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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.
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.
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.
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.
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).
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.
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.