplified squatting position was investigated by modeling in AnyBody Modeling System 6.0 software. M.gastrocnemius (lateralis et medialis) in the initial phase of motion in all variants of the peripheral fragment displacement did not develop sufficient muscular effort in comparison to the intact calcaneus. M.soleus medialis et lateralis showed significant increase in muscle activity rates in the initial phase of motion (41.87 ± 1.90 H and 52.07 ± 2.10 H) before reaching its maximum values, as compared with those of the intact calcaneus. In the final phase of the movement, upon muscle reaches its maximum length, muscular strength indicators of the m.soleus returned to their original values or were significantly below them. The decline in muscle strength was due to shortening of the moment arm or muscle excursion in case of convergence of muscle attachment points. When the peripheral fragment is displaced, due to putting down the heel to the surface of the support in terms of anatomical muscle lengthening, it takes extra effort to achieve rest length and its maximum power. In all types of the displacement of the peripheral fragment, the function of three-headed calf muscle is disturbed with involvement of additional muscular effort and energy expenditure. This fact should motivate the surgeon on the need for accurate repositioning of bone fragments in calcaneal fractures with the displacement of the peripheral fragment.
The Impact of the ObamaCare Excise Tax on Innovation and Entrepreneurship – Early Empirical Findings
(2015)
This study addresses aspects of governmental influence on innovation by analyzing the impact of the ObamaCare excise tax on the medical device industry. We initially give an overview of common approaches to measuring innovativeness and entrepreneurship, empirically assess whether existing metrics are suitable for investigating the innovation performance of the U.S. medical device industry, and define a new measure (firm innovation activity) for entrepreneurship. Then we perform a quantitative analysis to explore the impact of the tax. We analyze more than 60,000 product clearances from 1996 to 2013, using the FDA database. We find a significant relationship between product counts and revenues for one segment. Contrary to the present criticism of the excise tax, we find hardly any noteworthy response in either firm innovation activity or number of products launched in the year after the tax was introduced. The 2013 reduction of new product submissions is well within the limits of typical annual fluctuations observed in previous years. This provides a first indication that the excise tax act did not have a strong impact on innovative activities through the present.
Innovation diffusion points toward how innovations spread into the market after launch. This paper investigates diffusion dynamics at market entry time and proposes a new evolution pattern at the intersection between inventions and innovations. With this in mind, we initially prove that patent filings correlate with new product introductions in the U.S. spine market. Then we test our new theory supposing that certain patent filing threshold numbers accelerate strong economic returns in terms of innovations. We find that firms hitting certain patent filing thresholds significantly increase their product launches in the mentioned market. Moreover, the results seem to indicate that economic returns of inventions may be measured substantially. Thus, this paper suggests a new research area by utilizing our proposed concept about an Innovation Outcome Trigger Value (IOTV). Furthermore, the implications may also be interesting for practitioners, since we empirically prove that inventive activities turn out to be worthwhile, indeed.
Introduction:
Neointimal hyperplasia after percutaneous coronary intervention remains a major determinant of in-stent restenosis (ISR). The extent of mechanical vessel injury correlates with ISR. A new ex vivo porcine stent model was introduced and evaluated comparing different stent designs.
Methods:
Coronary arteries were prepared from pig hearts from the slaughterhouse and used for ex vivo implantations of coronary stents. One basic stent design in two configurations (dogbone, DB; non-dogbone, NDB) was used. Vascular injury was determined according to a modified injury score (IS).
Results:
Standardized experimental conditions ensured comparable vessel dimensions and overstretch data. DB stents caused more severe IS compared to NDB stents. The mean IS and the IS at the distal end of all stents were significantly reduced for NDB stents (ISMean, DB, 1.16 ±0.12; NDB, 1.02 ±0.12; p=0.018; ISDist, DB, 1.39 ±0.28; NDB, 1.13 ±0.24; p=0.03).
Discussion/Conclusion:
The introduced ex-vivo model allowed the evaluation of different stent designs exclude unfavorable stent designs.
The good availability and the large content of adult stem cells in adipose tissue has made it one of the most interesting tissues in regenerative medicine. Although lipofilling is one of the most frequent procedures in plastic surgery, the method still struggles with high absorption rates and volume losses of up to 70%. Therefore, many efforts have been made to optimize liposuction and to process the harvested tissue in order to increase fat graft retention. Because of their immunomodulatory properties, their cytokine secretory activity, and their differentiation potential, enrichment with adipose tissue-derived stem cells was identified as a promising tool to promote transplant survival. Here, we review the important parameters for lipofilling optimization. Finally, we present a new method for the enrichment of lipoaspirate with adipose tissue-derived stem cells and discuss the parameters that contribute to fat graft survival.
Elbow stability is derived from a combination of muscular, ligamentous, and bony structures. After an elbow trauma the stability of the joint is an important decision criterion for the subsequent treatment. The decision regarding non-operative/operative care depends mostly on subjective assessments of medical experts. Therefore, the aim of this study is to use musculoskeletal simulations as an objective assessment tool to investigate the extent to which failure of different stabilizers affects the elbow stability and how these observations correspond to the assessment from clinical practice. A musculoskeletal elbow simulation model was developed for this aim. To investigate the stability of the elbow, varus/valgus moments were applied under 0°, 45°and 90° flexion while the respective cubital angle was analyzed. This was performed for nine different injury scenarios, which were also evaluated for stability by clinical experts. With the results, it can be determined by which injury pattern and under which flexion angle the elbow stability is impaired regarding varus/valgus moments. The scenario with a complete failure of the medial and lateral ligaments and a fracture of the radial head was identified as having the greatest instability. The study presented a numerical determination of elbow stability against varus/valgus moments regarding clinical injury patterns, as well as a comparison of the numerical outcome with experience gained in clinical practice. The numerical predictions agree well with the assessments of the clinical specialists. Thus, the results from musculoskeletal simulation can make an important contribution to a more objective assessment of the elbow stability.
Purpose
Lipofilling has been established as a standard technique for contour enhancement following breast reconstruction. However, there is a paucity in current literature regarding the use of this technique for complete reconstruction of the female breast as an alternative to conventional techniques, such as expander or flap-based procedures. In particular, the influence of pre-operative irradiation for successful reconstruction has rarely been examined in published studies. Here, the authors describe their experience with successful fat injection in pre-radiated breasts in comparison with non-pre-radiated patients.
Methods
In this retrospective study, we examined a total of 95 lipofilling treatments on 26 patients (28 breasts). All of them experienced mastectomy following breast cancer; local breast defects after partial resection of the gland were not included in this study. In total, 47 lipofilling procedures in 12 non-irradiated patients (14 breasts) and 48 procedures in 14 irradiated women (also 14 breasts) were performed. Per session, approximately 297 +/- 112 cc of adipose tissue was grafted in group A (no radiotherapy) and approximately 259 +/- 93 cc was grafted in group B (radiotherapy).
Results
Among the group of women without pre-operative radiation, 71% of breast reconstructions limited to lipofilling only showed constant engraftment of fat tissue with a successful reconstructive result, whereas only 21% of the patients with pre-radiated breasts showed complete reconstruction of the breast with a permanent fat in-growth.
Conclusion
Preoperative radiotherapy significantly impedes successful completion of breast reconstructions planned only by autologous fat transfer. Patients should be selected individually and carefully for complete breast reconstruction using lipofilling only.
Accurate and reliable information about three-dimensional (3D) knee joint laxity can prevent misdiagnosis and avoid incorrect treatments. Nevertheless, knee laxity assessments presented in the literature suffer from significant drawbacks such as soft tissue artifacts, restricting the knee within the measurement, and the absence of quantitative knee ligament property information. In this study, we demonstrated the applicability of a novel methodology for measuring 3D knee laxity, combining robotics- and image-based technology. As such technology has never been applied to healthy living subjects, the aims of this study were to develop novel technology to measure 3D knee laxity in vivo and to provide proof-of-concept 3D knee laxity measurements. To measure tibiofemoral movements, four healthy subjects were placed on a custom-built arthrometer located inside a low dose biplanar X-ray system with an approximately 60 deg knee flexion angle. Anteroposterior and mediolateral translation as well as internal and external rotation loads were subsequently applied to the unconstrained leg, which was placed inside a pneumatic cast boot. Bone contours were segmented in the obtained X-rays, to which subject-specific bone geometries from magnetic resonance imaging (MRI) scans were registered. Afterward, tibiofemoral poses were computed. Measurements of primary and secondary laxity revealed considerable interpersonal differences. The method differs from those available by the ability to accurately track secondary laxity of the unrestricted knee and to apply coupled forces in multiple planes. Our methodology can provide reliable information for academic knee ligament research as well as for clinical diagnostics in the future.
Autologous lipotransfer is a promising method for tissue regeneration, because white adipose tissue contains a heterogeneous cell population, including mesenchymal stem cells, endothelial cells, immune cells, and adipocytes. In order to improve the outcome, adipose tissue can be processed before application. In this study, we investigated changes caused by mechanical processing.
Lipoaspirates were processed using sedimentation, first-time centrifugation, shear-force homogenization, and second-time centrifugation. The average adipocyte size, stromal vascular cell count, and adipocyte depot size were examined histologically at every processing step. In addition, the adipose derived stem cells (ADSCs) were isolated and differentiated osteogenically and adipogenically. While homogenization causes a disruption of adipocyte depots, the shape of the remaining adipocytes is not changed. On average, these adipocytes are smaller than the depot adipocytes, they are surrounded by the ECM, and therefore mechanically more stable. The volume loss of adipocyte depots leads to a significant enrichment of stromal vascular cells such as ADSCs. However, the mechanical processing does not change the potential of the ADSCs to differentiate adipogenically or steogenically. It thus appears that mechanically processed lipoaspirates are promising for the reparation of even mechanically stressed tissue as that found in nasolabial folds. The changes resulting from the processing correspond more to a filtration of mechanically less stable components than to a manipulation of the tissue.
Brain lesions in language-related cortical areas remain a challenge in the clinical routine. In recent years, the resting-state fMRI (RS-fMRI) was shown to be a feasible method for preoperative language assessment. The aim of this study was to examine whether language-related resting-state components, which have been obtained using a data-driven independent-component-based identification algorithm, can be supportive in determining language dominance in the left or right hemisphere. Twenty patients suffering from brain lesions close to supposed language-relevant cortical areas were included. RS-fMRI and task-based (TB-fMRI) were performed for the purpose of preoperative language assessment. TB-fMRI included a verb generation task with an appropriate control condition (a syllable switching task) to decompose language-critical and language-supportive processes. Subsequently, the best fitting ICA component for the resting-state language network (RSLN) referential to general linear models (GLMs) of the TB-fMRI (including models with and without linguistic control conditions) was identified using an algorithm based on the Dice index. Thereby, the RSLNs associated with GLMs using a linguistic control condition led to significantly higher laterality indices than GLM baseline contrasts. LIs derived from GLM contrasts with and without control conditions alone did not differ significantly. In general, the results suggest that determining language dominance in the human brain is feasible both with TB-fMRI and RS-fMRI, and in particular, the combination of both approaches yields a higher specificity in preoperative language assessment. Moreover, we can conclude that the choice of the language mapping paradigm is crucial for the mentioned benefits.
Medical Device Regulation
(2019)
BACKGROUND: Autologous fat grafting (AFG) has been established over the past two decades as an additive technique during and after breast reconstruction. Complete reconstruction of the breast mound with AFG alone represents an exceptional technique that has been published mostly in case reports or in studies with limited cases.The purpose of this study is to investigate the influence of three different techniques for breast reconstruction on the recovery of skin sensitivity at the reconstructed breast.
METHODS: The study included 30 patients after mastectomy following breast cancer. Three groups were examined: A) breast reconstruction by autologous fat grafting (AFG), B) breast reconstruction by deep inferior epigastric artery perforator flap (DIEP) and C) breast reconstruction by expander/implant (TE).Biometric data were compared; sensitivity tests were performed using Semmes-Weinstein monofilaments.The non-operated, healthy contralateral breasts of the patients were used as a reference.
RESULTS: While the traditional reconstruction techniques by microsurgical anastomosed perforator flap or expander/implant showed a strongly decreased or completely missing sensitivity of the skin, the tests after reconstruction by AFG represented high values of sensory recovery, which came close to the reference group of non-operated breasts.
CONCLUSION: To our knowledge, this is the first study to compare skin sensitivity after AFG-based reconstruction to established techniques for breast reconstruction. We could demonstrate in a limited group of patients, that breast reconstruction by autologous fat grafting can achieve higher values of skin sensitivity compared to traditional techniques.
Die Aufmerksamkeit für Unternehmensgründungen hat in den letzten Jahren extrem zugenommen. Grundsätzlich muss ein Start-up in einem kompetitiven Umfeld erfolgreich sein, um bestehen zu können. Der Weg dorthin wird maßgeblich beeinflusst durch Planung und finanzielle Ressourcen, die die Gründer bereitstellen müssen. In der Medizinprodukteindustrie kommen zusätzlich große Hürden hinzu, die u. a. einen kurzen Produktlebenszyklus, lange Projektlaufzeiten, aufwendige klinische Studien und aktuell neue gesetzliche Verordnungen betreffen. Dieser Beitrag konzentriert sich zunächst auf mögliche Fördermittel und Beratung von Start-up-Projekten aus dem Hochschulbereich. Aus einer Analyse derzeit existierender Gründerwettbewerbe im Hinblick auf das Gesundheitswesen werden dem Leser entsprechende Adressen zum Einwerben von Fördermitteln geliefert. Darüber hinaus wird ein Pilot-Prozess vorgestellt, wie eine Ausgründungsberatung an der Hochschule Ulm im Studiengang Medizintechnik derzeit verläuft. Dies kann möglicherweise ein Anknüpfungspunkt für eine zukünftige Institutionalisierung von Spin-off-Vorhaben aus dem Hochschulbereich sein.
Tissue-engineered vessel grafts have to mimic the biomechanical properties of native blood vessels. Manufacturing processes often condition grafts to adapt them to the target flow conditions. Graft stiffness is influenced by material properties and dimensions and determines graft compliance. This proof-of-concept study evaluated a contact-free method to monitor biomechanical properties without compromising sterility. Forced vibration response analysis was performed on human umbilical vein (HUV) segments mounted in a buffer-filled tubing system. A linear motor and a dynamic signal analyser were used to excite the fluid by white noise (0-200 Hz). Vein responses were read out by laser triangulation and analysed by fast Fourier transformation. Modal analysis was performed by monitoring multiple positions of the vessel surface. As an inverse model of graft stiffening during conditioning, HUV were digested proteolytically, and the course of natural frequencies (NFs) was monitored over 120 min. Human umbilical vein showed up to five modes with NFs in the range of 5-100 Hz. The first natural frequencies of HUV did not alter over time while incubated in buffer (p = 0.555), whereas both collagenase (-35%, p = 0.0061) and elastase (-45%, p < 0.001) treatments caused significant decreases of NF within 120 min. Decellularized HUV showed similar results, indicating that changes of the extracellular matrix were responsible for the observed shift in NF. Performing vibration response analysis on vessel grafts is feasible without compromising sterility or integrity of the samples. This technique allows direct measurement of stiffness as an important biomechanical property, obviating the need to monitor surrogate parameters. Copyright (C) 2016 John Wiley & Sons, Ltd.
This paper discusses modeling and nonlinear control of a joint antagonistically actuated by two pneumatic, artificial muscles. A single model of the whole system is obtained by a combined physical and phenomenological modeling approach. The combined model for the joint, the muscles and the proportional valves results in a nonlinear, affine-in-control system description. The model is used to derive control laws for an input/output linearization approach to linearize the plant. Modeling and parametrization errors are covered via an outer control loop consisting of a state-feedback which is extended by an additional feedback of error integral. Extensive experimental results show the quality of the model and the performance of the respective control laws.
Einleitung:
Blutdruck gilt als sogenannter Vitalparameter als einer der grundlegenden Indikatoren für den Gesundheitszustand einer Person. Sowohl zu niedriger als auch zu hoher Blutdruck kann lebensbedrohend sein, letzerer ist darüber hinaus ein Risikofaktor insbesondere für Herz-Kreislauferkrankungen, die trotz wichtiger Fortschritte in der Behandlung immer noch die häufigste Todesursache in Deutschland darstellen. Die Hämodynamik, also die raumzeitliche Dynamik des Blutflusses, und der Gefäßzustand sind eng verbunden mit dem Blutdruck und ebenfalls von hoher klinischer Relevanz, u.a. zur Identifikation von Durchblutungsstörungen und ungünstigen Druckverteilungen der Gefäßwand. Innovationen in der Messtechnik als auch in der Datenanalyse bieten heute neue Möglichkeiten der Erfassung und Bewertung von Blutdruck, Hämodynamik und Gefäßzustand [1], [2], [3], [4].
Methodik:
In einer gemeinsamen Workshopserie der AG Medizinische Bild- und Signalverarbeitung der GMDS und des Fachausschusses Biosignale der DGBMT werden wir neue Ansätze und Lösungen für Mess- und Analyseverfahren zu Blutdruck und -fluss sowie zum Gefäßzustand vorstellen und diskutieren. Dabei stehen im ersten Workshop auf der GMDS Jahrestagung Bildbasierte Verfahren im Zentrum, während der zweite Workshop auf der DGBMT Jahrestagung den Fokus auf Biosignalbasierten Verfahren legt. Es werden aktuelle Forschungsergebnisse vorgestellt und diskutiert. Es sind jeweils mehrere Vorträge geplant mit ausreichend Zeit zur Diskussion. Folgende Vorträge sind geplant (Arbeitstitel):
Sebastian Zaunseder: Videobasierte Erfassung des Blutdrucks
Anja Hennemuth: A Visualization Toolkit for the Analysis of Aortic Anatomy and Pressure Distribution
Lars Krenkel: Numerische Analyse der Rupturwahrscheinlichkeit zerebraler Aneurysmata
Susanne Schnell: Messung des Blutflusses und hämodynamischer Parameter mit 4D flow MRI: Möglichkeiten und Herausforderungen
Ergebnisse:
Ziel des Workshops ist die Identifikation von innovativen Ansätzen und neuen Methoden zur qualitativen und quantitativen Bestimmung von hämodynamischen Parametern sowie deren kritische Bewertung durch die Community für die Eignung in der klinischen Entscheidungsunterstützung.
Diskussion:
Der Workshop leistet inhaltlich einen Beitrag zu zentralen Aspekten für die Herz-Kreislauf-Medizin. Er bringt dabei Expertise aus verschiedenen Bereichen zusammen und schlägt die Brücke zwischen Kardiologie, Medizininformatik und Medizintechnik.
Schlussfolgerung:
Innovative Technologien aus Medizintechnik und Informatik ermöglichen zunehmend einfache und raumzeitlich aufgelöste Erfassung und Bewertung wichtiger Informationen zur Unterstützung von Diagnose und Therapieverfolgung.
[1] Zaunseder S, Trumpp A, Wedekind D, Malberg H. Cardiovascular assessment by imaging photoplethysmography - a review. Biomed Tech (Berl). 2018 Oct 25;63(5):617–34.
[2] Huellebrand M, Messroghli D, Tautz L, Kuehne T, Hennemuth A. An extensible software platform for interdisciplinary cardiovascular imaging research. Comput Methods Programs Biomed. 2020 Feb;184:105277.
[3] Schmitter S, Adriany G, Waks M, Moeller S, Aristova M, Vali A, et al. Bilateral Multiband 4D Flow MRI of the Carotid Arteries at 7T. Magn Reson Med. 2020 Oct;84(4):1947–60.
[4] Birkenmaier C, and Krenkel, L. Flow in Artificial Lungs. In: New Results in Numerical and Experimental Fluid Mechanics XIII. Contributions to the 22nd STAB/DGLR Symposium. Springer; 2021.
Convolutional Neural Networks for Approximation of Internal Non-Newtonian Multiphase Flow Fields
(2021)
Neural networks (NNs) as an alternative method for universal approximation of differential equations have proven to be computationally efficient and still sufficiently accurate compared to established methods such as the finite volume method (FVM). Additionally, analysing weights and biases can give insights into the underlying physical laws. FVM and NNs are both based upon spacial discretisation. Since a Cartesian and equidistant grid is a raster graphics, image-to-image regression techniques can be used to predict phase velocity fields as well as particle and pressure distributions from simple mass flow boundary conditions. The impact of convolution layer depth and number of channels of a ConvolutionDeconvolution Regression Network (CDRN), on prediction performance of internal non-Newtownian multiphase flows is investigated. Parametric training data with 2055 sets is computed using FVM. To capture significant non-Newtownian effects of a particle-laden fluid (e.g. blood) flowing through small and non-straight channels, an Euler-Euler multiphase approach is used. The FVM results are normalized and mapped onto an equidistant grid as supervised learning target. The investigated NNs consist of n= {3, 5, 7} corresponding encoding/decoding blocks and different skip connections. Regardless of the convolution depth (i.e. number of blocks), the deepest spacial down-sampling via strided convolution is adjusted to result in a 1 × 1 × f · 2nfeature map, with f = {8, 16, 32}. The prediction performance expressed is as channel-averaged normalized root mean squared error (NRMSE). With a NRMSE of < 2 · 10-3, the best preforming NN has f = 32 initial feature maps, a kernel size of k = 4, n = 5 blocks and dense skip connections. Average inference time from this NN takes < 7 · 10-3s. Worst accuracy at NRMSE of approx 9 · 10-3is achieved without any skips, at k = 2, f = 16 and n = 3, but deployment takes only < 2 · 10-3s Given an adequate training, the prediction accuracy improves with convolution depth, where more features have higher impact on deeper NNs. Due to skip connections and batch normalisation, training is similarly efficient, regardless of the depth. This is further improved by blocks with dense connections, but at the price of a drastically larger model. Depending on geometrical complexity, spacial resolution is critical, as it increases the number of learnables and memory requirements massively.
Anatomical differences between individuals are often neglected in musculoskeletal models, but they are necessary in case of subject-specific questions regarding the lumbar spine. A modification of models to each subject is complex and the effects on lumbar loading are difficult to assess. One objective of this work is to create a validated musculoskeletal human model, which facilitates a subject-specific modification of the lumbar geometry. In a second step, important parameters are identified in sensitivity studies and at last, a case study regarding multifidus muscle atrophy after a disc herniation is conducted.
The results of the studies indicate that lumbar motion and loading is dependent on lumbar ligament stiffness. Furthermore, subject-specific modelling of the lumbar spine should include at least the vertebral height, disc height and lumbar lordosis. The results of the case study suggest that an overloading of the multifidus muscle could follow disc herniation. Additionally, a subsequent atrophy of the muscles could expose adjacent levels to an increased loading, but these findings are highly dependent on the individual.
The implant stability and biomechanical response of periprosthetic bone in acetabulum around total hip joint replacement (THR) devices depend on a host of parameters, including design of articulating materials, gait cycle and subject parameters. In this study, the impact of shell design (conventional, finned, spiked, and combined design) and liner material on the biomechanical response of periprosthetic bone has been analyzed using finite element (FE) method. Two different liner materials: high density polyethylene-20% hydroxyapatite-20% alumina (HDPE-20%HA-20%Al2O3) and highly cross-linked ultrahigh molecular weight polyethylene (HC-UHMWPE) were used. The subject parameters included bone condition and bodyweight. Physiologically relevant load cases of a gait cycle were considered. The deviation of mechanical condition of the periprosthetic bone due to implantation was least for the finned shell design. No significant deviation was observed at the bone region adjacent to the spikes and the fins. This study recommends the use of the finned design, particularly for weaker bone conditions. For stronger bones, the combined design may also be recommended for higher stability. The use of HC-UHMWPE liner was found to be better for convensional shell design. However, similar biomechanical response was captured in our FE analysis for both the liner materials in case of other shell designs. Overall, the study establishes the biomechanical response of periprosthetic bone in the acetabular with preclinically tested liner materials together with new shell design for different subject conditions.
Epigenetic modifiers of the histone deacetylase (HDAC) family contribute to autoimmunity, cancer, HIV infection, inflammation, and neurodegeneration. Hence, histone deacetylase inhibitors (HDACi), which alter protein acetylation, gene expression patterns, and cell fate decisions, represent promising new drugs for the therapy of these diseases. Whereas pan-HDACi inhibit all 11 Zn2+-dependent histone deacetylases (HDACs) and cause a broad spectrum of side effects, specific inhibitors of histone deacetylase 6 (HDAC6i) are supposed to have less side effects. We present the synthesis and biological evaluation of Marbostats, novel HDAC6i that contain the hydroxamic acid moiety linked to tetrahydro-β-carboline derivatives. Our lead compound Marbostat-100 is a more potent and more selective HDAC6i than previously established well-characterized compounds in vitro as well as in cells. Moreover, Marbostat-100 is well tolerated by mice and effective against collagen type II induced arthritis. Thus, Marbostat-100 represents a most selective known HDAC6i and the possibility for clinical evaluation of a HDAC isoform-specific drug.
Over the past decade, veno-venous extracorporeal membrane oxygenation (vvECMO) has been increasingly utilized in respiratory failure in patients. This study presents our institution´s experience focusing on the life span of ECMO systems reflecting the performance of a particular system. A retrospective review of our ECMO database identified 461 adult patients undergoing vvECMO (2010-2017). Patients that required more than one system and survived the first exchange >24 hours (n = 139) were included. Life span until the first exchange and exchange criteria were analyzed for all systems (PLS, Cardiohelp HLS-set, both Maquet Cardiopulmonary, Rastatt, Germany; Deltastream/Hilite7000LT, iLA-activve, Xenios/NovaLung, Heilbronn, Germany; ECC.O5, LivaNova, Mirandola, Italy). At our ECMO center, the frequency of a system exchange was 30%. The median (IQR) life span was 9 (6-12) days. There was no difference regarding the different systems (p = 0.145 and p = 0.108, respectively). However, the Deltastream systems were exchanged more frequently due to elective technical complications (e. g. worsened gas transfer, development of coagulation disorder, increased bleedings complications) compared to the other exchanged systems (p = 0.013). In summary, the used ECMO systems are safe and effective for acute respiratory failure. There is no evidence for the usage of a specific system. Only the increased predictability of an imminent exchange preferred the usage of a Deltastream system. However, the decision to use a particular system should not depend solely on the possible criteria for an exchange.