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Delphi Markets
(2023)
Delphi markets refer to approaches and implementations of integrating prediction markets and Delphi studies (Real-time Delphi). The combination of the two methods for producing forecasts can potentially compensate for each other´s weaknesses. For example, prediction markets can be used to select participants with expertise and also motivate long-term participation through their gamified approach and incentive mechanisms. In this paper, two potentials for prediction markets and four potentials for Delphi studies, which are made possible by integration, are derived theoretically. Subsequently, three different integration approaches are presented, on the basis of which the integration on user, market and Delphi question-level is exemplified and it is shown that, depending on the approach, not all potentials can be achieved. At the end, recommendations for the use of Delphi markets are derived, existing limitations for Delphi markets as well as future developments are pointed out.
In dieser Arbeit werden Anforderungen an ein digitales Referenzmodell der Cell and Gene Therapy (CGT) Supply Chain mittels systematischer Literaturrecherche unter partieller Anwendung der Preferred-Reporting-Items-for-Systematic-Reviews-and-Meta-Analyses(PRISMA)-2020-Methode erarbeitet und erläutert. Die Ergebnisse der Literaturrecherche untermauern, dass die CGT Supply Chain standardisierte und automatisierte Prozesse benötigt, gewissen Transportanforderungen gerecht werden sowie eine lückenlose Rückverfolgbarkeit gewährleisten können muss. Die Anforderungen an das Referenzmodell lehnen sich z. T. an die Anforderungen des klassischen Supply-Chain-Operations-Reference(SCOR)-Modells an, bedürfen jedoch einer Veränderung und Weiterentwicklung unter Beachtung der Besonderheiten der CGT Supply Chain. Auf Basis eines Referenzmodells für die CGT Supply Chain, das die aus dieser Arbeit identifizierten Anforderungen beachtet, kann eine übergeordnete Managementplattform aufgebaut werden. Mit der digitalen Abbildung und Vernetzung aller Aktivitäten ist der Grundstein für die Integration in ein Enterprise-Resource-Planning(ERP)-System zum effektiven Data und Process Mining gelegt. Durch eine zunehmend bessere Datenqualität und -quantität entlang der Prozesse der CGT Supply Chain lassen sich verstärkt Informationen über die Prozesse selbst generieren, aus denen weitere Verbesserungsansätze hervorgehen. Eine CGT-Managementplattform bildet demnach die Grundlage für alle Prozesse innerhalb der CGT Supply Chain für einen kontinuierlichen Verbesserungsprozess.
Motivation
In order to enable context-aware behavior of surgical assistance systems, the acquisition of various information about the current intraoperative situation is crucial. To achieve this, the complex task of situation recognition can be delegated to a specialized system. Consequently, a standardized interface is required for the seamless transfer of the recognized contextual information to the assistance systems, enabling them to adapt accordingly.
Methods
Our group analyzed four medical interface standards to determine their suitability for exchanging intraoperative contextual information. The assessment was based on a harmonized data and service model derived from the requirements of expected context-aware use cases. The Digital Imaging and Communications in Medicine (DICOM) and IEEE 11073 for Service-oriented Device Connectivity (SDC) were identified as the most appropriate standards.
Results
We specified how DICOM Unified Procedure Steps (UPS), can be used to effectively communicate contextual information. We proposed the inclusion of attributes to formalize different granularity levels of the surgical workflow.
Conclusions
DICOM UPS SOP classes can be used for the exchange of intraoperative contextual information between a situation recognition system and surgical assistance systems. This can pave the way for vendor-independent context awareness in the OR, leading to targeted assistance of the surgical team and an improvement of the surgical workflow.
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 order to evaluate the performance of different stapes prosthesis types, a coupled finite element (FE) model of human ear was developed. First, the middle-ear FE model was developed and validated using the middle-ear transfer function measurements available in literature including pathological cases. Then, the inner-ear FE model was developed and validated using tonotopy, impedance, and level of cochlea amplification curves from literature. Both models are based on pre-existing research with some improvements and were combined into one coupled FE model. The stapes in the coupled FE ear model was replaced with a model of a stapes prosthesis to create a reconstructed ear model that can be used to estimate how different types of protheses perform relative to each other as well as to the natural ear. This will help in designing of new innovative types of stapes prostheses or any other type of middle-ear prostheses as well as to improve the ones that are already available on the market.
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.
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.
Personalized remote healthcare monitoring is in continuous development due to the technology improvements of sensors and wearable electronic systems. A state of the art of research works on wearable sensors for healthcare applications is presented in this work. Furthermore, a state of the art of wearable devices, chest and wrist band and smartwatches available on the market for health and sport monitoring is presented in this paper. Many activity trackers are commercially available. The prices are continuously reducing and the performances are improving, but commercial devices do not provide raw data and are therefore not useful for research purposes.
Gamification is one of the recognized methods of motivating people in various life processes, and it has spread to many spheres of life, including healthcare. This article proposes a system design for long-term care patients using the method mentioned. The proposed system aims to increase patient engagement in the treatment and rehabilitation process via gamification. Literature research on available and earlier proposed systems was conducted to develop a suited system design. The primary target group includes bedridden patients and a sedentary lifestyle (predominantly lying in bed). One of the main criteria for selecting a suitable option was its contactless realization for the mentioned target groups in long-term care cases. As a result, we developed the system design for hardware and software that could prevent bedsores and other health problems from occurring because of low activity. The proposed design can be tested in hospitals, nursing homes, and rehabilitation centers.
In recent decades, it can be observed that a steady increase in the volume of tourism is a stable trend. To offer travel opportunities to all groups, it is also necessary to prepare offers for people in need of long-term care or people with disabilities. One of the ways to improve accessibility could be digital technologies, which could help in planning as well as in carrying out trips. In the work presented, a study of barriers was first conducted, which led to selecting technologies for a test setup after analysis. The main focus was on a mobile app with travel information and 360° tours. The evaluation results showed that both technologies could increase accessibility, but some essential aspects (such as usability, completeness, relevance, etc.) need to be considered when implementing them.
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.
In many cases continuous monitoring of vital signals is required and low intrusiveness is an important requirement. Incorporating monitoring systems in the hospital or home bed could have benefits for patients and caregivers. The objective of this work is the definition of a measurement protocol and the creation of a data set of measurements using commercial and low-cost prototypes devices to estimate heart rate and breathing rate. The experimental data will be used to compare results achieved by the devices and to develop algorithms for feature extraction of vital signals.
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.
Health monitoring in a home environment can have broader use since it may provide continuous control of health parameters with relatively minor intrusiveness into regular life. This work aims to verify if it is possible to replace the typical in some sleep medicine areas subjective questioning by an objective measurement using electronic devices. For this purpose, a study was conducted with ten subjects, in which objective and subjective measurement of relevant sleep parameters took place. The results of both measurement methods were evaluated and analyzed. The results showed that while for some measures, such as Total Time in Bed, there is a high agreement between objective and subjective measurements, for others, such as sleep quality, there are significant differences. For this reason, currently, a combination of both measurement methods may be beneficial and provide the most detailed results, while a partial replacement can already reduce the number of questions at the subjective measurement by measurement through electronic devices.
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’.
The recovery of our body and brain from fatigue directly depends on the quality of sleep, which can be determined from the results of a sleep study. The classification of sleep stages is the first step of this study and includes the measurement of vital data and their further processing. The non-invasive sleep analysis system is based on a hardware sensor network of 24 pressure sensors providing sleep phase detection. The pressure sensors are connected to an energy-efficient microcontroller via a system-wide bus. A significant difference between this system and other approaches is the innovative way in which the sensors are placed under the mattress. This feature facilitates the continuous use of the system without any noticeable influence on the sleeping person. The system was tested by conducting experiments that recorded the sleep of various healthy young people. Results indicate the potential to capture respiratory rate and body movement.
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.
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.
This book contains the proceedings of the KES International conferences on Innovation in Medicine and Healthcare (KES-InMed-19) and Intelligent Interactive Multimedia Systems and Services (KES-IIMSS-19), held on 17–19 June 2019 and co-located in St. Julians, on the island of Malta, as part of the KES Smart Digital Futures 2019 multi theme conference.
The major areas covered by KES-InMed-19 include: Digital IT Architecture in Healthcare; Advanced ICT for Medical and Healthcare; Biomedical Engineering, Trends, Research and Technologies and Healthcare Support System. The major areas covered by KES-IIMSS-19 were: Interactive Technologies; Artificial Intelligence and Data Analytics; Intelligent Services and Architectures and Applications.
This book is of use to researchers in these vibrant areas, managers, industrialists and anyone wishing to gain an overview of the latest research in these fields.
Size and function of bioartificial tissue models are still limited due to the lack of blood vessels and dynamic perfusion for nutrient supply. In this study, we evaluated the use of cytocompatible methacryl-modified gelatin for the fabrication of a hydrogel-based tube by dip-coating and subsequent photo-initiated cross-linking. The wall thickness of the tubes and the diameter were tuned by the degree of gelatin methacryl-modification and the number of dipping cycles. The dipping temperature of the gelatin solution was adjusted to achieve low viscous fluids of approximately 0.1 Pa s and was different for gelatin derivatives with different modification degrees. A versatile perfusion bioreactor for the supply of surrounding tissue models was developed, which can be adaped to several geometries and sizes of blood-vessel mimicking tubes. The manufactured bendable gelatin tubes were permeable for water and dissolved substances, like Nile Blue and serum albumin. As a proof of concept, human fibroblasts in a three-dimensional collagen tissue model were sucessfully supplied with nutrients via the central gelatin tube under dynamic conditions for 2 days. Moreover, the tubes could be used as scaffolds to build-up a functional and viable endothelial layer. Hence, the presented tools can contribute to solving current challenges in tissue engineering.
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.
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.
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.
OR-Pad - Entwicklung eines Prototyps zur sterilen Informationsanzeige am OP-Situs : meeting abstract
(2019)
Hintergrund: Oftmals werden Informationen aus der Krankenakte oder von Bildgebungsverfahren nur auf recht weit vom Operationsgebiet entfernten Monitoren, außerhalb der ergonomischen Sichtachse des Operateurs, dargestellt. Dies führt dazu, dass relevante Informationen übersehen werden oder ihr Informationspotenzial nicht ausgeschöpft werden kann. In Papierform mitgenommene Notizen befinden sich während der OP außerhalb des sterilen Bereichs und sind dadurch für den Operateur nicht ohne Weiteres zugänglich. Auch bei intraoperativen Einträgen für die OP Dokumentation ist der Operateur auf die Mithilfe der Assistenz angewiesen. Durch die zusätzlichen Kommunikationswege entstehen dabei ein personeller und zeitlicher Mehraufwand und das Fehlerpotenzial nimmt zu. Das anwendungsorientierte Forschungsprojekt OR-Pad - Nutzung von portablen Informationsanzeigen im Operationssaal - soll dem Operateur zu einem verbesserten Informationsfluss verhelfen. Die Idee entstand aus der klinischen Routine der Anatomie und Urologie des Universitätsklinikums Tübingen und wird nun durch Fördermittel vom Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg sowie vom Europäischen Fonds für regionale Entwicklung an der Hochschule Reutlingen zu einem High Fidelity-Prototypen weiterentwickelt.
Ziel: Ziel des OR-Pad Projekts ist es, während einer OP zum aktuellen Zeitpunkt klinisch relevante Informationen in unmittelbarer Nähe zum Operateur darzustellen. Mithilfe des Systems soll der Informationsfluss zwischen dem Eingriff sowie dessen Vor- und Nachbereitung optimiert werden. Der Operateur soll vorab relevante Informationen, wie aktuelle Röntgenbilder oder persönliche Notizen, zur intraoperativen Anzeige auswählen können, die dann am OP-Situs auf einer sterilen Informationsanzeige dargestellt werden. Durch die Positionierung soll eine ergonomische Sichtachse sowie die direkte Interaktion mit dem System ermöglicht werden. Kontextrelevante Informationen sollen basierend auf dem aktuellen OP-Verlauf durch die Entwicklung einer Situationserkennung automatisch bereitgestellt werden. Zur Optimierung des Informationsflusses gehört ebenfalls die Unterstützung der OP-Dokumentation. Für diese sollen während des Eingriffs manuell vom Operateur sowie automatisch vom System Einträge, wie Zeitpunkte oder intraoperative Aufnahmen, erstellt werden. Aus diesen soll nach dem Eingriff die OP-Dokumentation generiert und damit der Prozess qualitativer und zeiteffizienter gestaltet werden.
Methodik: Zur Erreichung des Ziels werden zunächst die klinischen Anforderungen spezifiziert und in ein Lastenheft überführt. Hierfür werden Interviews und Beobachtungen bei mehreren Interventionen durchgeführt. Nach dem User-Centered-Designprozess werden Personas und Nutzungsszenarien entworfen und mit klinischen Projektpartnern in mehreren Iterationen evaluiert. Es gilt eine Informationsarchitektur aufzubauen, die eine Einbettung klinischer Informationssysteme sowie Bild- und Gerätedaten aus dem OP-Netzwerk erlaubt. Eine Situationserkennung, basierend auf Prozessmodellen, soll zur Abschätzung des Operationsfortschritts entwickelt werden. Zur Befestigung der Informationsanzeige sollen geeignete Haltemechanismen eingesetzt werden. Das OR-Pad System soll laufend im Lehr- und Forschungs-OP der Hochschule Reutlingen getestet und im Sinne agiler Produktentwicklung mit den klinischen Projektpartnern abgestimmt werden. Der finale Funktionsprototyp soll abschließend in den Versuchs-OPs der Anatomie Tübingen getestet und evaluiert werden.
Ergebnisse: Über eine erste Datenerhebung mittels Contextual Inquiry konnten erste Anforderungen an das OR-Pad System erfasst werden, woraus ein Low-Fidelity-Prototyp resultierte. Die Evaluation über Experteninterviews führte in die zweite Iteration, in der das Konzept entsprechend der Ergebnisse angepasst wurde. Über Hospitationen am Uniklinikum Tübingen fand eine weitere Datenerhebung zur Erstellung von Szenarien für die intraoperativen Anwendungsfälle statt. Anhand der Anforderungen wurde ein Konzept für die Benutzerschnittstelle entworfen, die im weiteren Verlauf mit den klinischen Projektpartnern evaluiert wird.
Die Erholung unseres Körpers und Gehirns von Müdigkeit ist direkt abhängig von der Qualität des Schlafes, die aus den Ergebnissen einer Schlafstudie ermittelt werden kann. Die Klassifizierung der Schlafstadien ist der erste Schritt dieser Studie und beinhaltet die Messung von Biovitaldaten und deren weitere Verarbeitung. Das non-invasive Schlafanalyse-System basiert auf einem Hardware-Sensornetz aus 24 Drucksensoren, das die Schlafphasenerkennung ermöglicht. Die Drucksensoren sind mit einem energieeffizienten Mikrocontroller über einen systemweiten Bus mit Adressarbitrierung verbunden. Ein wesentlicher Unterschied dieses Systems im Vergleich zu anderen Ansätzen ist die innovative Art, die Sensoren unter der Matratze zu platzieren. Diese Eigenschaft erleichtert die kontinuierliche Nutzung des Systems ohne fühlbaren Einfluss auf das gewohnte Bett. Das System wurde getestet, indem Experimente durchgeführt wurden, die den Schlaf verschiedener gesunder junger Personen aufzeichneten. Die ersten Ergebnisse weisen auf das Potenzial hin, nicht nur Atemfrequenz und Körperbewegung, sondern auch Herzfrequenz zu erfassen.
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.
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.
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.
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.
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.
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.
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.
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.
Influence of the respirator on volatile organic compounds : an animal study in rats over 24 hours
(2015)
Long-term animal studies are needed to accomplish measurements of volatile organic compounds (VOCs) for medical diagnostics. In order to analyze the time course of VOCs, it is necessary to ventilate these animals. Therefore, a total of 10 male Sprague–Dawley rats were anaesthetized and ventilated with synthetic air via tracheotomy for 24 h. An ion mobility spectrometry coupled to multi-capillary columns (MCC–IMS) was used to analyze the expired air. To identify background contaminations produced by the respirator itself, six comparative measurements were conducted with ventilators only. Overall, a number of 37 peaks could be detected within the positive mode. According to the ratio peak intensity rat/ peak intensity ventilator blank, 22 peaks with a ratio >1.5 were defined as expired VOCs, 12 peaks with a ratio between 0.5 and 1.5 as unaffected VOCs, and three peaks with a ratio <0.5 as resorbed VOCs. The peak intensity of 12 expired VOCs changed significantly during the 24 h measurement. These results represent the basis for future intervention studies. Notably, online VOC analysis with MCC–IMS is possible over 24 h in ventilated rats and allows different experimental approaches.
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.
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.
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 number of publications in the field of breath analysis using different types of ion mobility spectrometers (IMS) has increased over the last few years. In this paper, the publications between 2010 and 2013 are reviewed with respect to different types of IMS such as differential mobility spectrometers, high-field asymmetric waveform ion mobility spectrometers and multi-capillary columns coupled to conventional IMS. The analytes detected by IMS and declared with significance to a specific medical question were considered further with respect to medical and analytical questions. In total, 42 different analytes were found to be detected using IMS on a high significance level and were compared to findings using other analytical methods with respect to the individual analyte.