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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.
In dieser Arbeit werden Anforderungen an ein digitales Referenzmodell der Cell and Gene Therapy (CGT) Supply Chain mittels systematischer Literaturrecherche unter partieller Anwendung der Preferred-Reporting-Items-for-Systematic-Reviews-and-Meta-Analyses(PRISMA)-2020-Methode erarbeitet und erläutert. Die Ergebnisse der Literaturrecherche untermauern, dass die CGT Supply Chain standardisierte und automatisierte Prozesse benötigt, gewissen Transportanforderungen gerecht werden sowie eine lückenlose Rückverfolgbarkeit gewährleisten können muss. Die Anforderungen an das Referenzmodell lehnen sich z. T. an die Anforderungen des klassischen Supply-Chain-Operations-Reference(SCOR)-Modells an, bedürfen jedoch einer Veränderung und Weiterentwicklung unter Beachtung der Besonderheiten der CGT Supply Chain. Auf Basis eines Referenzmodells für die CGT Supply Chain, das die aus dieser Arbeit identifizierten Anforderungen beachtet, kann eine übergeordnete Managementplattform aufgebaut werden. Mit der digitalen Abbildung und Vernetzung aller Aktivitäten ist der Grundstein für die Integration in ein Enterprise-Resource-Planning(ERP)-System zum effektiven Data und Process Mining gelegt. Durch eine zunehmend bessere Datenqualität und -quantität entlang der Prozesse der CGT Supply Chain lassen sich verstärkt Informationen über die Prozesse selbst generieren, aus denen weitere Verbesserungsansätze hervorgehen. Eine CGT-Managementplattform bildet demnach die Grundlage für alle Prozesse innerhalb der CGT Supply Chain für einen kontinuierlichen Verbesserungsprozess.
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.
Salivary gland tumors (SGTs) are a relevant, highly diverse subgroup of head and neck tumors whose entity determination can be difficult. Confocal Raman imaging in combination with multivariate data analysis may possibly support their correct classification. For the analysis of the translational potential of Raman imaging in SGT determination, a multi-stage evaluation process is necessary. By measuring a sample set of Warthin tumor, pleomorphic adenoma and non-tumor salivary gland tissue, Raman data were obtained and a thorough Raman band analysis was performed. This evaluation revealed highly overlapping Raman patterns with only minor spectral differences. Consequently, a principal component analysis (PCA) was calculated and further combined with a discriminant analysis (DA) to enable the best possible distinction. The PCA-DA model was characterized by accuracy, sensitivity, selectivity and precision values above 90% and validated by predicting model-unknown Raman spectra, of which 93% were classified correctly. Thus, we state our PCA-DA to be suitable for parotid tumor and non-salivary salivary gland tissue discrimination and prediction. For evaluation of the translational potential, further validation steps are necessary.
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.
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.
Purpose
Injury or inflammation of the middle ear often results in the persistent tympanic membrane (TM) perforations, leading to conductive hearing loss (HL). However, in some cases the magnitude of HL exceeds that attributable by the TM perforation alone. The aim of the study is to better understand the effects of location and size of TM perforations on the sound transmission properties of the middle ear.
Methods
The middle ear transfer functions (METF) of six human temporal bones (TB) were compared before and after perforating the TM at different locations (anterior or posterior lower quadrant) and to different degrees (1 mm, ¼ of the TM, ½ of the TM, and full ablation). The sound-induced velocity of the stapes footplate was measured using single-point laser-Doppler-vibrometry (LDV). The METF were correlated with a Finite Element (FE) model of the middle ear, in which similar alterations were simulated.
Results
The measured and calculated METF showed frequency and perforation size dependent losses at all perforation locations. Starting at low frequencies, the loss expanded to higher frequencies with increased perforation size. In direct comparison, posterior TM perforations affected the transmission properties to a larger degree than anterior perforations. The asymmetry of the TM causes the malleus-incus complex to rotate and results in larger deflections in the posterior TM quadrants than in the anterior TM quadrants. Simulations in the FE model with a sealed cavity show that small perforations lead to a decrease in TM rigidity and thus to an increase in oscillation amplitude of the TM mainly above 1 kHz.
Conclusion
Size and location of TM perforations have a characteristic influence on the METF. The correlation of the experimental LDV measurements with an FE model contributes to a better understanding of the pathologic mechanisms of middle-ear diseases. If small perforations with significant HL are observed in daily clinical practice, additional middle ear pathologies should be considered. Further investigations on the loss of TM pretension due to perforations may be informative.
Motivation
In order to enable context-aware behavior of surgical assistance systems, the acquisition of various information about the current intraoperative situation is crucial. To achieve this, the complex task of situation recognition can be delegated to a specialized system. Consequently, a standardized interface is required for the seamless transfer of the recognized contextual information to the assistance systems, enabling them to adapt accordingly.
Methods
Our group analyzed four medical interface standards to determine their suitability for exchanging intraoperative contextual information. The assessment was based on a harmonized data and service model derived from the requirements of expected context-aware use cases. The Digital Imaging and Communications in Medicine (DICOM) and IEEE 11073 for Service-oriented Device Connectivity (SDC) were identified as the most appropriate standards.
Results
We specified how DICOM Unified Procedure Steps (UPS), can be used to effectively communicate contextual information. We proposed the inclusion of attributes to formalize different granularity levels of the surgical workflow.
Conclusions
DICOM UPS SOP classes can be used for the exchange of intraoperative contextual information between a situation recognition system and surgical assistance systems. This can pave the way for vendor-independent context awareness in the OR, leading to targeted assistance of the surgical team and an improvement of the surgical workflow.
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.
Gamification is one of the recognized methods of motivating people in various life processes, and it has spread to many spheres of life, including healthcare. This article proposes a system design for long-term care patients using the method mentioned. The proposed system aims to increase patient engagement in the treatment and rehabilitation process via gamification. Literature research on available and earlier proposed systems was conducted to develop a suited system design. The primary target group includes bedridden patients and a sedentary lifestyle (predominantly lying in bed). One of the main criteria for selecting a suitable option was its contactless realization for the mentioned target groups in long-term care cases. As a result, we developed the system design for hardware and software that could prevent bedsores and other health problems from occurring because of low activity. The proposed design can be tested in hospitals, nursing homes, and rehabilitation centers.
Evaluation of a contactless accelerometer sensor system for heart rate monitoring during sleep
(2024)
The monitoring of a patient's heart rate (HR) is critical in the diagnosis of diseases. In the detection of sleep disorders, it also plays an important role. Several techniques have been proposed, including using sensors to record physiological signals that are automatically examined and analysed. This work aims to evaluate using a contactless HR monitoring system based on an accelerometer sensor during sleep. For this purpose, the oscillations caused by chest movements during heart contractions are recorded by an installation mounted under the bed mattress. The processing algorithm presented in this paper filters the signals and determines the HR. As a result, an average error of about 5 bpm has been documented, i.e., the system can be considered to be used for the forecasted domain.
Sleep is extremely important for physical and mental health. Although polysomnography is an established approach in sleep analysis, it is quite intrusive and expensive. Consequently, developing a non-invasive and non-intrusive home sleep monitoring system with minimal influence on patients, that can reliably and accurately measure cardiorespiratory parameters, is of great interest. The aim of this study is to validate a non-invasive and unobtrusive cardiorespiratory parameter monitoring system based on an accelerometer sensor. This system includes a special holder to install the system under the bed mattress. The additional aim is to determine the optimum relative system position (in relation to the subject) at which the most accurate and precise values of measured parameters could be achieved. The data were collected from 23 subjects (13 males and 10 females). The obtained ballistocardiogram signal was sequentially processed using a sixth-order Butterworth bandpass filter and a moving average filter. As a result, an average error (compared to reference values) of 2.24 beats per minute for heart rate and 1.52 breaths per minute for respiratory rate was achieved, regardless of the subject’s sleep position. For males and females, the errors were 2.28 bpm and 2.19 bpm for heart rate and 1.41 rpm and 1.30 rpm for respiratory rate. We determined that placing the sensor and system at chest level is the preferred configuration for cardiorespiratory measurement. Further studies of the system’s performance in larger groups of subjects are required, despite the promising results of the current tests in healthy subjects.
Die Bereitstellung klinischer Informationen im Operationssaal ist ein wichtiger Aspekt zur Unterstützung des chirurgischen Teams. Die roboter-assistierte Ösophagusresektion ist ein besonders komplexer Eingriff, der Potenzial zur workflowbasierten Unterstützung bietet. Wir präsentieren erste Ergebnisse der Entwicklung eines Checklisten-Tools mit der zugrundeliegenden Modellierung des chirurgischen Workflows und Informationsbedarf der Chirurgen. Das Checklisten-Tool zeigt hierfür die durchzuführenden Schritte chronologisch an und stellt zusätzliche Informationen kontextadaptiert bereit. Eine automatische Dokumentation von Start- und Endzeiten einzelner OP-Phasen und Schritte soll zukünftige Prozessanalysen der Operation ermöglichen.
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.
In order to evaluate the performance of different stapes prosthesis types, a coupled finite element (FE) model of human ear was developed. First, the middle-ear FE model was developed and validated using the middle-ear transfer function measurements available in literature including pathological cases. Then, the inner-ear FE model was developed and validated using tonotopy, impedance, and level of cochlea amplification curves from literature. Both models are based on pre-existing research with some improvements and were combined into one coupled FE model. The stapes in the coupled FE ear model was replaced with a model of a stapes prosthesis to create a reconstructed ear model that can be used to estimate how different types of protheses perform relative to each other as well as to the natural ear. This will help in designing of new innovative types of stapes prostheses or any other type of middle-ear prostheses as well as to improve the ones that are already available on the market.
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.
Motivation: Aim of this project is the automatic classification of total hip endoprosthesis (THEP) components in 2D Xray images. Revision surgeries of total hip arthroplasty (THA) are common procedures in orthopedics and trauma surgery. Currently, around 400.000 procedures per year are performed in the United States (US) alone. To achieve the best possible result, preoperative planning is crucial. Especially if parts of the current THEP system are to be retained.
Methods: First, a ground truth based on 76 X-ray images was created: We used an image processing pipeline consisting of a segmentation step performed by a convolutional neural network and a classification step performed by a support vector machine (SVM). In total, 11 classes (5 pans and 6 shafts) shall be classified.
Results: The ground truth generated was of good quality even though the initial segmentation was performed by technicians. The best segmentation results were achieved using a U-net architecture. For classification, SVM architectures performed much better than additional neural networks.
Conclusions: The overall image processing pipeline performed well, but the ground truth needs to be extended to include a broader variability of implant types and more examples per training class.
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 ballistocardiography is a technique that measures the heart rate from the mechanical vibrations of the body due to the heart movement. In this work a novel noninvasive device placed under the mattress of a bed estimates the heart rate using the ballistocardiography. Different algorithms for heart rate estimation have been developed.
Personalized remote healthcare monitoring is in continuous development due to the technology improvements of sensors and wearable electronic systems. A state of the art of research works on wearable sensors for healthcare applications is presented in this work. Furthermore, a state of the art of wearable devices, chest and wrist band and smartwatches available on the market for health and sport monitoring is presented in this paper. Many activity trackers are commercially available. The prices are continuously reducing and the performances are improving, but commercial devices do not provide raw data and are therefore not useful for research purposes.
Perforations of the tympanic membrane (TM) can occur as a result of injury or inflammation of the middle ear. These perforations can lead to conductive hearing loss (HL), where in some cases the magnitude of HL exceeds that attributable to the observed TM perforation alone. We aim with this study to better understand the effects of location and size of TM perforations on the sound transmitting properties of the middle ear.
The middle ear transfer function (METF) of six human temporal bones (TB; freshly frozen specimen of body donors) were compared before and after perforation of the TM at different locations (anterior or posterior lower quadrant) and of different sizes (1mm, ¼ of the TM, ½ of the TM, and full ablation). The
METF were correlated with a Finite Element (FE) model of the middle ear, in which similar alterations were simulated.
The measured and simulated FE model METFs exhibited frequency and perforation size dependent amplitude losses at all locations and severities. In direct comparison, posterior TM perforations affected the transmission properties to a larger degree than perforations of the anterior quadrant. This could possibly be caused by an asymmetry of the TM, where the malleus-incus complex rotates and results in larger deflections in the posterior TM half than in the anterior TM half. The FE model of the TM with a sealed cavity suggest that small perforations result in a decrease of TM rigidity and thus to an increase in oscillation amplitude of the TM, mostly above 1 kHz.
The location and size of TM perforations influence the METF in a reproducible way. Correlating our data with the FE model could help to better understand the pathologic mechanisms of middle-ear diseases. If small TM perforations with uncharacteristically significant HL are observed in daily clinical practice, additional middle ear pathologies should be considered. Further investigations on the loss of TM pretension due to perforations may be informative.
Programmable nano-bio interfaces driven by tuneable vertically configured nanostructures have recently emerged as a powerful tool for cellular manipulations and interrogations. Such interfaces have strong potential for ground-breaking advances, particularly in cellular nanobiotechnology and mechanobiology. However, the opaque nature of many nanostructured surfaces makes non-destructive, live-cell characterization of cellular behavior on vertically aligned nanostructures challenging to observe. Here, a new nanofabrication route is proposed that enables harvesting of vertically aligned silicon (Si) nanowires and their subsequent transfer onto an optically transparent substrate, with high efficiency and without artefacts. We demonstrate the potential of this route for efficient live-cell phase contrast imaging and subsequent characterization of cells growing on vertically aligned Si nanowires. This approach provides the first opportunity to understand dynamic cellular responses to a cell-nanowire interface, and thus has the potential to inform the design of future nanoscale cellular manipulation technologies.
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 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.
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.
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.
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.
Accurate monitoring of a patient's heart rate is a key element in the medical observation and health monitoring. In particular, its importance extends to the identification of sleep-related disorders. Various methods have been established that involve sensor-based recording of physiological signals followed by automated examination and analysis. This study attempts to evaluate the efficacy of a non-invasive HR monitoring framework based on an accelerometer sensor specifically during sleep. To achieve this goal, the motion induced by thoracic movements during cardiac contractions is captured by a device installed under the mattress. Signal filtering techniques and heart rate estimation using the symlets6 wavelet are part of the implemented computational framework described in this article. Subsequent analysis indicates the potential applicability of this system in the prognostic domain, with an average error margin of approximately 3 beats per minute. The results obtained represent a promising advancement in non-invasive heart rate monitoring during sleep, with potential implications for improved diagnosis and management of cardiovascular and sleep-related disorders.
In many cases continuous monitoring of vital signals is required and low intrusiveness is an important requirement. Incorporating monitoring systems in the hospital or home bed could have benefits for patients and caregivers. The objective of this work is the definition of a measurement protocol and the creation of a data set of measurements using commercial and low-cost prototypes devices to estimate heart rate and breathing rate. The experimental data will be used to compare results achieved by the devices and to develop algorithms for feature extraction of vital signals.
The scoring of sleep stages is an essential part of sleep studies. The main objective of this research is to provide an algorithm for the automatic classification of sleep stages using signals that may be obtained in a non-obtrusive way. After reviewing the relevant research, the authors selected a multinomial logistic regression as the basis for their approach. Several parameters were derived from movement and breathing signals, and their combinations were investigated to develop an accurate and stable algorithm. The algorithm was implemented to produce successful results: the accuracy of the recognition of Wake/NREM/REM stages is equal to 73%, with Cohen's kappa of 0.44 for the analyzed 19324 sleep epochs of 30 seconds each. This approach has the advantage of using the only movement and breathing signals, which can be recorded with less effort than heart or brainwave signals, and requiring only four derived parameters for the calculations. Therefore, the new system is a significant improvement for non-obtrusive sleep stage identification compared to existing approaches.
Health monitoring in a home environment can have broader use since it may provide continuous control of health parameters with relatively minor intrusiveness into regular life. This work aims to verify if it is possible to replace the typical in some sleep medicine areas subjective questioning by an objective measurement using electronic devices. For this purpose, a study was conducted with ten subjects, in which objective and subjective measurement of relevant sleep parameters took place. The results of both measurement methods were evaluated and analyzed. The results showed that while for some measures, such as Total Time in Bed, there is a high agreement between objective and subjective measurements, for others, such as sleep quality, there are significant differences. For this reason, currently, a combination of both measurement methods may be beneficial and provide the most detailed results, while a partial replacement can already reduce the number of questions at the subjective measurement by measurement through electronic devices.
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.
The recovery of our body and brain from fatigue directly depends on the quality of sleep, which can be determined from the results of a sleep study. The classification of sleep stages is the first step of this study and includes the measurement of vital data and their further processing. The non-invasive sleep analysis system is based on a hardware sensor network of 24 pressure sensors providing sleep phase detection. The pressure sensors are connected to an energy-efficient microcontroller via a system-wide bus. A significant difference between this system and other approaches is the innovative way in which the sensors are placed under the mattress. This feature facilitates the continuous use of the system without any noticeable influence on the sleeping person. The system was tested by conducting experiments that recorded the sleep of various healthy young people. Results indicate the potential to capture respiratory rate and body movement.
In order to ensure sufficient recovery of the human body and brain, healthy sleep is indispensable. For this purpose, appropriate therapy should be initiated at an early stage in the case of sleep disorders. For some sleep disorders (e.g., insomnia), a sleep diary is essential for diagnosis and therapy monitoring. However, subjective measurement with a sleep diary has several disadvantages, requiring regular action from the user and leading to decreased comfort and potential data loss. To automate sleep monitoring and increase user comfort, one could consider replacing a sleep diary with an automatic measurement, such as a smartwatch, which would not disturb sleep. To obtain accurate results on the evaluation of the possibility of such a replacement, a field study was conducted with a total of 166 overnight recordings, followed by an analysis of the results. In this evaluation, objective sleep measurement with a Samsung Galaxy Watch 4 was compared to a subjective approach with a sleep diary, which is a standard method in sleep medicine. The focus was on comparing four relevant sleep characteristics: falling asleep time, waking up time, total sleep time (TST), and sleep efficiency (SE). After evaluating the results, it was concluded that a smartwatch could replace subjective measurement to determine falling asleep and waking up time, considering some level of inaccuracy. In the case of SE, substitution was also proved to be possible. However, some individual recordings showed a higher discrepancy in results between the two approaches. For its part, the evaluation of the TST measurement currently does not allow us to recommend substituting the measurement method for this sleep parameter. The appropriateness of replacing sleep diary measurement with a smartwatch depends on the acceptable levels of discrepancy. We propose four levels of similarity of results, defining ranges of absolute differences between objective and subjective measurements. By considering the values in the provided table and knowing the required accuracy, it is possible to determine the suitability of substitution in each individual case. The introduction of a “similarity level” parameter increases the adaptability and reusability of study findings in individual practical cases.
The main aim of presented in this manuscript research is to compare the results of objective and subjective measurement of sleep quality for older adults (65+) in the home environment. A total amount of 73 nights was evaluated in this study. Placing under the mattress device was used to obtain objective measurement data, and a common question on perceived sleep quality was asked to collect the subjective sleep quality level. The achieved results confirm the correlation between objective and subjective measurement of sleep quality with the average standard deviation equal to 2 of 10 possible quality points.
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.
Identifikation von Schlaf- und Wachzuständen durch die Auswertung von Atem- und Bewegungssignalen
(2021)
Fragestellung: Das klinische Standardverfahren und Referenz der Schlafmessung und der Klassifizierung der einzelnen Schlafstadien ist die Polysomnographie (PSG). Alternative Ansätze zu diesem aufwändigen Verfahren könnten einige Vorteile bieten, wenn die Messungen auf eine komfortablere Weise durchgeführt werden. Das Hauptziel dieser Forschung Studie ist es, einen Algorithmus für die automatische Klassifizierung von Schlafstadien zu entwickeln, der ausschließlich Bewegungs- und Atmungssignale verwendet [1].
Patienten und Methoden: Nach der Analyse der aktuellen Forschungsarbeiten haben wir multinomiale logistische Regression als Grundlage für den Ansatz gewählt [2]. Um die Genauigkeit der Auswertung zu erhöhen, wurden vier Features entwickelt, die aus Bewegungs- und Atemsignalen abgeleitet wurden. Für die Auswertung wurden die nächtlichen Aufzeichnungen von 35 Personen verwendet, die von der Charité-Universitätsmedizin Berlin zur Verfügung gestellt wurden. Das Durchschnittsalter der Teilnehmer betrug 38,6 +/– 14,5 Jahre und der BMI lag bei durchschnittlich 24,4 +/– 4,9 kg/m2. Da der Algorithmus mit drei Stadien arbeitet, wurden die Stadien N1, N2 und N3 zum NREM-Stadium zusammengeführt. Der verfügbare Datensatz wurde strikt aufgeteilt: in einen Trainingsdatensatz von etwa 100 h und in einen Testdatensatz mit etwa 160 h nächtlicher Aufzeichnungen. Beide Datensätze wiesen ein ähnliches Verhältnis zwischen Männern und Frauen auf, und der durchschnittliche BMI wies keine signifikante Abweichung auf.
Ergebnisse: Der Algorithmus wurde implementiert und lieferte erfolgreiche Ergebnisse: die Genauigkeit der Erkennung von Wach-/NREM-/REM-Phasen liegt bei 73 %, mit einem Cohen’s Kappa von 0,44 für die analysierten 19.324 Schlafepochen von jeweils 30 s. Die beobachtete gewisse Überschätzung der NREM-Phase lässt sich teilweise durch ihre Prävalenz in einem typischen Schlafmuster erklären. Selbst die Verwendung eines ausbalancierten Trainingsdatensatzes konnte dieses Problem nicht vollständig lösen.
Schlussfolgerungen: Die erreichten Ergebnisse haben die Tauglichkeit des Ansatzes prinzipiell bestätigt. Dieser hat den Vorteil, dass nur Bewegungs- und Atemsignale verwendet werden, die mit weniger Aufwand und komfortabler für Benutzer aufgezeichnet werden können als z. B. Herz- oder EEG-Signale. Daher stellt das neue System eine deutliche Verbesserung im Vergleich zu bestehenden Ansätzen dar. Die Zusammenführung der beschriebenen algorithmischen Software mit dem in [1] beschriebenen Hardwaresystem zur Messung von Atem- und Körperbewegungssignalen zu einem autonomen, berührungslosen System zur kontinuierlichen Schlafüberwachung ist eine mögliche Richtung zukünftiger Arbeiten.
Recognition of sleep and wake states is one of the relevant parts of sleep analysis. Performing this measurement in a contactless way increases comfort for the users. We present an approach evaluating only movement and respiratory signals to achieve recognition, which can be measured non-obtrusively. The algorithm is based on multinomial logistic regression and analyses features extracted out of mentioned above signals. These features were identified and developed after performing fundamental research on characteristics of vital signals during sleep. The achieved accuracy of 87% with the Cohen’s kappa of 0.40 demonstrates the appropriateness of a chosen method and encourages continuing research on this topic.
The scoring of sleep stages is one of the essential tasks in sleep analysis. Since a manual procedure requires considerable human and financial resources, and incorporates some subjectivity, an automated approach could result in several advantages. There have been many developments in this area, and in order to provide a comprehensive overview, it is essential to review relevant recent works and summarise the characteristics of the approaches, which is the main aim of this article. To achieve it, we examined articles published between 2018 and 2022 that dealt with the automated scoring of sleep stages. In the final selection for in-depth analysis, 125 articles were included after reviewing a total of 515 publications. The results revealed that automatic scoring demonstrates good quality (with Cohen's kappa up to over 0.80 and accuracy up to over 90%) in analysing EEG/EEG + EOG + EMG signals. At the same time, it should be noted that there has been no breakthrough in the quality of results using these signals in recent years. Systems involving other signals that could potentially be acquired more conveniently for the user (e.g. respiratory, cardiac or movement signals) remain more challenging in the implementation with a high level of reliability but have considerable innovation capability. In general, automatic sleep stage scoring has excellent potential to assist medical professionals while providing an objective assessment.
In recent decades, it can be observed that a steady increase in the volume of tourism is a stable trend. To offer travel opportunities to all groups, it is also necessary to prepare offers for people in need of long-term care or people with disabilities. One of the ways to improve accessibility could be digital technologies, which could help in planning as well as in carrying out trips. In the work presented, a study of barriers was first conducted, which led to selecting technologies for a test setup after analysis. The main focus was on a mobile app with travel information and 360° tours. The evaluation results showed that both technologies could increase accessibility, but some essential aspects (such as usability, completeness, relevance, etc.) need to be considered when implementing them.
The 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.
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).
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.
In the era of precision medicine, digital technologies and artificial intelligence, drug discovery and development face unprecedented opportunities for product and business model innovation, fundamentally changing the traditional approach of how drugs are discovered, developed and marketed. Critical to this transformation is the adoption of new technologies in the drug development process, catalyzing the transition from serendipity-driven to data-driven medicine. This paradigm shift comes with a need for both translation and precision, leading to a modern Translational Precision Medicine approach to drug discovery and development. Key components of Translational Precision Medicine are multi-omics profiling, digital biomarkers, model-based data integration, artificial intelligence, biomarker-guided trial designs and patient-centric companion diagnostics. In this review, we summarize and critically discuss the potential and challenges of Translational Precision Medicine from a cross-industry perspective.
Die Corona-Pandemie hat zu einer Einschränkung des Alltags der medizinischen Versorgung geführt. Das zeigt sich u.a. in zum Teil erheblichen Zugangsbeschränkungen zu Krankenhäusern und Praxen mit stark reduzierter Einbestellung von Patienten, der Einhaltung von gesteigerten Hygienemaßnahmen mit entsprechend längeren Wartezeiten, dem Zugangsverbot für Begleitpersonen und nicht zuletzt der Angst vieler Patienten vor einer Ansteckung bei einem Aufenthalt in medizinischen Bereichen. Folge dessen war und ist, dass ein deutlich wahrnehmbarer Rückgang der Patientenzahlen in den Krankenhausambulanzen und Praxen zu verzeichnen war. Davon war die Augenheilkunde als Fachdisziplin mit einem hohen Anteil an ambulanten und geplanten, chirurgischen Eingriffen in besonderem Maße betroffen.
Rational behavior is a standard assumption in science. Indeed, rationality is required for environmental action towards net-zero emissions or public health interventions during the SARS-CoV-2 pandemic. Yet, little is known about the elements of rationality. This paper explores a dualism of rationality comprised of optimality and consistency. By designing a new guessing game, we experimentally uncover and disentangle two building blocks of human rationality: the notions of optimality and consistency. We find evidence that rationality is largely associated to optimality and weakly to consistency. Remarkably, under uncertainty, rationality gradually shifts to a heuristic notion. Our findings provide insights to better understand human decision making.
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.
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.
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.
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.
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.
Background/Aim: The aim of this study was the conception, production, material analysis and cytocompatibility analysis of a new collagen foam for medical applications. Materials and Methods: After the innovative production of various collagen sponges from bovine sources, the foams were analyzed ex vivo in terms of their structure (including pore size) and in vitro in terms of cytocompatibility according to EN ISO 10993-5/-12. In vitro, the collagen foams were compared with the established soft and hard tissue materials cerabone and Jason membrane (both botiss biomaterials GmbH, Zossen, Germany). Results: Collagen foams with different compositions were successfully produced from bovine sources. Ex vivo, the foams showed a stable and long-lasting primary structure quality with a bubble area of 1,000 to 2,000 μm2. In vitro, all foams showed sufficient cytocompatibility. Conclusion: Collagen sponges represent a promising material for hard and soft tissue regeneration. Future studies could focus on integrating and investigating different additives in the foams.
Purpose
Context awareness in the operating room (OR) is important to realize targeted assistance to support actors during surgery. A situation recognition system (SRS) is used to interpret intraoperative events and derive an intraoperative situation from these. To achieve a modular system architecture, it is desirable to de-couple the SRS from other system components. This leads to the need of an interface between such an SRS and context-aware systems (CAS). This work aims to provide an open standardized interface to enable loose coupling of the SRS with varying CAS to allow vendor-independent device orchestrations.
Methods
A requirements analysis investigated limiting factors that currently prevent the integration of CAS in today's ORs. These elicited requirements enabled the selection of a suitable base architecture. We examined how to specify this architecture with the constraints of an interoperability standard. The resulting middleware was integrated into a prototypic SRS and our system for intraoperative support, the OR-Pad, as exemplary CAS for evaluating whether our solution can enable context-aware assistance during simulated orthopedical interventions.
Results
The emerging Service-oriented Device Connectivity (SDC) standard series was selected to specify and implement a middleware for providing the interpreted contextual information while the SRS and CAS are loosely coupled. The results were verified within a proof of concept study using the OR-Pad demonstration scenario. The fulfillment of the CAS’ requirements to act context-aware, conformity to the SDC standard series, and the effort for integrating the middleware in individual systems were evaluated. The semantically unambiguous encoding of contextual information depends on the further standardization process of the SDC nomenclature. The discussion of the validity of these results proved the applicability and transferability of the middleware.
Conclusion
The specified and implemented SDC-based middleware shows the feasibility of loose coupling an SRS with unknown CAS to realize context-aware assistance in the OR.
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.
One of the key challenges for automatic assistance is the support of actors in the operating room depending on the status of the procedure. Therefore, context information collected in the operating room is used to gain knowledge about the current situation. In literature, solutions already exist for specific use cases, but it is doubtful to what extent these approaches can be transferred to other conditions. We conducted a comprehensive literature research on existing situation recognition systems for the intraoperative area, covering 274 articles and 95 cross-references published between 2010 and 2019. We contrasted and compared 58 identified approaches based on defined aspects such as used sensor data or application area. In addition, we discussed applicability and transferability. Most of the papers focus on video data for recognizing situations within laparoscopic and cataract surgeries. Not all of the approaches can be used online for real-time recognition. Using different methods, good results with recognition accuracies above 90% could be achieved. Overall, transferability is less addressed. The applicability of approaches to other circumstances seems to be possible to a limited extent. Future research should place a stronger focus on adaptability. The literature review shows differences within existing approaches for situation recognition and outlines research trends. Applicability and transferability to other conditions are less addressed in current work.
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.
Context-aware systems to support actors in the operating room depending on the status of the intervention require knowledge about the current situation in the intra-operative area. In literature, solutions to achieve situation awareness already exist for specific use cases, but applicability and transferability to other conditions are less addressed. It is assumed that a unified solution that can be adapted to different processes and sensors would allow for greater flexibility, applicability, and thus transferability to different applications. To enable a flexible and intervention-independent system, this work proposes a concept for an adaptable situation recognition system. The system consists of four layers with several modular components for different functionalities. The feasibility is demonstrated via prototypical implementation and functional evaluation of a first basic framework prototype. Further development goal is the stepwise extension of the prototype.
Purpose
For the modeling, execution, and control of complex, non-standardized intraoperative processes, a modeling language is needed that reflects the variability of interventions. As the established Business Process Model and Notation (BPMN) reaches its limits in terms of flexibility, the Case Management Model and Notation (CMMN) was considered as it addresses weakly structured processes.
Methods
To analyze the suitability of the modeling languages, BPMN and CMMN models of a Robot-Assisted Minimally Invasive Esophagectomy and Cochlea Implantation were derived and integrated into a situation recognition workflow. Test cases were used to contrast the differences and compare the advantages and disadvantages of the models concerning modeling, execution, and control. Furthermore, the impact on transferability was investigated.
Results
Compared to BPMN, CMMN allows flexibility for modeling intraoperative processes while remaining understandable. Although more effort and process knowledge are needed for execution and control within a situation recognition system, CMMN enables better transferability of the models and therefore the system. Concluding, CMMN should be chosen as a supplement to BPMN for flexible process parts that can only be covered insufficiently by BPMN, or otherwise as a replacement for the entire process.
Conclusion
CMMN offers the flexibility for variable, weakly structured process parts, and is thus suitable for surgical interventions. A combination of both notations could allow optimal use of their advantages and support the transferability of the situation recognition system.
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.
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.
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.
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.
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.
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.
Documentation of clinical processes, especially in the perioperative are, is a base requirement for quality of service. Nonetheless, the documentation is a burden for the medical staff since it distracts from the clinical core process. An intuitive and user-friendly documentation system could increase documentation quality and reduce documentation workload. The optimal system solution would know what happened and the person documenting the step would need a single “confirm” button. In many cases, such a linear flow of activities is given as long as only one profession (e.g. anaestesiology, scrub nurse) is considered, but even in such cases, there might be derivations from the linear process flow and further interaction is required.
This project aims to evaluate existing big data infrastructures for their applicability in the operating room to support medical staff with context-sensitive systems. Requirements for the system design were generated. The project compares different data mining technologies, interfaces, and software system infrastructures with a focus on their usefulness in the peri-operative setting. The lambda architecture was chosen for the proposed system design, which will provide data for both postoperative analysis and real-time support during surgery.
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.
Delphi Markets
(2023)
Delphi markets refer to approaches and implementations of integrating prediction markets and Delphi studies (Real-time Delphi). The combination of the two methods for producing forecasts can potentially compensate for each other´s weaknesses. For example, prediction markets can be used to select participants with expertise and also motivate long-term participation through their gamified approach and incentive mechanisms. In this paper, two potentials for prediction markets and four potentials for Delphi studies, which are made possible by integration, are derived theoretically. Subsequently, three different integration approaches are presented, on the basis of which the integration on user, market and Delphi question-level is exemplified and it is shown that, depending on the approach, not all potentials can be achieved. At the end, recommendations for the use of Delphi markets are derived, existing limitations for Delphi markets as well as future developments are pointed out.
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.
Background
Although teledermatology has been proven internationally to be an effective and safe addition to the care of patients in primary care, there are few pilot projects implementing teledermatology in routine outpatient care in Germany. The aim of this cluster randomized controlled trial was to evaluate whether referrals to dermatologists are reduced by implementing a store-and-forward teleconsultation system in general practitioner practices.
Methods
Eight counties were cluster randomized to the intervention and control conditions. During the 1-year intervention period between July 2018 and June 2019, 46 general practitioner practices in the 4 intervention counties implemented a store-and-forward teledermatology system with Patient Data Management System interoperability. It allowed practice teams to initiate teleconsultations for patients with dermatologic complaints. In the four control counties, treatment as usual was performed. As primary outcome, number of referrals was calculated from routine health care data. Poisson regression was used to compare referral rates between the intervention practices and 342 control practices.
Results
The primary analysis revealed no significant difference in referral rates (relative risk = 1.02; 95% confidence interval = 0.911–1.141; p = .74). Secondary analyses accounting for sociodemographic and practice characteristics but omitting county pairing resulted in significant differences of referral rates between intervention practices and control practices. Matched county pair, general practitioner age, patient age, and patient sex distribution in the practices were significantly related to referral rates.
Conclusions
While a store-and-forward teleconsultation system was successfully implemented in the German primary health care setting, the intervention's effect was superimposed by regional factors. Such regional factors should be considered in future teledermatology research.
Mobile monitoring of outpatients during cancer therapy becomes possible through technological advancements. This study leveraged a new remote patient monitoring app for in-between systemic therapy sessions. Patients’ evaluation showed that the handling is feasible. Clinical implementation must consider an adaptive development cycle for reliable operations.
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
In Zusammenarbeit mit dem Medizinproduktehersteller ulrich medical wird eine User Experience und Usability Studie an der Software der im Moment eingesetzten Kontrastmittelinjektoren durchgeführt. Das Unternehmen möchte eine neue Variante eines Kontrastmittelinjektors entwickeln, der als Basis eine verbesserte Version dieser Softwares enthält. Benutzerstudien können mit den unterschiedlichsten Methoden durchgeführt werden. Das geeignete Vorgehen muss definiert und die Testpersonen in Bezug zur eingesetzten Methode ermittelt werden. Bei Medizinprodukten muss zusätzlich auf strikte Auflagen in Normen und Gesetzen geachtet werden. Die Grundlage zur Methodenauswahl bildet eine Recherche zu Usability und User Experience Vorgaben für Medizinprodukte. Die Studie wird anhand quantitativer Daten eines Usability Tests im Labor, Fragebögen zur User Experience und qualitativen Post Test- Interviews evaluiert. In erster Linie dient diese Studie der Ermittlung von möglichen Verbesserungen, welche in der darauf folgenden Masterthesis vertieft und umgesetzt werden.
Background: One of the most promising health care development areas is introducing telemedicine services and creating solutions based on blockchain technology. The study of systems combining both these domains indicates the ongoing expansion of digital technologies in this market segment.
Objective: This paper aims to review the feasibility of blockchain technology for telemedicine.
Methods: The authors identified relevant studies via systematic searches of databases including PubMed, Scopus, Web of Science, IEEE Xplore, and Google Scholar. The suitability of each for inclusion in this review was assessed independently. Owing to the lack of publications, available blockchain-based tokens were discovered via conventional web search engines (Google, Yahoo, and Yandex).
Results: Of the 40 discovered projects, only 18 met the selection criteria. The 5 most prevalent features of the available solutions (N=18) were medical data access (14/18, 78%), medical service processing (14/18, 78%), diagnostic support (10/18, 56%), payment transactions (10/18, 56%), and fundraising for telemedical instrument development (5/18, 28%).
Conclusions: These different features (eg, medical data access, medical service processing, epidemiology reporting, diagnostic support, and treatment support) allow us to discuss the possibilities for integration of blockchain technology into telemedicine and health care on different levels. In this area, a wide range of tasks can be identified that could be accomplished based on digital technologies using blockchains.
Die digitale Transformation und gesellschaftliche Entwicklungen verändern die Arbeitswelt nicht erst seit der Corona-Pandemie. Kommunikation, Kreativität und agile Vorgehensweisen in der Arbeitsorganisation rücken in den Vordergrund und werden gerade in Krisenzeiten zu wichtigen Stärken von Unternehmen. Der Grad der Selbstorganisation von Teams steigt und erfordert mehr individuelle Selbstorganisation der Beschäftigten. Dies birgt neben vielen Chancen auch Gesundheitsrisiken.
Der Report beleuchtet die agile Organisation und weitere moderne Organisationsmodelle wie die Soziokratie, die Holokratie und die evolutionäre Organisation unter dem Gesundheitsaspekt. All diese Organisationsmodelle sind gekennzeichnet durch die Abflachung von Hierarchien, eine stärkere Sinnorientierung, mehr Flexibilität sowie die Integration von Leistungspotentialen der Beschäftigten. Die Gemeinsamkeiten, aber auch Unterschiede und Konfliktpotenziale werden ausführlich erklärt.
Mit diesem Hintergrundwissen können Beratende Gesundheitsthemen besser in Phasen gesundheitlicher Belastungen einbringen und richtig adressieren. Der iga.Report 44 gibt einen Überblick zum noch jungen Stand der Forschung und liefert zahlreiche Ansatzpunkte für die Präventionsarbeit und die Betriebliche Gesundheitsförderung in einer neuen Arbeitswelt.
Menopause is the permanent cessation of menstruation occurring naturally in women's aging. The most frequent symptoms associated with menopausal phases are mucosal dryness, increased weight and body fat, and changes in sleep patterns. Oral symptoms in menopause derived from saliva flow reduction can lead to dry mouth, ulcers, and alterations of taste and swallowing patterns. However, the oral health phenotype of postmenopausal women has not been characterized. The aim of the study was to determine postmenopausal women's oral phenotype, including medical history, lifestyle, and oral assessment through artificial intelligence algorithms. We enrolled 100 postmenopausal women attending the Dental School of the University of Seville were included in the study. We collected an extensive questionnaire, including lifestyle, medication, and medical history. We used an unsupervised k-means algorithm to cluster the data following standard features for data analysis. Our results showed the main oral symptoms in our postmenopausal cohort were reduced salivary flow and periodontal disease. Relying on the classical assessment of the collected data, we might have a biased evaluation of postmenopausal women. Then, we used artificial intelligence analysis to evaluate our data obtaining the main features and providing a reduced feature defining the oral health phenotype. We found 6 clusters with similar features, including medication affecting salivation or smoking as essential features to obtain different phenotypes. Thus, we could obtain main features considering differential oral health phenotypes of postmenopausal women with an integrative approach providing new tools to assess the women in the dental clinic.
In der Kryochirurgie wird Kälte verwendet, um tumoröses Gewebe abzutöten. Dazu werden Kryosonden in den Tumor gestochen und stark abgekühlt. Hierbei gibt es verschiedene Herausforderungen, welchen computergestützt begegnet werden kann. Diese Arbeit gibt die Ergebnisse einer Literaturrecherche zu den Herausforderungen wieder. Die vorgestellten Arbeiten beschäftigten sich mit der Simulation des im Tumor entstehenden Eisballs, dem korrekten Positionieren der Kryosonden im Tumor, dem Überwachen des Eingriffs sowie dem Entwickeln von Simulationen für Trainingszwecke. Dabei zeigt sich, dass der Einsatz von computergestützten Lösungen die Kryochirurgie für Operateur und Patient verbessern kann.
In networked operating room environments, there is an emerging trend towards standardized non-proprietary communication protocols which allow to build new integration solutions and flexible human-machine interaction concepts. The most prominent endeavor is the IEEE 11073 SDC protocol. For some uses cases, it would be helpful if not just medical devices could be controlled based on SDC, but also building automation systems like light, shutters, air condition, etc. For those systems, the KNX protocol is widely used. We build an SDC-to-KNX gateway which allows to use the SDC protocol for sending commands to connected KNX devices. The first prototype system was successfully implemented at the demonstration operating room at Reutlingen University. This is a first step toward the integration of a broader variety of KNX devices.
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.
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.
The hearing contact lens® (HCL) is a new type of hearing aid devices. One of its main components is a piezo-electric actuator. In order to evaluate and maximize the HCL’s performance, a model of the HCL coupled to the middle ear was developed using finite element approach. The model was validated step by step starting with the HCL only. To validate the HCL model, vibrational measurements on the HCL were performed using a Laser-Doppler-Vibrometer (LDV). Then, a silicone cap was placed onto the HCL to provide an interface between the HCL and the tympanic membrane of the middle-ear model and additional LDV measurements on temporal bones were performed to validate the coupled model. The coupled model was used to evaluate the equivalent sound pressure of the HCL. Moreover, a deeper insight was gained into the contact between the HCL and tympanic membrane and its effects on the HCL performance. The model can be used to investigate the sensitivity of geometrical and material parameters with respect to performance measures of the HCL and evaluate the feedback behavior.
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.
Physicians in interventional radiology are exposed to high physical stress. To avoid negative long-term effects resulting from unergonomic working conditions, we demonstrated the feasibility of a system that gives feedback about unergonomic
situations arising during the intervention based on the Azure Kinect camera. The overall feasibility of the approach could be shown.
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.
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.
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.
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.
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.
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.
Die prä-, intra- und postoperative Entitäts- und Dignitätsbestimmung von Speicheldrüsen-tumoren (ST) allein anhand von histomorphologischen Kriterien ist häufig mit großen Unsicherheiten verbunden.
Die Spektren der Raman-Spektroskopie (RS) und der Infrarot-Spektroskopie (IS) enthalten Informationen zu der molekularen Zusammensetzung des untersuchten Gewebes. Ziel der Arbeit war die Etablierung eines Gewebe-Aufarbeitungs-Workflows und die Analyse des Einflusses der Fixierung auf die spektrale Bioinformation. Zudem wird ein Überblick über den Einsatz der RS und IS im Kopf-Hals Bereich gegeben.
Es wurden 10 mm dicke, konsekutive kryo-, formalin- und paraffinfixierte ST-Gewebeschnitte von Zystadenolymphomen (n=5) und pleomorphen Adenomen (n=4) mit der RS und IS untersucht und die Daten multivariat ausgewertet. Die Messungen erfolgten in Korrelation zur Histomorphologie über einen korrespondierenden HE-Schnitt sowohl im Tumorgewebe als auch im gesunden Speicheldrüsengewebe.
In der Mittelwertspektrenanalyse zeigte sich eine deutliche Paraffin-Signatur, Formalin-Fixierung hatte keinen wesentlichen Einfluss. Dies konnte durch die Hauptkomponentenanalyse (PCA) bestätigt werden. Eine Diskriminierung von Tumor- und Nicht-Tumorgewebe durch die PCA und gekoppelte Diskriminanzanalyse war ebenfalls mit beiden spektroskopischen Methoden mit einer hohen Sensitivität möglich.
Für eine Translation von spektralen Verfahren ist das Wissen über Einflussfaktoren auf die spektrale Bioinformation der Gewebeaufarbeitung und -fixierung unabdingbar. Die Integration spektraler Verfahren additiv in bestehende Arbeitsabläufe ist möglich. Der Einfluss der Formalinfixierung auf die spektrale Bioinformation ist gering. Die bioinformatische Analyse der umfangreichen Datensätze ist herausfordernd.
IZKF Würzburg
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.
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.
The implementation of a web based portal QA solution will lead to a high acceptance of the staff as the usage of commonly known standard software (e.g. web browser) allows intuitive handling. In the daily use a significant simplification of the workflow and Performance enhancement can be achieved by easy access to the check documents. As the data is now saved in a database it can easily be processed and long-term trends can be displayed. Therefore possible errors can be detected much easier and earlier. By the usage of time stamps and user authentication procedures and user responsibilities are comprehensibly documented. As the software is browser based, integration into an existing software Environment is not critical. As only technical QA data is processed, no further data security measures are necessary. A certification as a medical product is not required.
In 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.
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.