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Bag-of-Visual Words (BoVW) and deep learning techniques have been widely used in several domains, which include computer-assisted medical diagnoses. In this work, we are interested in developing tools for the automatic identification of Parkinson’s disease using machine learning and the concept of BoVW. The proposed approach concerns a hierarchical-based learning technique to design visual dictionaries through the Deep Optimum-Path Forest classifier. The proposed method was evaluated in six datasets derived from data collected from individuals when performing handwriting exams. Experimental results showed the potential of the technique, with robust achievements.
Parkinson's disease (PD) is a neurodegenerative disease that affects millions of people worldwide, causing mental and mainly motor dysfunctions. The negative impact on the patient's daily routine has moved the science in search of new techniques that can reduce its negative effects and also identify the disease in individuals. One of the main motor characteristics of PD is the hand tremor faced by patients, which turns out to be a crucial information to be used towards a computer-aided diagnosis. In this context, we make use of handwriting dynamics data acquired from individuals when submitted to some tasks that measure abilities related to writing skills. This work proposes the application of recurrence plots to map the signals onto the image domain, which are further used to feed a Convolutional Neural Network for learning proper information that can help the automatic identification of PD. The proposed approach was assessed in a public dataset under several scenarios that comprise different combinations of deep-based architectures, image resolutions, and training set sizes. Experimental results showed significant accuracy improvement compared to our previous work with an average accuracy of over 87%. Moreover, it was observed an improvement in accuracy concerning the classification of patients (i.e., mean recognition rates above to 90%). The promising results showed the potential of the proposed approach towards the automatic identification of Parkinson's disease.
High loads can appear in the individual joints of the human foot while the driver uses the pedals, in particular, during breaking. Measuring these internal forces is very difficult or almost impossible; therefore, advanced models are necessary to perform musculoskeletal simulations. The objective of this investigation was to see what loads are acting in the individual foot joints from the phalanges to calcaneus and talus during different brake scenarios. The Glasgow-Maastricht AnyBody Foot Model with 26 separate segments, connected by joints, ligaments and muscles was used inside the AnyBody Modeling System to compute individual mid foot joint loads. The amount, the direction of the force and additionally also the load insertion point was varied for several simulations. Figure 1: Seated musculoskeletal body model with applied brake force and forces for the lateral, intermediate and medial cuneiform-navicular joint for two different brake forces. The simulation showed that for the different brake scenarios, different muscles will be activated in the human and therefore different loads are apply in the fore-and mid-foot, respectively. The torso of the subject was assumed to be fixed in the seat. Further studies are ongoing to simulate the seat as an elastic element that allows different H-point locations according to the different loadings in the foot from the brake pedal using a new inverse dynamics analysis method called force-dependent kinematics.
In 2015 we began a sub-challenge at the EndoVis workshop at MICCAI in Munich using endoscope images of exvivo tissue with automatically generated annotations from robot forward kinematics and instrument CAD models. However, the limited background variation and simple motion rendered the dataset uninformative in learning about which techniques would be suitable for segmentation in real surgery. In 2017, at the same workshop in Quebec we introduced the robotic instrument segmentation dataset with 10 teams participating in the challenge to perform binary, articulating parts and type segmentation of da Vinci instruments. This challenge included realistic instrument motion and more complex porcine tissue as background and was widely addressed with modfications on U-Nets and other popular CNN architectures [1].
In 2018 we added to the complexity by introducing a set of anatomical objects and medical devices to the segmented classes. To avoid over-complicating the challenge, we continued with porcine data which is dramatically simpler than human tissue due to the lack of fatty tissue occluding many organs.
Background: This preparatory study accelerates an implementation of individualized monitoring and feedback of physical motion using conventional motion trackers in the rehabilitation process of geriatric trauma patients. Regaining mobility is accompanied with improved quality of life in persons of very advanced age recovering from fragility fractures.
Objectives: Quantitative survey of regaining physical mobility provides recommendations for action on how to use motion trackers effectively in a clinical geriatric setting.
Methods: Method mix of quantitative and qualitative interdisciplinary and mutual complementary research approaches (sociology, health research, philosophy/ethics, medical informatics, nursing science, gerontology and physical therapy). While validating motion tracker use in geriatric traumatology preliminary data are used to develop a target group oriented motion feedback. In addition measurement accuracy of a questionnaire about quality of life of multimorbid geriatric patients (FLQM) is tested.
Conclusion: Implementing a new technology in a complex clinical setting needs to be based on a strong theoretical background but will not succeed without careful field testing.
Therapieabbruch oder -unterbrechung erhöhen das Risiko von Krankheitsschüben in der MS-Behandlung (Ennis et al., 2008). Der Abbruchanteil für die immunmodulatorische Basistherapie mit COPAXONE® betrug 2008 in den ersten drei Monaten bis zu 30 % (COPAKTIV Schwestern-Service, 2008), worauf das Aktiv-mit-MS-Patientenbetreuungsprogramm, eine begleitende pflegerische Fachberatung und ein Servicetelefon, installiert wurde. Die Auswirkungen der Zusammenarbeit innerhalb des Teams und mit Ärzt/innen sowie die peer-to-peer Beratung in einem Online-Forum auf Therapietreue und Krankheitsbewältigung der Patient/innen wurde im Längsschnitt untersucht. Ein Methoden-Mix wurde erfolgreich zur Evaluation der pflegerischen Multiprofessionalität eingesetzt. Es zeigte sich, dass die Angebote im Betreuungsprogramm zu einer Verminderung der Abbruchquote führten und die Patient/innen eine gute Therapietreue einhalten.
Hintergrund:
Eltern stehen im Rahmen der eigenen Impfung und der Kinderimpfung mit einem COVID-19-Vakzin vor einer Impfentscheidung. Zum aktuellen Zeitpunkt gibt es keine (vollständige) Impfempfehlung.
Fragestellung:
Die Studie untersucht die Impfbereitschaft von Eltern minderjähriger Kinder und Personen ohne minderjährige Kinder, wobei insbesondere Geschlechtsunterschiede überprüft werden.
Methoden:
Die Studie basiert auf einer Zufallsstichprobe (Telefon-Survey, n = 2014, Erhebung zwischen 12.11.2020 und 10.12.2020). Die Auswertung stützt sich insbesondere auf die Teilstichprobe von Personen mit minderjährigen Kindern im Haushalt (n = 461).
Ergebnisse:
Eltern weisen durchgängig eine geringere Impfbereitschaft mit einem COVID-19-Vakzin auf als Befragte ohne minderjährige Kinder (54,1 % vs. 71,1 %). Väter weisen eine stärker ausgeprägte eigene Impfbereitschaft auf als Mütter. Darüber hinaus sind Männer eher als Frauen bereit, das eigene Kind mit einem COVID-19-Vakzin impfen zu lassen.
Schlussfolgerungen:
Bei Eltern und insbesondere Müttern ist eine erhebliche Fehleinschätzung von Impfrisiken und häufiger Glaube an Impfverschwörungstheorien zu beobachten. Empfohlen werden anschauliche und leicht verständliche Informationen über die Wirkung und Nebenwirkungen der Impfung mit einem COVID-19-Vakzin durch zuständige Institutionen und Ärzte.
Background: This article is based on an ongoing long-term study, in which customary motion trackers measure steps during rehabilitation of geriatric trauma patients (Med=86 years).
Objectives: Exploring steps after 28 days of measurement. Finding similarities in the data by running cluster analysis and formulating linear regressions models to predict steps through time.
Methods: Two types of motion trackers (FitBitAlta HR and Garmin vívofit 3) have been used to measure patients' (N=24) steps after hip fracture in two study groups. Cluster analysis detected three clusters for progress in number of steps that were tested for group differences with ANOVA. Regression analysis tested models for individual patients.
Results: Three-cluster solutions showed significant differences for the average amount of steps after 5, 14, 21 and 28 days. Regression models could predict 71 % of the individual patients' progress in study group 2.
Conclusion: The long-term study will provide more data in the future to examine the three-cluster solution and to find out in what stage of rehabilitation the measurement of the steps could be used to predict individual rehabilitation.
Es handelt sich um eine prospektive Studie zu einem beantragten BMBF-Projekt in einer Kooperation zwischen dem Institut für Sozialforschung und Technikfolgenabschätzung (IST), der Professur für E-Health der Fakultät Informatik und Mathematik an der OTH Regensburg sowie der Alterstraumatologie im Caritas Krankenhaus St. Josef Regensburg. Die geplante Machbarkeitsstudie forciert die Implementierung eines individualisierten Bewegungsmonitorings und feedbacks durch Einsatz eines alltagstauglichen Motion-Trackers in der Rehabilitation geriatrischer Traumapatient/innen. Das Wiedererlangen von Mobilität nach einer Fraktur geht einher mit dem Erhalt der subjektiven Lebensqualität (LQ) hochaltriger Menschen. Durch diagnostische Überwachung mithilfe der Motion-Tracker wird das Wiedererlangen bzw. der Erhalt von Mobilität quantitativ begleitet, um daraus Handlungsempfehlungen für deren nützlichen und kostengünstigen Einsatz in der geriatrischen Rehabilitation abzuleiten. Die Vorstudie dient der Validierung des Einsatzes handelsüblicher Motion-Tracker in der Alterstraumatologie, einschließlich der Entwicklung eines für die Zielgruppe geeigneten Bewegungsfeedbacks sowie der Überprüfung des Fragebogens zur LQ multimorbider älterer Menschen (FLQM). Hierfür werden quantitative und qualitative Methoden der Disziplinen Soziologie, Gesundheitsforschung, Philosophie/Ethik, Datenschutzrecht und medizinische Informatik, Medizin, Pflege, Gerontologie und Physiotherapie, die sich gegenseitig ergänzen (Methoden-Mix), herangezogen.
Nach einer Fraktur ist Mobilisierung Behandlungsziel und Therapiesäule. Das Festlegen von Outcomes basiert jedoch auf vielen Unsicherheiten, da Assessments nicht für alle Patient/-innen geeignet sind. Sie können agesabhängig beeinflusst und subjektiv geprägt sein. Sensorbasiertes Bewegungsmonitoring bietet eine Ergänzung zur Operationalisierung der Gehfähigkeit. Für Längsschnittuntersuchungen, die auch im häuslichen Umfeld durchgeführt werden, eignet sich die tägliche Schrittzahl als Variable. Sie kann durch einen handelsüblichen Fitnesstracker beobachtet
werden.
Straßenzeitungen haben sich zum Ziel gesetzt, einen Zuverdienst für Menschen in Not zu bieten und zugleich Vorurteile gegenüber Obdachlosen öffentlich zu bekämpfen. Eine Leserumfrage der Regensburger Straßenzeitung DONAUSTRUDL untersuchte die Wirksamkeit der Zeitung hinsichtlich ihrer Aufklärungsorientierung. Das Ergebnis zeigte, dass die Leser_innenschaft kaum weniger Vorurteile gegen Obdachlose hatte als die Gesamtbevölkerung.
This article highlights methodological and ethical challenges in research with adults of older and oldest age, by presenting field experiences of the current research project “Motion Monitoring of Geriatric Trauma Patients - Explorative Study on the Rehabilitation Process after Hip Fracture Using Sensor-based Data”. Depiction of the survey situation, with regard to the subjects in particular, can serve as practical examples for designing future research projects.
The group of older adults is a rather large and growing group for which research is required, especially concerning their heterogeneity, their individual autonomy and quality of life. It is assumed, that research designs of studies on the target group must be specifically adjusted, in particular when considering the attribution of vulnerability of the group members. At the same time, it is not clear yet what exact specifics of the subjects and target group must be considered in research designs, as surprisingly little is known about the target group as subjects and corresponding theories have been insufficiently tested.
The exploratory long-term design of the research project presented in the second section of this chapter has a positive evaluation of an ethics committee. Still ethical challenges occurred in the field situation, that are illustrated in the third section of this chapter, by providing information on the patients, their role as research subjects, how they were recruited, how an informed consensus was reached, and in some cases how participation was rejected or abandoned. After a summary, the end of the paper is marked by recommendations on how to design future research projects.
Cumulatively it must always be expected that interaction between researchers and research subjects of this target group can become very intensive, what requires to follow clearly defined procedures and at the same time to be prepared to act flexibly.
Nützlichkeit und Nutzung
(2019)
Pediatric patients suffering from ependymoma are usually treated with cranial or craniospinal three-dimensional (3D) conformal radiotherapy (3DCRT). Intensity-modulated techniques spare dose to the surrounding tissue, but the risk for second malignancies may be increased due to the increase in low-dose volume. The aim of this study is to investigate if the flattening filter free (FFF) mode allows reducing the risk for second malignancies compared to the mode with flattening filter (FF) for intensity-modulated techniques and to 3DCRT. A reduction of the risk would be advantageous for treating pediatric ependymoma. 3DCRT was compared to intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) with and without flattening filter. Dose-volume histograms (DVHs) were compared to evaluate the plan quality and used to calculate the excess absolute risk (EAR) to develop second cancer in the brain. Dose verification was performed with a two-dimensional (2D) ionization chamber array and the out-of-field dose was measured with an ionization chamber to determine the EAR in peripheral organs. Delivery times were measured. Both VMAT and IMRT achieved similar plan quality in terms of dose sparing in the OAR and higher PTV coverage as compared to 3DCRT. Peripheral dose in low-dose region, which is proportional to the EAR in organs located in this region, for example, gonads, bladder, or bowel, could be significantly reduced using FFF. The lowest peripheral EAR and lowest delivery times were hereby achieved with VMATFFF . The EAR calculated based on DVH in the brain could not be reduced using FFF mode. VMATFFF improved the target coverage and homogeneity and kept the dose in the OAR similar compared to 3DCRT. In addition, delivery times were significantly reduced using VMATFFF . Therefore, for radiotherapy of ependymoma patients, VMATFFF may be considered advantageous for the combination of Elekta Synergy linac and Oncentra External Beam planning system used in this study.
Gib mir doch eine Chance!
(2017)
Against the background of the huge rise in the number of asylum seekers and refugees absorbed into German society over the last couple of years this article examines the innovative Bavarian programme of preparatory classes for asylum seekers between 16 and 21 years of age. The challenges faced by educational and social work professionals working with this target group are documented alongside the particular resources which these highly-motivated young people as a rule bring with them. Specific requirements for psychotherapy professionals are addressed as well as a range of recommendations formulated by the author to enable the longer-term success of this vocational training programme in integrating these young people into the German educational and employment system. It has become apparent that a holistic approach to the lives of the target group by professionals in education, social work and therapy is necessary to enable young asylums seekers to complete vocational training successfully. Transitional management is a key part of the process of setting asylum seekers on the path to an apprenticeship. Coordination with the Labour Office, local authority administration and local decision-makers are further parts of the equation. This must intermesh with civil society engagement to provide the maximum use of resources giving young refugees access to training, the labour market and long term integration into German life.
Dieser Beitrag befasst sich mit dem Freizeitverständnis und -verhalten von Menschen mit Migrationshintergrund. Für ein umfassendes Verständnis des Freizeitverhaltens in der Migration ist es sinnvoll, sich mit kulturbedingten Vorstellungen von der Freizeit zu befassen. In diesem Aufsatz bilden deswegen solche Überlegungen den Einstieg in die Thematik. Eine kurze historische Betrachtung der Rolle der Freizeit für die erste "Gastarbeitergeneration" folgt diesen einleitenden Anmerkungen. Dann werden der Zusammenhang zwischen Schule und Bildung für junge MigrantInnen und der daraus hergeleitete Einfluss auf das Freizeitverhalten sowie auf die Rolle von MigrantInnensportvereinen betrachtet.
Germany received around 300,000 refugee newcomers ages 16–25 in 2015. Educational participation is a key process for the integration of these young people. This is especially true for the German vocational education and training (VET) system that provides opportunities for a fast and successful transition into the labor market. The few extant studies on migrant students in Germany have shown considerable problems in achieving educational equity. Based on the theoretical assumption that systemic discrimination creates important barriers to educational equity, we investigate how institutional and systemic factors infl uence the educational participation of refugee-background youth and how these youth cope with such barriers. Using a two-case study in the cities of Hamburg and Munich, we performed a meta-analysis of research reports, complemented by secondary analysis of primary data. Results show institutional barriers in both the education and asylum systems, and that youth cope with these barriers through high educational aspirations.
Objective: Artificial intelligence (AI) may reduce underdiagnosed or overlooked upper GI (UGI) neoplastic and preneoplastic conditions, due to subtle appearance and low disease prevalence. Only disease-specific AI performances have been reported, generating uncertainty on its clinical value.
Design: We searched PubMed, Embase and Scopus until July 2020, for studies on the diagnostic performance of AI in detection and characterisation of UGI lesions. Primary outcomes were pooled diagnostic accuracy, sensitivity and specificity of AI. Secondary outcomes were pooled positive (PPV) and negative (NPV) predictive values. We calculated pooled proportion rates (%), designed summary receiving operating characteristic curves with respective area under the curves (AUCs) and performed metaregression and sensitivity analysis.
Results: Overall, 19 studies on detection of oesophageal squamous cell neoplasia (ESCN) or Barrett's esophagus-related neoplasia (BERN) or gastric adenocarcinoma (GCA) were included with 218, 445, 453 patients and 7976, 2340, 13 562 images, respectively. AI-sensitivity/specificity/PPV/NPV/positive likelihood ratio/negative likelihood ratio for UGI neoplasia detection were 90% (CI 85% to 94%)/89% (CI 85% to 92%)/87% (CI 83% to 91%)/91% (CI 87% to 94%)/8.2 (CI 5.7 to 11.7)/0.111 (CI 0.071 to 0.175), respectively, with an overall AUC of 0.95 (CI 0.93 to 0.97). No difference in AI performance across ESCN, BERN and GCA was found, AUC being 0.94 (CI 0.52 to 0.99), 0.96 (CI 0.95 to 0.98), 0.93 (CI 0.83 to 0.99), respectively. Overall, study quality was low, with high risk of selection bias. No significant publication bias was found.
Conclusion: We found a high overall AI accuracy for the diagnosis of any neoplastic lesion of the UGI tract that was independent of the underlying condition. This may be expected to substantially reduce the miss rate of precancerous lesions and early cancer when implemented in clinical practice.
Football players have a high risk of leg muscle injuries, especially when exposed to mental stress. Injuries to muscles of the thigh are common in amateur and professional football, representing almost a third of all injuries. These injuries occur primarily in non-contact situations and from overuse. They can lead to a range of costs, including financial costs associated with treatment as well as those associated with long-term recovery, and absence from training and/or competition. Further, there is a high risk of injury recurrence and subsequent injury.
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.
Soccer is one of the most popular sports all around the world. It is an injurious type of sport with a focus on lower extremities and high psychological pressure during matches. The stressor is linked with injuries and an increased musculoskeletal loading. This study investigates the influence of cognitive stress on the load profile of the knee joint. Twelve professional youth soccer players performed highly dynamic runs with and without additional cognitive stress. The runs were analysed with a musculoskeletal simulation software. The data analysis shows no difference in knee joint reaction loading under additional mental stress compared to the baseline. Yet running times are significantly lower in the baseline. While there is no increase in the joint loads, the running times indicate an altered movement behaviour when the subjects are exposed to additional mental demand.
Mental stress reduces performance and changes musculoskeletal loading in football-related movements
(2020)
Purpose:
Football players have a high risk of leg muscle injuries, especially when exposed to mental stress. Hence, this study investigated the musculoskeletal response of elite youth football players during highly dynamic movements under stress. The hypothesis is that mental stress reduces performance and changes the muscular forces exerted.
Materials & methods:
Twelve elite youth football players were subjected to mental stress while performing sports-specific change-of-direction movements. A modified version of the d2 attention test was used as stressor. The kinetics are computed using inverse dynamics. Running times and exerted forces of injury-prone muscles were analysed.
Results:
The stressor runs were rated more mentally demanding by the players (p = 0.006, rs = 0.37) with unchanged physical demand (p = 0.777, rs = 0.45). This resulted in 10% longer running times under stress (p < 0.001, d = −1.62). The musculoskeletal analysis revealed higher peak muscle forces under mental stress for some players but not for others.
Discussion:
The study shows that motion capture combined with musculoskeletal computation is suitable to analyse the effects of stress on athletes in highly dynamic movements. For the first time in football medicine, our data quantifies an association between mental stress with reduced football players’ performance and changes in muscle force.
Evaluation of muscle recruitment and muscle models in musculoskeletal simulation of dynamic motion
(2021)
Musculoskeletal simulation plays an increasingly important role in sports biomechanics. In the last years, the field of application widened from orthopaedics and ergonomics to sports [1]. A muscle recruitment algorithm with a quadratic objective function is usually used to calculate muscle activity in dynamic movements. The agreement of calculated and measured thigh muscle activity has already been investigated [2]. They found a strong agreement for sprinting and running, while the correlation decreased for side-cutting manoeuvres. Nevertheless, the influence of different muscle recruitment criteria on muscle activity in dynamic musculoskeletal simulations is currently unknown. Hence, this study aimed to analyse the effect of different muscle recruitment criteria and muscle models on the correlation of numerical and measured muscle activity in highly dynamic movements.
Football players have a high risk of leg muscle injuries, especially when exposed to mental stress. Injuries to muscles of the thigh are common in amateur and professional football, representing almost a third of all injuries. These injuries occur primarily in non-contact situations and from overuse. They can lead to a range of costs, including financial costs associated with treatment as well as those associated with long-term recovery, and absence from training and/or competition. Further, there is a high risk of injury recurrence and subsequent injury.
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.
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.
Based on electromyographic data and force measurements within the shoulder joint, there is an indication that muscle and resulting joint reaction forces keep increasing over an abduction angle of 90°. In inverse dynamics models, no single parameter could be attributed to simulate this force behaviour accordingly. The aim of this work is to implement kinematic, kinetic and muscle model modifications to an existing model of the shoulder (AnyBody™) and assess their single and combined effects during abduction up to 140° humeral elevation. The kinematics and the EMG activity of 10 test subjects were measured during humeral abduction. Six modifications were implemented in the model: alternative wrapping of the virtual deltoid muscle elements, utilization of a three element Hill model, strength scaling, motion capture driven clavicle elevation/protraction, translation of the GH joint in dependency of the acting forces and an alteration of the scapula/clavicle rhythm. From the six modifications, 16 different combinations were considered. Parameter combinations with the Hill model changed the resultant GH joint reaction force and led to an increase in force during abduction of the humerus above 90°. Under the premise of muscle activities and forces within the GH joint rising after 90° of humeral abduction, we propose that the Hill type muscle model is a crucial parameter for accurately modelling the shoulder. Furthermore, the outcome of this study indicates that the Hill model induces the co-contraction of the muscles of the shoulder without the need of an additional stability criterion for an inverse dynamics approach.
Musculoskeletal modelling of the shoulder – effects on muscle recruitment and joint reaction force
(2019)
The gold standard for the analysis of human kinematics and kinetics is a camera-based motion capture system in combination with force measurement platforms. Alternatively, inertial measurement units can be utilized to obtain human kinematics, while ground reaction forces are computed from full body dynamics. This setup represents a system independent from the spatial confinement of a gait laboratory. The aim of this study is the comparison of the two methods by the investigation of lower limb kinematics and the resulting joint reaction forces within the ankle-, knee- and hip joints. For this purpose, human motion during gait was captured simultaneously by both measurement techniques. 13 trials from 8 different test subjects were evaluated in total. IMU data was processed with a quaternion based Kalman Filter. The data sets were implemented into a musculoskeletal simulation program in order to drive a virtual human body model. Each sensor was aligned to the gravitational and magnetic field vectors of the earth. The angles of flexions, extensions and rotations were analyzed to determine kinematic differences. Joint reaction forces defined kinetic dissimilarities. The overall kinematic differences of both models yielded root mean square errors of 7.62°, 6.02°, 4.95°, 2.79°, 2.38° and 3.56° for ankle flexion, subtalar eversion, knee flexion, hip external rotation, hip abduction and hip flexion, respectively. The proximo-distal differences in force peaks between the models yielded overall for the ankle, 57.33 %Bodyweight(BW) ± 46.86 %BW (16.66 %(Maximum peak to peak) ± 13.62 %) for the knee 37.09 %BW ± 29.33 %BW (17.65 % ± 15.44 %) and 32.03 %BW ± 24.33 %BW (15.6 % ± 12.54 %) for the hip. The overall outcome of this work investigated an approach independent of the common setup of the gait laboratory, thus enabling a cheaper and more flexible technology as an alternative. However, kinematic and thus kinetic differences remain rather large. Future work aims to improve the contact criterion for the calculation of the ground reaction forces and the implementation of a full-body calibration algorithm for the IMU system in order to counteract magnetic field disturbances.
Musculoskeletal models of the shoulder complex are valuable research aids to investigate tears of the supraspinatus and the resulting mechanical impact during abduction of the humerus. One of the major contributors to this motion is the deltoid muscle group and for this, an accurate modeling of the lines of action is indispensable. The aim of this work was to utilize a torus obstacle wrapping approach for the deltoids of an existing shoulder model and assess the feasibility of the approach during humeral abduction. The shoulder model from the AnyBody™ modeling system was used as a platform. The size of the tori is based on a magnetic resonance imaging (MRI) approach and several kinematic couplings are implemented to determine the trajectories of the tori during abduction. To assess the model behavior, the moment arms of the virtual muscle elements and the resultant glenohumeral joint reaction force (GHJF) were compared with reference data from the literature during abduction of the humerus in the range 20°–120°. The root mean square error for the anterior, lateral and posterior part between the simulated muscle elements and reference data from the literature was 3.9, 1.7 and 5.8 mm, respectively. The largest deviation occurred on the outer elements of the muscle groups, with 12.6, 10.4 and 20.5 mm, respectively. During abduction, there is no overlapping of the muscle elements and these are in continuous contact with the torus obstacles, thus enabling a continuous force transmission. This results in a rising trend of the resultant GHJF.
The torus obstacle approach as a wrapping method for the deltoid muscles provides a guided muscle pathing by simultaneously approximating the curvature of the deltoid muscle. The results from the comparison of the simulated moment arms and the resultant GHJF are in accordance with those in the literature in the range 20°–120° of abduction.
Although this study shows the strength of the torus obstacle as a wrapping approach, the method of fitting the tori according to MRI data was not suitable. A cadaver study is recommended to better validate and mathematically describe the torus approach.
Inklusive Jugendforschung
(2018)
Signal transmission between different brain regions requires connecting fiber tracts, the structural basis of the human connectome. In contrast to animal brains, where a multitude of tract tracing methods can be used, magnetic resonance (MR)-based diffusion imaging is presently the only promising approach to study fiber tracts between specific human brain regions. However, this procedure has various inherent restrictions caused by its relatively low spatial resolution. Here, we introduce 3D-polarized light imaging (3D-PLI) to map the three-dimensional course of fiber tracts in the human brain with a resolution at a submillimeter scale based on a voxel size of 100 μm isotropic or less. 3D-PLI demonstrates nerve fibers by utilizing their intrinsic birefringence of myelin sheaths surrounding axons. This optical method enables the demonstration of 3D fiber orientations in serial microtome sections of entire human brains. Examples for the feasibility of this novel approach are given here. 3D-PLI enables the study of brain regions of intense fiber crossing in unprecedented detail, and provides an independent evaluation of fiber tracts derived from diffusion imaging data.
The German National Educational Panel Study (NEPS) was set up to provide an empirical basis for longitudinal analyses of individuals’ educational careers and competencies and how they unfold over the life course in relation to family, formal educational institutions, and private life. Educational developments and decisions over the life span are being tracked in six starting cohorts as a foundation for characterizing and analyzing educational processes. These six starting cohorts include newborns, Kindergarten children, secondary school children (5th and 9th grade), first-year undergraduate students, and adults. Because access to the target population in several starting cohorts was gained via educational institutions such as Kindergartens and schools, multistage sampling approaches were implemented that reflect the clustered structure of the target populations. Samples in individual contexts, such as those in the adult and newborn cohorts, were established via register-based stratified cluster approaches. This chapter briefly reviews the designs of the implemented sampling strategies for each established starting cohort and provides information on the levels of attrition in the panel development.
Subacromiales Impingment
(2021)
Background and aims:
Rapid pre-hospital identification of stroke symptoms result in therapy directed admission to dedicated stroke units. Widespread application of stroke scales reveal high sensitivity but low specificity, especially in non-academic first aid personal. In our previous work we show that prehospital stroke diagnostics based on neurolo-gical examination and transcranial color-coded Duplex so-nography (TCCS) is feasible and results in high sensitivity and specificity for middle cerebral artery / distal internal carotid artery occlusion. The aim of our ongoing study is to design and evaluate a dedicated stroke educational program for paramedics including transcranial ultrasound. This is a prerequisite for a telemedical decision support system in the absence of stroke experienced emergency doctors.
Methods:
We currently educate 6 paramedics in advanced stroke neurology and also transcranial ultrasound examina-tion during a course of 2 months. The web-based curricu-lum was designed in two parts. The first was theoretical and the second will be the real-life training under neurological supervision. For final assessment of the theoretical know-ledge a control group will be implemented without specific stroke expertise. The stroke-educated paramedics will have to assist stroke investigation, perform pre-hospital TCCS and enter the date in a mobile telestroke pad. The data set will be send to an in-hospital stroke physician. We will as-sess the mean time to reach the diagnostic assessment, its sensitivity and specificity and the patient outcome after 30 days.
Results:
Our study is ongoing
Conclusion:
The study just reach the 2 part and we will be glad to present our data on the meeting EAN 2015.
Disclosure:
Nothing to disclose
Degradation and release of tannic acid from an injectable tissue regeneration bead matrix in vivo
(2021)
The development of multifunctional biomaterials as both tissue regeneration and drug delivery devices is currently a major focus in biomedical research. Tannic Acid (TA), a naturally occurring plant polyphenol, displays unique medicinal abilities as an antioxidant, an antibiotic, and as an anticancer agent. TA has applications in biomaterials acting as a crosslinker in polymer hydrogels improving thermal stability and mechanical properties. We have developed injectable cell seeded collagen beads crosslinked with TA for breast reconstruction and anticancer activity following lumpectomy. This study determined the longevity of the bead implants by establishing a degradation time line and TA release profile in vivo. Beads crosslinked with 0.1% TA and 1% TA were compared to observe the differences in TA concentration on degradation and release. We found collagen/TA beads degrade at similar rates in vivo, yet are resistant to complete degradation after 16 weeks. TA is released over time in vivo through diffusion and cellular activity. Changes in mechanical properties in collagen/TA beads before implantation to after 8 weeks in vivo also indicate loss of TA over a longer period of time. Elastic moduli decreased uniformly in both 0.1% and 1% TA beads. This study establishes that collagen/TA materials can act as a drug delivery system, rapidly releasing TA within the first week following implantation. However, the beads retain TA long term allowing them to resist degradation and remain in situ acting as a cell scaffold and tissue filler. This confirms its potential use as an anticancer and minimally invasive breast reconstructive device following lumpectomy.
Ältere Patienten und Frauen warten länger auf einen Arzttermin als junge Versicherte und Männer, gesetzlich Versicherte länger als Privatpatienten. Die meisten Patienten sind aber keineswegs unzufrieden. 90 Prozent bekommen entweder am selben Tag einen Termin oder halten die Wartezeit für angemessen.
In dieser Veröffentlichung präsentieren die Autoren erste Ergebnisse Ihrer Forschungsarbeit an einem Manifest für spielifizierte Hochschullehre. Ausgehend von einer Literaturrecherche über den aktuellen Forschungsstand werden erste Auszüge der aktuellen Arbeit dargestellt, auf deren Basis ein aktiver wissenschaftlicher Diskurs angeregt werden soll.
Following a ban on many materials containing bisphenol-A, new bisphenol-free Boron silicates have been found as substitutes. The purpose of this study is to describe the mechanical properties of these bisphenol-free magnetoactive borosilicate polymers containing hard magnetic particles. Samples of 0%, 33% and 66% by wt. were loaded for compression using a universal testing machine. The maximum forces occurring for different travel speeds were compared before and after post-magnetization treatments. The post-magnetization included 2 stages. In addition, the change in mechanical properties within 24 hours after the post-magnetization process was investigated. Furthermore, the influence of speed and particle content were investigated. In general, there is a correlation between the required compressive force and, the level of post-magnetization stress, the increase in travel speed and particle content in the boron silicate. Comparison of the non-post-magnetized and post-magnetized samples using two-tailed t-tests shows that the p-values for all weight fraction changes in NdPrFeB particles and travel speeds are less than 0.001. Also, a comparison between tests in which the traverse speed was varied also showed significant changes in the resulting compression forces. The same is valid for changes in the weight ratio of the NdPrFeB particles in the samples. For post-magnetized samples, no significant difference can be observed in the first 24 hours following magnetization. In summary, the material presents viscoelastic, plastic force-displacement behavior, which can be well recognized by its bi-linear curve shape.
The investigation shows that borosilicate polymers based on NdPrFeB can have their mechanical behavior modified and controlled by post-magnetization processes. This opens new possibilities for many future applications.
Seit der Einführung des Euro-Bargelds ist der Umlauf deutscher Banknoten außerordentlich stark gestiegen. Vor allem der Auslandsumlauf spielt dabei eine Rolle – und hier wiederum der Umlauf außerhalb des Euroraums. Die Autoren schätzen die regionale Verteilung dieses Umlaufs mithilfe verschiedener Methoden und kommen zu dem Ergebnis, dass der Anteil der inländischen Geldnachfrage für Transaktionskasse und für die Wertaufbewahrung nur bei rund einem Drittel des gesamten Umlaufs deutscher Euro-Banknoten liegt.
Currency movements within and outside a currency union: The case of Germany and the euro area
(2013)
In this paper, we analyse the volume of euro banknotes issued by Germany within the euro area with several seasonal methods. We draw a distinction between movements within Germany, circulation outside Germany but within the euro area and demand from non-euro-area countries. Our approach suggests that only about 20% of euro notes issued by Germany are used for transactions in Germany. The rest is hoarded (10%), circulates in other euro area countries (25%) or is held outside the euro area (45%).
In this paper, we analyze the volume of Euro banknotes issued by Germany and circulating in other Euro area countries as well as outside the Euro area with a banknotes’ age model. Our approach suggests that about 60% of banknotes, the equivalent of around € 225 billion, is held abroad.
Highlights
► We analyze the volume of Euro banknotes issued by Germany and circulating abroad. ► We use a model of the age of banknotes. ► The model captures demand from other Euro area countries and outside the Euro area. ► About 60% of “German” banknotes (€ 225 billion) are held abroad.
In dem vorliegenden Papier versuchen wir den Bestand der Euro-Banknoten zu ermitteln, der sich von der deutschen Banknotenemission im Ausland befindet. Dabei unterscheiden wir nach Beständen, die außerhalb des Euro-Währungsraumes gehalten werden, und solchen, die in anderen Ländern der EWU zirkulieren. Die Analyse basiert auf Ansätzen, die den Auslandsumlauf auf indirektem Wege abschätzen. Der Untersuchungszeitraum reicht von 2002 bis 2009. Wir finden heraus, dass Ende 2009 insgesamt rund zwei Drittel der deutschen kumulierten Nettoemissionen im Ausland umliefen. Der größte Teil, etwa 160 Mrd. €, befand sich außerhalb des Euro-Raums, der Rest - 80 Mrd. € - lief in anderen EWU-Ländern um. Somit entsprach der Inlandsumlauf deutscher Euro-Banknoten nur rund einem Drittel aller von der Bundesbank in Höhe von 350 Mrd. € in Umlauf gegebenen Banknoten. Damit werden die Ergebnisse direkter Ansätze bestätigt.
In this paper, we endeavour to determine the volume of euro banknotes issued by Germany that is in circulation outside Germany. In so doing, we draw a distinction between banknotes outstanding in non-euro-area countries and those that are in circulation in other euro-area countries. The analysis is based on approaches that estimate the volume of banknotes in circulation outside Germany indirectly. The observation period runs from 2002 to 2009. We discover that, at the end of 2009, a total of roughly two-thirds of Germany's cumulated net issuance of euro banknotes was in circulation outside Germany. The lion's share of roughly €160 billion was in non-euro-area countries, with the remaining €80 billion in other euro-area countries. Thus, the volume of German euro banknotes in circulation in Germany accounted for only roughly one-third of all banknotes issued by the Deutsche Bundesbank (€350 billion). This confirms the results of direct approaches.
Although it has long been presumed that d-amino acids are uncommon in mammalians, substantial amounts of free d-serine have been detected in the mammalian brain. d-Serine has been demonstrated to be an important modulator of glutamatergic neurotransmission and acts as an agonist at the strychnine-insensitive glycine site of N-methyl-d-aspartate receptors. The blood-to-brain transfer of d-serine is thought to be extremely low, and it is assumed that d-serine is generated by isomerization of l-serine in the brain. Stimulated by the observation of a preferred transport of the d-isomer of proline at the blood–brain barrier, we investigated the differential uptake of [3H]-d-serine and [3H]-l-serine in the rat brain 1 h after intravenous injection using quantitative autoradiography. Surprisingly, brain uptake of [3H]-d-serine was significantly higher than that of [3H]-l-serine, indicating a preferred transport of the d-enantiomer of serine at the blood–brain barrier. This finding indicates that exogenous d-serine may have a direct influence on glutamatergic neurotransmission and associated diseases.
Objectives: C-11-methionine (MET) is particularly useful in brain tumor diagnosis but unspecific uptake e.g. in cerebral ischemia has been reported (1). The F-18-labeled amino acid O-(2-[F-18]fluoroethyl)-L-tyrosine (FET) shows a similar clinical potential as MET in brain tumor diagnosis but is applicable on a wider clinical scale. The aim of this study was to evaluate the uptake of FET and H-3-MET in focal cortical ischemia in rats by dual tracer autoradiography.
Methods: Focal cortical ischemia was induced in 12 Fisher CDF rats using the photothrombosis model (PT). One day (n=3) , two days (n=5) and 7 days (n=4) after induction of the lesion FET and H-3-MET were injected intravenously. One hour after tracer injection animals were killed, the brains were removed immediately and frozen in 2-methylbutane at -50°C. Brains were cut in coronal sections (thickness: 20 µm) and exposed first to H-3 insensitive photoimager plates to measure FET distribution. After decay of F-18 the distribution of H-3-MET was determined. The autoradiograms were evaluated by regions of interest (ROIs) placed on areas with increased tracer uptake in the PT and the contralateral brain. Lesion to brain ratios (L/B) were calculated by dividing the mean uptake in the lesion and the brain. Based on previous studies in gliomas a L/B ratio > 1.6 was considered as pathological for FET.
Results: Variable increased uptake of both tracers was observed in the PT and its demarcation zone at all stages after PT. The cut-off level of 1.6 for FET was exceeded in 9/12 animals. One day after PT the L/B ratios were 2.0 ± 0.6 for FET vs. 2.1 ± 1.0 for MET (mean ± SD); two days after lesion 2.2 ± 0.7 for FET vs. 2.7 ± 1.0 for MET and 7 days after lesion 2.4 ± 0.4 for FET vs. 2.4 ± 0.1 for MET. In single cases discrepancies in the uptake pattern of FET and MET were observed.
Conclusions: FET like MET may exhibit significant uptake in infarcted areas or the immediate vincinity which has to be considered in the differential diagnosis of unkown brain lesions. The discrepancies in the uptake pattern of FET and MET in some cases indicates either differences in the transport mechanisms of both amino acids or a different affinity for certain cellular components.
The effective use of digital technology and disruptive innovations are increasingly shaping the way companies survive in today’s markets. Consequently, the need for German Small and Medium Enterprises (SMEs) to perform a digital transformation, which implies the creation of a new business model through sophisticated technologies, is gaining significance for succeeding in the digital age. While most German SMEs have already accomplished a digitization of their collaboration and communication,a profound digital transformation is still imminent for the majority. Based on the investigation of existing literature on the subject, this paper demonstrates the suitability of design thinking methods to develop strategic thrust for a digital transformation. The key potential of design thinking is rooted in its ability to creatively solve problems and reinforce skills needed to address dynamic environments. An exemplary result of using design thinking to develop strategic thrust is presented with the fictional business model GreenCube. The concept aims to assist German SMEs in performing a digital transformation by simplifying the incorporation of sophisticated digital technologies and providing opportunities for networking and thus integrating into an ecosystem. Despite their potential, design thinking activities involve several challenges including the incongruence of pre-defined specifications and designed concepts, the gap between a focus on time-reduction and a focus on experimentation, and the lack of measurability of design thinking gains. Nevertheless, the nature of businesses’internal and external environment is becoming ever more fast-paced, making the ability to manage change increasingly critical for German SMEs to establish competitive advantage.
Die Digitalisierung hat neben Kreditkarten auch unterschiedliche Bezahlsysteme möglich gemacht. Mittlerweile sind diese neuen Systeme auf dem Weg, das Bargeld abzulösen. Tatsächlich gibt es aus der Wissenschaft sogar Empfehlungen, das Bargeld ganz abzuschaffen. Die Autoren des Zeitgesprächs setzen sich mit den Argumenten für die Abschaffung auseinander und kommen zu dem Ergebnis, dass Bargeld wichtige Funktionen hat, auf die nicht so leicht verzichtet werden sollte.
Mass spectrometric imaging (MSI) is a young innovative analytical technique and combines different fields of advanced mass spectrometry and biomedical research with the aim to provide maps of elements and molecules, complexes or fragments. Especially essential metals such as zinc, copper, iron and manganese play a functional role in signaling, metabolism and homeostasis of the cell. Due to the high degree of spatial organization of metals in biological systems their distribution analysis is of key interest in life sciences. We have developed analytical techniques termed BrainMet using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging to measure the distribution of trace metals in biological tissues for biomedical research and feasibility studies—including bioaccumulation and bioavailability studies, ecological risk assessment and toxicity studies in humans and other organisms. The analytical BrainMet techniques provide quantitative images of metal distributions in brain tissue slices which can be combined with other imaging modalities such as photomicrography of native or processed tissue (histochemistry, immunostaining) and autoradiography or with in vivo techniques such as positron emission tomography or magnetic resonance tomography.
Prospective and instrumental developments will be discussed concerning the development of the metalloprotein microscopy using a laser microdissection (LMD) apparatus for specific sample introduction into an inductively coupled plasma mass spectrometer (LMD-ICP-MS) or an application of the near field effect in LA-ICP-MS (NF-LA-ICP-MS). These nano-scale mass spectrometric techniques provide improved spatial resolution down to the single cell level.
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed and established as an emerging technique in the generation of quantitative images of metal distributions in thin tissue sections of brain samples (such as human, rat and mouse brain), with applications in research related to neurodegenerative disorders. A new analytical protocol is described which includes sample preparation by cryo-cutting of thin tissue sections and matrix-matched laboratory standards, mass spectrometric measurements, data acquisition, and quantitative analysis. Specific examples of the bioimaging of metal distributions in normal rodent brains are provided. Differences to the normal were assessed in a Parkinson’s disease and a stroke brain model. Furthermore, changes during normal aging were studied. Powerful analytical techniques are also required for the determination and characterization of metal-containing proteins within a large pool of proteins, e.g., after denaturing or non-denaturing electrophoretic separation of proteins in one-dimensional and two-dimensional gels. LA-ICP-MS can be employed to detect metalloproteins in protein bands or spots separated after gel electrophoresis. MALDI-MS can then be used to identify specific metal-containing proteins in these bands or spots. The combination of these techniques is described in the second section.
Bioimaging of Metals by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS)
(2010)
The distribution analysis of (essential, beneficial, or toxic) metals (e.g., Cu, Fe, Zn, Pb, and others), metalloids, and non‐metals in biological tissues is of key interest in life science. Over the past few years, the development and application of several imaging mass spectrometric techniques has been rapidly growing in biology and medicine. Especially, in brain research metalloproteins are in the focus of targeted therapy approaches of neurodegenerative diseases such as Alzheimer's and Parkinson's disease, or stroke, or tumor growth. Laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) using double‐focusing sector field (LA‐ICP‐SFMS) or quadrupole‐based mass spectrometers (LA‐ICP‐QMS) has been successfully applied as a powerful imaging (mapping) technique to produce quantitative images of detailed regionally specific element distributions in thin tissue sections of human or rodent brain. Imaging LA‐ICP‐QMS was also applied to investigate metal distributions in plant and animal sections to study, for example, the uptake and transport of nutrient and toxic elements or environmental contamination. The combination of imaging LA‐ICP‐MS of metals with proteomic studies using biomolecular mass spectrometry identifies metal‐containing proteins and also phosphoproteins. Metal‐containing proteins were imaged in a two‐dimensional gel after electrophoretic separation of proteins (SDS or Blue Native PAGE). Recent progress in LA‐ICP‐MS imaging as a stand‐alone technique and in combination with MALDI/ESI‐MS for selected life science applications is summarized.
The bond between methacrylic polymer adhesives and dental restoratives is not perfect and may fail either in the short or in the long term. This study aims to evaluate the effects of particle incorporation in a self-etch model adhesive on mechanical and physical properties that are relevant during application and service. Filled adhesives containing 5, 10, 15 or 25 wt% glass fillers were compared to their unfilled counterpart in terms of water sorption and solubility; viscosity and dynamic viscosity during polymerization were recorded using rheological measurements and compared to FTIR analysis of the real-time degree of cure. Elastic modulus and ultimate tensile strength measurements were performed in uniaxial tension; the energy to fracture was used to calculate the fracture toughness of the adhesives. Finally, the experimental adhesives were applied on dentin substrate to test the bond strength using the microtensile test. Results showed that the incorporation of 5–10 wt% nanofiller to self-etching dental adhesives is efficient in accelerating the polymerization reaction and increasing the degree of cure without compromising the film viscosity for good wettability or water sorption and solubility. Fillers increased the elastic modulus, tensile strength and fracture toughness to a plateau between 5 and 15 wt% filler concentration, and despite the tendency to form agglomerations, active crack pinning/deflection toughening mechanisms have been observed. The bond strength between resin composite and dentin was also improved when adhesives with up to 10 wt% fillers were used, with no additional improvements with further packing. The use of fillers to reinforce dental adhesives may therefore be of great practical benefit by improving curing and mechanical properties.
CRISPR (clustered regularly interspaced short palindromic repeats) systems are one of the most fascinating tools of the current era in molecular biotechnology. With the ease that they provide in genome editing, CRISPR systems generate broad opportunities for targeting mutations. Specifically in recent years, disease-causing mutations targeted by the CRISPR systems have been of main research interest; particularly for those diseases where there is no current cure, including cancer. KRAS mutations remain untargetable in cancer. Mutations in this oncogene are main drivers in common cancers, including lung, colorectal and pancreatic cancers, which are severe causes of public health burden and mortality worldwide, with no cure at hand. CRISPR systems provide an opportunity for targeting cancer causing mutations. In this review, we highlight the work published on CRISPR applications targeting KRAS mutations directly, as well as CRISPR applications targeting mutations in KRAS-related molecules. In specific, we focus on lung, colorectal and pancreatic cancers. To date, the limited literature on CRISPR applications targeting KRAS, reflect promising results. Namely, direct targeting of mutant KRAS variants using various CRISPR systems resulted in significant decrease in cell viability and proliferation in vitro, as well as tumor growth inhibition in vivo. In addition, the effect of mutant KRAS knockdown, via CRISPR, has been observed to exert regulatory effects on the downstream molecules including PI3K, ERK, Akt, Stat3, and c-myc. Molecules in the KRAS pathway have been subjected to CRISPR applications more often than KRAS itself. The aim of using CRISPR systems in these studies was mainly to analyze the therapeutic potential of possible downstream and upstream effectors of KRAS, as well as to discover further potential molecules. Although there have been molecules identified to have such potential in treatment of KRAS-driven cancers, a substantial amount of effort is still needed to establish treatment strategies based on these discoveries. We conclude that, at this point in time, despite being such a powerful directed genome editing tool, CRISPR remains to be underutilized for targeting KRAS mutations in cancer. Efforts channelled in this direction, might pave the way in solving the long-standing challenge of targeting the KRAS mutations in cancers.
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.
The pedagogic motivation of this contribution is to develop, to adapt and to examine a specific tertiary teaching-learning situation and its changes due to a constant reflection. Within the scope of the BMBF fostered project " EVELIN " the learning teaching-Arrangement (TLA) " The Online Learning Journal (OLJ) – a tool complementing the software engineering lecture " is realized a second time at the OTH Regensburg. This further development is examined from a pedagogic perspective. This paper deals with issues concerning the conscious modification of specific teaching actions, therefore the changes of the teachers' attitude as well as the reaction of the students regarding this teaching actions. Two important findings are: (1) The teaching staff is able to adapt their teaching–actions on given conditions because of the awareness of their own teaching-attitude. (2) Due to a reflective teaching practice, there is a great potential for goal oriented learning in the context of higher education.
Purpose
MR-based attenuation correction (AC) will become an integral part of combined PET/MR systems. Here, we propose a toolbox to validate MR-AC of clinical PET/MRI data sets.
Methods
Torso scans of ten patients were acquired on a combined PET/CT and on a 1.5-T MRI system. MR-based attenuation data were derived from the CT following MR–CT image co-registration and subsequent histogram matching. PET images were reconstructed after CT- (PET/CT) and MR-based AC (PET/MRI). Lesion-to-background (L/B) ratios were estimated on PET/CT and PET/MRI.
Results
MR–CT histogram matching leads to a mean voxel intensity difference in the CT- and MR-based attenuation images of 12% (max). Mean differences between PET/MRI and PET/CT were 19% (max). L/B ratios were similar except for the lung where local misregistration and intensity transformation leads to a biased PET/MRI.
Conclusion
Our toolbox can be used to study pitfalls in MR-AC. We found that co-registration accuracy and pixel value transformation determine the accuracy of PET/MRI.
Inklusion
(2022)
Inklusion
(2016)
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.
Blood flow in channels of varying diameters <500μm exhibits strong non-linear effects. Multiphase finite volume approaches are feasible, but still computationally costly. Here, the feasibility of applying convolutional neural networks for blood flow prediction in artificial lungs is investigated. Training targets are precomputed using an Eulerian two-phase approach. To match with experimental data, the interphase drag and lift, as well as intraphase shear-thinning are adapted. A recursively branching regression network and convolution/deconvolution networks with plain skip connections and densely connected skips are investigated. A priori knowledge is incorporated in the loss functional to prevent the network from learning non-physical solutions. Inference from neural networks is approximately six orders of magnitude faster than the classical finite volume approach. Even if resulting in comparably coarse flow fields, the neural network predictions can be used as close to convergence initial solutions greatly accelerating classical flow computations.
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.
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.
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.
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.
Ethische Leitlinien der GI
(2003)
Seit Ihrer Verabschiedung im Jahr 1994 waren die Ethischen Leitlinien der Gesellschaft für Informatik Gegenstand zuweilen kontroverser Diskussionen. Einerseits wurde begrüßt, dass sich die GI verbindlich an ein ethisches Regelwerk bindet und dadurch ihren Mitgliedern einen Leitfaden an die Hand gibt, um in Konfliktsituationen besser entscheiden zu können. Andererseits wurde bemängelt, dass die Ethischen Leitlinien Forderungen stellten, die für professionelles Handeln unabdingbar seien und deshalb keine ethischen Ansprüche darstellten. Des Weiteren wurde kritisiert, dass die Ethischen Leitlinien zu sehr im Abstrakten verharrten und deshalb keine konkrete Handlungsanweisung geben könnten. Die fachlichen und überfachlichen Anforderungen wurden zuweilen als zu anspruchsvoll empfunden. Einige dieser Kritikpunkte sind sicherlich berechtigt.
Im November 2001 begann der Arbeitskreis „Informatik und Verantwortung“ im Fachbereich Informatik und Gesellschaft (IuG) mit der Überarbeitung der Ethischen Leitlinien. Der hier vorgelegte Entwurf greift einige dieser Kritikpunkte auf. Seine Publikation soll eine breitere Diskussion innerhalb der GI ermöglichen. Die Autorinnen und Autoren dieses Entwurfs freuen sich auf diese Auseinandersetzung, die in der letzten Sitzung des Arbeitskreises durch den Vertreter der Selbständigen in der GI mit dem Hinweis begonnen wurde, dass den Leitlinien ein Berufsbild zugrunde liegt, in dem die Selbständigen nicht vorkommen.
Die anlässlich der Informatik 2003 gegründete Fachgruppe “Informatik und Ethik“ wird sich zu ihrer ersten Aufgabe machen, die Ergebnisse dieser Diskussion in die endgültige Version einfließen zu lassen. Entsprechende Diskussionsbeiträge und Anregungen sollten an Karl-Heinz Rödiger (E-Mail: roediger@informatik.uni-bremen.de), kommissarischer Sprecher der Fachgruppe, gerichtet werden.
Ausgehend von einer Betrachtung des Einflusses von InformatikerInnen und ihren Handlungsmustern auf Arbeitsprozesse und vor dem Hintergrund einer kritischen Auseinandersetzung mit bisherigen berufsethischen Leitlinien wollen wir einen neuen Ansatz wagen, über Informatik und Verantwortung nachzudenken. Eine Rekonstruktion des Begriffs Verantwortung bietet uns ein reichhaltiges begriffliches Instrumentarium zur Reflexion des Verhältnisses von Verantwortung und informatischer Praxis. Wir plädieren dafür, dass informatisch Handelnde lernen müssen, ethische Probleme zu erkennen, implizite Annahmen von Arbeitskulturen zu durchschauen und ein Bewusstsein für die Veränderbarkeit dieser Arbeitskulturen entwickeln sollten. Zusätzlich bedarf es kollektiver und rechtlicher Veränderungen der Rahmenbedingungen für verantwortliches Handeln.