scholarly journals A Novel Chronic Dural Port Platform for Continuous Collection of Large Volumes of Cerebrospinal Fluid and Intrathecal Drug Delivery in Free-Moving Mice.

2021 ◽  
Author(s):  
Tsuneo Nakajima ◽  
Shuko Takeda ◽  
Yuki Ito ◽  
Akane Oyama ◽  
Yoichi Takami ◽  
...  
Keyword(s):  
Real Time ◽  
Mouse Models ◽  
Large Volume ◽  
Behavioral Assessment ◽  
Intrathecal Injection ◽  
Direct Access ◽  
Therapeutic Drug ◽  
High Quality ◽  
Cns Disorders ◽  
Intrathecal Space

Abstract BackgroundCerebrospinal fluid (CSF) provides a direct representation of the pathophysiological changes occurring in the central nervous system (CNS); therefore, it has been used for pathogenesis research and biomarker development for CNS disorders. The CSF obtained from valid mouse models relevant to CNS disorders can be an important resource for successful biomarker and drug development. However, the limited volume of CSF that can be collected from the tiny intrathecal space and the technical difficulties involved in CSF sampling have been bottlenecks that have hindered the detailed analysis of CSF in mouse models. ResultsWe have developed a novel chronic dural port (CDP) method without cannulation for mouse CSF collection. This method allows easy and repeated access to the intrathecal space in a free-moving, unanesthetized mouse, thereby enabling continuous long-term CSF collection with minimal tissue damage and providing a large volume of high-quality CSF from a single mouse. When combined with chemical biosensors, the CDP method allows real-time monitoring of the dynamic changes in neurochemicals in the CSF at a one-second temporal resolution in free-moving mice. The CDP can also serve as a direct access point for intrathecal injection of CSF tracers and drugs. The spatio-temporal distribution of CSF tracers delivered via CDP revealed a dynamic metabolism of CSF at distinct brain areas. Direct intrathecal delivery of centrally acting drugs via CDP enabled real-time behavioral assessment in free-moving mice. ConclusionsThe CDP method allows collection of a large volume of high-quality CSF and direct intrathecal drug administration with real-time behavioral assessment in free-moving mice. Combined with animal models relevant to CNS disorders, this method provides a unique and valuable platform for biomarker and therapeutic drug research.

Sky Segmentation for Enhanced Depth Reconstruction and Bokeh Rendering with Efficient Architectures

2020 ◽  
Vol 2020 (14) ◽  
pp. 378-1-378-7
Author(s):  
Tyler Nuanes ◽  
Matt Elsey ◽  
Radek Grzeszczuk ◽  
John Paul Shen
Keyword(s):  
Real Time ◽  
Mobile Device ◽  
Computational Cost ◽  
False Positives ◽  
Compact Model ◽  
High Quality ◽  
False Negatives ◽  
Trade Off ◽  
Depth Reconstruction ◽  
Binary Classifiers

We present a high-quality sky segmentation model for depth refinement and investigate residual architecture performance to inform optimally shrinking the network. We describe a model that runs in near real-time on mobile device, present a new, highquality dataset, and detail a unique weighing to trade off false positives and false negatives in binary classifiers. We show how the optimizations improve bokeh rendering by correcting stereo depth misprediction in sky regions. We detail techniques used to preserve edges, reject false positives, and ensure generalization to the diversity of sky scenes. Finally, we present a compact model and compare performance of four popular residual architectures (ShuffleNet, MobileNetV2, Resnet-101, and Resnet-34-like) at constant computational cost.

scholarly journals Gauge invariant canonical symplectic algorithms for real-time lattice strong-field quantum electrodynamics

2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
Qiang Chen ◽  
Jianyuan Xiao ◽  
Peifeng Fan
Keyword(s):  
Field Theory ◽  
Real Time ◽  
Quantum Electrodynamics ◽  
Symplectic Form ◽  
Strong Field ◽  
Relativistic Quantum ◽  
High Order ◽  
High Quality ◽  
Geometric Structures ◽  
Gauge Invariant

Abstract A class of high-order canonical symplectic structure-preserving geometric algorithms are developed for high-quality simulations of the quantized Dirac-Maxwell theory based strong-field quantum electrodynamics (SFQED) and relativistic quantum plasmas (RQP) phenomena. With minimal coupling, the Lagrangian density of an interacting bispinor-gauge fields theory is constructed in a conjugate real fields form. The canonical symplectic form and canonical equations of this field theory are obtained by the general Hamilton’s principle on cotangent bundle. Based on discrete exterior calculus, the gauge field components are discreted to form a cochain complex, and the bispinor components are naturally discreted on a staggered dual lattice as combinations of differential forms. With pull-back and push-forward gauge covariant derivatives, the discrete action is gauge invariant. A well-defined discrete canonical Poisson bracket generates a semi-discrete lattice canonical field theory (LCFT), which admits the canonical symplectic form, unitary property, gauge symmetry and discrete Poincaré subgroup, which are good approximations of the original continuous geometric structures. The Hamiltonian splitting method, Cayley transformation and symmetric composition technique are introduced to construct a class of high-order numerical schemes for the semi-discrete LCFT. These schemes involve two degenerate fermion flavors and are locally unconditional stable, which also preserve the geometric structures. Admitting Nielsen-Ninomiya theorem, the continuous chiral symmetry is partially broken on the lattice. As an extension, a pair of discrete chiral operators are introduced to reconstruct the lattice chirality. Equipped with statistically quantization-equivalent ensemble models of the Dirac vacuum and non-trivial plasma backgrounds, the schemes are expected to have excellent performance in secular simulations of relativistic quantum effects, where the numerical errors of conserved quantities are well bounded by very small values without coherent accumulation. The algorithms are verified in detail by numerical energy spectra. Real-time LCFT simulations are successfully implemented for the nonlinear Schwinger mechanism induced e-e+ pairs creation and vacuum Kerr effect, where the nonlinear and non-perturbative features captured by the solutions provide a complete strong-field physical picture in a very wide range, which open a new door toward high-quality simulations in SFQED and RQP fields.

Immunosuppressant quantification in intravenous microdialysate – towards novel quasi-continuous therapeutic drug monitoring in transplanted patients

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Susanne Weber ◽  
Sara Tombelli ◽  
Ambra Giannetti ◽  
Cosimo Trono ◽  
Mark O’Connell ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Real Time ◽  
Drug Monitoring ◽  
Time Course ◽  
Drug Dosage ◽  
Immunosuppressive Drug ◽  
Therapeutic Drug ◽  
Continuous Sampling ◽  
Real Time Analysis ◽  
Drug Concentrations

AbstractObjectivesTherapeutic drug monitoring (TDM) plays a crucial role in personalized medicine. It helps clinicians to tailor drug dosage for optimized therapy through understanding the underlying complex pharmacokinetics and pharmacodynamics. Conventional, non-continuous TDM fails to provide real-time information, which is particularly important for the initial phase of immunosuppressant therapy, e.g., with cyclosporine (CsA) and mycophenolic acid (MPA).MethodsWe analyzed the time course over 8 h of total and free of immunosuppressive drug (CsA and MPA) concentrations measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 16 kidney transplant patients. Besides repeated blood sampling, intravenous microdialysis was used for continuous sampling. Free drug concentrations were determined from ultracentrifuged EDTA-plasma (UC) and compared with the drug concentrations in the respective microdialysate (µD). µDs were additionally analyzed for free CsA using a novel immunosensor chip integrated into a fluorescence detection platform. The potential of microdialysis coupled with an optical immunosensor for the TDM of immunosuppressants was assessed.ResultsUsing LC-MS/MS, the free concentrations of CsA (fCsA) and MPA (fMPA) were detectable and the time courses of total and free CsA comparable. fCsA and fMPA and area-under-the-curves (AUCs) in µDs correlated well with those determined in UCs (r≥0.79 and r≥0.88, respectively). Moreover, fCsA in µDs measured with the immunosensor correlated clearly with those determined by LC-MS/MS (r=0.82).ConclusionsThe new microdialysis-supported immunosensor allows real-time analysis of immunosuppressants and tailor-made dosing according to the AUC concept. It readily lends itself to future applications as minimally invasive and continuous near-patient TDM.

Low-Cost Measurement of Hydraulic Fracture Dimensions Using Pressure Data in Treatment and Observation Wells – A Workflow for Every Well

2021 ◽  
Author(s):  
A. Kirby Nicholson ◽  
Robert C. Bachman ◽  
R. Yvonne Scherz ◽  
Robert V. Hawkes
Keyword(s):  
Hydraulic Fracturing ◽  
Real Time ◽  
Hydraulic Fracture ◽  
Full Scale ◽  
Pressure Data ◽  
Observation Well ◽  
High Quality ◽  
Fracture Length ◽  
Geometry Model ◽  
Observation Wells

Abstract Pressure and stage volume are the least expensive and most readily available data for diagnostic analysis of hydraulic fracturing operations. Case history data from the Midland Basin is used to demonstrate how high-quality, time-synchronized pressure measurements at a treatment and an offsetting shut-in producing well can provide the necessary input to calculate fracture geometries at both wells and estimate perforation cluster efficiency at the treatment well. No special wellbore monitoring equipment is required. In summary, the methods outlined in this paper quantifies fracture geometries as compared to the more general observations of Daneshy (2020) and Haustveit et al. (2020). Pressures collected in Diagnostic Fracture Injection Tests (DFITs), select toe-stage full-scale fracture treatments, and offset observation wells are used to demonstrate a simple workflow. The pressure data combined with Volume to First Response (Vfr) at the observation well is used to create a geometry model of fracture length, width, and height estimates at the treatment well as illustrated in Figure 1. The producing fracture length of the observation well is also determined. Pressure Transient Analysis (PTA) techniques, a Perkins-Kern-Nordgren (PKN) fracture propagation model and offset well Fracture Driven Interaction (FDI) pressures are used to quantify hydraulic fracture dimensions. The PTA-derived Farfield Fracture Extension Pressure, FFEP, concept was introduced in Nicholson et al. (2019) and is summarized in Appendix B of this paper. FFEP replaces Instantaneous Shut-In Pressure, ISIP, for use in net pressure calculations. FFEP is determined and utilized in both DFITs and full-scale fracture inter-stage fall-off data. The use of the Primary Pressure Derivative (PPD) to accurately identify FFEP simplifies and speeds up the analysis, allowing for real time treatment decisions. This new technique is called Rapid-PTA. Additionally, the plotted shape and gradient of the observation-well pressure response can identify whether FDI's are hydraulic or poroelastic before a fracture stage is completed and may be used to change stage volume on the fly. Figure 1Fracture Geometry Model with FDI Pressure Matching Case studies are presented showing the full workflow required to generate the fracture geometry model. The component inputs for the model are presented including a toe-stage DFIT, inter-stage pressure fall-off, and the FDI pressure build-up. We discuss how to optimize these hydraulic fractures in hindsight (look-back) and what might have been done in real time during the completion operations given this workflow and field-ready advanced data-handling capability. Hydraulic fracturing operations can be optimized in real time using new Rapid-PTA techniques for high quality pressure data collected on treating and observation wells. This process opens the door for more advanced geometry modeling and for rapid design changes to save costs and improve well productivity and ultimate recovery.

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