Cascade Technologies (United States)

Background: Ablation of atrial fibrillation (AF) by pulmonary vein (PV) isolation has limited success in some patients. However, identifying additional ablation targets in such patients currently requires mapping the entire atrium, which is time-consuming and poorly accounts for real-time changes. Objectives: We developed an Artificial-Intelligence (AI) based system that can guide an electrophysiology catheter in real-time (i.e. left/right, superior/inferior) during AF from an arbitrary location directly to sites leading to AF termination or 1Y success (fig. A). We validated the system in a large registry, and evaluated projected time savings from this approach. Methods: coPilot is an AI-system developed and tested in separate cohorts on ~20 million electrograms in a N=236 patient registry with physiological and clinical ground truth labels. First, we trained recurrent neural network (RNN) models to estimate AF activation times using unipolar and bipolar electrogram features (first derivative dV/dt, shape), tuned in a random forest classifier to experts informed by monophasic action potential (MAP) tracings (fig. B; top). Second, we applied this AI-model to multi-electrode catheters (e.g. local HDGrid, global Basket), to calculate predominant AF wave direction (fig. B bottom). Third, we validated if moving a catheter in AI-indicated directions reached successful AF ablation sites in a hold-out set not used for training. Results: The validation cohort was 69.0±8.3 years’ and 72.6% had non-paroxysmal AF. In Fig. B, AF activation times by traditional electrogram features were noisy versus MAPs (arrows). Fig. B (bottom) shows AI-activation times on a multi-electrode array in a 67Y woman in persistent AF, showing predominantly up/left activity over time. The array was moved accordingly and analysis repeated (steps 1-4 in fig. A, top), until the AF termination site was reached. coPilot pointed to 85.7% of AF termination versus 13.1% of control sites (p<0.01, fig. C). coPilot also reached sites ablated in cases of long-term success (68.8% at 1Y). Time to the successful region was 4.2±1.1 movements (estimated <5 minutes) that was shorter than atrial mapping time (>10-15 minutes). Conclusions: A novel AI-based system trained to physiological and clinical gold standards can rapidly steer a clinical catheter during AF to successful ablation sites. This approach has promise for improving the success of AF ablation while reducing case time over existing strategies.

This paper describes a method for the nonlinear analysis of oscillators. We define a matrix whose eigenvalues give the oscillator’s start-up conditions and create an accurate, fundamental-frequency initial estimate of the large-signal oscillation. A relaxation method is used to obtain the large-signal results, avoiding the well known ill conditioning of Newton iterations.

Mesenchymal stem cells derived from adipose tissue (ADMSCs) are being increasingly considered in regenerative medicine-based clinical applications. Apart from possessing therapeutic applications themselves, ADMSCs also secrete a myriad of soluble factors which are promising candidates for treating several degenerative diseases such as osteoarthritis and neurodegenerative diseases, wound repair as well as for cosmeceutical purposes. In our research study, we successfully isolated ADMSCs in-house, now called CKC-Endeavour-1 from the lipoaspirate sample of a patient who underwent liposuction. The subsequent expansion of cells was performed in xeno-free and serum-free conditions and their characterisation was performed using tri-lineage differentiation studies. The levels of differentiation were assessed by staining and gene expression which was observed to be comparable between the in-house developed ADMSC cell line and the commercially purchased ADMSCs. Following characterisation, the secretory components from these MSCs, namely, conditioned media (ADMSC-CM) and exosomes (ADMSC-EXO) were harvested from CKC-Endeavour-1 under xeno-free, serum-free, and supplement-free conditions followed by lyophilisation in order to attempt to prolong its shelf-life. The comprehensive analysis of the secretome profile of ADMSC-CM using carried out using cytokine array and demonstrated the presence of 105 cytokines and growth factors. Also, clinical grade Izon columns were used to isolate the exosomes from ADMSC-CM obtaining exosomes in the size range of <200nm, analysed using nanoparticle tracking analysis. Overall, our study developed an ADMSC cell line, CKC-Endeavour-1, along with their CM and exosome (EXO) products under clinically safe conditions. Additionally, we have obtained a comprehensive understanding of the secreted factors present in the ADMSC-CM which could be further explored in detail to tap the best therapeutic benefits from them.

In this work, the substrate holders of three principal geometries (flat, pocket, and pedestal) were designed based on E-field simulations. They were fabricated and then tested in microwave plasma-assisted chemical vapor deposition process with the purpose of the homogeneous growth of 100-μm-thick, low-stress polycrystalline diamond film over 2-inch Si substrates with a thickness of 0.35 mm. The effectiveness of each holder design was estimated by the criteria of the PCD film quality, its homogeneity, stress, and the curvature of the resulting “diamond-on-Si” plates. The structure and phase composition of the synthesized samples were studied with scanning electron microscopy and Raman spectroscopy, the curvature was measured using white light interferometry, and the thermal conductivity was measured using the laser flash technique. The proposed pedestal design of the substrate holder could reduce the stress of the thick PCD film down to 1.1–1.4 GPa, which resulted in an extremely low value of displacement for the resulting “diamond-on-Si” plate of Δh = 50 μm. The obtained results may be used for the improvement of already existing, and the design of the novel-type, MPCVD reactors aimed at the growth of large-area thick homogeneous PCD layers and plates for electronic applications.

The benefits of meadow restoration can be assessed by understanding the connections among geomorphology, hydrology, and vegetation; and multispectral imagery captured from unpiloted aerial systems (UASs) can provide the best method in terms of cost, resolution, and support for vegetation indices. Our field studies were conducted on northern Sierra montane meadows (with ≤70 km2 watershed area). The meadows exist in various stages of ecological restoration. Field survey methods included GPS + laser-leveling channel survey, cross-sections, LiDAR, vegetation sampling, soil measurements, and UAS imaging. A sensor captured calibrated blue (465–485 nm), green (550–570 nm), red (663–673 nm), near infrared (NIR) (820–860 nm), and red-edge (712–722 nm) bands at 5.5 cm resolution (as well as thermal at 81 cm resolution) and provided multispectral images and derivative vegetation indices such as the normalized difference vegetation index (NDVI) and red-edge chlorophyll index (Clre). This fine-scale imagery extended our morphometric assessment of post-restoration channel bedform patterns and sinuosity related to Carex-influenced soil properties and Salix influence, and also documented groundwater-related effects via Carex patterns evident from spring snowmelt images, as well as NDVI and Clre (derived from spring and summer images) in growing to senescent phenological stages. Carex was significantly associated with low bulk density and high soil moisture, NDVI, and Clre in low-lying areas, and channel sinuosity was significantly associated with willow influence. Our methods can be applied by restoration managers to assess where projects are threatened by renewed incision and to document levels of carbon sequestration significant to addressing climate change.

We examine the problem of optimizing the linearity and dynamic range of a FET device, with application to carbon-nanotube (CNT) FETs. To develop insight into the way FET parameters affect linearity, we derive expressions for noise figure, intermodulation distortion, and dynamic range of a FET described by a unilateral equivalent circuit. This exercise identifies criteria for optimizing linearity and comparing the linearity of dissimilar devices. Measurements prove that CNT devices are signify-cantly more linear than modern microwave FETs.

Human cognitive and perception processes have a great tolerance for imprecision or uncertainty. For this reason, the notions of perception and cognition have great importance in solving many decision making problems in engineering, medicine, science, and social science as there are innumerable uncertainties in real-world phenomena. These uncertainties can be broadly classified as either type one uncertainty arising from the random behavior of physical processes or type two uncertainty arising from human perception and cognition processes. Statistical theory can be used to model the former, but lacks the sophistication to process the latter. The theory of fuzzy logic has proven to be very effective in processing type two uncertainty. New computing methods based on fuzzy logic can lead to greater adaptability, tractability, robustness, a lower cost solution, and better rapport with reality in the development of intelligent systems. Fuzzy logic is needed to properly pose and answer queries about quantitatively defining imprecise linguistic terms like middle class, poor, low inflation, medium inflation, and high inflation. Imprecise terms like these in natural languages should be considered to have qualitative definitions, quantitative definitions, crisp quantitative definitions, fuzzy quantitative definitions, type-one fuzzy quantitative definitions, and interval type-two fuzzy quantitative definitions. There can be crisp queries, crisp answers, type-one fuzzy queries, type-one fuzzy answers, interval type-two fuzzy queries, and interval type-two fuzzy answers.

Two-dimensional open-cavity flows for free stream Mach number of 0.1 to 1.6 are investigated with direct numerical simulations for cavities of aspect ratio 2 and 6 to characterize the flow stability. We determine the neutral stability curve over a wide range of Mach numbers and Reynolds numbers. In particular, we examine the effects of compressibility on the flow in transonic regime at low Reynolds numbers. Rossiter modes are identified by spectral analysis. The corresponding spatial structures associated with the dominant and subdominant Rossiter modes are extracted with dynamic mode decomposition. The nature of these structures provides us insight to their contribution to instability of the flow. The interaction between the shock waves and the shear layer modes for the transonic flows are investigated.