Low-energy differential target multiplexed SCS derivative reduces pain and improves quality of life through 12 months in patients with chronic back and/or leg pain.

INTRODUCTION: Energy-reducing spinal cord stimulation (SCS) approaches have the potential to impact patient experience with rechargeable and non-rechargeable SCS devices through reducing device recharge time or enhancing device longevity. This prospective, multi-center study evaluated the safety, effectiveness, and actual energy usage of differential target multiplexed (DTM) endurance therapy, a reduced energy DTM SCS derivative. METHODS: Subjects who reported an overall pain visual analog score (VAS) of ≥6/10 cm and an Oswestry Disability Index score of 21-80 out of 100 at baseline with moderate to severe chronic, intractable back and/or leg pain were eligible. Evaluation visits occurred at 1, 3, 6, and 12 months post-device activation. The primary objective was to characterize change in overall pain intensity, as measured by VAS, from baseline to 3-month visit. RESULTS: Fifty-seven subjects enrolled at 12 US sites from November 2020 through June 2021, 35 were implanted with a rechargeable SCS device, and 27 completed the 12-month visit. Subjects experienced a 50.4% mean reduction in overall pain from baseline at the 3-month follow-up that was sustained through 12 months. Additional outcomes including changes in overall, back, and leg pain intensity, quality of life, disability, therapy satisfaction, safety, and current battery usage are shown through 12-month follow-up. CONCLUSION: The use of DTM endurance SCS therapy in this study resulted in reductions in pain relief through 12 months, demonstrating that energy-reducing stimulation patterns can provide clinical benefit. Clinically effective, reduced energy SCS derivatives have the potential to impact patient experience through either reduced recharge requirements or increased device longevity.

Visualizing the modulation of neurokinin 1 receptor-positive neurons in the superficial dorsal horn by spinal cord stimulation in vivo.

ABSTRACT: Spinal cord stimulation (SCS) is an effective modality for pain treatment, yet its underlying mechanisms remain elusive. Neurokinin 1 receptor-positive (NK1R+) neurons in spinal lamina I play a pivotal role in pain transmission. To enhance our mechanistic understanding of SCS-induced analgesia, we investigated how different SCS paradigms modulate the activation of NK1R+ neurons, by developing NK1R-Cre;GCaMP6s transgenic mice and using in vivo calcium imaging of superficial NK1R+ neurons under anesthesia (1.5% isoflurane). Neurokinin 1 receptor-positive neurons in the lumbar spinal cord (L4-5) showed a greater activation by electrical test stimulation (TS, 3.0 mA, 1 Hz) at the hindpaw at 2 weeks after tibia-sparing nerve injury (SNI-t) than in naïve mice. Spinal cord stimulation was then delivered through a bipolar plate electrode placed epidurally at L1-2 level. The short-term 50-Hz high-intensity SCS (80% motor threshold [MoT], 10 minutes) induced robust and prolonged inhibition of NK1R+ neuronal responses to TS in both naïve and SNI-t mice. The 30-minute 50-Hz and 900-Hz SCS applied at moderate intensity (50% MoT) also significantly inhibited neuronal responses in SNI-t mice. However, at low intensity (20% MoT), the 30-minute 900-Hz SCS only induced persistent neuronal inhibition in naïve mice, but not in SNI-t mice. In conclusion, both 10-minute high-intensity SCS and 30-minute SCS at moderate intensity inhibit the activation of superficial NK1R+ neurons, potentially attenuating spinal nociceptive transmission. Furthermore, in vivo calcium imaging of NK1R+ neurons provides a new approach for exploring the spinal neuronal mechanisms of pain inhibition by neuromodulation pain therapies.

Bidirectional Multiphoton Communication between Remote Superconducting Nodes.

Quantum communication test beds provide a useful resource for experimentally investigating a variety of communication protocols. Here we demonstrate a superconducting circuit test bed with bidirectional multiphoton state transfer capability using time-domain shaped wave packets. The system we use to achieve this comprises two remote nodes, each including a tunable superconducting transmon qubit and a tunable microwave-frequency resonator, linked by a 2 m-long superconducting coplanar waveguide, which serves as a transmission line. We transfer both individual and superposition Fock states between the two remote nodes, and additionally show that this bidirectional state transfer can be done simultaneously, as well as being used to entangle elements in the two nodes.

Distributed Quantum Error Correction for Chip-Level Catastrophic Errors.

Quantum error correction holds the key to scaling up quantum computers. Cosmic ray events severely impact the operation of a quantum computer by causing chip-level catastrophic errors, essentially erasing the information encoded in a chip. Here, we present a distributed error correction scheme to combat the devastating effect of such events by introducing an additional layer of quantum erasure error correcting code across separate chips. We show that our scheme is fault tolerant against chip-level catastrophic errors and discuss its experimental implementation using superconducting qubits with microwave links. Our analysis shows that in state-of-the-art experiments, it is possible to suppress the rate of these errors from 1 per 10 s to less than 1 per month.

Entanglement Purification and Protection in a Superconducting Quantum Network.

High-fidelity quantum entanglement is a key resource for quantum communication and distributed quantum computing, enabling quantum state teleportation, dense coding, and quantum encryption. Any sources of decoherence in the communication channel, however, degrade entanglement fidelity, thereby increasing the error rates of entangled state protocols. Entanglement purification provides a method to alleviate these nonidealities by distilling impure states into higher-fidelity entangled states. Here we demonstrate the entanglement purification of Bell pairs shared between two remote superconducting quantum nodes connected by a moderately lossy, 1-meter long superconducting communication cable. We use a purification process to correct the dominant amplitude damping errors caused by transmission through the cable, with fractional increases in fidelity as large as 25%, achieved for higher damping errors. The best final fidelity the purification achieves is 94.09±0.98%. In addition, we use both dynamical decoupling and Rabi driving to protect the entangled states from local noise, increasing the effective qubit dephasing time by a factor of 4, from 3 to 12 µs. These methods demonstrate the potential for the generation and preservation of very high-fidelity entanglement in a superconducting quantum communication network.

Deterministic multi-qubit entanglement in a quantum network.

The generation of high-fidelity distributed multi-qubit entanglement is a challenging task for large-scale quantum communication and computational networks1-4. The deterministic entanglement of two remote qubits has recently been demonstrated with both photons5-10 and phonons11. However, the deterministic generation and transmission of multi-qubit entanglement has not been demonstrated, primarily owing to limited state-transfer fidelities. Here we report a quantum network comprising two superconducting quantum nodes connected by a one-metre-long superconducting coaxial cable, where each node includes three interconnected qubits. By directly connecting the cable to one qubit in each node, we transfer quantum states between the nodes with a process fidelity of 0.911 ± 0.008. We also prepare a three-qubit Greenberger-Horne-Zeilinger (GHZ) state12-14 in one node and deterministically transfer this state to the other node, with a transferred-state fidelity of 0.656 ± 0.014. We further use this system to deterministically generate a globally distributed two-node, six-qubit GHZ state with a state fidelity of 0.722 ± 0.021. The GHZ state fidelities are clearly above the threshold of 1/2 for genuine multipartite entanglement15, showing that this architecture can be used to coherently link together multiple superconducting quantum processors, providing a modular approach for building large-scale quantum computers16,17.

Fast frequency discrimination and phoneme recognition using a biomimetic membrane coupled to a neural network.

In the human ear, the basilar membrane plays a central role in sound recognition. When excited by sound, this membrane responds with a frequency-dependent displacement pattern that is detected and identified by the auditory hair cells combined with the human neural system. Inspired by this structure, we designed and fabricated an artificial membrane that produces a spatial displacement pattern in response to an audible signal, which we used to train a convolutional neural network. When trained with single frequency tones, this system can unambiguously distinguish tones closely spaced in frequency. When instead trained to recognize spoken vowels, this system outperforms existing methods for phoneme recognition, including the discrete Fourier transform, zoom FFT and chirp z-transform, especially when tested in short time windows. This sound recognition scheme therefore promises significant benefits in fast and accurate sound identification compared to existing methods.

A simple microfluidic aggregation analyzer for the specific, sensitive and multiplexed quantification of proteins in a serum environment.

Portable and low-cost platforms for protein biomarker detection are highly sought after for point of care applications. We demonstrate a simple microfluidic device for the rapid, electrically-based detection of proteins in serum. Our aggregation analyzer relies on detecting the protein-induced aggregation of sub-micron particles, using a one-step procedure followed by a fast, particle-by-particle measurement with a very high count rate. This enables the rapid and precise quantification of C-Reactive protein levels, within the clinically relevant range, using unprocessed human serum and a disposable microfluidic device; no optics are involved in the implementation. Due to the single particle detection format and the use of microfluidics, only a small volume of serum (~50 nL) is needed to complete the analysis. The method can be easily extended to multiplexed biomarker detection by combining an assay using differently sized particles, each targeting a separate protein. We illustrate this by using two sizes of latex beads and demonstrating the simultaneous detection of two different proteins in a serum environment with minimal cross-interference. This confirms that our aggregation analyzer platform provides a simple and straightforward method for multiplexed biomarker detection in a low cost, portable design.

Salvaging catastrophe in transcatheter aortic valve implantation: rehearsal, preassigned roles, and emergency preparedness.

PURPOSE: Emergency rescue plans for acute complications during transcatheter aortic valve implantation (TAVI) commonly include cardiopulmonary resuscitation, femoro-femoral cardiopulmonary bypass (CPB), and hemodynamic stabilization before definitive intervention is achieved. Nevertheless, most cases of emergency resuscitation remain chaotic and disorganized and often take longer than necessary, even in experienced centres. We sought to determine which factors and procedures may be associated with improved patient outcomes when emergencies arise during TAVI. SOURCES: MEDLINE(®) and EMBASE™ were searched with the following key words: "TAVI" or "TAVR" or "transcatheter valve implantation" or "transcatheter valve replacement" and "emergency cardiac surgery" or "conversion". Two hundred seventeen articles met the criteria and were reviewed. PRINCIPAL FINDINGS: Utilization of a formal emergency checklist by a multidisciplinary TAVI team may reduce procedural errors, smooth the transition to CPB, and ultimately speed the delivery of corrective measures including emergency cardiac surgery. CONCLUSION: A well-organized regularly-rehearsed emergency rescue plan that preassigns resuscitative roles may shorten the duration of patient instability and resuscitation and improve patient outcomes when catastrophe occurs in TAVI. The anesthesia team plays a central role in preventing, detecting, and treating intraprocedural complications during TAVI.

High-speed discrimination and sorting of submicron particles using a microfluidic device.

The size- and fluorescence-based sorting of micro- and nanoscale particles suspended in fluid presents a significant and important challenge for both sample analysis and for manufacturing of nanoparticle-based products. Here, we demonstrate a disposable microfluidic particle sorter that enables high-throughput, on-demand counting and binary sorting of submicron particles and cells using either fluorescence or an electrically based determination of particle size. Size-based sorting uses a resistive pulse sensor integrated on-chip, whereas fluorescence-based discrimination is achieved using on-the-fly optical image capture and analysis. Following detection and analysis, the individual particles are deflected using a pair of piezoelectric actuators, directing the particles into one of two desired output channels; the main flow goes into a third waste channel. The integrated system can achieve sorting fidelities of better than 98%, and the mechanism can successfully count and actuate, on demand, more than 60,000 particles/min.

Percutaneous superior vena cava drainage during minimally invasive mitral valve surgery: a randomized, crossover study.

OBJECTIVE: Minimally invasive techniques commonly are applied to mitral valve surgery; however, there has been little research investigating the optimal methods of cardiopulmonary bypass for the right minithoracotomy approach. Controversy exists as to whether a percutaneous superior vena cava drainage cannula (PSVC) is necessary during these operations. The authors, therefore, sought to determine the effect of using a percutaneous superior vena cava catheter on brain near-infrared spectroscopy, blood lactate levels, hemodynamics and surgical parameters. DESIGN: Randomized, blinded, crossover trial. SETTING: Tertiary care university hospital. PARTICIPANTS: Patients undergoing minimally invasive mitral valve surgery via a right minithoracotomy. INTERVENTIONS: Twenty minutes of either clamped or unclamped percutaneous superior vena cava neck catheter drainage, during mitral valve repair. MEASUREMENT AND MAIN RESULTS: For the primary outcome of brain near-infrared spectroscopy, there were no differences between the two groups (percutaneous superior vena cava clamped 55.0%±11.6% versus unclamped 56.1%±10.2%) (p = 0.283). For the secondary outcomes pH (clamped 7.35±0.05 versus unclamped 7.37±0.05 p = 0.015), surgical score (clamped 1.96±1.14 versus unclamped 1.22±0.51 p = 0.002) and CVP (clamped 11.6 mmHg±4.8 mmHg versus unclamped 6.1 mmHg±6.1 mmHg p<0.001) were significantly different. CONCLUSIONS: The use of a percutaneous superior vena cava drainage improved surgical visualization and lowered CVP, but had no effect on brain near infrared spectroscopy during minimally invasive mitral valve surgery. (ClinicalTrials.gov Identifier: NCT01166841).

Electron spin resonance of nitrogen-vacancy centers in optically trapped nanodiamonds.

Using an optical tweezers apparatus, we demonstrate three-dimensional control of nanodiamonds in solution with simultaneous readout of ground-state electron-spin resonance (ESR) transitions in an ensemble of diamond nitrogen-vacancy color centers. Despite the motion and random orientation of nitrogen-vacancy centers suspended in the optical trap, we observe distinct peaks in the measured ESR spectra qualitatively similar to the same measurement in bulk. Accounting for the random dynamics, we model the ESR spectra observed in an externally applied magnetic field to enable dc magnetometry in solution. We estimate the dc magnetic field sensitivity based on variations in ESR line shapes to be approximately 50 µT/√Hz. This technique may provide a pathway for spin-based magnetic, electric, and thermal sensing in fluidic environments and biophysical systems inaccessible to existing scanning probe techniques.

The early inflammatory response in a mini-cardiopulmonary bypass system: a prospective randomized study.

OBJECTIVE: The aim of this study was to compare the early systemic inflammatory response of the Resting Heart System (RHS; Medtronic, Minneapolis, MN USA), a miniaturized cardiopulmonary bypass (CPB) system, with two groups using a standard extracorporeal circulation system during on-pump coronary artery bypass grafting (CABG) surgery. METHODS: A total of 60 consecutive patients requiring CABG were prospectively randomized to undergo on-pump CABG using conventional CPB without cardiotomy suction (group A), conventional CPB with cardiotomy suction (group B), or the RHS (group C). Blood samples were collected at five time points: immediately before CPB, 30 minutes into CPB, immediately at the end of CPB, 30 minutes post-CPB, and 1 hour post-CPB. Inflammation was analyzed by changes in (a) levels of plasma proteins, including inflammatory cytokines (interleukin-6 [IL-6], IL-10, and tumor necrosis factor-α), chemokines (IL-8, monokine induced by interferon-γ, monocyte chemotactic protein-1, regulated on activation normal T cell expressed and secreted, and interferon-inducible protein-10), and acute phase proteins (C-reactive protein and complement protein 3); (b) biochemical variables (cardiac troponin I, hematocrit, and immunoglobulin G); and (c) cell numbers (leukocytes, neutrophils, and thrombocytes). RESULTS: The RHS showed more delayed secretion of the cytokines tumor necrosis factor-α and IL-10, chemokines monokine induced by interferon-γ (P < 0.001); IL-8, and interferon-inducible protein-10; and complement protein 3 than conventional CPB systems did. Median thrombocyte numbers were higher in the RHS group. Levels of cardiac troponin I, monocyte chemotactic protein-1, and IL-6 were lower in both the RHS and conventional CPB without suction than with suction. Levels of C-reactive protein and regulated on activation normal T cell expressed and secreted, plus leukocyte and neutrophil numbers, were similar in all groups. CONCLUSIONS: The Medtronic RHS may induce less systemic inflammation than conventional CPB systems, particularly when cardiotomy suction was used, but it did not result in improved clinical benefit.

Strain-promoted "click" chemistry for terminal labeling of DNA.

1,3-Dipolar [3 + 2] cycloaddition between azides and alkynes--an archetypal "click" chemistry--has been used increasingly for the functionalization of nucleic acids. Copper(I)-catalyzed 1,3-dipolar cycloaddition reactions between alkyne-tagged DNA molecules and azides work well, but they require optimization of multiple reagents, and Cu ions are known to mediate DNA cleavage. For many applications, it would be preferable to eliminate the Cu(I) catalyst from these reactions. Here, we describe the solid-phase synthesis and characterization of 5'-dibenzocyclooctyne (DIBO)-modified oligonucleotides, using a new DIBO phosphoramidite, which react with azides via copper-free, strain-promoted alkyne-azide cycloaddition (SPAAC). We found that the DIBO group not only survived the standard acidic and oxidative reactions of solid-phase oligonucleotide synthesis (SPOS), but that it also survived the thermal cycling and standard conditions of the polymerase chain reaction (PCR). As a result, PCR with DIBO-modified primers yielded "clickable" amplicons that could be tagged with azide-modified fluorophores or immobilized on azide-modified surfaces. Given its simplicity, SPAAC on DNA could streamline the bioconjugate chemistry of nucleic acids in a number of modern biotechnologies.

A high-throughput label-free nanoparticle analyser.

Synthetic nanoparticles and genetically modified viruses are used in a range of applications, but high-throughput analytical tools for the physical characterization of these objects are needed. Here we present a microfluidic analyser that detects individual nanoparticles and characterizes complex, unlabelled nanoparticle suspensions. We demonstrate the detection, concentration analysis and sizing of individual synthetic nanoparticles in a multicomponent mixture with sufficient throughput to analyse 500,000 particles per second. We also report the rapid size and titre analysis of unlabelled bacteriophage T7 in both salt solution and mouse blood plasma, using just ~1 × 10⁻6 l of analyte. Unexpectedly, in the native blood plasma we discover a large background of naturally occurring nanoparticles with a power-law size distribution. The high-throughput detection capability, scalable fabrication and simple electronics of this instrument make it well suited for diverse applications.

Emulation of a quantum spin with a superconducting phase qudit.

In quantum information processing, qudits (d-level systems) are an extension of qubits that could speed up certain computing tasks. We demonstrate the operation of a superconducting phase qudit with a number of levels d up to d = 5 and show how to manipulate and measure the qudit state, including simultaneous control of multiple transitions. We used the qudit to emulate the dynamics of single spins with principal quantum number s = 1/2, 1, and 3/2, allowing a measurement of Berry's phase and the even parity of integer spins (and odd parity of half-integer spins) under 2pi-rotation. This extension of the two-level qubit to a multilevel qudit holds promise for more-complex quantum computational architectures and for richer simulations of quantum mechanical systems.

Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective study.

BACKGROUND: Cerebral deoxygenation is associated with various adverse systemic outcomes. We hypothesized, by using the brain as an index organ, that interventions to improve cerebral oxygenation would have systemic benefits in cardiac surgical patients. METHODS: Two-hundred coronary artery bypass patients were randomized to either intraoperative cerebral regional oxygen saturation (rSO2) monitoring with active display and treatment intervention protocol (intervention, n = 100), or underwent blinded rSO2 monitoring (control, n = 100). Predefined clinical outcomes were assessed by a blinded observer. RESULTS: Significantly more patients in the control group demonstrated prolonged cerebral desaturation (P = 0.014) and longer duration in the intensive care unit (P = 0.029) versus intervention patients. There was no difference in overall incidence of adverse complications, but significantly more control patients had major organ morbidity or mortality (death, ventilation >48 h, stroke, myocardial infarction, return for re-exploration) versus intervention group patients (P = 0.048). Patients experiencing major organ morbidity or mortality had lower baseline and mean rSO2, more cerebral desaturations and longer lengths of stay in the intensive care unit and postoperative hospitalization, than patients without such complications. There was a significant (r(2) = 0.29) inverse correlation between intraoperative rSO2 and duration of postoperative hospitalization in patients requiring > or =10 days postoperative length of stay. CONCLUSION: Monitoring cerebral rSO2 in coronary artery bypass patients avoids profound cerebral desaturation and is associated with significantly fewer incidences of major organ dysfunction.

Nanometre-scale displacement sensing using a single electron transistor.

It has been a long-standing goal to detect the effects of quantum mechanics on a macroscopic mechanical oscillator. Position measurements of an oscillator are ultimately limited by quantum mechanics, where 'zero-point motion' fluctuations in the quantum ground state combine with the uncertainty relation to yield a lower limit on the measured average displacement. Development of a position transducer, integrated with a mechanical resonator, that can approach this limit could have important applications in the detection of very weak forces, for example in magnetic resonance force microscopy and a variety of other precision experiments. One implementation that might allow near quantum-limited sensitivity is to use a single electron transistor (SET) as a displacement sensor: the exquisite charge sensitivity of the SET at cryogenic temperatures is exploited to measure motion by capacitively coupling it to the mechanical resonator. Here we present the experimental realization of such a device, yielding an unequalled displacement sensitivity of 2 x 10(-15) m x Hz(-1/2) for a 116-MHz mechanical oscillator at a temperature of 30 mK-a sensitivity roughly a factor of 100 larger than the quantum limit for this oscillator.