610 Medizin, Gesundheit
Refine
Document Type
- Journal article (82)
- Conference proceeding (81)
- Book chapter (8)
- Doctoral Thesis (2)
- Book (1)
- Patent / Standard / Guidelines (1)
- Report (1)
Is part of the Bibliography
- yes (176)
Institute
- Informatik (113)
- Life Sciences (47)
- Technik (8)
- ESB Business School (7)
Publisher
- Springer (39)
- Hochschule Reutlingen (17)
- Università Politecnica delle Marche (9)
- Elsevier (8)
- Deutsche Gesellschaft für Computer- und Roboterassistierte Chirurgie e.V. (7)
- MDPI (7)
- IEEE (6)
- IOP (6)
- SPIE (5)
- De Gruyter (4)
Radiofrequency ablation is an ablation technique to treat tumors with focused heat. Computer tomography, ultrasound and magnetic resonance imaging (MRI) are imaging modalities which can be used for image-guided procedures. MRI offers several advantages in comparison to the other imaging modalities, such as radiation-free fluoroscopic imaging, temperature mapping, a high-soft-tissue contrast and free selection of imaging planes. This work addresses the application of 3Dcontrollers for controlling interventional, fluoroscopic MR sequences at the scenario of MR guided radiofrequency ablation of hepatic malignancies. During this procedure, the interventionalist can monitor the targeting of the tumor with near-real time fluoroscopic sequences. In general, adjustments of the imaging planes are necessary during tumor targeting, which is performed by an assistant in the control room. Therefore, communication between the interventionalist in the scanner room and the assistant in the control room is essential. However, verbal communication is impaired due to the loud scanning noises. Alternatively, non-verbal communication between the two persons is possible, however limited to a few gestures and susceptible to misunderstandings. This work is analyzing different 3D-controllers to enable control of interventional MR sequences during MR-guided procedures directly by the interventionalist. Leap Motion, Wii Remote, SpaceNavigator, Phantom Omni and Foot Switch were selected. For that a simulation was built in C++ with VTK to feign the real scenario for test purposes. Previous results showed that Leap Motion is not suitable for the application while Wii Remote and Foot Switch are possible input devices. Final evaluation showed a generally time reduction with the use of 3D-controllers. Best results were reached with Wii Remote in 34 seconds. Handholding input devices like Wii Remote have further potential to integrate them in real environment to reduce intervention time.
Glioblastomas are the most aggressive fast-growing primary brain cancer which originate in the glial cells of the brain. Accurate identification of the malignant brain tumor and its sub-regions is still one of the most challenging problems in medical image segmentation. The Brain Tumor Segmentation Challenge (BraTS) has been a popular benchmark for automatic brain glioblastomas segmentation algorithms since its initiation. In this year, BraTS 2021 challenge provides the largest multi-parametric (mpMRI) dataset of 2,000 pre-operative patients. In this paper, we propose a new aggregation of two deep learning frameworksnamely, DeepSeg and nnU-Net for automatic glioblastoma recognition in pre-operative mpMRI. Our ensemble method obtains Dice similarity scores of 92.00, 87.33, and 84.10 and Hausdorff Distances of 3.81, 8.91, and 16.02 for the enhancing tumor, tumor core, and whole tumor regions, respectively, on the BraTS 2021 validation set, ranking us among the top ten teams. These experimental findings provide evidence that it can be readily applied clinically and thereby aiding in the brain cancer prognosis, therapy planning, and therapy response monitoring. A docker image for reproducing our segmentation results is available online at (https://hub.docker.com/r/razeineldin/deepseg21).
Intraoperative brain deformation, so called brain shift, affects the applicability of preoperative magnetic resonance imaging (MRI) data to assist the procedures of intraoperative ultrasound (iUS) guidance during neurosurgery. This paper proposes a deep learning-based approach for fast and accurate deformable registration of preoperative MRI to iUS images to correct brain shift. Based on the architecture of 3D convolutional neural networks, the proposed deep MRI-iUS registration method has been successfully tested and evaluated on the retrospective evaluation of cerebral tumors (RESECT) dataset. This study showed that our proposed method outperforms other registration methods in previous studies with an average mean squared error (MSE) of 85. Moreover, this method can register three 3D MRI-US pair in less than a second, improving the expected outcomes of brain surgery.
Purpose: Gliomas are the most common and aggressive type of brain tumors due to their infiltrative nature and rapid progression. The process of distinguishing tumor boundaries from healthy cells is still a challenging task in the clinical routine. Fluid attenuated inversion recovery (FLAIR) MRI modality can provide the physician with information about tumor infiltration. Therefore, this paper proposes a new generic deep learning architecture, namely DeepSeg, for fully automated detection and segmentation of the brain lesion using FLAIR MRI data.
Methods: The developed DeepSeg is a modular decoupling framework. It consists of two connected core parts based on an encoding and decoding relationship. The encoder part is a convolutional neural network (CNN) responsible for spatial information extraction. The resulting semantic map is inserted into the decoder part to get the full-resolution probability map. Based on modified U-Net architecture, different CNN models such as residual neural network (ResNet), dense convolutional network (DenseNet), and NASNet have been utilized in this study.
Results: The proposed deep learning architectures have been successfully tested and evaluated on-line based on MRI datasets of brain tumor segmentation (BraTS 2019) challenge, including s336 cases as training data and 125 cases for validation data. The dice and Hausdorff distance scores of obtained segmentation results are about 0.81 to 0.84 and 9.8 to 19.7 correspondingly.
Conclusion: This study showed successful feasibility and comparative performance of applying different deep learning models in a new DeepSeg framework for automated brain tumor segmentation in FLAIR MR images. The proposed DeepSeg is open source and freely available at https://github.com/razeineldin/DeepSeg/.
Purpose
Artificial intelligence (AI), in particular deep neural networks, has achieved remarkable results for medical image analysis in several applications. Yet the lack of explainability of deep neural models is considered the principal restriction before applying these methods in clinical practice.
Methods
In this study, we propose a NeuroXAI framework for explainable AI of deep learning networks to increase the trust of medical experts. NeuroXAI implements seven state-of-the-art explanation methods providing visualization maps to help make deep learning models transparent.
Results
NeuroXAI has been applied to two applications of the most widely investigated problems in brain imaging analysis, i.e., image classification and segmentation using magnetic resonance (MR) modality. Visual attention maps of multiple XAI methods have been generated and compared for both applications. Another experiment demonstrated that NeuroXAI can provide information flow visualization on internal layers of a segmentation CNN.
Conclusion
Due to its open architecture, ease of implementation, and scalability to new XAI methods, NeuroXAI could be utilized to assist radiologists and medical professionals in the detection and diagnosis of brain tumors in the clinical routine of cancer patients. The code of NeuroXAI is publicly accessible at https://github.com/razeineldin/NeuroXAI.
Automatic segmentation is essential for the brain tumor diagnosis, disease prognosis, and follow-up therapy of patients with gliomas. Still, accurate detection of gliomas and their sub-regions in multimodal MRI is very challenging due to the variety of scanners and imaging protocols. Over the last years, the BraTS Challenge has provided a large number of multi-institutional MRI scans as a benchmark for glioma segmentation algorithms. This paper describes our contribution to the BraTS 2022 Continuous Evaluation challenge. We propose a new ensemble of multiple deep learning frameworks namely, DeepSeg, nnU-Net, and DeepSCAN for automatic glioma boundaries detection in pre-operative MRI. It is worth noting that our ensemble models took first place in the final evaluation on the BraTS testing dataset with Dice scores of 0.9294, 0.8788, and 0.8803, and Hausdorf distance of 5.23, 13.54, and 12.05, for the whole tumor, tumor core, and enhancing tumor, respectively. Furthermore, the proposed ensemble method ranked first in the final ranking on another unseen test dataset, namely Sub-Saharan Africa dataset, achieving mean Dice scores of 0.9737, 0.9593, and 0.9022, and HD95 of 2.66, 1.72, 3.32 for the whole tumor, tumor core, and enhancing tumor, respectively.
Recent advances in artificial intelligence have enabled promising applications in neurosurgery that can enhance patient outcomes and minimize risks. This paper presents a novel system that utilizes AI to aid neurosurgeons in precisely identifying and localizing brain tumors. The system was trained on a dataset of brain MRI scans and utilized deep learning algorithms for segmentation and classification. Evaluation of the system on a separate set of brain MRI scans demonstrated an average Dice similarity coefficient of 0.87. The system was also evaluated through a user experience test involving the Department of Neurosurgery at the University Hospital Ulm, with results showing significant improvements in accuracy, efficiency, and reduced cognitive load and stress levels. Additionally, the system has demonstrated adaptability to various surgical scenarios and provides personalized guidance to users. These findings indicate the potential for AI to enhance the quality of neurosurgical interventions and improve patient outcomes. Future work will explore integrating this system with robotic surgical tools for minimally invasive surgeries.
Purpose
Artificial intelligence (AI), in particular deep learning (DL), has achieved remarkable results for medical image analysis in several applications. Yet the lack of human-like explanations of such systems is considered the principal restriction before utilizing these methods in clinical practice (Yang, Ye, & Xia, 2022).
Methods
Explainable Artificial Intelligence (XAI) provides a human-explainable and interpretable description of the “black-box” nature of DL (Gulum, Trombley, & Kantardzic, 2021). An effective XAI diagnosis generator, namely NeuroXAI (refer to Fig. 1), has been developed to extract 3D explanations from convolutional neural networks (CNN) models of brain gliomas (Zeineldin et al., 2022). By providing visual justification maps, NeuroXAI can help make DL models transparent and thus increase the trust of medical experts.
Results
NeuroXAI has been applied to two applications of the most widely investigated problems in brain imaging analysis, i.e. image classification and segmentation using magnetic resonance imaging (MRI). Visual attention maps of multiple XAI methods have been generated and compared for both applications, which could help to provide transparency about the performance of DL systems.
Conclusion
NeuroXAI helps to understand the prediction process of 3D CNN networks for brain glioma using human-understandable explanations. Results revealed that the investigated DL models behave in a logical human-like manner and can improve the analytical process of the MRI images systematically. Due to its open architecture, ease of implementation, and scalability to new XAI methods, NeuroXAI could be utilized to assist medical professionals in the detection and diagnosis of brain tumors. NeuroXAI code is publicly accessible at https://github.com/razeineldin/NeuroXAI
In the last decades, several driving systems were developed to improve the driving behaviour in energy efficiency or safety. However, these driving systems cover either the area of energy-efficiency or safety. Furthermore, they do not consider the stress level of the driver when showing a recommendation, although stress can lead to an unsafe or inefficient driving behaviour. In this paper, an approach is presented to consider the driver stress level in a driving system for safe and energy-efficient driving behaviour. The driving system tries to suppress a recommendation when the driver is in stress in order not to stress the driver additionally with recommendations in a stressful driving situation. This can lead to an increase in the road safety and in the user acceptance of the driving system, as the driver is not getting bothered or stressed by the driving system.
The evaluation of the approach showed, that the driving system
is able to show recommendations to the driver, while also reacting
to a high stress level by suppressing recommendations in
order not to stress the driver additionally.
Besides the optimisation of the car, energy-efficiency and safety can also be increased by optimising the driving behaviour. Based on this fact, a driving system is in development whose goal is to educate the driver in energy-efficient and safe driving. It monitors the driver, the car and the environment and gives energy-efficiency and safety relevant recommendations. However, the driving system tries not to distract or bother the driver by giving recommendations for example during stressful driving situations or when the driver is not interested in that recommendation. Therefore, the driving system monitors the stress level of the driver as well as the reaction of the driver to a given recommendation and decides whether to give a recommendation or not. This allows to suppress recommendations when needed and, thus, to increase the road safety and the user acceptance of the driving system.
Purpose: Human breath analysis is proposed with increasing frequency as a useful tool in clinical application. We performed this study to find the characteristic volatile organic compounds (VOCs) in the exhaled breath of patients with idiopathic pulmonary fibrosis (IPF) for discrimination from healthy subjects. Methods: VOCs in the exhaled breath of 40 IPF patients and 55 healthy controls were measured using a multi-capillary column and ion mobility spectrometer. The patients were examined by pulmonary function tests, blood gas analysis, and serum biomarkers of interstitial pneumonia. Results: We detected 85 VOC peaks in the exhaled breath of IPF patients and controls. IPF patients showed 5 significant VOC peaks; p-cymene, acetoin, isoprene, ethylbenzene, and an unknown compound. The VOC peak of p-cymene was significantly lower (p < 0.001), while the VOC peaks of acetoin, isoprene, ethylbenzene, and the unknown compound were significantly higher (p < 0.001 for all) compared with the peaks of controls. Comparing VOC peaks with clinical parameters, negative correlations with VC (r =−0.393, p = 0.013), %VC (r =−0.569, p < 0.001), FVC (r = −0.440, p = 0.004), %FVC (r =−0.539, p < 0.001), DLco (r =−0.394, p = 0.018), and %DLco (r =−0.413, p = 0.008) and a positive correlation with KL-6 (r = 0.432, p = 0.005) were found for p-cymene. Conclusion: We found characteristic 5 VOCs in the exhaled breath of IPF patients. Among them, the VOC peaks of p-cymene were related to the clinical parameters of IPF. These VOCs may be useful biomarkers of IPF.
This review gives a short overview of the physical processes involved in the formation of the polyelectrolyte multilayers (PEMs) and their destruction. These two processes are vital for the formation of PEMs with desired physical and chemical structures, and for loading them with active substances and their spatial controlled release. It includes a survey of the physical and chemical properties that are key points for controlling film nanostructure in relation to biological processes and different possibilities for controlling cell behavior by means of film composition, bioactivity, mechanical properties, and three-dimensional organization.
Rats are commonly used in medical research as they enable a high grade of standardization. The exhalome of ventilated rats has not as yet been investigated using an ion mobility spectrometer coupled with a multi-capillary column (MCC-IMS). As a first step, a rat model has to be established to measure potential biomarkers in the exhale with long-term settings, allowing constant and continuous analysis of exhaled air in time series. Therefore, eight animals were anaesthetized, prepared and ventilated for 1 h. A total of 73 peaks were directly detected with the IMS chromatogram. Thirty five of them were assigned to the ventilator system and 38 to the animals. Peak intensity varied within three measurements. The intensity of analytes of individual rats varied by a factor of up to 18. This new model will also enable continuous measurements of volatile organic compounds (VOCs) from rat's breath in long-term experiments. It is hoped that, in the future, variability and progression of VOCs can be monitored in different models of diseases using this set-up.
The metric and qualitative analysis of models of the upper and lower dental arches is an important aspect of orthodontic treatment planning. Currently available eLearning systems for dental education only allow access to digital learning materials, and do not interactively support the learning progress. Moreover, to date no study compared the efficiency of learning methods based on physical or digital study models. For this pilot study, 18 dental students were separated into two groups to investigate whether the learning success in study model analysis with an interactive elearning system is higher based on digital models or on conventional plaster models. The results show that with the digital method less time is needed per model analysis. Moreover, the digital approach leads to higher total scores than that based on plaster models. We conclude that interactive eLearning using digital dental arch models is a promising tool for dental education.
Diese Arbeit liefert einen Konzeptentwurf, der die Integration verschiedener Systeme mit prozessrelevanten klinischen Diensten gewährleistet. Chirurgische Abläufe werden in Form von Prozessen modelliert. Die Wahl der Notation und die Art der Modellierung dieser Prozesse spielt in der heutigen Forschung in diesem Gebiet eine zentrale Rolle. Sind diese Prozesse modelliert, besteht die Möglichkeit, diese in einer Workflow-Engine automatisiert auszuführen. Im Rahmen der Entwicklung eines Workflow-Managment-Systems stellt sich die Frage, wie die Anbindung dieser Workflow-Engine mit anderen Systemen erfolgen soll. In der Arbeit werden Schnittstellen abstrakt in der Web Services Description Language (WSDL) definiert. Darum werden automatisiert Artefakte erzeugt. Auf der Grundlage dieser Artefakte erfolgt die Integration der Systeme. Die Workflow-Engine kommunizieren über SOAP-Nachrichten (Simple Object Access Protocol) mit den entsprechenden Systemen. Dieser Ansatz wurde mithilfe eines Prototyps validiert und umgesetzt.
Purpose: Medical processes can be modeled using different methods and notations.Currently used modeling systems like Business Process Model and Notation (BPMN) are not capable of describing the highly flexible and variable medical processes in sufficient detail.
Methods: We combined two modeling systems, Business Process Management (BPM) and Adaptive Case Management (ACM), to be able to model non-deterministic medical processes. We used the new Standards Case Management Model and Notation (CMMN) and Decision Management Notation (DMN).
Results: First, we explain how CMMN, DMN and BPMN could be used to model non-deterministic medical processes. We applied this methodology to model 79 cataract operations provided by University Hospital Leipzig, Germany, and four cataract operations provided by University Eye Hospital Tuebingen, Germany. Our model consists of 85 tasks and about 20 decisions in BPMN. We were able to expand the system with more complex situations that might appear during an intervention.
Conclusion: An effective modeling of the cataract intervention is possible using the combination of BPM and ACM. The combination gives the possibility to depict complex processes with complex decisions. This combination allows a significant advantage for modeling perioperative processes.
Informationstechnische Systeme, die den Arbeitsablauf im klinischen Bereich unterstützen, sind aktuell auf organisatorische Abläufe beschränkt. Diese Arbeit stellt einen ersten Ansatz vor, wie solch ein System in den perioperativen Bereich eingebracht werden kann. Hierzu wurde eine Workflow Engine mit einer perioperativen Prozess-Visualisierung verknüpft. Das System wurde nach Modell-View-Controller-Prinzip implementiert. Als "Controller" kommt die Workflow Engine zum Einsatz; also "Modell" ein Prozessmodell, mit den erforderlichen klinischen Daten. Der "View" wurde durch eine abgekoppelte Anwendung realisiert, welche auf Web-Technologien basiert. Drei Visualisierungen, die Workflow Engine sowie die Anbindung beider über eine Datenbankschnittstelle, wurden erfolgreich umgesetzt. Bei den drei Visualisierungen wurden jeweils eine Ansicht für den OP-Koordinator, den Springer und eine Ansicht für die Übersicht einer OP erstellt.
Workflow driven support systems in the peri-operative area have the potential to optimize clinical processes and to allow new situation-adaptive support systems. We started to develop a workflow management system supporting all involved actors in the operating theatre with the goal to synchronize the tasks of the different stakeholders by giving relevant information to the right team members. Using the OMG standards BPMN, CMMN and DMN gives us the opportunity to bring established methods from other industries into the medical field. The system shows each addressed actor their information in the right place at the right time to make sure every member can execute their task in time to ensure a smooth workflow. The system has the overall view of all tasks. Accordingly, a workflow management system including the Camunda BPM workflow engine to run the models, and a middleware to connect different systems to the workflow engine and some graphical user interfaces to show necessary information or to interact with the system are used. The complete pipeline is implemented with a RESTful web service. The system is designed to include different systems like hospital information system (HIS) via the RESTful web service very easily and without loss of data. The first prototype is implemented and will be expanded.
An operation room is a stressful work environment. Nevertheless, all involved persons have to work safely as there is no space for making mistakes. To ensure a high level of concentration and seamless interaction, all involved persons have to know their own tasks and tasks of their colleagues. The entire team must work synchronously at all times. However, the operation room (OR) is a noisy environment and the actors have to set their focus on their work. To optimize the overall workflow, a task manager supporting the team was developed. Each actor is equipped with a client terminal showing a summary of their own tasks. Moreover, a big screen displays all tasks of all actors. The architecture is a distributed system based on a communication framework that supports the interaction of all clients with the task manager. A prototype of the task manager and several clients have been developed and implemented. The system represents a proof-of-concept for further development. This paper describes the concept of the task manager.
Durch das stetige Wachstum an neuen Technologien und Möglichkeiten steht der Verschmelzung von Technologien mit dem Menschen kaum noch etwas im Wege. Die Untersuchung der Implantate und die damit verbundenen Risiken sind ein Teil dieser Arbeit. Von Bedeutung sind hier die Funktionsweise und die IT-Sicherheitsaspekte. Alle in dieser Arbeit dargestellten Implantate benötigen eine Kommunikation nach außen. Diese Kommunikationsmöglichkeit birgt Risiken, die nicht nur auf die Daten der Träger beschränkt sind, sondern auch gesundheitliche Risiken beinhalten.
There have been substantial research efforts for algorithms to improve continuous and automated assessment of various health-related questions in recent years. This paper addresses the deployment gap between those improving algorithms and their usability in care and mobile health applications. In practice, most algorithms require significant and founded technical knowledge to be deployed at home or support healthcare professionals. Therefore, the digital participation of persons in need of health care professionals lacks a usable interface to use the current technological advances. In this paper, we propose applying algorithms taken from research as web-based microservices following the common approach of a RESTful service to bridge the gap and make algorithms accessible to caregivers and patients without technical knowledge and extended hardware capabilities. We address implementation details, interpretation and realization of guidelines, and privacy concerns using our self-implemented example. Also, we address further usability guidelines and our approach to those.
This paper presents a generic method to enhance performance and incorporate temporal information for cardiorespiratory-based sleep stage classification with a limited feature set and limited data. The classification algorithm relies on random forests and a feature set extracted from long-time home monitoring for sleep analysis. Employing temporal feature stacking, the system could be significantly improved in terms of Cohen’s κ and accuracy. The detection performance could be improved for three classes of sleep stages (Wake, REM, Non-REM sleep), four classes (Wake, Non-REM-Light sleep, Non-REM Deep sleep, REM sleep), and five classes (Wake, N1, N2, N3/4, REM sleep) from a κ of 0.44 to 0.58, 0.33 to 0.51, and 0.28 to 0.44 respectively by stacking features before and after the epoch to be classified. Further analysis was done for the optimal length and combination method for this stacking approach. Overall, three methods and a variable duration between 30 s and 30 min have been analyzed. Overnight recordings of 36 healthy subjects from the Interdisciplinary Center for Sleep Medicine at Charité-Universitätsmedizin Berlin and Leave-One-Out-Cross-Validation on a patient-level have been used to validate the method.
Functionally impaired people have problems with choosing and finding the right clothing. So, they need help in their daily life to wash and manage the clothing. The goal of this work is to support the user by giving recommendations to choose the right clothing, to find the clothing and how to wash the clothing. The idea behind eKlarA is to generate a gateway based system that uses sensors to identify the clothing and their state in the clothing cycle. The clothing cycle consists of (one and more) closet, laundry basket and washing machine in one or several places. The gateway uses the information about the clothing, weather and calendar to support the user in the different steps of the clothing cycle. This allows to give more freedom to the functionally impaired people in their daily life.
How to protect the skin from getting sun burnt? The sun can damage your skin e.g. skin cancer. But the sun has a positive effect to the human. The time in sun and the intensity are key values between enjoy the sunbath and having a negative effect to the skin. A smart device like a UV flower could help you to enjoy the sunbath. It measures the UV index around you and gives this information to a smartphone app. The development steps of such a device are described in this paper. The UV flower is made of textile fabrics.
Background
Personalized medicine requires the integration and analysis of vast amounts of patient data to realize individualized care. With Surgomics, we aim to facilitate personalized therapy recommendations in surgery by integration of intraoperative surgical data and their analysis with machine learning methods to leverage the potential of this data in analogy to Radiomics and Genomics.
Methods
We defined Surgomics as the entirety of surgomic features that are process characteristics of a surgical procedure automatically derived from multimodal intraoperative data to quantify processes in the operating room. In a multidisciplinary team we discussed potential data sources like endoscopic videos, vital sign monitoring, medical devices and instruments and respective surgomic features. Subsequently, an online questionnaire was sent to experts from surgery and (computer) science at multiple centers for rating the features’ clinical relevance and technical feasibility.
Results
In total, 52 surgomic features were identified and assigned to eight feature categories. Based on the expert survey (n = 66 participants) the feature category with the highest clinical relevance as rated by surgeons was “surgical skill and quality of performance” for morbidity and mortality (9.0 ± 1.3 on a numerical rating scale from 1 to 10) as well as for long-term (oncological) outcome (8.2 ± 1.8). The feature category with the highest feasibility to be automatically extracted as rated by (computer) scientists was “Instrument” (8.5 ± 1.7). Among the surgomic features ranked as most relevant in their respective category were “intraoperative adverse events”, “action performed with instruments”, “vital sign monitoring”, and “difficulty of surgery”.
Conclusion
Surgomics is a promising concept for the analysis of intraoperative data. Surgomics may be used together with preoperative features from clinical data and Radiomics to predict postoperative morbidity, mortality and long-term outcome, as well as to provide tailored feedback for surgeons.
The aim of this work was to investigate the mean fill weight control of a continuous capsule-filling process, whether it is possible to derive controller settings from an appendant process model. To that end, a system composed out of fully automated capsule filler and an online gravimetric scale was used to control the filled weight. This setup allows to examine challenges associated with continuous manufacturing processes, such as variations in the amount of active pharmaceutical ingredient (API) in the mixture due to fluctuations of the feeders or due to altered excipient batch qualities. Two types of controllers were investigated: a feedback control and a combination of feedback and feedforward control. Although both of those are common in the industry, determining the optimal parameter settings remains an issue. In this study, we developed a method to derive the control parameters based on process models in order to obtain optimal control for each filled product. Determined via rapid automated process development (RAPD), this method is an effective and fast way of determining control parameters. The method allowed us to optimize the weight control for three pharmaceutical excipients. By conducting experiments, we verified the feasibility of the proposed method and studied the dynamics of the controlled system. Our work provides important basic data on how capsule filler can be implemented into continuous manufacturing systems.
Background aims: In vitro engineered adipose tissue is in great demand to treat lost or damaged soft tissue or to screen for new drugs, among other applications.However, today most attempts depend on the use of animal-derived sera. To pave the way for the application of adipose tissue-engineered
products in clinical trials or as reliable and robust in vitro test systems, sera should be completely excluded from the production process. In this study, we aimed to develop an in vitro adipose tissue model in the absence of sera and maintain its function long-term.
Methods: Human adipose tissue-derived stem cells were expanded and characterized in a xeno- and serum-free environment. Adipogenic differentiation was induced using a completely defined medium. Developed adipocytes were maintained in a completely defined maturation medium for additional 28 days. In addition to cell-viability and adherence, adipocyte-specific markers such as perilipin A expression of leptin release were evaluated.
Results: The defined differentiation medium enhanced cell adherence and lipid
accumulation at a significant level compared with the corresponding negative control. The defined maturation medium also significantly supported cell adherence and functional adipocyte maturation during the long-term culture period.
Conclusions: The process described here enables functional adipocyte generation and maintenance without the addition fo unknown or unimal-derived constituents, achieving an important milestone in the introduction of adipose tissue engineered products into clinical trials or in vitro screening.
Completely defined co-culture of adipogenic differentiated ASCs and microvascular endothelial cells
(2018)
Vascularized adipose tissue models are in high demand as alternatives to animal models to elucidate the mechanisms of widespread diseases, screen for new drugs or assess drug safety levels. Animal-derived sera such as fetal bovine serum (FBS), which are commonly used in these models, are associated with ethical concerns, risk of contaminations and inconsistencies of their composition and impact on cells. In this study, we developed a serum-free, defined co culture medium and implemented it in an adipocyte/endothelial cell (EC) co culture model.
Human adipose-derived stem cells were differentiated under defined conditions (diffASCs) and, like human microvascular ECs (mvECs), cultured in a defined co culture medium in mono-, indirect or direct co-culture for 14 days. The defined co-culture medium was superior when compared to mono-culture media and facilitated the functional maintenance and maturation of diffASCs including perilipin A expression, lipid accumulation, and also glycerol and leptin release. The medium also allowed mvEC maintenance, confirmed by the expression of CD31 and von Willebrand factor (vWF), and by acetylated low density lipoprotein (acLDL) uptake. Thereby, mvECs showed strong dependence on EC-specific factors. Additionally, mvECs formed vascular structures in direct co-culture with diffASCs.
The completely defined co-culture system allows for the serum-free culture of adipocyte/EC co-cultures and thereby represents a valuable and ethically acceptable tool for the culture and study of vascularized adipose tissue models.
The field of breath analysis has developed to be of growing interest in medical diagnosis and patient monitoring. The main advantages are that it’s noninvasive, painless and repeatable in flexible cycles. Even though breath analysis is being researched for a couple of decades there are still many unanswered questions. Human breath contains volatile organic compounds which are emitted from inside the body. Some of these compounds can be assigned to specific sources, such as inflammation or cancer, but also to non health related origins. This paper gives an overview of breath analysis for the purpose of disease diagnosis and health monitoring. Therefore, literature regarding breath analysis in the medical field has been analyzed, from its early stages to the present. As a result, this paper gives an outline of the topic of breath analysis.
Type 1 diabetes is a chronic and a life threatening disease: an adjusted treatment and a proper management of the disease are crucial to prevent or delay the complications of diabetes. Although during the last decade the development of the artificial pancreas has presented great advances in diabetes care, the multiple daily injections therapy still represents the most widely used treatment option for type 1 diabetes. This work presents the proposal and first development stages of an application focused on guiding patients using the continuous glucose monitors and smart pens together with insulin and carbohydrates recommendations. Our proposal aims to develop a platform to integrate a series of innovative machine learning models and tools rigorously tested together with the use of the latest IoT devices to manage type 1 diabetes. The resulting system actually closes the loop, like the artificial pancreas, but in an intermittent way.
During two researches the influence of technologies on sleep were analyzed. The first one is about the effect of light on the circadian rhythm and as consequence on sleep quality of persons in a vegetative state. The second one, which is still running, surveys the influence of several technical tools on the sleep of elderly people living in a nursing home.
The imaging and force-distance curve modes of atomic force microscopy (AFM) are explored to compare the morphological and mechanical signatures of platelets from patients diagnosed with classical neurodegenerative diseases (NDDs) and healthy individuals. Our data demonstrate the potential of AFM to distinguish between the three NDDs-Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD), and normal healthy platelets. The common features of platelets in the three pathologies are reduced membrane surface roughness, area and height, and enhanced nanomechanics in comparison with healthy cells. These changes might be related to general phenomena associated with reorganization in the platelet membrane morphology and cytoskeleton, a key factor for all platelets’ functions. Importantly, the platelets’ signatures are modified to a different extent in the three pathologies, most significant in ALS, less pronounced in PD and the least in AD platelets, which shows the specificity associated with each pathology. Moreover, different degree of activation, distinct pseudopodia and nanocluster formation characterize ALS, PD and AD platelets. The strongest alterations in the biophysical properties correlate with the highest activation of ALS platelets, which reflect the most significant changes in their nanoarchitecture. The specific platelet signatures that mark each of the studied pathologies can be added as novel biomarkers to the currently used diagnostic tools.
Die minimal-invasive Chirurgie (MIC) entwickelt sich durch den Einsatz von medizinischen Robotern wie dem da Vinci System von Intuitive Surgical stetig weiter. Hierdurch kann eine bessere oder gleichwertige Operation bei deutlich geringerer körperlicher Belastung des Operateurs erreicht werden. Dabei entstehen jedoch neue Problemstellungen wie beispielsweise Kollision zwischen Roboterarmen und die benötigte Zeit zum Einrichten einer geeigneten Roboterkonfiguration. Daher ist eine effiziente Vorbereitung und Planung der Interventionen erforderlich. Diese Arbeit präsentiert einen Ansatz für eine verbesserte Planung mit Augmented Reality (AR) und einer Robotik Simulationssoftware (RS). Die Robotik Simulation dient zur Berechnung einer Roboterkonfiguration unter Vorgabe der Port-Positionen. Augmented Reality wird verwendet, um die berechneten Pose in der realen Umgebung zu visualisieren und somit leichter in den Operationssaal zu übertragen.
Positively charged metallic oxides prevent blood coagulation whereas negatively charged metallic oxides are thrombogenic. This study was performed to examine whether this effect extends to metallic oxide nanoparticles. Oscillation shear rheometry was used to study the effect of zinc oxide and silicon dioxide nanoparticles on thrombus formation in human whole blood. Our data show that oscillation shear rheometry is a sensitive and robust technique to analyze thrombogenicity induced by nanoparticles. Blood without previous contact with nanoparticles had a clotting time (CT) of 16.7 ± 1.0 min reaching a maximal clot strength (CS) of 16 ± 14 Pa (G') after 30 min. ZnO nanoparticles (diameter 70 nm, +37 mV zeta-potential) at a concentration of 1 mg/mL prolonged CT to 20.8 ± 3.6 min and provoked a weak clot (CS 1.5 ± 1.0 Pa). However, at a lower concentration of 100 µg/mL the ZnO particles dramatically reduced CT to 6.0 ± 0.5 min and increased CS to 171 ± 63 Pa. This procoagulant effect decreased at lower concentrations reaching the detection limit at 10 ng/mL. SiO2 nanoparticles (diameter 232 nm, −28 mV zeta-potential) at high concentrations (1 mg/mL) reduced CT (2.1 ± 0.2 min) and stimulated CS (249 ± 59 Pa). Similar to ZnO particles, this procoagulant effect reached a detection limit at 10 ng/mL. Nanoparticles in high concentrations reproduce the surface charge effects on blood coagulation previously observed with large particles or solid metal oxides. However, nanoparticles with different surface charges equally well stimulate coagulation at lower concentrations. This stimulation may be an effect which is not directly related to the surface charge.
Due to the wide variety of benign and malignant salivary gland tumors, classification and malignant behavior determination based on histomorphological criteria can be difficult and sometimes impossible. Spectroscopical procedures can acquire molecular biological information without destroying the tissue within the measurement processes. Since several tissue preparation procedures exist, our study investigated the impact of these preparations on the chemical composition of healthy and tumorous salivary gland tissue by Fourier-transform infrared (FTIR) microspectroscopy. Sequential tissue cross-sections were prepared from native, formalin-fixed and formalin-fixed paraffin-embedded (FFPE) tissue and analyzed. The FFPE cross-sections were dewaxed and remeasured. By using principal component analysis (PCA) combined with a discriminant analysis (DA), robust models for the distinction of sample preparations were built individually for each parotid tissue type. As a result, the PCA-DA model evaluation showed a high similarity between native and formalin-fixed tissues based on their chemical composition. Thus, formalin-fixed tissues are highly representative of the native samples and facilitate a transfer from scientific laboratory analysis into the clinical routine due to their robust nature. Furthermore, the dewaxing of the cross-sections entails the loss of molecular information. Our study successfully demonstrated how FTIR microspectroscopy can be used as a powerful tool within existing clinical workflows.
Die Erfindung betrifft einen Rollstuhl mit einem Gestell mit Rädern, einem Sitz sowie zwei gegenüber dem Sitz verlagerbaren Fußplatten und ein Trainingsgerät zur Bewegungstherapie der unteren Extremitäten einer in dem Rollstuhl sitzenden Person. Um das Trainingsgerät vereinfacht auszubilden, enthält das Trainingsgerät unabhängig von einer Fahrbewegung des Rollstuhls betreibbar eine an dem Gestell befestigbare, von einer Steuereinheit gesteuerte Elektromaschine, welche zur wechselweise erzwungenen Verlagerung der beiden Fußplatten mit den Fußplatten mechanisch gekoppelt ist.
Medical applications are becoming increasingly important in the current development of health care and therefore a crucial part of the medical industry. An essential component is the development of user interfaces for mobile medical applications. The conceptual process is crucial for the further development of the main development process. Inconsistency or errors in the conceptual phase, have a serious impact on all areas and could prevent the certification for market approval.
This paper presents a guide to support developer with this process. It was developed based on a requirement analysis of the legal requirements to publish a medical device.
The digital twin concept has been widely known for asset monitoring in the industry for a long time. A clear example is the automotive industry. Recently, there has also been significant interest in the application of digital twins in healthcare, especially in genomics in what is known as precision medicine. This work focuses on another medical speciality where digital twins can be applied, sleep medicine. However, there is still great controversy about the fundamentals that constitute digital twins, such as what this concept is based on and how it can be included in healthcare effectively and sustainably. This article reviews digital twins and their role so far in what is known as personalized medicine. In addition, a series of steps will be exposed for a possible implementation of a digital twin for a patient suffering from sleep disorders. For this, artificial intelligence techniques, clinical data management, and possible solutions for explaining the results derived from artificial intelligence models will be addressed.
Background: Polysomnography (PSG) is the gold standard for detecting obstructive sleep apnea (OSA). However, this technique has many disadvantages when using it outside the hospital or for daily use. Portable monitors (PMs) aim to streamline the OSA detection process through deep learning (DL).
Materials and methods: We studied how to detect OSA events and calculate the apnea-hypopnea index (AHI) by using deep learning models that aim to be implemented on PMs. Several deep learning models are presented after being trained on polysomnography data from the National Sleep Research Resource (NSRR) repository. The best hyperparameters for the DL architecture are presented. In addition, emphasis is focused on model explainability techniques, concretely on Gradient-weighted Class Activation Mapping (Grad-CAM).
Results: The results for the best DL model are presented and analyzed. The interpretability of the DL model is also analyzed by studying the regions of the signals that are most relevant for the model to make the decision. The model that yields the best result is a one-dimensional convolutional neural network (1D-CNN) with 84.3% accuracy.
Conclusion: The use of PMs using machine learning techniques for detecting OSA events still has a long way to go. However, our method for developing explainable DL models demonstrates that PMs appear to be a promising alternative to PSG in the future for the detection of obstructive apnea events and the automatic calculation of AHI.
The massive use of patient data for the training of artificial intelligence algorithms is common nowadays in medicine. In this scientific work, a statistical analysis of one of the most used datasets for the training of artificial intelligence models for the detection of sleep disorders is performed: sleep health heart study 2. This study focuses on determining whether the gender and age of the patients have a relevant influence to consider working with differentiated datasets based on these variables for the training of artificial intelligence models.
It has been widely shown that biomaterial surface topography can modulate host immune response, but a fundamental understanding of how different topographies contribute to pro-inflammatory or anti-inflammatory responses is still lacking. To investigate the impact of surface topography on immune response, we undertook a systematic approach by analyzing immune response to eight grades of medical grade polyurethane of increasing surface roughness in three in vitro models of the human immune system. Polyurethane specimens were produced with defined roughness values by injection molding according to the VDI 3400 industrial standard. Specimens ranged from 0.1 μm to 18 μm in average roughness (Ra), which was confirmed by confocal scanning microscopy. Immunological responses were assessed with THP-1-derived macrophages, human peripheral blood mononuclear cells (PBMCs), and whole blood following culture on polyurethane specimens. As shown by the release of pro-inflammatory and anti-inflammatory cytokines in all three models, a mild immune response to polyurethane was observed, however, this was not associated with the degree of surface roughness. Likewise, the cell morphology (cell spreading, circularity, and elongation) in THP-1-derived macrophages and the expression of CD molecules in the PBMC model on T cells (HLA-DR and CD16), NK cells (HLA-DR), and monocytes (HLA-DR, CD16, CD86, and CD163) showed no influence of surface roughness. In summary, this study shows that modifying surface roughness in the micrometer range on polyurethane has no impact on the pro-inflammatory immune response. Therefore, we propose that such modifications do not affect the immunocompatibility of polyurethane, thereby supporting the notion of polyurethane as a biocompatible material.
An ongoing challenge in our days is to lower the impact on the quality of life caused by dysfunctionality through individual support. With the background of an aging society and continuous increases in costs for care, a holistic solution is needed. This solution must integrate individual needs and preferences, locally available possibilities, regional conditions, professional and informal caregivers and provide the flexibility to implement future requirements. The proposed model is a result of a common initiative to overcome the major obstacles and to center a solution on individual needs caused by dysfunctionality.
Autism spectrum disorders (ASD) affect a large number of children both in the Russian Federation and in Germany. Early diagnosis is key for these children, because the sooner parents notice such disorders in a child and the rehabilitation and treatment program starts, the higher the likelihood of his social adaptation. The difficulties in raising such a child lie in the complexity of his learning outside of children's groups and the complexity of his medical care. In this regard, the development of digital applications that facilitate medical care and education of such children at home is important and relevant. The purpose of the project is to improve the availability and quality of healthcare and social adaptation at home of children with ASD through the use of digital technologies.
The goal of the presented project is to develop the concept of home e-health centers for barrier-free and cross-border telemedicine. AAL technologies are already present on the market but there is still a gap to close until they can be used for ordinary patient needs. The general idea needs to be accompanied by new services, which should be brought together in order to provide a full coverage of service for the users. Sleep and stress were chosen as predominant influence in the population. The executed scientific study of available home devices analyzing sleep has provided the necessary to select appropriate devices. The first choice for the project implementation is the device EMFIT QS+. This equipment provides a part of a complete system that a home telemedical hospital can provide at a level of precision and communication with internal and/or external health services.
Assistive environments are entering our homes faster than ever. However, there are still various barriers to be broken. One of the crucial points is a personalization of offered services and integration of assistive technologies in common objects and therefore in a regular daily routine. Recognition of sleep patterns for the preliminary sleep study is one of the Health services that could be performed in an undisturbing way. This article proposes the hardware system for the measurement of bio-vital signals necessary for initial sleep study in a nonobtrusive way. The first results confirm the potential of measurement of breathing and movement signals with the proposed system.
Measuring cardiorespiratory parameters in sleep, using non-contact sensors and the Ballistocardiography technique has received much attention due to the low-cost, unobtrusive, and non-invasive method. Designing a user-friendly, simple-to-use, and easy-to-deployment preserving less error-prone remains open and challenging due to the complex morphology of the signal. In this work, using four forcesensitive resistor sensors, we conducted a study by designing four distributions of sensors, in order to simplify the complexity of the system by identifying the region of interest for heartbeat and respiration measurement. The sensors are deployed under the mattress and attached to the bed frame without any interference with the subjects. The four distributions are combined in two linear horizontal, one linear vertical, and one square, covering the influencing region in cardiorespiratory activities. We recruited 4 subjects and acquired data in four regular sleeping positions, each for a duration of 80 seconds. The signal processing was performed using discrete wavelet transform bior 3.9 and smooth level of 4 as well as bandpass filtering. The results indicate that we have achieved the mean absolute error of 2.35 and 4.34 for respiration and heartbeat, respectively. The results recommend the efficiency of a triangleshaped structure of three sensors for measuring heartbeat and respiration parameters in all four regular sleeping positions.
Pharmaceutical companies are among the top investors into research and development (R&D) globally, as product innovation is still the main growth driver for the industry and because the related complexities necessitate enormous R&D investments. The market demand for new medicines to be more efficacious or to provide better safety than existing drugs and the regulatory need to prove superiority in clinical trials are reasons why drug R&D is increasingly expensive and pharmaceutical companies need to manage extraordinarily high costs per approved new compound.
We investigated the state of artificial intelligence (AI) in pharmaceutical research and development (R&D) and outline here a risk and reward perspective regarding digital R&D. Given the novelty of the research area, a combined qualitative and quantitative research method was chosen, including the analysis of annual company reports, investor relations information, patent applications, and scientific publications of 21 pharmaceutical companies for the years 2014 to 2019. As a result, we can confirm that the industry is in an ‘early mature’ phase of using AI in R&D. Furthermore, we can demonstrate that, despite the efforts that need to be managed, recent developments in the industry indicate that it is worthwhile to invest to become a ‘digital pharma player’.
Today, virtualizing pharma R&D is increasingly related with data analytics and artificial intelligence (AI), technologies that have been developed by software companies outside the healthcare sector. The process of virtualizing pharma R&D is closely related to the technological advancements that result in the generation of large data sets ranging from genomics, proteomics, metabolomics, medical imaging, IoT wearables and large clinical trials, making it necessary for pharma companies to find new ways to store and ultimately analyze information. As a consequence, pharma companies are experimenting with AI in R&D ranging from in-silico drug design to clinical trail participants identification or dosage error reduction.
Artificial intelligence (AI) technologies, such as machine learning or deep learning, have been predicted to highly impact future organizations and radically change the way how projects are managed. The Project Management Institute (PMI), the network of around 1.1 million certified project managers, ranked AI as one of the top three disruptors of their profession. In an own study on the effect of AI, 37% of the project management processes can be executed by machine learning and other AI technologies. In addition, Gartner recently postulated that 80% of the work of today's project managers may be eliminated by AI in 2030.
This editorial aims to outline today's project and portfolio management in context of pharmaceutical research and development (R&D), followed by an AI-vision and a more tangible mission, and illustrate what the consequences of an AI-enabled project and portfolio management could be for pharmaceutical R&D.
New drugs serving unmet medical needs are one of the key value drivers of research-based pharmaceutical companies. The efficiency of research and development (R&D), defined as the successful approval and launch of new medicines (output) in the rate of the monetary investments required for R&D (input), has declined since decades. We aimed to identify, analyze and describe the factors that impact the R&D efficiency. Based on publicly available information, we reviewed the R&D models of major research-based pharmaceutical companies and analyzed the key challenges and success factors of a sustainable R&D output. We calculated that the R&D efficiencies of major research-based pharmaceutical companies were in the range of USD 3.2–32.3 billion (2006–2014). As these numbers challenge the model of an innovation-driven pharmaceutical industry, we analyzed the concepts that companies are following to increase their R&D efficiencies: (A) Activities to reduce portfolio and project risk, (B) activities to reduce R&D costs, and (C) activities to increase the innovation potential. While category A comprises measures such as portfolio management and licensing, measures grouped in category B are outsourcing and risk-sharing in late-stage development. Companies made diverse steps to increase their innovation potential and open innovation, exemplified by open source, innovation centers, or crowdsourcing, plays a key role in doing so. In conclusion, research-based pharmaceutical companies need to be aware of the key factors, which impact the rate of innovation, R&D cost and probability of success. Depending on their company strategy and their R&D set-up they can opt for one of the following open innovators: knowledge creator, knowledge integrator or knowledge leverager.
In the period from the 1950s to 2013, the American Food and Drug Administration (FDA) approved 1346 new molecular entities (NMEs) or new biologics entities (NBEs). On average, the approval rate was 20 NMEs per year. In the past 40 years, the number of new drugs launched into the market increased slightly from 15 NMEs in the 1970s to 25–30 NMEs since the 1990s. The highest number of new drugs approved by FDA was in 1996 and 1997, which might be related to the enactment of the Prescription Drug User Fee Act (PDUFA) in 1993.
Introduction: Telemedicine reduces greenhouse gas emissions (CO2eq); however, results of studies vary extremely in dependence of the setting. This is the first study to focus on effects of telemedicine on CO2 imprint of primary care.
Methods: We conducted a comprehensive retrospective study to analyze total CO2eq emissions of kilometers (km) saved by telemedical consultations. We categorized prevented and provoked patient journeys, including pharmacy visits. We calculated CO2eq emission savings through primary care telemedical consultations in comparison to those that would have occurred without telemedicine. We used the comprehensive footprint approach, including all telemedical cases and the CO2eq emissions by the telemedicine center infrastructure. In order to determine the net ratio of CO2eq emissions avoided by the telemedical center, we calculated the emissions associated with the provision of telemedical consultations (including also the total consumption of physicians’ workstations) and subtracted them from the total of avoided CO2eq emissions. Furthermore, we also considered patient cases in our calculation that needed to have an in-person visit after the telemedical consultation. We calculated the savings taking into account the source of the consumed energy (renewable or not).
Results: 433 890 telemedical consultations overall helped save 1 800 391 km in travel. On average, 1 telemedical consultation saved 4.15 km of individual transport and consumed 0.15 kWh. We detected savings in almost every cluster of patients. After subtracting the CO2eq emissions caused by the telemedical center, the data reveal savings of 247.1 net tons of CO2eq emissions in total and of 0.57 kg CO2eq per telemedical consultation. The comprehensive footprint approach thus indicated a reduced footprint due to telemedicine in primary care.
Discussion: Integrating a telemedical center into the health care system reduces the CO2 footprint of primary care medicine; this is true even in a densely populated country with little use of cars like Switzerland. The insight of this study complements previous studies that focused on narrower aspects of telemedical consultations.
Haptisches Feedback ist nach zahlreichen Studien ein wichtiger Bestandteil in der medizinischen Robotik. Die meisten Systeme befinden sich jedoch noch im Forschungsstatus und verfolgen unterschiedliche Ansätze. In der Teleoperation wird mit sensorlosen und Sensor-Systemen geforscht. Sensoren bieten, im Gegensatz zu den Encodern in sensorlosen Systemen, genaue Messungen, sind allerdings teuer in der Anschaffung, schwer zu desinfizieren und müssen in OP-Besteck integriert werden. In Hands-On Systemen fühlt der Operateur im Gegensatz zu Teleoperationssystemen direkt die auftretenden Kräfte bei der Benutzung. Der Roboter bietet in diesen Systemen nur die benötigte Stabilität und Genauigkeit, gesteuert werden sie direkt durch den Menschen. Dagegen werden in Teleoperationssystemen gezielte Controller eingesetzt. Hier hat sich der für den OP entwickelte sigma.7 durchgesetzt. Gegenüber der für die Allgemeinheit entwickelten Konkurrenz bietet er haptisches Feedback in allen nötigen Freiheitsgraden und eine entsprechende Kraftrückkoppelung.
Bone remodeling can be mimicked in vitro by co-culture models. Based on bone cells, such co-cultures help to study synergistic morphological changes and the impact of materials and applied substances. Hence, we examined the formation of osteoclasts on bovine bone materials to prove the bone resorption functionality of the osteoclasts in three different co-culture set-ups using human monocytes (hMCs) and (I) human mesenchymal stem cells (hMSCs), (II) osteogenic differentiated hMSCs (hOBs), and (III) hOBs in addition of soluble monocyte-colony stimulating factor (M CSF) and cytokine receptor activator of NFkB ligand (RANKL).We detected osteoclast-specific actin morphology, as well as the expression of cathepsin K and CD51/61 in single cells in set-up II and in numerous cells in set-up III. Resorption pits on bone material as characteristic proof of functional osteoclasts were not found in set-up I and II, but we detected such resorption pits in set–up III. We conclude in co culture models without M-CSF and RANKL that monocytes can differentiate into osteoclasts that show the characteristic actin structures and protein expression. However, to receive functional bone resorbing osteoclasts in vitro, the addition of M-CSF and RANKL is needed. Moreover, we suggest the use of bone or bone-like materials for future studies evaluating osteoclastogenesis.
This paper contributes to the automatic detection of perioperative workflow by developing a binary endoscope localization. Automated situation recognition in the context of an intelligent operating room requires the automatic conversion of low level cues into more abstract high level information. Imagery from a laparoscope delivers rich content that is easy to obtain but hard to process. We introduce a system which detects if the endoscope's distal tip is inside or outsiede the patient based on the endoscope video. This information can be used as one parameter in a situation recognition pipeline. Our localization performs in real-time at a video resolution of 1280x720 and 5-fold cross validation yields mean F1-scores of up to 0,94 on videos of 7 laparoscopies.
Segmentierung von Polypen in Koloskopie-Bilddaten : eine Potentialanalyse von Deep-Learning-Methoden
(2018)
Kolorektale Karzinome haben eine hohe Sterblichkeitsrate, wenn sie spät entdeckt werden. Eine frühzeitige Entfernung von bösartigen Polypen im Magen-Darm-Trakt, die deren Vorstufen bilden, bietet jedoch hohe Überlebenschancen. Bei Darmspiegelungen werden gerade kleine Polypen aber recht häufig übersehen. Zuverlässige bildverarbeitende Systeme, die Polypen in einem Koloskopie-Frame nicht nur detektieren, sondern pixelgenau segmentieren, könnten Ärzten bei Darmkrebs-Screenings helfen. Diese Arbeit analysiert den aktuellen Stand der Segmentierung von Polypen im Gastrointestinaltrakt. Weiterführend wird untersucht, inwiefern die in letzter Zeit sehr erfolgreichen Methoden des Deep Learning hier Vorteile bieten.
Methods based exclusively on heart rate hardly allow to differentiate between physical activity, stress, relaxation, and rest, that is why an additional sensor like activity/movement sensor added for detection and classification. The response of the heart to physical activity, stress, relaxation, and no activity can be very similar. In this study, we can observe the influence of induced stress and analyze which metrics could be considered for its detection. The changes in the Root Mean Square of the Successive Differences provide us with information about physiological changes. A set of measurements collecting the RR intervals was taken. The intervals are used as a parameter to distinguish four different stages. Parameters like skin conductivity or skin temperature were not used because the main aim is to maintain a minimum number of sensors and devices and thereby to increase the wearability in the future.
Introduction: Even if there is a standard procedure of CI surgery, especially in pediatric surgery surgical steps often differ individually due to anatomical variations, malformations or unforseen events. This is why every surgical report should be created individually, which takes time and relies on the correct memory of the surgeon. A standardized recording of intraoperative data and subsequent storage as well as text processing would therefore be desirable and provides the basis for subsequent data processing, e.g. in the context of research or quality assurance.
Method: In cooperation with Reutlingen University, we conducted a workflow analysis of the prototype of a semi-automatic checklist tool. Based on automatically generated checklists generated from BPMN models a prototype user interface was developed for an android tablet. Functions such as uploading photos and files, manual user entries, the interception of foreseeable deviations from the normal course of operations and the automatic creation of OP documentation could be implemented. The system was tested in a remote usability test on a petrous bone model.
Result: The user interface allows a simple intuitive handling, which can be well implemented in the intraoperative setting. Clinical data as well as surgical steps could be individually recorded and saved via DICOM. An automatic surgery report could be created and saved.
Summary: The use of a dynamic checklist tool facilitates the capture, storage and processing of surgical data. Further applications in clinical practice are pending.
In summary, we believe that current “sleep monitoring” consumer devices on the market must undergo a more robust validation process before being made available and distributed in the general public. This is especially noteworthy as there have been first reports in the literature that inaccurate feedback of such consumer devices can worry subjects and may even lead to compromised well-being of the user.
Due to the large interindividual variances and the poor optical accessibility of the ear, the specificity of hearing diagnostics today is severely restricted to a certain clinical picture and quantitative assessment. Often only a yes or no decision is possible, which depends strongly on the subjective assessment of the ENT physician. A novel approach, in which objectively obtainable, non invasive audiometric measurements are evaluated using a numerical middle ear model, makes it possible to make the hidden middle ear properties visible and quantifiable. The central topic of this paper is a novel parameter identification algorithm that combines inverse fuzzy arithmetic with an artificial neural network in order to achieve a coherent diagnostic overall picture in the comparison of model and measurement. Its usage is shown at a pathological pattern called malleus fixation where the upper ligament of the malleus is pathologically stiffened.
Simulation models of the middle ear have rarely been used for diagnostic purposes due to their limited predictive ability with respect to pathologies. One big challenge is the large uncertainty and ambiguity in the choice of material parameters of the model.
Typically, the model parameters are determined by fitting simulation results to validation measurements. In a previous study, it was shown that fitting the model parameters of a finite-element model using the middle-ear transfer function and various other measurable output variables from normal ears alone is not sufficient to obtain a good predictive ability of the model on pathological middle-ear conditions. However, the inclusion of validation measurements on one pathological case resulted in a very good predictive ability also for other pathological cases. Although the found parameter set was plausible in all aspects, it was not yet possible to draw conclusions about the uniqueness and the accuracy or the uncertainty of the parameter set.
To answer these questions, statistical solution approaches are used in this study. Using the Monte Carlo method, a large number of plausible model data sets are generated that correctly represent the normal and pathological middle-ear characteristics in terms of various output variables like e.g., impedance, reflectance, umbo, and stapes transfer function. Subsequent principal component analyses (PCA) allow to draw conclusions about correlations, quantitative limits and statistical density of parameter values.
Furthermore, applying inverse PCA yields numerous plausible parameterizations of the middle-ear model, which can be used for data augmentation and training of a neural network which is capable of distinguishing between a normal middle ear and pathologies like otosclerosis, malleus fixation, and disarticulation based on objectively measured quantities like impedance, reflectance, and umbo velocity.
Stent graft visualization and planning tool for endovascular surgery using finite element analysis
(2014)
Purpose: A new approach to optimize stent graft selection for endovascular aortic repair is the use of finite element analysis. Once the finite element model is created and solved, a software module is needed to view the simulation results in the clinical work environment. A new tool for Interpretation of simulation results, named Medical Postprocessor, that enables comparison of different stent graft configurations and products was designed, implemented and tested. Methods Aortic endovascular stent graft ring forces and sealing states in the vessel landing zone of three different configurations were provided in a surgical planning software using the Medical Imaging Interaction Tool Kit (MITK) Software system. For data interpretation, software modules for 2D and 3D presentations were implemented. Ten surgeons evaluated the software features of the Medical Postprocessor. These surgeons performed usability tests and answered questionnaires based on their experience with the system.
Results: The Medical Postprocessor visualization system enabled vascular surgeons to determine the configuration with the highest overall fixation force in 16 ± 6 s, best proximal sealing in 56±24 s and highest proximal fixation force in 38 ± 12 s. The majority considered the multiformat data provided helpful and found the Medical Postprocessor to be an efficient decision support system for stent graft selection. The evaluation of the user interface results in an ISONORMconform user interface (113.5 points).
Conclusion: The Medical Postprocessor visualization Software tool for analyzing stent graft properties was evaluated by vascular surgeons. The results show that the software can assist the interpretation of simulation results to optimize stent graft configuration and sizing.
Im Fokus der Arbeit steht die Unterstützung der Stentgraftauswahl bei endovaskulärer Versorgung eines infrarenalen Aortenaneurysmas. Im Rahmen der Arbeit wurde eine Methode zur Auswertung von Ergebnissen einer Finite Elemente-Analyse zum Stentgraftverhalten konzipiert, implementiert und im Rahmen einer deutschlandweiten Benutzerstudie mit 16 Chirurgen diskutiert. Die entwickelte Mensch-Maschine-Schnittstelle ermöglicht dem Gefäßmediziner eine interaktive Analyse berechneter Fixierungskräfte und Kontaktzustände mehrerer Stentgrafts im Kontext mit dem zu behandelnden Aortenabschnitt. Die entwickelte Methode ermöglicht eine tiefergehende Auseinandersetzung der Mediziner mit numerischen Simulationen und Stentgraftbewertungsgrößen. Hierdurch konnte im Rahmen der Benutzerstudie das Einsatzpotenzial numerischer Simulationen zur Unterstützung der Stentgraftauswahl ermittelt und eine Anforderungsspezifikation an ein System zur simulationsbasierten Stentgraftplanung definiert werden. Im Ergebnis wurde als wesentliches Einsatzpotenzial die Festlegung eines Mindestmaßes an Überdimensionierung, die Optimierung der Schenkellänge von bifurkativen Stentgrafts sowie der Vergleich unterschiedlicher Stentgraftdesigns ermittelt. Zu den wesentlichen Funktionen eines Systems zur simulationsbasierten Stentgraftauswahl gehören eine Übersichtskarte zu farbkodiertem Migrationsrisiko pro Stentgraft und Landungszone, die Visualisierung des Abdichtungszustandes der Stentkomponenten sowie die Darstellung von Stentgraft- und Gefäßdeformationen im 3D-Modell.
Purpose
Supporting the surgeon during surgery is one of the main goals of intelligent ORs. The OR-Pad project aims to optimize the information flow within the perioperative area. A shared information space should enable appropriate preparation and provision of relevant information at any time before, during, and after surgery.
Methods
Based on previous work on an interaction concept and system architecture for the sterile OR-Pad system, we designed a user interface for mobile and intraoperative (stationary) use, focusing on the most important functionalities like clear information provision to reduce information overload. The concepts were transferred into a high-fidelity prototype for demonstration purposes. The prototype was evaluated from different perspectives, including a usability study.
Results
The prototype’s central element is a timeline displaying all available case information chronologically, like radiological images, labor findings, or notes. This information space can be adapted for individual purposes (e.g., highlighting a tumor, filtering for own material). With the mobile and intraoperative mode of the system, relevant information can be added, preselected, viewed, and extended during the perioperative process. Overall, the evaluation showed good results and confirmed the vision of the information system.
Conclusion
The high-fidelity prototype of the information system OR-Pad focuses on supporting the surgeon via a timeline making all available case information accessible before, during, and after surgery. The information space can be personalized to enable targeted support. Further development is reasonable to optimize the approach and address missing or insufficient aspects, like the holding arm and sterility concept or new desired features.
Checklists are a valuable tool to ensure process quality and quality of care. To ensure proper integration in clinical processes, it would be desirable to generate checklists directly from formal process descriptions. Those checklists could also be used for user interaction in context-aware surgical assist systems. We built a tool to automatically convert Business Process Model and Notation (BPMN) process models to checklists displayed as HTML websites. Gateways representing decisions are mapped to checklist items that trigger dynamic content loading based on the placed checkmark. The usability of the resulting system was positively evaluated regarding comprehensibility and end-user friendliness.
Mammographie-Geräte werden in der Diagnostik von Mammakarzinomen eingesetzt. Die ursprüngliche Technik wurde in den letzten Jahren von analogen Röntgenfilmen zu digital integrierten Systemen weiterentwickelt. Durch die Tomosynthese, bei der in einem Schnittbildverfahren mehrere Schichten des Organismus untersucht werden können, können auch überlagerte Strukturen sichtbar gemacht werden. Um als adäquate Grundlage zur Diagnostik von malignen Tumoren dienen zu können, müssen einige qualitative Anforderungen erfüllt werden. Bisher gibt es wenig Literatur, die Anforderungen und den Aufbau solcher Geräte systematisch beschreiben. Im Rahmen dieser Arbeit werden auf Basis der Literatur und bestehender Systeme die qualitativen Anforderungen identifiziert. Der prinzipielle Aufbau solcher Systeme wird anhand der einzelnen Systembausteine in der semiformalen Notationssprache SysML gezeigt. Die grundlegende Funktionsweise eines tomosynthesefähigen Mammographie Gerätes wird in dieser Arbeit zusammenfassend und anhand der einzelnen Systembausteine beschrieben. Diese Arbeit dient der Vermittlung eines umfassenden Verständnisses für die digitale Mammographie, um als Grundlage für die Dokumentation von qualitativen Anforderungen dienen zu können.
The potentials and opportunities created by digitized healthcare can be further customized through smart data processing and analysis using accurate patient information. This development and the associated new treatment concepts basing on digital smart sensors can lead to an increase in motivation by applying gamification approaches. This effect can also be used in the field of medical treatment, e.g. with the help of a digital spirometer combined with an app. In one of our exemplary applications, we show how to control an airplane within an app by breathing respectively inhaling and exhaling. Using this biofeedback within a game allows us to increase the motivation and fun for children that need to perform necessary exercises.
Artefaktkorrektur und verfeinerte Metriken für ein EEG-basiertes System zur Müdigkeitserkennung
(2019)
Fragestellung: Müdigkeit ist ein oft unterschätztes, aber dennoch großes Problem im Straßenverkehr. Von rund 2,5 Mio. Verkehrsunfällen 2015 in Deutschland, waren 2898 Unfälle, mit insgesamt 59 Toten (~1,7 % der Todesfälle), auf Übermüdung zurückzuführen. Schätzungen gehen von einer Dunkelziffer von bis zu 20 % aus. In einer ersten eigenen Studie wurde überprüft, ob ein mobiles EEG in einem Fahrsimulator Müdigkeitszustände zuverlässig erkennen kann. Die Erkennungsrate lag lediglich bei 61 %. Ziel dieser Arbeit ist, das verwendete Messsystem zu verbessern. Dazu wird die Genauigkeit durch eine Artefaktkorrektur und mit Hilfe von verfeinerten Qualitätsmetriken erhöht. Eine erkannte Übermüdung wird dem Fahrer dann in angemessener Weise angezeigt, so dass er entsprechend reagieren kann.
Patienten und Methoden: Die Independent Component Analysis (ICA) ist ein multivariates Verfahren, um mehrere Zufallsvariablen zu analysieren. Für die Entscheidung, ob ein Fahrer gerade müde oder wach ist, wird der erstellte Merkmalsvektor für jede Sequenz mit ICA klassifiziert. Dafür wird ein trainierter Machine-Learning-Algorithmus eingesetzt, der in der Lage ist, auch unbekannte Datensätze in Klassen einzuteilen. Um die benötigten Frequenzwerte zu erhalten, wurde für jeden EEG-Kanal eine Fourier Transformation durchgeführt. Der erstellte Merkmalsvektor wird im nächsten Schritt durch ein Künstliches Neuronales Netz klassifiziert. Für das Training werden vorab erstellte Merkmalsvektoren mit den Klassen „Wach“ und „Müde“ versehen. Diese Daten werden zufällig gemischt und im Verhältnis 2:1 in eine Trainings- und Testmenge geteilt. Das Experiment wurde mit acht Personen mit jeweils zweimal 45 min Testfahrt durchgeführt.
Ergebnisse: Der komplette Datensatz besteht aus 150.000 Signalwerten, welche zu ca. 7000 Sequenzen zusammengefasst werden. Durch die Anwendung der Qualitätsmetrik bleiben 4370 Sequenzen für das Training übrig. Bei invaliden Sequenzen aufgrund von EEG-Artefakten gibt es deutliche Unterschiede. Im „Wach“ Zustand werden dreimal so viele Sequenzen verworfen als im „Müde“ Zustand. Insgesamt werden bei wachen Probanden im Schnitt ca. 50 % der Sequenzen verworfen, bei Müden lediglich 25 %. Im Durchschnitt erreicht das System eine Erkennungsrate von 73 % für beide Zustände. Vergleicht man nun das Verhältnis von „Wach“ und „Müde“ und lässt „Leichte Müdigkeit“ außen vor, liegen die Ergebnisse bei über 90 %.
Schlussfolgerungen: Die Ergebnisse zeigen, dass die Aufmerksamkeit während des Experiments abnimmt bzw. die Müdigkeit zunimmt. Dies verdeutlichen zum einen subjektive und objektive Beobachtungen von Müdigkeitsanzeichen. Zum anderen lassen sich messbare und klassifizierbare Unterschiede im EEG Signal nachweisen. Die als Merkmale eingesetzten Theta-Wellen zeigten eine niedrigere Amplitude gegen Ende des Experiments. Die Erweiterung der binären Klassifizierung führt zu einer weiteren Stabilisierung der Ergebnisse. Artefaktkorrektur und Qualitätsmetriken steigern die Güte der Daten weiter. Die entwickelte Anwendung zur Müdigkeitserkennung ermittelt messbare Zeichen von Müdigkeit und kann eine gute Entscheidung über die Fahrtauglichkeit treffen.
The present work proposes the use of modern ICT technologies such as smartphones, NFCs, internet, and web technologies, to help patients in carrying out their therapies. The implemented system provides a calendar with a reminder of the assumptions, ensures the drug identification through NFC, allows remote assistance from healthcare staff and family members to check and manage the therapy in real-time. The system also provides centralized information on the patient's therapeutic situation, helpful in choosing new compatible therapies.
Gender Marketing gewinnt sowohl in der Marketing-Theorie als auch in der Unternehmenspraxis zunehmend an Bedeutung. Der Unterschied zwischen den Geschlechtern zeigt sich nicht nur in unterschiedlichen Fähigkeiten und Einstellungen, sondern auch in verschiedenen Bedürfnissen und im Kaufverhalten. Viele Produkte werden von Männern für Männer entwickelt. Produkte, die sich speziell an Frauen richten, werden häufig gemäß dem Motto „pink it and shrink it“ auf den Markt gebracht. Eine erfolgreiche Umsetzung von Gender-Aspekten ist für Unternehmen eine wichtige Marketing-Herausforderung für die Zukunft.
New approaches to respiratory assist: bioengineering an ambulatory, miniaturized bioartificial lung
(2019)
Although state-of-the-art treatments of respiratory failure clearly have made some progress in terms of survival in patients suffering from severe respiratory system disorders, such as acute respiratory distress syndrome (ARDS), they failed to significantly improve the quality of life in patients with acute or chronic lung failure, including severe acute exacerbations of chronic obstructive pulmonary disease or ARDS as well. Limitations of standard treatment modalities, which largely rely on conventional mechanical ventilation, emphasize the urgent, unmet clinical need for developing novel(bio)artificial respiratory assist devices that provide extracorporeal gas exchange with a focus on direct extracorporeal CO2 removal from the blood. In this review, we discuss some of the novel concepts and critical prerequisites for such respiratory lung assist devices that can be used with an adequate safety profile, in the intensive care setting, as well as for long-term domiciliary therapy in patients with chronic ventilatory failure. Specifically, we describe some of the pivotal steps, such as device miniaturization, passivation of the blood-contacting surfaces by chemical surface modifications, or endothelial cell seeding, all of which are required for converting current lung assist devices into ambulatory lung assist device for long-term use in critically ill patients. Finally, we also discuss some of the risks and challenges for the long-term use of ambulatory miniaturized bioartificial lungs.
In this paper a method for the generation of gSPM with ontology-based generalization was presented. The resulting gSPM was modeled with BPMN/BPMNsix in an efficient way and could be executed with BPMN workflow engines. In the next step the implementation of resource concepts, anatomical structures, and transition probabilities for workflow execution will be realized.
The implementation of a web based portal QA solution will lead to a high acceptance of the staff as the usage of commonly known standard software (e.g. web browser) allows intuitive handling. In the daily use a significant simplification of the workflow and Performance enhancement can be achieved by easy access to the check documents. As the data is now saved in a database it can easily be processed and long-term trends can be displayed. Therefore possible errors can be detected much easier and earlier. By the usage of time stamps and user authentication procedures and user responsibilities are comprehensibly documented. As the software is browser based, integration into an existing software Environment is not critical. As only technical QA data is processed, no further data security measures are necessary. A certification as a medical product is not required.
In 2017, Philips' goal was to use innovation to improve the lives of three billion people a year by 2025. To achieve that, the company was shifting from selling medical products in a transactional manner to providing integrated healthcare solutions based on digital health technology. Based on our interviews with 23 executives at Philips, the case examines the two directions of the transformation required by this shift: externally, Philips worked on transforming how healthcare was conducted. Healthcare professionals would have to change the way they worked and reimbursement schemes needed to change to incentivize payers, providers, and patients in vastly different ways. Internally, Philips needed to redesign how its employees worked. The company componentized its business, introduced digital platforms, and co-created integrated solutions with the various stakeholders of the healthcare industry. In other words: Philips was transforming itself in order the reinvent healthcare in the digital age.
It is well established that the mechanical environment influences cell functions in health and disease. Here, we address how the mechanical environment influences tumor growth, in particular, the shape of solid tumors. In an in vitro tumor model, which isolates mechanical interactions between cancer tumor cells and a hydrogel, we find that tumors grow as ellipsoids, resembling the same, oft-reported observation of in vivo tumors. Specifically, an oblate ellipsoidal tumor shape robustly occurs when the tumors grow in hydrogels that are stiffer than the tumors, but when they grow in more compliant hydrogels they remain closer to spherical in shape. Using large scale, nonlinear elasticity computations we Show that the oblate ellipsoidal shape minimizes the elastic free energy of the tumor-hydrogel system. Having eliminated a number of other candidate explanations, we hypothesize that minimization of the elastic free energy is the reason for predominance of the experimentally observed ellipsoidal shape. This result may hold significance for explaining the shape progressio.
Die prä-, intra- und postoperative Entitäts- und Dignitätsbestimmung von Speicheldrüsen-tumoren (ST) allein anhand von histomorphologischen Kriterien ist häufig mit großen Unsicherheiten verbunden.
Die Spektren der Raman-Spektroskopie (RS) und der Infrarot-Spektroskopie (IS) enthalten Informationen zu der molekularen Zusammensetzung des untersuchten Gewebes. Ziel der Arbeit war die Etablierung eines Gewebe-Aufarbeitungs-Workflows und die Analyse des Einflusses der Fixierung auf die spektrale Bioinformation. Zudem wird ein Überblick über den Einsatz der RS und IS im Kopf-Hals Bereich gegeben.
Es wurden 10 mm dicke, konsekutive kryo-, formalin- und paraffinfixierte ST-Gewebeschnitte von Zystadenolymphomen (n=5) und pleomorphen Adenomen (n=4) mit der RS und IS untersucht und die Daten multivariat ausgewertet. Die Messungen erfolgten in Korrelation zur Histomorphologie über einen korrespondierenden HE-Schnitt sowohl im Tumorgewebe als auch im gesunden Speicheldrüsengewebe.
In der Mittelwertspektrenanalyse zeigte sich eine deutliche Paraffin-Signatur, Formalin-Fixierung hatte keinen wesentlichen Einfluss. Dies konnte durch die Hauptkomponentenanalyse (PCA) bestätigt werden. Eine Diskriminierung von Tumor- und Nicht-Tumorgewebe durch die PCA und gekoppelte Diskriminanzanalyse war ebenfalls mit beiden spektroskopischen Methoden mit einer hohen Sensitivität möglich.
Für eine Translation von spektralen Verfahren ist das Wissen über Einflussfaktoren auf die spektrale Bioinformation der Gewebeaufarbeitung und -fixierung unabdingbar. Die Integration spektraler Verfahren additiv in bestehende Arbeitsabläufe ist möglich. Der Einfluss der Formalinfixierung auf die spektrale Bioinformation ist gering. Die bioinformatische Analyse der umfangreichen Datensätze ist herausfordernd.
IZKF Würzburg
There are several intra-operative use cases which require the surgeon to interact with medical devices. We used the Leap Motion Controller as input device and implemented two use-cases: 2D-Interaction (e.g. advancing EPR data) and selection of a value (e.g. room illumination brightness). The gesture detection was successful and we mapped its output to several devices and systems.
In breath analysis, ambient air contaminations are ubiquitous and difficult to eliminate. This study was designed to investigate the reduction of ambient air background by a lung wash-out with synthetic air. The reduction of the initial ambient air volatile organic compound (VOC) intensity was investigated in the breath of 20 volunteers inhaling synthetic air via a sealed full face mask in comparison to inhaling ambient air. Over a period of 30 minutes, breath analysis was conducted using ion mobility spectrometry coupled to a multi-capillary column. A total of 68 VOCs were identified for inhaling ambient air or inhaling synthetic air. By treatment with synthetic air, 39 VOCs decreased in intensity, whereas 29 increased in comparison to inhaling ambient air. In total, seven VOCs were significantly reduced (P-value < 0.05). A complete wash-out of VOCs in this setting was not observed, whereby a statistically significant reduction up to 65% as for terpinolene was achieved. Our setting successfully demonstrated a reduction of ambient air contaminations from the airways by a lung wash-out with synthetic air.
Propofol is a commonly used intravenous general anesthetic. Multi-capillary column (MCC) coupled ion-mobility spectrometry (IMS) can be used to quantify exhaled propofol, and thus estimate plasma drug concentration. Here, we present results of the calibration and analytical validation of a MCC/IMS pre-market prototype for propofol quantification in exhaled air.
Propofol is an intravenous anesthetic. Currently, it is not possible to routinely measure blood concentration of the drug in real time. However, multi-capillary column ion-mobility spectrometry of exhaled gas can estimate blood propofol concentration.Unfortunately, adhesion of volatile propofol on plastic materials complicates measurements. Therefore, it is necessary to consider the extent to which volatile propofol adheres to various plastics used in sampling tubing. Perfluoralkoxy (PFA), polytetrafluorethylene (PTFE), polyurethane (PUR), silicone, and Tygon tubing were investigated in an experimental setting using a calibration gas generator (HovaCAL). Propofol gas was measured for one hour at 26 °C, 50 °C, and 90 °C tubing temperature. Test tubing segments were then flushed with N2 to quantify desorption. PUR and Tygon sample tubing absorbed all volatile propofol. The silicone tubing reached the maximum propofol concentration after 119 min which was 29 min after propofol gas exposure stopped. The use of PFAor PTFE tubing produced comparable and reasonably accurate propofol measurements. The desaturation time for the PFA was 10 min shorter at 26 °C than for PTFE. PFA tubing thus seems most suitable for measurement of volatile propofol,with PTFE as an alternative.
Ion mobility spectrometry coupled to multi capillary columns (MCC/IMS) combines highly sensitive spectrometry with a rapid separation technique. MCC\IMS is widely used for biomedical breath analysis. The identification of molecules in such a complex sample necessitates a reference database. The existing IMS reference databases are still in their infancy and do not allow to actually identify all analytes. With a gas chromatograph coupled to a mass selective detector (GC/MSD) setup in parallel to a MCC/IMS instrumentation we may increase the accuracy of automatic analyte identification. To overcome the time-consuming manual evaluation and comparison of the results of both devices, we developed a software tool MIMA (MS-IMS-Mapper), which can computationally generate analyte layers for MCC/IMS spectra by using the corresponding GC/MSD data. We demonstrate the power of our method by successfully identifying the analytes of a seven-component mixture. In conclusion, the main contribution of MIMA is a fast and easy computational method for assigning analyte names to yet un-assigned signals in MCC/IMS data. We believe that this will greatly impact modern MCC/IMS-based biomarker research by 'giving a name' to previously detected disease-specific molecules.
This paper presents a new European initiative to support the sustainable empowerment of the ageing society. Empowerment in this context represents the capability to have a self-determined, autonomous and healthy life. The paper justifies the need of such an initiative and highlights the role that telemedicine and ambient assisted living can play in this environment.
Propofol in exhaled breath can be measured and may provide a real-time estimate of plasma concentration. However, propofol is absorbed in plastic tubing, thus estimates may fail to reflect lung/blood concentration if expired gas is not extracted directly from the endotracheal tube.We evaluated exhaled propofol in five ventilated ICU patients who were sedated with propofol. Exhaled propofol was measured once per minute using ion mobility spectrometry. Exhaled air was sampled directly from the endotracheal tube and at the ventilator end of the expiratory side of the anesthetic circuit. The circuit was disconnected from the patient and propofol was washed out with a separate clean ventilator. Propofol molecules, which discharged from the expiratory portion of the breathing circuit, were measured for up to 60 h.We also determined whether propofol passes through the plastic of breathing circuits. A total of 984 data pairs (presented as median values, with 95% confidence interval), consisting of both concentrations were collected. The concentration of propofol sampled near the patient was always substantially higher, at 10.4 [10.25–10.55] versus 5.73 [5.66–5.88] ppb (p<0.001). The reduction in concentration over the breathing circuit tubing was 4.58 [4.48–4.68] ppb, 3.46 [3.21–3.73] in the first hour, 4.05 [3.77–4.34] in the second hour, and 4.01 [3.36–4.40] in the third hour. Out-gassing propofol from the breathing circuit remained at 2.8 ppb after 60 h of washing out. Diffusion through the plastic was not observed. Volatile propofol binds or adsorbs to the plastic of a breathing circuit with saturation kinetics. The bond is reversible so propofol can be washed out from the plastic. Our data confirm earlier findings that accurate measurements of volatile propofol require exhaled air to be sampled as close as possible to the patient.
Physicians in interventional radiology are exposed to high physical stress. To avoid negative long-term effects resulting from unergonomic working conditions, we demonstrated the feasibility of a system that gives feedback about unergonomic
situations arising during the intervention based on the Azure Kinect camera. The overall feasibility of the approach could be shown.
Due to the rising need for palliative care in Russia, it is crucial to provide timely and high-quality solutions for patients, relatives, and caregivers. A methodology for remote monitoring of patients in need of palliative care and the requirements will be developed for a hardware-software complex for remote monitoring of patients' health at home.
The hearing contact lens® (HCL) is a new type of hearing aid devices. One of its main components is a piezo-electric actuator. In order to evaluate and maximize the HCL’s performance, a model of the HCL coupled to the middle ear was developed using finite element approach. The model was validated step by step starting with the HCL only. To validate the HCL model, vibrational measurements on the HCL were performed using a Laser-Doppler-Vibrometer (LDV). Then, a silicone cap was placed onto the HCL to provide an interface between the HCL and the tympanic membrane of the middle-ear model and additional LDV measurements on temporal bones were performed to validate the coupled model. The coupled model was used to evaluate the equivalent sound pressure of the HCL. Moreover, a deeper insight was gained into the contact between the HCL and tympanic membrane and its effects on the HCL performance. The model can be used to investigate the sensitivity of geometrical and material parameters with respect to performance measures of the HCL and evaluate the feedback behavior.
Online measurement of drug concentrations in patient's breath is a promising approach for individualized dosage. A direct transfer from breath- to blood-concentrations is not possible. Measured exhaled concentrations are following the blood-concentration with a delay in non-steady-state situations. Therefore, it is necessary to integrate the breath-concentration into a pharmacological model. Two different approaches for pharmacokinetic modelling are presented. Usually a 3-compartment model is used for pharmacokinetic calculations of blood concentrations. This 3-compartment model is extended with a 2-compartment model based on the first compartment of the 3-compartment model and a new lung compartment. The second approach is to calculate a time delay of changes in the concentration of the first compartment to describe the lung-concentration. Exemplarily both approaches are used for modelling of exhaled propofol. Based on time series of exhaled propofol measurements using an ion-mobility-spectrometer every minute for 346 min a correlation of calculated plasma and the breath concentration was used for modelling to deliver R2 = 0.99 interdependencies. Including the time delay modelling approach the new compartment coefficient ke0lung was calculated to ke0lung = 0.27 min−1 with R2 = 0.96. The described models are not limited to propofol. They could be used for any kind of drugs, which are measurable in patient's breath.
Several diseases occur due to asbestos exposure. Until today, asbestos predicted mortality and morbidity will increase because of the long latency period. Actually, the methods to investigate asbestos related disease are mostly invasive. Therefore, the aim of the present paper was to investigate, whether signals in human breath could be correlated to Asbestos related lung diseases using a multi-capillary column (MCC) connected to an ion mobility spectrometer (IMS) as non-invasive method. Here, the breath samples of 10 mL of 25 patients suffering from asbestos related diseases. This group includes patients with asbestos related pleural thickening with and without pulmonary fibrosis. Twelve healthy persons constitute the control group and the breath samples are compared with those of the BK4103 patients. In total 83 peaks are found in the IMS-Chromatogram. A discrimination was possible with p-values <0.001 for two peaks (99.9 %), <0.01 (99 %) for 5 peaks and <0.05 (95 %) for 17 peaks. The most discrimination peaks alpha pinene and 4-ethyltoluol were identified among some others with lower p-values. The corresponding Box-and-Whisker-Plots comparing both groups are presented. In addition, a decision tree including all peaks was created that shows a differentiation with alpha pinene between BK4103 (pleural plaques group) and the control group. In addition, the sensitivity was calculated to 96 %, specificity was 50 %, positive and negative predictive values were 80 % and 86 %. Ion mobility spectrometry was introduced as non-invasive method to separate both groups Asbestos related and healthy. Naturally, the findings need further confirmation on larger population groups, but encourage further investigations, too.
In networked operating room environments, there is an emerging trend towards standardized non-proprietary communication protocols which allow to build new integration solutions and flexible human-machine interaction concepts. The most prominent endeavor is the IEEE 11073 SDC protocol. For some uses cases, it would be helpful if not just medical devices could be controlled based on SDC, but also building automation systems like light, shutters, air condition, etc. For those systems, the KNX protocol is widely used. We build an SDC-to-KNX gateway which allows to use the SDC protocol for sending commands to connected KNX devices. The first prototype system was successfully implemented at the demonstration operating room at Reutlingen University. This is a first step toward the integration of a broader variety of KNX devices.
In der Kryochirurgie wird Kälte verwendet, um tumoröses Gewebe abzutöten. Dazu werden Kryosonden in den Tumor gestochen und stark abgekühlt. Hierbei gibt es verschiedene Herausforderungen, welchen computergestützt begegnet werden kann. Diese Arbeit gibt die Ergebnisse einer Literaturrecherche zu den Herausforderungen wieder. Die vorgestellten Arbeiten beschäftigten sich mit der Simulation des im Tumor entstehenden Eisballs, dem korrekten Positionieren der Kryosonden im Tumor, dem Überwachen des Eingriffs sowie dem Entwickeln von Simulationen für Trainingszwecke. Dabei zeigt sich, dass der Einsatz von computergestützten Lösungen die Kryochirurgie für Operateur und Patient verbessern kann.
Die digitale Transformation und gesellschaftliche Entwicklungen verändern die Arbeitswelt nicht erst seit der Corona-Pandemie. Kommunikation, Kreativität und agile Vorgehensweisen in der Arbeitsorganisation rücken in den Vordergrund und werden gerade in Krisenzeiten zu wichtigen Stärken von Unternehmen. Der Grad der Selbstorganisation von Teams steigt und erfordert mehr individuelle Selbstorganisation der Beschäftigten. Dies birgt neben vielen Chancen auch Gesundheitsrisiken.
Der Report beleuchtet die agile Organisation und weitere moderne Organisationsmodelle wie die Soziokratie, die Holokratie und die evolutionäre Organisation unter dem Gesundheitsaspekt. All diese Organisationsmodelle sind gekennzeichnet durch die Abflachung von Hierarchien, eine stärkere Sinnorientierung, mehr Flexibilität sowie die Integration von Leistungspotentialen der Beschäftigten. Die Gemeinsamkeiten, aber auch Unterschiede und Konfliktpotenziale werden ausführlich erklärt.
Mit diesem Hintergrundwissen können Beratende Gesundheitsthemen besser in Phasen gesundheitlicher Belastungen einbringen und richtig adressieren. Der iga.Report 44 gibt einen Überblick zum noch jungen Stand der Forschung und liefert zahlreiche Ansatzpunkte für die Präventionsarbeit und die Betriebliche Gesundheitsförderung in einer neuen Arbeitswelt.
Background: One of the most promising health care development areas is introducing telemedicine services and creating solutions based on blockchain technology. The study of systems combining both these domains indicates the ongoing expansion of digital technologies in this market segment.
Objective: This paper aims to review the feasibility of blockchain technology for telemedicine.
Methods: The authors identified relevant studies via systematic searches of databases including PubMed, Scopus, Web of Science, IEEE Xplore, and Google Scholar. The suitability of each for inclusion in this review was assessed independently. Owing to the lack of publications, available blockchain-based tokens were discovered via conventional web search engines (Google, Yahoo, and Yandex).
Results: Of the 40 discovered projects, only 18 met the selection criteria. The 5 most prevalent features of the available solutions (N=18) were medical data access (14/18, 78%), medical service processing (14/18, 78%), diagnostic support (10/18, 56%), payment transactions (10/18, 56%), and fundraising for telemedical instrument development (5/18, 28%).
Conclusions: These different features (eg, medical data access, medical service processing, epidemiology reporting, diagnostic support, and treatment support) allow us to discuss the possibilities for integration of blockchain technology into telemedicine and health care on different levels. In this area, a wide range of tasks can be identified that could be accomplished based on digital technologies using blockchains.
In Zusammenarbeit mit dem Medizinproduktehersteller ulrich medical wird eine User Experience und Usability Studie an der Software der im Moment eingesetzten Kontrastmittelinjektoren durchgeführt. Das Unternehmen möchte eine neue Variante eines Kontrastmittelinjektors entwickeln, der als Basis eine verbesserte Version dieser Softwares enthält. Benutzerstudien können mit den unterschiedlichsten Methoden durchgeführt werden. Das geeignete Vorgehen muss definiert und die Testpersonen in Bezug zur eingesetzten Methode ermittelt werden. Bei Medizinprodukten muss zusätzlich auf strikte Auflagen in Normen und Gesetzen geachtet werden. Die Grundlage zur Methodenauswahl bildet eine Recherche zu Usability und User Experience Vorgaben für Medizinprodukte. Die Studie wird anhand quantitativer Daten eines Usability Tests im Labor, Fragebögen zur User Experience und qualitativen Post Test- Interviews evaluiert. In erster Linie dient diese Studie der Ermittlung von möglichen Verbesserungen, welche in der darauf folgenden Masterthesis vertieft und umgesetzt werden.
Telemedicine is becoming an increasingly important approach to diagnostic, treat or prevent diseases. However, the usage of Information Communication Technologies in healthcare results in a considerable amount of data that must be efficiently and securely transmitted. Many manufacturers provide telemedicine platforms without regarding interoperability, mobility and collaboration. This paper describes a collaborative mobile telemonitoring platform that can use the IEEE 11073 and HL7 communication standards or adapt proprietary protocols. The proposed platform also covers the security and modularity aspects. Furthermore this work introduces an Android-based prototype implementation
Mobile monitoring of outpatients during cancer therapy becomes possible through technological advancements. This study leveraged a new remote patient monitoring app for in-between systemic therapy sessions. Patients’ evaluation showed that the handling is feasible. Clinical implementation must consider an adaptive development cycle for reliable operations.
Background
Although teledermatology has been proven internationally to be an effective and safe addition to the care of patients in primary care, there are few pilot projects implementing teledermatology in routine outpatient care in Germany. The aim of this cluster randomized controlled trial was to evaluate whether referrals to dermatologists are reduced by implementing a store-and-forward teleconsultation system in general practitioner practices.
Methods
Eight counties were cluster randomized to the intervention and control conditions. During the 1-year intervention period between July 2018 and June 2019, 46 general practitioner practices in the 4 intervention counties implemented a store-and-forward teledermatology system with Patient Data Management System interoperability. It allowed practice teams to initiate teleconsultations for patients with dermatologic complaints. In the four control counties, treatment as usual was performed. As primary outcome, number of referrals was calculated from routine health care data. Poisson regression was used to compare referral rates between the intervention practices and 342 control practices.
Results
The primary analysis revealed no significant difference in referral rates (relative risk = 1.02; 95% confidence interval = 0.911–1.141; p = .74). Secondary analyses accounting for sociodemographic and practice characteristics but omitting county pairing resulted in significant differences of referral rates between intervention practices and control practices. Matched county pair, general practitioner age, patient age, and patient sex distribution in the practices were significantly related to referral rates.
Conclusions
While a store-and-forward teleconsultation system was successfully implemented in the German primary health care setting, the intervention's effect was superimposed by regional factors. Such regional factors should be considered in future teledermatology research.
Background: Internationally, teledermatology has proven to be a viable alternative to conventional physical referrals. Travel cost and referral times are reduced while patient safety is preserved. Especially patients from rural areas benefit from this healthcare innovation. Despite these established facts and positive experiences from EU neighboring countries like the Netherlands or the United Kingdom, Germany has not yet implemented store-and-forward teledermatology in routine care.
Methods: The TeleDerm study will implement and evaluate store-and-forward teledermatology in 50 general practitioner (GP) practices as an alternative to conventional referrals. TeleDerm aims to confirm that the possibility of store-and-forward teledermatology in GP practices is going to lead to a 15% (n = 260) reduction in referrals in the intervention arm. The study uses a cluster-randomized controlled trial design. Randomization is planned for the cluster “county”. The main observational unit is the GP practice. Poisson distribution of referrals is assumed. The evaluation of secondary outcomes like acceptance, enablers and barriers uses a mixed methods design with questionnaires and interviews.
Discussion: Due to the heterogeneity of GP practice organization, patient management software, information technology service providers, GP personal technical affinity and training, we expect several challenges in implementing teledermatology in German GP routine care. Therefore, we plan to recruit 30% more GPs than required by the power calculation. The implementation design and accompanying evaluation is expected to deliver vital insights into the specifics of implementing telemedicine in German routine care.