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Multi-dimensional patient data, such as time varying volume data, data of different imaging modalities, surface segmentations etc. are of growing importance in the clinical routine. For many use cases, it is of major importance to replicate a certain visualization of a data set created on one machine on a different computer using different software tools. Up until now, there exists no standardized methodology for this consistent presentation. We propose an extension of the Digital Imaging und Communications in Medicine (DICOM) called “Multi dimensional Presentation State” and outline scope and first results of the standardization process.
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
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.
The workshop aims to discuss leading edge contributions to the interdisciplinary research area of ambient intelligence (AmI) applied to the domains of telemedicine and driving assistance. AmI refers to human centered environments attributed with sensors. The development of AmI in the two application domains of the workshop shares several commonalities: the extensive usage of networked devices and sensors, the design of artificial intelligence algorithms for diagnosis, including recommendation systems and qualitative reasoning or the application of mobile and wireless communication to their distributed systems. Together with the presentation of common aspects of Ambient Intelligence, a further goal of the workshop is to stimulate synergies among both application domains and present examples. The telemedicine domain can benefit from methodologies in designing complex devices, real-time conform system design, audiovisual or computer vision system design used in automotive driving assistance. Furthermore, the automotive domain can benefit from the usercentric view, biometric sensor data design, multi-user data bases for aggregation and diagnosis using big data like used in telemedicine. The German Government supports these research lines in its Hightec-Strategie under the domains “Health and Nutrition” and “Climate and Energy”. In Spain the term “Spanish Program for R&D Challenged Oriented Society – Challenge in energy safe, efficient and clean & Challenge in sustainable transport, smart and integrated” is used. Scientific contributions to the event are peer-reviewed by a suited program committee having members from Germany and Spain. The same committee is serving the JARCA workshop (Jornadas sobre Sistemas cualitativos y sus Aplicaciones en Diagnosis, Robótica e Inteligencia Ambiental - Conference on Qualitative Systems and their Applications in Diagnoses, Robotics and Ambient Intelligence) since 15 years. This workshop is sponsored by the German Academic Exchange Service (DAAD) under contract number 57070010.
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.
Proceedings of the International Workshop on Mobile Networks for Biometric Data Analysis (mBiDA)
(2014)
Prevention and treatment of common and widesprea (chronic) diseases is a challenge in any modern Society and vitally important for health maintenance in aging societies. Capturing biometric data is a cornerstone for any analysis and Treatment strategy. Latest advances in sensor technology allow accurate data measurement in a non-intrusive way. In many cases, it is necessary to provide online monitoring and real-time data capturing to support patients´ prevention plans or to allow medical professionals to access the current status. Different communication standards are required to push sensor data and to store and analyze them on different (mobile) platforms. The objective of the workshop is to show new and innovative approaches dedicated to biometric data capture and analysis in a non-intrusive way maintaining mobility. Examples can be found in human centered ambient intelligence attributed with sensors or even in methodologies applied in automotive real-time conform mobile system design. The workshop´s main challenge is to focus on approaches promoting non-intrusiveness, reliable prediction algorithms and high user-acceptance. The workshop will provide overview presentations, Young researcher poster tracks, doctoral tracks and classical peer-review full paper tracks. Especially, would like to encourage students and young researchers to participate and to contribute to the workshop. Scientific contributions to the event are peer-reviewed by a suited program committee.
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.
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.
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 vivo, cells encounter different physical and chemical signals in the extracellular matrix (ECM) which regulate their behavior. Examples of these signals are micro- and nanometer-sized features, the rigidity, and the chemical composition of the ECM. The study of cell responses to such cues is important to understand complex cell functions, some diseases, and is basis for the development of new biomaterials for applications in medical implants or regenerative medicine. Therefore, the development of new methods for surface modifications with controlled physical and chemical features is crucial. In this work, we report a new combination of micelle nanolithography (BCML) and soft micro-lithography, for the production of polyethylene glycol (PEG) hydrogels, with a micro-grooved surface and decoration with hexagonally precisely arranged gold nanoparticles (AU NPs). The Au-NPs are used for binding adhesive ligands in a well-defined density. First tests were performed by culturing human fibroblasts on the gels. Adhesion and alignment of the cells along the parallel grooves of the surface were investigated. The substrates could provide a new platform for studying cell contact guidance by micro structures, and may enable a more precise control of cell behavior by nanometrically controlled surface functionalization.
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.
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.
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.
Plasma polymerization is used for the modification and control of surface properties of a highly transparent, thermoplastic elastomeric silicone copolymer, GENIOMER® 80 (G80). PEG-like diglyme plasma polymer films were deposited with ether retentions varying between 20% and 70% as measured by X-ray photoelectron spectroscopy analysis which did not affect the transparency of the substrate. Films with ether retentions of greater than 70% inhibit protein binding (bovine serum albumin and fibrinogen) and cell proliferation. A short oxygen plasma pretreatment enhances the adhesion and stability of the film as shown by protein binding and cell adhesion experiments. The transparency of the material and the stability of the coating makes this material a versatile bulk material for technical (e.g., lab-on-a-chip) and biomedical (e.g., intraocular lens) applications. The G80/plasma polymer composite is stable against vigorous washing and storage over 5 months and, therefore, offers an attractive alternative to poly(dimethylsiloxane).
Intra-operative fluoroscopy-guided assistance system for transcatheter aortic valve implantation
(2014)
A new surgical assistance system has been developed to assist the correct positioning of the AVP during transapical TAVI. The developed assistance system automatically defines the target area for implanting the AVP under live 2-D fluoroscopy guidance. Moreover, this surgical assistance system works with low levels of contrast agent for the final deployment of AVP, reducing therefore long-term negative effects, such as renal failure in the elderly and high-risk patients.
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.
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.
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.
Children undergoing systemic chemotherapy often suffer from severe immunosuppression usually associated to severe neutropenia (neutrophils < 0.5 x 109/l). Clinical courses during those periods range from asymptomatic to septic general conditions. Development of septic symptoms can be very fast and life-threatening. Swift detection of risk factors in those patients is therefore needed. So far no early, rapid and reliable marker or tool exists. Ion-Mobility-Spectrometry coupled with a Multi-Capillary-Column (IMS-MCC) can analyze more than 600 volatile components from exhaled air within a few minutes and hence is a potential, rapid detection-tool. As a proof of concept we measured the exhaled breath of 11 patients with neutropenia and 10 healthy controls ranging from 3 to 18 years of age at the time of measurement. Ten milliliters breath samples were taken at the outpatient clinic and analyzed with an onsite IMS-MCC (BreathDiscovery, B&S Analytik, Dortmund, Germany). Dead-space-volume was adapted to two groups (small 250 ml, large 500 ml). Interestingly 59 differing peaks were measured. Eleven were significantly different (p ≤ 0.05), three of which highly significant (p ≤ 0.01) in Mann-Whitney-Rank-Sum-testing. The corresponding analytes used in the decision tree are 2-Propanol, D-Limonene and Acetone. The analytes with the lowest rank sum identified are 2-Hexanone, Iso-Propylamine and 1-Butanol. Eventually we were able to show a three-step-decision-tree, which discerns the 21 samples except one from each group. Sensitivity was 90 % and specificity was 91 %. Naturally these findings need further confirmation within a bigger population. Our pilot-study proves that Ion-Mobility-Spectrometry coupled with a Multi-Capillary-Column is a feasible rapid diagnostic tool in the setting of a pediatric oncology out-patient clinic for patients 3 years and older. Our first results furthermore encourage additional analysis as to whether patients at risk for septic events during immunosuppression can be diagnosed in advance by rapidly assessing risk factors such as Neutropenia in exhaled breath.
Background: Conventional methods for lung cancer detection including computed tomography (CT) and bronchoscopy are expensive and invasive. Thus, there is still a need for an optimal lung cancer detection technique. Methods: The exhaled breath of 50 patients with lung cancer histologically proven by bronchoscopic biopsy samples (32 adenocarcinomas, 10 squamous cell carcinomas, 8 small cell carcinomas), were analyzed using ion mobility spectrometry (IMS) and compared with 39 healthy volunteers. As a secondary assessment, we compared adenocarcinoma patients with and without epidermal growth factor receptor (EGFR) mutation. Results: A decision tree algorithm could separate patients with lung cancer including adenocarcinoma, squamous cell carcinoma and small cell carcinoma. One hundred-fifteen separated volatile organic compound (VOC) peaks were analyzed. Peak-2 noted as n-Dodecane using the IMS database was able to separate values with a sensitivity of 70.0% and a specificity of 89.7%. Incorporating a decision tree algorithm starting with n-Dodecane, a sensitivity of 76% and specificity of 100% was achieved. Comparing VOC peaks between adenocarcinoma and healthy subjects, n-Dodecane was able to separate values with a sensitivity of 81.3% and a specificity of 89.7%. Fourteen patients positive for EGFR mutation displayed a significantly higher n-Dodecane than for the 14 patients negative for EGFR (p<0.01), with a sensitivity of 85.7% and a specificity of 78.6%. Conclusion: In this prospective study, VOC peak patterns using a decision tree algorithm were useful in the detection of lung cancer. Moreover, n-Dodecane analysis from adenocarcinoma patients might be useful to discriminate the EGFR mutation.
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.
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.
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.
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.
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.
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.
Background: Multicapillary column ion-mobility spectrometry (MCC-IMS) may identify volatile components in exhaled gas. The authors therefore used MCC-IMS to evaluate exhaled gas in a rat model of sepsis, inflammation, and hemorrhagic shock.
Methods: Male Sprague-Dawley rats were anesthetized and ventilated via tracheostomy for 10 h or until death. Sepsis was induced by cecal ligation and incision in 10 rats; a sham operation was performed in 10 others. In 10 other rats, endotoxemia was induced by intravenous administration of 10 mg/kg lipopolysaccharide. In a final 10 rats, hemorrhagic shock was induced to a mean arterial pressure of 35 +/- 5 mmHg. Exhaled gas was analyzed with MCC-IMS, and volatile compounds were identified using the BS-MCC/IMS-analytes database (Version 1209; B&S Analytik, Dortmund, Germany).
Results: All sham animals survived the observation period, whereas mean survival time was 7.9 h in the septic animals, 9.1 h in endotoxemic animals, and 2.5 h in hemorrhagic shock. Volatile compounds showed statistically significant differences in septic and endotoxemic rats compared with sham rats for 3-pentanone and acetone. Endotoxic rats differed significantly from sham for 1-propanol, butanal, acetophenone, 1,2-butandiol, and 2-hexanone. Statistically significant differences were observed between septic and endotoxemic rats for butanal, 3-pentanone, and 2-hexanone. 2-Hexanone differed from all other groups in the rats with shock.
Conclusions: Breath analysis of expired organic compounds differed significantly in septic, inflammation, and sham rats. MCC-IMS of exhaled breath deserves additional study as a noninvasive approach for distinguishing sepsis from inflammation.
The analysis of exhaled metabolites has become a promising field of research in recent decades. Several volatile organic compounds reflecting metabolic disturbance and nutrition status have even been reported. These are particularly important for long-term measurements, as needed in medical research for detection of disease progression and therapeutic efficacy. In this context, it has become urgent to investigate the effect of fasting and glucose treatment for breath analysis. In the present study, we used amodel of ventilated rats that fasted for 12 h prior to the experiment. Ten rats per group were randomly assigned for continuous intravenous infusion without glucose or an infusion including 25 mg glucose per 100 g per hour during an observation period of 12 h. Exhaled gas was analysed using multicapillary column ion-mobility spectrometry. Analytes were identified by the BS-MCC/IMS database (version 1209; B & S Analytik, Dortmund, Germany). Glucose infusion led to a significant increase in blood glucose levels (p<0.05 at 4 h and thereafter) and cardiac output (p<0.05 at 4 h and thereafter). During the observation period, 39 peaks were found collectively. There were significant differences between groups in the concentration of ten volatile organic compounds: p<0.001 at 4 h and thereafter for isoprene, cyclohexanone, acetone, p-cymol, 2-hexanone, phenylacetylene, and one unknown compound, and p<0.001 at 8 h and thereafter for 1-pentanol, 1-propanol, and 2-heptanol. Our results indicate that for long-term measurement, fasting and the withholding of glucose could contribute to changes of volatile metabolites in exhaled air.
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.
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.
Die DGCH registriert vermehrt Klagen aus der klinischen Praxis hinsichtlich der nicht vollständigen Vernetzung bzw. Integration von Gerätesystemen im Chirurgischen OP. Die Anzahl, der Funktionsumfang und der Komplexitätsgrad der verwendeten Geräte nehmen ständig zu und machen die Bedienung immer aufwendiger und damit schwieriger und fehleranfälliger, sodass eine Verbesserung bei der Unterstützung im Ablauf wünschenswert ist. Die Sektion Computer- und telematikassistierte Chirurgie (CTAC) der DGCH hat es auf Veranlassung des Generalsekretärs deshalb übernommen, eine aktuelle Bestandsaufnahme vorzunehmen und mögliche Ansätze zur Verbesserung des derzeitigen Status zu bewerten.
An operating room is a stressful work environment. Nevertheless, all involved persons have to work safely as there is no space for mistakes. To ensure a high level of concentration and seamless interaction, all involved persons have to know their own tasks and the tasks of their colleagues. The entire team must work synchronously at all times. To optimize the overall workflow, a task manager supporting the team was developed. In parallel, a common conceptual design of a business process visualization was developed, which makes all relevant information accessible in real-time during a surgery. In this context an overview of all processes in the operating room was created and different concepts for the graphical representation of these user-dependent processes were developed. This paper describes the concept of the task manager as well as the general concept in the field of surgery.
The physiology of vascular cells depends on stimulating mechanical forces caused by pulsatile flow. Thus, mechano-transduction processes and responses of primary human endothelial cells (ECs) and smooth muscle cells (SMCs) have been studied to reveal cell-type specific differences which may contribute to vascular tissue integrity. Here, we investigate the dynamic reorientation response of ECs and SMCs cultured on elastic membranes over a range of stretch frequencies from 0.01 to 1 Hz. ECs and SMCs show different cell shape adaptation responses (reorientation) dependent on the frequency. ECs reveal a specific threshold frequency (0.01 Hz) below which no responses is detectable while the threshold frequency for SMCs could not be determined and is speculated to be above 1 Hz. Interestingly, the reorganization of the actin cytoskeleton and focal adhesions system, as well as changes in the focal adhesion area, can be observed for both cell types and is dependent on the frequency. RhoA and Rac1 activities are increased for ECs but not for SMCs upon application of a uniaxial cyclic tensile strain. Analysis of membrane protrusions revealed that the spatial protrusion activity of ECs and SMCs is independent of the application of a uniaxial cyclic tensile strain of 1 Hz while the total number of protrusions is increased for ECs only. Our study indicates differences in the reorientation response and the reaction times of the two cell types in dependence of the stretching frequency, with matching data for actin cytoskeleton, focal adhesion realignment, RhoA/Rac1 activities, and membrane protrusion activity. These are promising results which may allow cell-type specific activation of vascular cells by frequency selective mechanical stretching. This specific activation of different vascular cell types might be helpful in improving strategies in regenerative medicine.
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.
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.
From raw ion mobility measurements to disease classification : a comparison of analysis processes
(2015)
Ion mobility spectrometry (IMS) is a technology for the detection of volatile compounds in the air of exhaled breath that is increasingly used in medical applications. One major goal is to classify patients into disease groups, for example diseased versus healthy, from simple breath samples. Raw IMS measurements are data matrices in which peak regions representing the compounds have to be identified and quantified. A typical analysis process consists of pre-processing and peak detection in single experiments, peak clustering to obtain consensus peaks across several experiments, and classification of samples based on the resulting multivariate peak intensities. Recently several automated algorithms for peak detection and peak clustering have been introduced, in order to overcome the current need for human-based analysis that is slow, subjective and sometimes not reproducible. We present an unbiased comparison of a multitude of combinations of peak processing and multivariate classification algorithms on a disease dataset. The specific combination of the algorithms for the different analysis steps determines the classification accuracy, with the encouraging result that certain fully-automated combinations perform even better than current manual approaches.
Methacrylated gelatin and mature adipocytes are promising components for adipose tissue engineering
(2016)
In vitro engineering of autologous fatty tissue constructs is still a major challenge for the treatment of congenital deformities, tumor resections or high-graded burns. In this study, we evaluated the suitability of photo-crosslinkable methacrylated gelatin (GM) and mature adipocytes as components for the composition of three-dimensional fatty tissue constructs. Cytocompatibility evaluations of the GM and the photoinitiator Lithium phenyl-2,4,6 trimethylbenzoylphosphinate (LAP) showed no cytotoxicity in the relevant range of concentrations. Matrix stiffness of cell-laden hydrogels was adjusted to native fatty tissue by tuning the degree of crosslinking and was shown to be comparable to that of native fatty tissue. Mature adipocytes were then cultured for 14 days within the GM resulting in a fatty tissue construct loaded with viable cells expressing cell markers perilipin A and laminin. This work demonstrates that mature adipocytes are a highly valuable cell source for the composition of fatty tissue equivalents in vitro. Photo-crosslinkable methacrylated gelatin is an excellent tissue scaffold and a promising bioink for new printing techniques due to its biocompatibility and tunable properties.
Tumorzellen on the move : mikrosystem-basierter Assay zur Untersuchung der Tumorzellen-Migration
(2016)
Die Invasion von Tumorzellen in umliegendes Gewebe und die Bildung von Metastasen transformieren einen lokal wachsenden Tumor in eine systemische und lebensbedrohliche Krankheit mit schlechter Prognose. Dabei spielt die aktive Migration der Tumorzellen eine entscheidende Rolle. Tumorzellen gelangen durch die aktive Zellbewegung in das Lymph- oder Blutsystem und breiten sich im Körper aus. Bei der Invasion in ein neues Organ migrieren die Zellen ebenfalls wieder in komplexer Weise durch das Gewebe und können schließlich dort Metastasen bilden. Auf Grund der enormen medizinischen Relevanz der Tumorzell-Invasion, wird die Bewegung von Tumorzellen seit Jahrzehnten unter Laborbedingungen umfassend untersucht und ist ein wichtiger Marker für die Aggressivität der Tumorzellen. Zur Bewegungsanalyse gibt es mehrere experimentelle und auch kommerziell erhältliche in-vitro Untersuchungsmethoden. Ziel des interdisziplinären Projektes „MigChip“ ist die Entwicklung, Herstellung und experimentelle Validierung eines Mikrofludik-Chips zur verbesserten, detailgenauen in-vitro Untersuchung der Tumorzellen-Migration.
Background and purpose: Transapical aortic valve replacement (TAVR) is a recent minimally invasive surgical treatment technique for elderly and high-risk patients with severe aortic stenosis. In this paper,a simple and accurate image-based method is introduced to aid the intra-operative guidance of TAVR procedure under 2-D X-ray fluoroscopy.
Methods: The proposed method fuses a 3-D aortic mesh model and anatomical valve landmarks with live 2-D fluoroscopic images. The 3-D aortic mesh model and landmarks are reconstructed from interventional X-ray C-arm CT system, and a target area for valve implantation is automatically estimated using these aortic mesh models.Based on template-based tracking approach, the overlay of visualized 3-D aortic mesh model, land-marks and target area of implantation is updated onto fluoroscopic images by approximating the aortic root motion from a pigtail catheter motion without contrast agent. Also, a rigid intensity-based registration algorithm is used to track continuously the aortic root motion in the presence of contrast agent.Furthermore, a sensorless tracking of the aortic valve prosthesis is provided to guide the physician to perform the appropriate placement of prosthesis into the estimated target area of implantation.
Results: Retrospective experiments were carried out on fifteen patient datasets from the clinical routine of the TAVR. The maximum displacement errors were less than 2.0 mm for both the dynamic overlay of aortic mesh models and image-based tracking of the prosthesis, and within the clinically accepted ranges. Moreover, high success rates of the proposed method were obtained above 91.0% for all tested patient datasets.
Conclusion: The results showed that the proposed method for computer-aided TAVR is potentially a helpful tool for physicians by automatically defining the accurate placement position of the prosthesis during the surgical procedure.
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.
Knee osteoarthritis is a common complication and can lead to total loss of joint function in patients. Treatment by either partial or total knee replacement with appropriate UHMWPE based implantsis highly invasive, may cause complications and may show unsatisfying results. Alternatively, treatment may be done by insertion of an elastic interpositional knee spacer with optimized material characteristics.
We report the development of high performance polyurethane-based polymers modified with bioactive molecules for fabrication of such knee spacers. In order to tailor mechanical and tribological properties and to improve resist to enzymatic degradation we propose a core-shell model for the spacer with specifically adapted properties.
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.
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.
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.
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 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.
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.
The best fully automated analysis process achieves even better classification results than the established manual process. The best algorithms for the three analysis steps are (i) SGLTR (Savitzky-Golay Laplace operator filter thresholding regions) and LM (Local Maxima) for automated peak identification, (ii) EM clustering (Expectation Maximization) and DBSCAN (Density-Based Spatial Clustering of Applications with Noise) for the clustering step and (iii) RF (Random Forest) for multivariate classification. Thus, automated methods can replace the manual steps in the analysis process to enable an unbiased high throughput use of the technology.
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.
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.
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.
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.
To analyze the humans’ sleep it is necessary as to identify the sleep stages, occurring during the sleep, their durations and sleep cycles. The gold standard procedure for this approach is polysomnography (PSG), which classify the sleep stages based on Rechtschaffen and Kales (R-K) method. This method aside the advantages as high accuracy has however some disadvantages, among others time-consuming and uncomfortable for the patient procedure. Therefore, the development of further methods for the sleep classification in addition to PSG is a promising topic for the investigation and this work has as its aim the presentation of possible ways and goals for this development.
A sleep study is a test used to diagnose sleep disorders and is usually done in sleep laboratories. The golden standard for evaluation of sleep is overnight polysomnography (PSG). Unfortunately, in-lab sleep studies are expensive and complex procedures. Furthermore, with a minimum of 22 wire attachments to the patient for sleep recording, this medical procedure is invasive and unfamiliar for the subjects. To solve this problem, low-cost home diagnostic systems, based on noninvasive recording methods requires further researches.
For this intention it is important to find suitable bio vital parameters for classifying sleep phases WAKE, REM, light sleep and deep sleep without any physical impairment at the same time. We decided to analyse body movement (BM), respiration rate (RR) and heart rate variability (HRV) from existing sleep recordings to develop an algorithm which is able to classify the sleep phases automatically. The preliminary results of this project show that BM, RR and HRV are suitable to identify WAKE, REM and NREM stage.
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.
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.
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.
Perceptual integration of kinematic components in the recognition of emotional facial expressions
(2018)
According to a long-standing hypothesis in motor control, complex body motion is organized in terms of movement primitives, reducing massively the dimensionality of the underlying control problems. For body movements, this low dimensional organization has been convincingly demonstrated by the learning of low-dimensional representations from kinematic and EMG data. In contrast, the effective dimensionality of dynamic facial expressions is unknown, and dominant analysis approaches have been based on heuristically defined facial ‘‘action units,’’ which reflect contributions of individual face muscles. We determined the effective dimensionality of dynamic facial expressions by learning of a low dimensional model from 11 facial expressions. We found an amazingly low dimensionality with only two movement primitives being sufficient to simulate these dynamic expressions with high accuracy. This low dimensionality is confirmed statistically, by Bayesian model comparison of models with different numbers of primitives, and by a psychophysical experiment that demonstrates that expressions, simulated with only two primitives, are indistinguishable from natural ones.
In addition, we find statistically optimal integration of the emotion information specified by these primitives in visual perception. Taken together, our results indicate that facial expressions might be controlled by a very small number of independent control units, permitting very low dimensional parametrization of the associated facial expression.
The focus of the developed maturity model was set on processes. The concept of the widespread CMM and its practices has been transferred to the perioperative domain and the concept of the new maturity model. Additional optimization goals and technological as well as networking-specific aspects enable a process- and object-focused view of the maturity model in order to ensure broad coverage of different subareas. The evaluation showed that the model is applicable to the perioperative field. Adjustments and extensions of the maturity model are future steps to improve the rating and classification of the new maturity model.
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.
Die Segmentierung und das Tracking von minimal-invasiven robotergeführten Instrumenten ist ein wesentlicher Bestandteil für verschiedene computer assistierte Eingriffe. Allerdings treten in der minimal-invasiven Chirurgie, die das Anwendungsfeld für den hier beschriebenen Ansatz darstellt, häufig Schwierigkeiten durch Reflexionen, Schatten oder visuelle Verdeckungen durch Rauch und Organe auf und erschweren die Segmentierung und das Tracking der Instrumente.
Dieser Beitrag stellt einen Deep Learning Ansatz für ein markerloses Tracking von minimal-invasiven Instrumenten vor und wird sowohl auf simulierten als auch realen Daten getestet. Es wird ein simulierter als auch realer Datensatz mit Ground Truth Kennzeichnung für die binäre Segmentierung von Instrument und Hintergrund erstellt. Für den simulierten Datensatz werden Bilder aus einem simulierten Instrument und realem Hintergrund zusammengesetzt. Im Falle des realen Datensatzes spricht man von der Zusammensetzung der Bilder aus einem realen Instrument und Hintergrund. Insgesamt wird auf den simulierten Daten eine Pixelgenauigkeit von 94.70 Prozent und auf den realen Daten eine Pixelgenauigkeit von 87.30 Prozent erreicht.
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.
Perivascular stromal cells, including mesenchymal stem/stromal cells (MSCs), secrete paracrine factor in response to exercise training that can facilitate improvements in muscle remodeling. This study was designed to test the capacity for muscle-resident MSCs (mMSCs) isolated from young mice to release regenerative proteins in response to mechanical strain in vitro, and subsequently determine the extent to which strain-stimulated mMSCs can enhance skeletal muscle and cognitive performance in a mouse model of uncomplicated aging. Protein arrays confirmed a robust increase in protein release at 24 h following an acute bout of mechanical strain in vitro (10%, 1 Hz, 5 h) compared to non-strain controls. Aged (24 month old), C57BL/6 mice were provided bilateral intramuscular injection of saline, non strain control mMSCs, or mMSCs subjected to a single bout of mechanical strain in vitro (4 ×104). No significant changes were observed in muscle weight, myofiber size, maximal force, or satellite cell quantity at 1 or 4 wks between groups. Peripheral perfusion was significantly increased in muscle at 4 wks post-mMSC injection (p < 0.05), yet no difference was noted between control and preconditioned mMSCs. Intramuscular injection of preconditioned mMSCs increased the number of new neurons and astrocytes in the dentate gyrus of the hippocampus compared to both control groups (p < 0.05), with a trend toward an increase in water maze performance noted (p=0.07). Results from this study demonstrate that acute injection of exogenously stimulated muscle-resident stromal cells do not robustly impact aged muscle structure and function, yet increase the survival of new neurons in the hippocampus.
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.
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.
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.
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.
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.
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.
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.
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.
Information and communication technologies support telemedicine to lower health access barriers and to provide better health care. While the potential in Active Assisted Living (AAL) is increasing, it is difficult to evaluate its benefits for the user, and it requires coordinated actions to launch it. The European Commission’s action plan 2012–2020 provides a roadmap to patient empowerment and healthcare, to link up devices and technologies, and to invest in research towards the personalized medicine of the future. As a quickly developing area in medicine, telemonitoring is a demanding field in research and development. Telemonitoring is an essential component of personalized medicine, where health providers can obtain precise information on outcare or chronic patients to improve diagnosis and therapy and also help healthy persons with prevention support. Telemonitoring combines mobile and wearable devices with the personal AAL home environment, a private or (partly) supervised home, most often called ’smart home’. The focus of this workshop is on new hardware and software solutions specifically designed to be applicable in AAL environments to empower patients. This workshop presents system-oriented solutions covering wearable and AAL-embedded devices, computer science infrastructure both at the users’ and the medical premises, to handle the data and decision support systems to support diagnose and treatment.
Integrating tools and applications into a clinically useful system for individual continuous health data surveillance requires an architecture considering all relevant medical and technical conditions. Therefore, the requirements of an integrated system including a health app to collect and monitor sensor data to support personalized medicine are analyzed. The structure and behavior of the system are defined regarding the specific health use cases and scenarios. A vendor-independent architecture, which enables the collection of vital data from arbitrary wearables using a smartphone, is presented. The data is centrally managed and processed by attending physicians. The modular architecture allows the system to extend to new scenarios, data formats, etc. A prototypical implementation of the system shows the feasibility of the approach.
A clinically useful system for individual continuous health data monitoring needs an architecture that takes into account all relevant medical and technical conditions. The requirements for a health app to support such a system are collected, and a vendor independent architecture is designed that allows the collection of vital data from arbitrary wearables using a smartphone. A prototypical implementation for the main scenario shows the feasibility of the approach.
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.
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.
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.
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.
This paper investigates the possibility to effectively monitor and control the respiratory action using a very simple and non invasive technique based on a single lightweight reduced-size wireless surface electromyography (sEMG) sensor placed below the sternum. The captured sEMG signal, due to the critical sensor position, is characterized by a low energy level and it is affected by motion artifacts and cardiac noise. In this work we present a preliminary study performed on adults for assessing the correlation of the spirometry signal and the sEMG signal after the removal of the superimposed heart signal. This study and the related findings could be useful in respiratory monitoring of preterm infants.
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
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.
Background/Aim: The aim of this study was the development of a new osteoconductivity index to determine the bone healing capacities of bone substitute materials (BSM) on the basis of 3D microcomputed tomographic (μ-CT) data. Materials and Methods: Sinus biopsies were used for the comparative analysis of the integration behavior of two xenogeneic BSM (cerabone® and Bio Oss®). 3D μ-CT and data sets from histomorphometrical measurements based on 2D histological slices were used to measure the bone-material-contact and the tissue distribution within the biopsies. The tissue reactions to both BSM were microscopically analyzed. Results: The 3D and 2D results of the osteoconductivity measurements showed comparable material-bone contacts for both BSM, but the 2D data were significantly lower. The same results were found when tissue distribution was measured in both groups. The histopathological analysis showed comparative tissue reactions in both BSM. Conclusion: Osteoconductivity index is a reliable measurement parameter for determining the healing capacities of BSM. The observed differences between both measurement methods could be assigned to the resolution capacity of μ-CT data that did not allow for a precise interface distinction between both BSM and bone tissue. Histomorphometrical data based on histological slides still allow for a more exact evaluation.
This study describes a non-contact measuring and parameter identification procedure designed to evaluate inhomogeneous stiffness and damping characteristics of the annular ligament in the physiological amplitude and frequency range without the application of large static external forces that can cause unnatural displacements of the stapes. To verify the procedure, measurements were first conducted on a steel beam. Then, measurements on an individual human cadaveric temporal bone sample were performed. The estimated results support the inhomogeneous stiffness and damping distribution of the annular ligament and are in a good agreement with the multiphoton microscopy results which show that the posterior-inferior corner of the stapes footplate is the stiffest region of the annular ligament. This method can potentially help to establish a correlation between stiffness and damping characteristics of the annular ligament and inertia properties of the stapes and, thus, help to reduce the number of independent parameters in the model-based hearing diagnosis.
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.
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.
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.
Die rasante Entwicklung der Sensortechnik im Endverbraucherbereich lässt einen klinischen Nutzen der verfügbaren dezentral erhobenen Daten aus dem Patientenalltag zur Überwachung des individuellen Gesundheitszustands vermuten. Zur Überprüfung dieser Vermutung ist die Bereitstellung einer entsprechenden Plattform in den klinischen Alltag erforderlich. Hierzu wird die bwHealthApp entwickelt, mit der sowohl die aktuelle Bandbreite als auch die Evolution der Sensortechnik auf die klinische Anwendung abbildbar ist. Mit dem flexiblen Entwurf lässt sich der klinische Nutzen für die personalisierte Medizin evaluieren. Außerdem bietet die bwHealthApp einen an Machbarkeit orientierten Diskussionsbeitrag zu offenen rechtlichen, regulatorischen und ethischen Fragestellungen der Digitalisierung in der Medizin in Deutschland.
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/.