Development and characterization of a scaffold-free 3D spheroid model of iPSC-derived human cardiomyocytes

Purpose: Cardiomyocytes are terminally differentiated cells in the adult heart and ischemia and cardiotoxic compounds can lead to cell death and irreversible decline of cardiac function. As testing platforms, isolated organs and primary cells from rodents have been the standard in research and toxicology, but there is a need for better models that more faithfully recapitulate native human biology. Hence, a new in vitro model comprising the advantages of 3D cell culture and the availability of induced pluripotent stem cells (iPSC) from human origin was developed and characterized. Methods: Human cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPSCs) were studied in standard 2D culture and as cardiac microtissues (MTs) formed in hanging drops. 2D cultures were examined using immunofluorescence microscopy and Western blotting while the cardiac MTs were subjected to immunofluorescence, contractility, and pharmacological investigations. Results: iPSC-derived CMs in 2D culture showed well-formed myofibrils, cell-cell contacts positive for connexin-43, and other typical cardiac proteins. The cells reacted to pro-hypertrophic growth factors with a substantial increase in myofibrils and sarcomeric proteins. In hanging drop cultures, iPSC-derived cardiomyocytes formed spheroidal MTs within 4 days showing a homogeneous tissue structure with well-developed myofibrils extending throughout the whole spheroid without a necrotic core. MTs showed spontaneous contractions for more than 4 weeks that were recorded by optical motion tracking, sensitive to temperature, and responsive to electrical pacing. Contractile pharmacology was tested with several agents known to modulate cardiac rate and viability. Calcium-transients underlay the contractile activity and were also responsive to electrical stimulation, caffeine-induced Ca2+-release, extracellular calcium levels. Conclusions: 3D culture using iPSC-derived human cardiomyocytes provides an organoid human-based cellular platform that is free of necrosis and recapitulates vital cardiac functionality, thereby providing new and promising relevant model for the evaluation and development of new therapies and detection of cardiotoxicity.

Development and Evaluation of a New Tablet Computer Application for the Therapy of Brain-Injured Patients with Aphasia

Introduction Language is the most important mean of communication and plays a central role in our everyday life. Brain damage (e.g. stroke) can lead to acquired disorders of lan- guage affecting the four linguistic modalities (i.e. reading, writing, speech production and comprehension) in different combinations and levels of severity. Every year, more than 5000 people (Aphasie Suisse) are affected by aphasia in Switzerland alone. Since aphasia is highly individual, the level of difficulty and the content of tasks have to be adapted continuously by the speech therapists. Computer-based assignments allow patients to train independently at home and thus increasing the frequency of ther- apy. Recent developments in tablet computers have opened new opportunities to use these devices for rehabilitation purposes. Especially older people, who have no prior experience with computers, can benefit from the new technologies. Methods The aim of this project was to develop an application that enables patients to train language related tasks autonomously and, on the other hand, allows speech therapists to assign exercises to the patients and to track their results online. Seven categories with various types of assignments were implemented. The application has two parts which are separated by a user management system into a patient interface and a therapist interface. Both interfaces were evaluated using the SUS (Subject Usability Scale). The patient interface was tested by 15 healthy controls and 5 patients. For the patients, we also collected tracking data for further analysis. The therapist interface was evaluated by 5 speech therapists. Results The SUS score are xpatients = 98 and xhealthy = 92.7 (median = 95, SD = 7, 95% CI [88.8, 96.6]) in case of the patient interface and xtherapists = 68 in case of the therapist interface. Conclusion Both, the patients and the healthy subjects, attested high SUS scores to the patient interface. These scores are considered as "best imaginable". The therapist interface got a lower SUS score compared to the patient interface, but is still considered as "good" and "usable". The user tracking system and the interviews revealed that there is room for improvements and inspired new ideas for future versions.

Passively Track WiFi Users with an Enhanced Particle Filter using Power-based Ranging

Passive positioning systems produce user location information for third-party providers of positioning services. Since the tracked wireless devices do not participate in the positioning process, passive positioning can only rely on simple, measurable radio signal parameters, such as timing or power information. In this work, we provide a passive tracking system for WiFi signals with an enhanced particle filter using fine-grained power-based ranging. Our proposed particle filter provides an improved likelihood function on observation parameters and is equipped with a modified coordinated turn model to address the challenges in a passive positioning system. The anchor nodes for WiFi signal sniffing and target positioning use software defined radio techniques to extract channel state information to mitigate multipath effects. By combining the enhanced particle filter and a set of enhanced ranging methods, our system can track mobile targets with an accuracy of 1.5m for 50% and 2.3m for 90% in a complex indoor environment. Our proposed particle filter significantly outperforms the typical bootstrap particle filter, extended Kalman filter and trilateration algorithms.

Real-time computer-based visual feedback improves visual acuity in downbeat nystagmus - a pilot study.

BACKGROUND Patients with downbeat nystagmus syndrome suffer from oscillopsia, which leads to an unstable visual perception and therefore impaired visual acuity. The aim of this study was to use real-time computer-based visual feedback to compensate for the destabilizing slow phase eye movements. METHODS The patients were sitting in front of a computer screen with the head fixed on a chin rest. The eye movements were recorded by an eye tracking system (EyeSeeCam®). We tested the visual acuity with a fixed Landolt C (static) and during real-time feedback driven condition (dynamic) in gaze straight ahead and (20°) sideward gaze. In the dynamic condition, the Landolt C moved according to the slow phase eye velocity of the downbeat nystagmus. The Shapiro-Wilk test was used to test for normal distribution and one-way ANOVA for comparison. RESULTS Ten patients with downbeat nystagmus were included in the study. Median age was 76 years and the median duration of symptoms was 6.3 years (SD +/- 3.1y). The mean slow phase velocity was moderate during gaze straight ahead (1.44°/s, SD +/- 1.18°/s) and increased significantly in sideward gaze (mean left 3.36°/s; right 3.58°/s). In gaze straight ahead, we found no difference between the static and feedback driven condition. In sideward gaze, visual acuity improved in five out of ten subjects during the feedback-driven condition (p = 0.043). CONCLUSIONS This study provides proof of concept that non-invasive real-time computer-based visual feedback compensates for the SPV in DBN. Therefore, real-time visual feedback may be a promising aid for patients suffering from oscillopsia and impaired text reading on screen. Recent technological advances in the area of virtual reality displays might soon render this approach feasible in fully mobile settings.

Who cares about my feature request?

Previous studies on issue tracking systems for open source software (OSS) focused mainly on requests for bug fixes. However, requests to add a new feature or an improvement to an OSS project are often also made in an issue tracking system. These inquiries are particularly important because they determine the further development of the software. This study examines if there is any difference between requests of the IBM developer community and other sources in terms of the likelihood of successful implementation. Our study consists of a case study of the issue tracking system BugZilla in the Eclipse integrated development environment (IDE). Our hypothesis, which was that feature requests from outsiders have less chances of being implemented, than feature requests from IBM developers, was confirmed.

Real-Time Multimodal Retinal Image Registration for a Computer Assisted Laser Photocoagulation System

An algorithm for the real-time registration of a retinal video sequence captured with a scanning digital ophthalmoscope (SDO) to a retinal composite image is presented. This method is designed for a computer-assisted retinal laser photocoagulation system to compensate for retinal motion and hence enhance the accuracy, speed, and patient safety of retinal laser treatments. The procedure combines intensity and feature-based registration techniques. For the registration of an individual frame, the translational frame-to-frame motion between preceding and current frame is detected by normalized cross correlation. Next, vessel points on the current video frame are identified and an initial transformation estimate is constructed from the calculated translation vector and the quadratic registration matrix of the previous frame. The vessel points are then iteratively matched to the segmented vessel centerline of the composite image to refine the initial transformation and register the video frame to the composite image. Criteria for image quality and algorithm convergence are introduced, which assess the exclusion of single frames from the registration process and enable a loss of tracking signal if necessary. The algorithm was successfully applied to ten different video sequences recorded from patients. It revealed an average accuracy of 2.47 ± 2.0 pixels (∼23.2 ± 18.8 μm) for 2764 evaluated video frames and demonstrated that it meets the clinical requirements.

Space-based space surveillance and tracking demonstrator: mission and system design

This paper presents the capabilities of a Space-Based Space Surveillance (SBSS) demonstration mission for Space Surveillance and Tracking (SST) based on a micro-satellite platform. The results have been produced in the frame of ESA’s "Assessment Study for Space Based Space Surveillance Demonstration Mission" performed by the Airbus Defence and Space consortium. The assessment of SBSS in an SST system architecture has shown that both an operational SBSS and also already a well- designed space-based demonstrator can provide substantial performance in terms of surveillance and tracking of beyond-LEO objects. Especially the early deployment of a demonstrator, possible by using standard equipment, could boost initial operating capability and create a self-maintained object catalogue. Furthermore, unique statistical information about small-size LEO debris (mm size) can be collected in-situ. Unlike classical technology demonstration missions, the primary goal is the demonstration and optimisation of the functional elements in a complex end-to-end chain (mission planning, observation strategies, data acquisition, processing, etc.) until the final products can be offered to the users and with low technological effort and risk. The SBSS system concept takes the ESA SST System Requirements into account and aims at fulfilling SST core requirements in a stand-alone manner. Additionally, requirements for detection and characterisation of small-sizedLEO debris are considered. The paper presents details of the system concept, candidate micro-satellite platforms, the instrument design and the operational modes. Note that the detailed results of performance simulations for space debris coverage and cataloguing accuracy are presented in a separate paper “Capability of a Space-based Space Surveillance System to Detect and Track Objects in GEO, MEO and LEO Orbits” by J. Silha (AIUB) et al., IAC-14, A6, 1.1x25640.

Range-based Weighted-likelihood Particle Filter for RSS-based Indoor Tracking

Attractive business cases in various application fields contribute to the sustained long-term interest in indoor localization and tracking by the research community. Location tracking is generally treated as a dynamic state estimation problem, consisting of two steps: (i) location estimation through measurement, and (ii) location prediction. For the estimation step, one of the most efficient and low-cost solutions is Received Signal Strength (RSS)-based ranging. However, various challenges - unrealistic propagation model, non-line of sight (NLOS), and multipath propagation - are yet to be addressed. Particle filters are a popular choice for dealing with the inherent non-linearities in both location measurements and motion dynamics. While such filters have been successfully applied to accurate, time-based ranging measurements, dealing with the more error-prone RSS based ranging is still challenging. In this work, we address the above issues with a novel, weighted likelihood, bootstrap particle filter for tracking via RSS-based ranging. Our filter weights the individual likelihoods from different anchor nodes exponentially, according to the ranging estimation. We also employ an improved propagation model for more accurate RSS-based ranging, which we suggested in recent work. We implemented and tested our algorithm in a passive localization system with IEEE 802.15.4 signals, showing that our proposed solution largely outperforms a traditional bootstrap particle filter.

A clinically applicable laser-based image-guided system for laparoscopic liver procedures

PURPOSE Laser range scanners (LRS) allow performing a surface scan without physical contact with the organ, yielding higher registration accuracy for image-guided surgery (IGS) systems. However, the use of LRS-based registration in laparoscopic liver surgery is still limited because current solutions are composed of expensive and bulky equipment which can hardly be integrated in a surgical scenario. METHODS In this work, we present a novel LRS-based IGS system for laparoscopic liver procedures. A triangulation process is formulated to compute the 3D coordinates of laser points by using the existing IGS system tracking devices. This allows the use of a compact and cost-effective LRS and therefore facilitates the integration into the laparoscopic setup. The 3D laser points are then reconstructed into a surface to register to the preoperative liver model using a multi-level registration process. RESULTS Experimental results show that the proposed system provides submillimeter scanning precision and accuracy comparable to those reported in the literature. Further quantitative analysis shows that the proposed system is able to achieve a patient-to-image registration accuracy, described as target registration error, of [Formula: see text]. CONCLUSIONS We believe that the presented approach will lead to a faster integration of LRS-based registration techniques in the surgical environment. Further studies will focus on optimizing scanning time and on the respiratory motion compensation.

A robotic system to train activities of daily living in a virtual environment

In the past decade, several arm rehabilitation robots have been developed to assist neurological patients during therapy. Early devices were limited in their number of degrees of freedom and range of motion, whereas newer robots such as the ARMin robot can support the entire arm. Often, these devices are combined with virtual environments to integrate motivating game-like scenarios. Several studies have shown a positive effect of game-playing on therapy outcome by increasing motivation. In addition, we assume that practicing highly functional movements can further enhance therapy outcome by facilitating the transfer of motor abilities acquired in therapy to daily life. Therefore, we present a rehabilitation system that enables the training of activities of daily living (ADL) with the support of an assistive robot. Important ADL tasks have been identified and implemented in a virtual environment. A patient-cooperative control strategy with adaptable freedom in timing and space was developed to assist the patient during the task. The technical feasibility and usability of the system was evaluated with seven healthy subjects and three chronic stroke patients.

Percutaneous radiofrequency ablation of virtual tumours in canine kidney using Global Positioning System-like technology

What's known on the subject? And what does the study add? We have previously shown that percutaneous radiofrequency ablation guided by image-fusion technology allows for precise needle placement with real time ultrasound superimposed with pre-loaded imaging, removing the need for real-time CT or MR guidance. Emerging technology also allows real-time tracking of a treatment needle within an organ in a virtually created 3D format. To our knowledge, this is the first study utilising a sophisticated ultrasound-based navigation system that uses both image-fusion and real-time probe-tracking technologies for in-vivo renal ablative intervention.

Multimodal augmented reality system for surgical microscopy

Image-guided, computer-assisted neurosurgery has emerged to improve localization and targeting, to provide a better anatomic definition of the surgical field, and to decrease invasiveness. Usually, in image-guided surgery, a computer displays the surgical field in a CT/MR environment, using axial, coronal or sagittal views, or even a 3D representation of the patient. Such a system forces the surgeon to look away from the surgical scene to the computer screen. Moreover, this kind of information, being pre-operative imaging, can not be modified during the operation, so it remains valid for guidance in the first stage of the surgical procedure, and mainly for rigid structures like bones. In order to solve the two constraints mentioned before, we are developing an ultrasoundguided surgical microscope. Such a system takes the advantage that surgical microscopy and ultrasound systems are already used in neurosurgery, so it does not add more complexity to the surgical procedure. We have integrated an optical tracking device in the microscope and an augmented reality overlay system with which we avoid the need to look away from the scene, providing correctly aligned surgical images with sub-millimeter accuracy. In addition to the standard CT and 3D views, we are able to track an ultrasound probe, and using a previous calibration and registration of the imaging, the image obtained is correctly projected to the overlay system, so the surgeon can always localize the target and verify the effects of the intervention. Several tests of the system have been already performed to evaluate the accuracy, and clinical experiments are currently in progress in order to validate the clinical usefulness of the system.

Impact of a self-developed planning and self-constructed navigation system on skull base surgery: 10 years experience

CONCLUSION: Our self-developed planning and navigation system has proven its capacity for accurate surgery on the anterior and lateral skull base. With the incorporation of augmented reality, image-guided surgery will evolve into 'information-guided surgery'. OBJECTIVE: Microscopic or endoscopic skull base surgery is technically demanding and its outcome has a great impact on a patient's quality of life. The goal of the project was aimed at developing and evaluating enabling navigation surgery tools for simulation, planning, training, education, and performance. This clinically applied technological research was complemented by a series of patients (n=406) who were treated by anterior and lateral skull base procedures between 1997 and 2006. MATERIALS AND METHODS: Optical tracking technology was used for positional sensing of instruments. A newly designed dynamic reference base with specific registration techniques using fine needle pointer or ultrasound enables the surgeon to work with a target error of < 1 mm. An automatic registration assessment method, which provides the user with a color-coded fused representation of CT and MR images, indicates to the surgeon the location and extent of registration (in)accuracy. Integration of a small tracker camera mounted directly on the microscope permits an advantageous ergonomic way of working in the operating room. Additionally, guidance information (augmented reality) from multimodal datasets (CT, MRI, angiography) can be overlaid directly onto the surgical microscope view. The virtual simulator as a training tool in endonasal and otological skull base surgery provides an understanding of the anatomy as well as preoperative practice using real patient data. RESULTS: Using our navigation system, no major complications occurred in spite of the fact that the series included difficult skull base procedures. An improved quality in the surgical outcome was identified compared with our control group without navigation and compared with the literature. The surgical time consumption was reduced and more minimally invasive approaches were possible. According to the participants' questionnaires, the educational effect of the virtual simulator in our residency program received a high ranking.

An integrated system for 3D hip joint reconstruction from 2D X-rays: a preliminary validation study

The acquisition of conventional X-ray radiographs remains the standard imaging procedure for the diagnosis of hip-related problems. However, recent studies demonstrated the benefit of using three-dimensional (3D) surface models in the clinical routine. 3D surface models of the hip joint are useful for assessing the dynamic range of motion in order to identify possible pathologies such as femoroacetabular impingement. In this paper, we present an integrated system which consists of X-ray radiograph calibration and subsequent 2D/3D hip joint reconstruction for diagnosis and planning of hip-related problems. A mobile phantom with two different sizes of fiducials was developed for X-ray radiograph calibration, which can be robustly detected within the images. On the basis of the calibrated X-ray images, a 3D reconstruction method of the acetabulum was developed and applied together with existing techniques to reconstruct a 3D surface model of the hip joint. X-ray radiographs of dry cadaveric hip bones and one cadaveric specimen with soft tissue were used to prove the robustness of the developed fiducial detection algorithm. Computed tomography scans of the cadaveric bones were used to validate the accuracy of the integrated system. The fiducial detection sensitivity was in the same range for both sizes of fiducials. While the detection sensitivity was 97.96% for the large fiducials, it was 97.62% for the small fiducials. The acetabulum and the proximal femur were reconstructed with a mean surface distance error of 1.06 and 1.01 mm, respectively. The results for fiducial detection sensitivity and 3D surface reconstruction demonstrated the capability of the integrated system for 3D hip joint reconstruction from 2D calibrated X-ray radiographs.