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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.
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.
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.
Introduction
Aim of this study is to validate some constitutive models by assessing their capabilities in describing and predicting uniaxial and biaxial behavior of porcine aortic tissue.
Methods
14 samples from porcine aortas were used to perform 2 uniaxial and 5 biaxial tensile tests. Transversal strains were furthermore stored for uniaxial data. The experimental data were fitted by four constitutive models: Holzapfel-Gasser-Ogden model (HGO), model based on generalized structure tensor (GST), Four-Fiber-Family model (FFF) and Microfiber model. Fitting was performed to uniaxial and biaxial data sets separately and descriptive capabilities of the models were compared. Their predictive capabilities were assessed in two ways. Firstly each model was fitted to biaxial data and its accuracy (in term of R2 and NRMSE) in prediction of both uniaxial responses was evaluated. Then this procedure was performed conversely: each model was fitted to both uniaxial tests and its accuracy in prediction of 5 biaxial responses was observed.
Results
Descriptive capabilities of all models were excellent. In predicting uniaxial response from biaxial data, microfiber model was the most accurate while the other models showed also reasonable accuracy. Microfiber and FFF models were capable to reasonably predict biaxial responses from uniaxial data while HGO and GST models failed completely in this task.
Conclusions
HGO and GST models are not capable to predict biaxial arterial wall behavior while FFF model is the most robust of the investigated constitutive models. Knowledge of transversal strains in uniaxial tests improves robustness of constitutive models.
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.
BACKGROUND:
Validation and verification of multibody musculoskeletal models sEMG is a difficult process because of the reliability of sEMG data and the complex relationship of muscle force and sEMG.
OBJECTIVE:
This work aims at comparing experimentally recorded and simulated muscle activities considering a numerical model for crosstalk. METHODS:
For providing an experimentally derived reference data set, subjects were performing elevations of the arm, where the activities of the contemplated muscle groups were measured by sEMG sensors. Computed muscle activities were further processed and transformed into an artificial electromyographical signal, which includes a numerical crosstalk model. In order to determine whether the crosstalk model provides a better agreement with the measured muscle activities, the Pearson correlation coefficient has been computed as a qualitative way of assessing the curve progression of the data sets.
RESULTS:
The results show an improvement in the correlation coefficient between the experimental data and the simulated muscle activities when taking crosstalk into account.
CONCLUSIONS:
Although the correlation coefficient increased when the crosstalk model was utilized, it is questionable if the discretization of both, the crosstalk and the musculoskeletal model, is accurate enough.
BACKGROUND: Validation and verification of multibody musculoskeletal models sEMG is a difficult process because of the reliability of sEMG data and the complex relationship of muscle force and sEMG. OBJECTIVE: This work aims at comparing experimentally recorded and simulated muscle activities considering a numerical model for crosstalk. METHODS: For providing an experimentally derived reference data set, subjects were performing elevations of the arm, where the activities of the contemplated muscle groups were measured by sEMG sensors. Computed muscle activities were further processed and transformed into an artificial electromyographical signal, which includes a numerical crosstalk model. In order to determine whether the crosstalk model provides a better agreement with the measured muscle activities, the Pearson correlation coefficient has been computed as a qualitative way of assessing the curve progression of the data sets. RESULTS: The results show an improvement in the correlation coefficient between the experimental data and the simulated muscle activities when taking crosstalk into account. CONCLUSIONS: Although the correlation coefficient increased when the crosstalk model was utilized, it is questionable if the discretization of both, the crosstalk and the musculoskeletal model, is accurate enough.
In recent years, musculoskeletal computation has become a widely used tool to investigate joint and muscle forces within the human body. However, the issue of muscle fatigue is not considered adequately in most models and is a challenging task. One aspect that needs to be examined is the interaction of muscles during an exhausting task. Therefore, an experimental study was designed to analyze the changes of back muscle recruitment pattern during such exercises.
In this study 38 subjects (27 male, 11 female, height = 177±8.5 cm, weight = 74.0±13.6 kg) participated. Each subject had to perform three static and three dynamic exhausting exercises where the back muscles were loaded with subject specific forces using a dynamometer adapter especially designed for the trunk muscles. To collect the muscle activity, twelve surface electromyography sensors were applied on the back, and four on the abdominal muscles. Muscle activity and fatigue were analyzed by calculating the maximum voluntary contraction normalized signal and the median frequency. At first the fatigue of m. erector spinae and m. multifidi was analyzed, since these muscles carry the main load during the exercises. Subsequently the activity of the m. trapezius, m. rectus abdominis and m. obliquus externus were investigated to determine recruitment patterns. To gain more detailed information of these patterns a numerical model was built using the AnyBody Modeling System™. Analyzing the measurements, we can observe an increasing muscle activity during isokinetic exercises while the force is constant. Since the activity in the simulation is defined as the current force output divided by the strength of the muscle, the strength parameter was scaled down based on the measured data, assuming a linear force – activity correlation, and using a numerical algorithm considering the influence of cross talk.
The results show, that changes in recruitment pattern can be divided into three major subgroups. Prior to total exhaustion, some of the subjects show additional activation of muscles in the trapezius region, while other subjects show an additional activation of abdominal muscles, increasing the intra-abdominal pressure which supports the spine. In the third group an activation in both regions can be observed.
The numerical simulations show an increasing activity of abdominal muscles as well as muscles in the upper back. Especially the m. latissimus dorsi shows a significantly higher activity.
The results lead to the conclusion that prior to total exhaustion, additional muscles are recruited to support the main muscles. It was shown that abdominal muscles are activated to support back muscles by pressurizing the trunk cavity to delay total exhaustion as long as possible. In conclusion, the results show that changes in muscle recruitment pattern need to be considered when introducing muscle fatigue to musculoskeletal models.
Die fortschreitende Digitalisierung des Gesundheitswesens ebnet auch den Weg einer stärkeren Verbreitung der telemedizinischen Versorgung in Deutschland. Die Politik erleichtert diesen Weg, z.B. mit dem eHealth-Gesetz oder mit der Lockerung des "Fernbehandlungsverbots" durch den Deutschen Ärztetag. Dabei wird schon aus der Definition (siehe z.B. die unten stehende Definition der AG Telemedizin) klar, dass Telemedizin keine neue medizinische Disziplin begründet. Bei Telemedizin handelt es sich nur um ein technisches Werkzeug in Kombination mit geeigneten klinischen Prozessen, damit bestehende medizinische Expertise unter Einsatz von Informations- und Kommunikationstechnologien räumliche Entfernungen oder einen zeitlichen Versatz überbrücken kann. Patientinnen und Patienten können also behandelt werden, auch wenn sie vom Arzt räumlich entfernt sind.
The number of spinal fusion surgeries is steadily increasing and biomechanical consequences are still in debate. The aim of this study is to provide biomechanical insights into the sagittal balance of the spine and to compare spinal load before and after spinal fusion.
METHOD:
The joint reaction forces of 52 patients were analyzed in proximo-distal and antero-posterior direction from the levels T12-L1 to L5-S1 using musculoskeletal simulations.
RESULTS:
In 104 simulations, pre-surgical forces were equal to post-surgical. The levels L4-L5 and T12-L1, however, showed increased spinal forces compression forces with higher sagittal displacement. Improved restauration of sagittal balance was accompanied by lower spinal load. AP shear stress, interestingly decreased with sagittal imbalance.
CONCLUSION:
Imbalanced spines have a risk of increased compression forces at Th12-L1. L4-L5 always has increased spinal loads. These slides can be retrieved under Electronic Supplementary Material.
Background
Iliac crest bone harvesting is a frequently performed surgical procedure widely used to treat bone defects. The objective of this study is to assess the biomechanical quantities related to risk for pelvic fracture after harvesting an autologous bone graft at the anterior iliac crest.
Methods
Finite element models with a simulated harvest site (sized 15 × 20 mm, 15 × 35 mm, 30 × 20 mm and 30 × 35 mm) in the iliac wing are created. The relevant loading case is when the ipsilateral leg is lifted off the ground. Musculoskeletal analysis is utilized to compute the muscle and joint forces involved in this motion. These forces are used as boundary conditions for the finite element analyses. Bone tissue stress is analyzed.
Results
Critical stress peaks are located between the anterior superior iliac spine (ASIS) and the anterior edge of the harvest site. Irrespective of the graft size, the iliac wing does not show any significant stress peaks with the harvest site being 20 to 25 mm posterior to the ASIS. The harvest area itself inhibits the distribution of the forces applied on the ASIS to extend to the posterior iliac wing. This leads to a lack of stress posterior to the harvest site. A balanced stress distribution with no stress peaks appears when the bone graft is taken below the iliac crest.
Conclusion
A harvest site located at least 20 to 25 mm posterior to the ASIS should be preferred to minimize the risk of iliac fatigue fracture.
Virtual training of bone milling requires realtime and realistic haptics of the interaction between the ”virtual mill” and a ”virtual bone”. We propose an exponential abrasion model between a virtual one and the mill bit and combine it with a coarse representation of the virtual bone and the mill shaft for collision detection using the Bullet Physics Engine. We compare our exponential abrasion model to a widely used linear abrasion model and evaluate it quantitatively and qualitatively. The evaluation results show, that we can provide virtual milling in real-time, with an abrasion behavior similar to that proposed in the literature and with a realistic feeling of five different surgeons.
Backround
Scaphoidectomy and midcarpal fusion can be performed using traditional fixation methods like K-wires, staples, screws or different dorsal (non)locking arthrodesis systems. The aim of this study is to test the Aptus four corner locking plate and to compare the clinical findings to the data revealed by CT scans and semi-automated segmentation.
Methods:
This is a retrospective review of eleven patients suffering from scapholunate advanced collapse (SLAC) or scaphoid non-union advanced collapse (SNAC) wrist, who received a four corner fusion between August 2011 and July 2014. The clinical evaluation consisted of measuring the range of motion (ROM), strength and pain on a visual analogue scale (VAS). Additionally, the Disabilities of the Arm, Shoulder and Hand (QuickDASH) and the Mayo Wrist Score were assessed. A computerized tomography (CT) of the wrist was obtained six weeks postoperatively. After semi-automated segmentation of the CT scans, the models were post processed and surveyed.
Results
During the six-month follow-up mean range of motion (ROM) of the operated wrist was 60°, consisting of 30° extension and 30° flexion. While pain levels decreased significantly, 54% of grip strength and 89% of pinch strength were preserved compared to the contralateral healthy wrist. Union could be detected in all CT scans of the wrist. While X-ray pictures obtained postoperatively revealed no pathology, two user related technical complications were found through the 3D analysis, which correlated to the clinical outcome.
Conclusion
Due to semi-automated segmentation and 3D analysis it has been proved that the plate design can keep up to the manufacturers’ promises. Over all, this case series confirmed that the plate can compete with the coexisting techniques concerning clinical outcome, union and complication rate.
In order to fix a fracture using minimally invasive surgery approaches, surgeons are drilling complex and tiny bones with a 2 dimensional X-ray as single imaging modality in the operating room. Our novel haptic force-feedback and visual assisted training system will potentially help hand surgeons to learn the drilling procedure in a realistic visual environment. Within the simulation, the collision detection as well as the interaction between virtual drill, bone voxels and surfaces are important. In this work, the chai3d collision detection and force calculation algorithms are combined with a physics engine to simulate the bone drilling process. The chosen Bullet-Physics-Engine provides a stable simulation of rigid bodies, if the collision model of the drill and the tool holder is generated as a compound shape. Three haptic points are added to the K-wire tip for removing single voxels from the bone. For the drilling process three modes are proposed to emulate the different phases of drilling in restricting the movement of a haptic device.
This work presents a systematic review concerning recent studies and technologies of machine learning for Barrett's esophagus (BE) diagnosis and treatment. The use of artificial intelligence is a brand new and promising way to evaluate such disease. We compile some works published at some well-established databases, such as Science Direct, IEEEXplore, PubMed, Plos One, Multidisciplinary Digital Publishing Institute (MDPI), Association for Computing Machinery (ACM), Springer, and Hindawi Publishing Corporation. Each selected work has been analyzed to present its objective, methodology, and results. The BE progression to dysplasia or adenocarcinoma shows a complex pattern to be detected during endoscopic surveillance. Therefore, it is valuable to assist its diagnosis and automatic identification using computer analysis. The evaluation of the BE dysplasia can be performed through manual or automated segmentation through machine learning techniques. Finally, in this survey, we reviewed recent studies focused on the automatic detection of the neoplastic region for classification purposes using machine learning methods.
Purpose
Age-related macular degeneration (AMD) is a common threat to vision. While classification of disease stages is critical to understanding disease risk and progression, several systems based on color fundus photographs are known. Most of these require in-depth and time-consuming analysis of fundus images. Herein, we present an automated computer-based classification algorithm.
Design Algorithm development for AMD classification based on a large collection of color fundus images. Validation is performed on a cross-sectional, population-based study.
Participants.
We included 120 656 manually graded color fundus images from 3654 Age-Related Eye Disease Study (AREDS) participants. AREDS participants were >55 years of age, and non-AMD sight-threatening diseases were excluded at recruitment. In addition, performance of our algorithm was evaluated in 5555 fundus images from the population-based Kooperative Gesundheitsforschung in der Region Augsburg (KORA; Cooperative Health Research in the Region of Augsburg) study.
Methods.
We defined 13 classes (9 AREDS steps, 3 late AMD stages, and 1 for ungradable images) and trained several convolution deep learning architectures. An ensemble of network architectures improved prediction accuracy. An independent dataset was used to evaluate the performance of our algorithm in a population-based study.
Main Outcome Measures.
κ Statistics and accuracy to evaluate the concordance between predicted and expert human grader classification.
Results.
A network ensemble of 6 different neural net architectures predicted the 13 classes in the AREDS test set with a quadratic weighted κ of 92% (95% confidence interval, 89%–92%) and an overall accuracy of 63.3%. In the independent KORA dataset, images wrongly classified as AMD were mainly the result of a macular reflex observed in young individuals. By restricting the KORA analysis to individuals >55 years of age and prior exclusion of other retinopathies, the weighted and unweighted κ increased to 50% and 63%, respectively. Importantly, the algorithm detected 84.2% of all fundus images with definite signs of early or late AMD. Overall, 94.3% of healthy fundus images were classified correctly.
Conclusions
Our deep learning algoritm revealed a weighted κ outperforming human graders in the AREDS study and is suitable to classify AMD fundus images in other datasets using individuals >55 years of age.
Im Rahmen der Entwicklung eines haptisch-visuellen Trainingssystems für das Fräsen am Felsenbein werden ein Haptikarm und ein autostereoskopischer 3D-Monitor genutzt, um Chirurgen die virtuelle Manipulation von knöchernen Strukturen im Kontext eines sog. Serious Game zu ermöglichen. Unter anderem sollen Assistenzärzte im Rahmen ihrer Ausbildung das Fräsen am Felsenbein für das chirurgische Einsetzen eines Cochlea-Implantats üben können. Die Visualisierung des virtuellen Fräsens muss dafür in Echtzeit und möglichst realistisch modelliert, implementiert und evaluiert werden. Wir verwenden verschiedene Raycasting Methoden mit linearer und Nearest Neighbor Interpolation und vergleichen die visuelle Qualität und die Bildwiederholfrequenzen der Methoden. Alle verglichenen Verfahren sind sind echtzeitfähig, unterscheiden sich aber in ihrer visuellen Qualität.