Sleep and motor learning in stroke (SMiLES): a longitudinal study investigating sleep-dependent consolidation of motor sequence learning in the context of recovery after stroke.

INTRODUCTION: There is growing evidence that sleep is disrupted after stroke, with worse sleep relating to poorer motor outcomes. It is also widely acknowledged that consolidation of motor learning, a critical component of poststroke recovery, is sleep-dependent. However, whether the relationship between disrupted sleep and poor outcomes after stroke is related to direct interference of sleep-dependent motor consolidation processes, is currently unknown. Therefore, the aim of the present study is to understand whether measures of motor consolidation mediate the relationship between sleep and clinical motor outcomes post stroke. METHODS AND ANALYSIS: We will conduct a longitudinal observational study of up to 150 participants diagnosed with stroke affecting the upper limb. Participants will be recruited and assessed within 7 days of their stroke and followed up at approximately 1 and 6 months. The primary objective of the study is to determine whether sleep in the subacute phase of recovery explains the variability in upper limb motor outcomes after stroke (over and above predicted recovery potential from the Predict Recovery Potential algorithm) and whether this relationship is dependent on consolidation of motor learning. We will also test whether motor consolidation mediates the relationship between sleep and whole-body clinical motor outcomes, whether motor consolidation is associated with specific electrophysiological sleep signals and sleep alterations during subacute recovery. ETHICS AND DISSEMINATION: This trial has received both Health Research Authority, Health and Care Research Wales and National Research Ethics Service approval (IRAS: 304135; REC: 22/LO/0353). The results of this trial will help to enhance our understanding of the role of sleep in recovery of motor function after stroke and will be disseminated via presentations at scientific conferences, peer-reviewed publication, public engagement events, stakeholder organisations and other forms of media where appropriate. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05746260, registered on 27 February 2023.

Quantum-Enhanced Magnetometry at Optimal Number Density.

We study the use of squeezed probe light and evasion of measurement backaction to enhance the sensitivity and measurement bandwidth of an optically pumped magnetometer (OPM) at sensitivity-optimal atom number density. By experimental observation, and in agreement with quantum noise modeling, a spin-exchange-limited OPM probed with off-resonance laser light is shown to have an optimal sensitivity determined by density-dependent quantum noise contributions. Application of squeezed probe light boosts the OPM sensitivity beyond this laser-light optimum, allowing the OPM to achieve sensitivities that it cannot reach with coherent-state probing at any density. The observed quantum sensitivity enhancement at optimal number density is enabled by measurement backaction evasion.

Loophole-free Bell inequality violation with superconducting circuits.

Superposition, entanglement and non-locality constitute fundamental features of quantum physics. The fact that quantum physics does not follow the principle of local causality1-3 can be experimentally demonstrated in Bell tests4 performed on pairs of spatially separated, entangled quantum systems. Although Bell tests, which are widely regarded as a litmus test of quantum physics, have been explored using a broad range of quantum systems over the past 50 years, only relatively recently have experiments free of so-called loopholes5 succeeded. Such experiments have been performed with spins in nitrogen-vacancy centres6, optical photons7-9 and neutral atoms10. Here we demonstrate a loophole-free violation of Bell's inequality with superconducting circuits, which are a prime contender for realizing quantum computing technology11. To evaluate a Clauser-Horne-Shimony-Holt-type Bell inequality4, we deterministically entangle a pair of qubits12 and perform fast and high-fidelity measurements13 along randomly chosen bases on the qubits connected through a cryogenic link14 spanning a distance of 30 metres. Evaluating more than 1 million experimental trials, we find an average S value of 2.0747 ± 0.0033, violating Bell's inequality with a P value smaller than 10-108. Our work demonstrates that non-locality is a viable new resource in quantum information technology realized with superconducting circuits with potential applications in quantum communication, quantum computing and fundamental physics15.

Real-Time Polarimetry of Hyperpolarized 13C Nuclear Spins Using an Atomic Magnetometer.

We introduce a method for nondestructive quantification of nuclear spin polarization, of relevance to hyperpolarized spin tracers widely used in magnetic resonance from spectroscopy to in vivo imaging. In a bias field of around 30 nT we use a high-sensitivity miniaturized 87Rb-vapor magnetometer to measure the field generated by the sample, as it is driven by a windowed dynamical decoupling pulse sequence that both maximizes the nuclear spin lifetime and modulates the polarization for easy detection. We demonstrate the procedure applied to a 0.08 M hyperpolarized [1-13C]-pyruvate solution produced by dissolution dynamic nuclear polarization, measuring polarization repeatedly during natural decay at Earth's field. Application to real-time and continuous quality monitoring of hyperpolarized substances is discussed.

MorpheusNet: Resource efficient sleep stage classifier for embedded on-line systems.

Sleep Stage Classification (SSC) is a labor-intensive task, requiring experts to examine hours of electrophysiological recordings for manual classification. This is a limiting factor when it comes to leveraging sleep stages for therapeutic purposes. With increasing affordability and expansion of wearable devices, automating SSC may enable deployment of sleep-based therapies at scale. Deep Learning has gained increasing attention as a potential method to automate this process. Previous research has shown accuracy comparable to manual expert scores. However, previous approaches require sizable amount of memory and computational resources. This constrains the ability to classify in real time and deploy models on the edge. To address this gap, we aim to provide a model capable of predicting sleep stages in real-time, without requiring access to external computational sources (e.g., mobile phone, cloud). The algorithm is power efficient to enable use on embedded battery powered systems. Our compact sleep stage classifier can be deployed on most off-the-shelf microcontrollers (MCU) with constrained hardware settings. This is due to the memory footprint of our approach requiring significantly fewer operations. The model was tested on three publicly available data bases and achieved performance comparable to the state of the art, whilst reducing model complexity by orders of magnitude (up to 280 times smaller compared to state of the art). We further optimized the model with quantization of parameters to 8 bits with only an average drop of 0.95% in accuracy. When implemented in firmware, the quantized model achieves a latency of 1.6 seconds on an Arm Cortex-M4 processor, allowing its use for on-line SSC-based therapies.

Laser-written vapor cells for chip-scale atomic sensing and spectroscopy.

We report the fabrication of alkali-metal vapor cells using femtosecond laser machining. This laser-written vapor-cell (LWVC) technology allows arbitrarily-shaped 3D interior volumes and has potential for integration with photonic structures and optical components. We use non-evaporable getters both to dispense rubidium and to absorb buffer gas. This enables us to produce cells with sub-atmospheric buffer gas pressures without vacuum apparatus. We demonstrate sub-Doppler saturated absorption spectroscopy and single beam optical magnetometry with a single LWVC. The LWVC technology may find application in miniaturized atomic quantum sensors and frequency references.

Improving Short-Term Stability in Optical Lattice Clocks by Quantum Nondemolition Measurement.

We propose a multimeasurement estimation protocol for quantum nondemolition (QND) measurements in a Rabi clock interferometer. The method is well suited for current state-of-the-art optical lattice clocks with QND measurement capabilities. The protocol exploits the correlations between multiple nondestructive measurements of the initially prepared coherent spin state. A suitable Gaussian estimator for the clock laser detuning is presented, and an analytic expression for the sensitivity of the protocol is derived. We use this analytic expression to optimize the protocol using available experimental parameters, achieving an improvement of 7.9 dB with respect to the standard quantum limit in terms of clock stability. We also discuss the measurement back-action effects of our protocol into the atomic state.

Single-domain Bose condensate magnetometer achieves energy resolution per bandwidth below ℏ.

We present a magnetic sensor with energy resolution per bandwidth [Formula: see text] We show how a 87Rb single-domain spinor Bose-Einstein condensate, detected by nondestructive Faraday rotation probing, achieves single-shot low-frequency magnetic sensitivity of 72(8) fT measuring a volume [Formula: see text] for 3.5 s, and thus, [Formula: see text] We measure experimentally the condensate volume, spin coherence time, and readout noise and use phase space methods, backed by three-dimensional mean-field simulations, to compute the spin noise. Contributions to the spin noise include one-body and three-body losses and shearing of the projection noise distribution, due to competition of ferromagnetic contact interactions and quadratic Zeeman shifts. Nonetheless, the fully coherent nature of the single-domain, ultracold two-body interactions allows the system to escape the coherence vs. density trade-off that imposes an energy resolution limit on traditional spin precession sensors. We predict that other Bose-condensed alkalis, especially the antiferromagnetic 23Na, can further improve the energy resolution of this method.

SU(2)-in-SU(1,1) Nested Interferometer for High Sensitivity, Loss-Tolerant Quantum Metrology.

We present experimental and theoretical results on a new interferometer topology that nests a SU(2) interferometer, e.g., a Mach-Zehnder or Michelson interferometer, inside a SU(1,1) interferometer, i.e., a Mach-Zehnder interferometer with parametric amplifiers in place of beam splitters. This SU(2)-in-SU(1,1) nested interferometer (SISNI) simultaneously achieves a high signal-to-noise ratio (SNR), sensitivity beyond the standard quantum limit (SQL) and tolerance to photon losses external to the interferometer, e.g., in detectors. We implement a SISNI using parametric amplification by four-wave mixing (FWM) in Rb vapor and a laser-fed Mach-Zehnder SU(2) interferometer. We observe path-length sensitivity with SNR 2.2 dB beyond the SQL at power levels (and thus SNR) 2 orders of magnitude beyond those of previous loss-tolerant interferometers. We find experimentally the optimal FWM gains and find agreement with a minimal quantum noise model for the FWM process. The results suggest ways to boost the in-practice sensitivity of high-power interferometers, e.g., gravitational wave interferometers, and may enable high-sensitivity, quantum-enhanced interferometry at wavelengths for which efficient detectors are not available.

Decoupling of Spin Decoherence Paths near Zero Magnetic Field.

We demonstrate a method to quantify and manipulate nuclear spin decoherence mechanisms that are active in zero to ultralow magnetic fields. These include (i) nonadiabatic switching of spin quantization axis due to residual background fields and (ii) scalar pathways due to through-bond couplings between 1H and heteronuclear spin species, such as 2H used partially as an isotopic substitute for 1H. Under conditions of free evolution, scalar relaxation due to 2H can significantly limit nuclear spin polarization lifetimes and thus the scope of magnetic resonance procedures near zero field. It is shown that robust trains of pulsed dc magnetic fields that apply π flip angles to one or multiple spin species may switch the effective symmetry of the nuclear spin Hamiltonian, imposing decoupled or coupled dynamic regimes on demand. The method should broaden the spectrum of hyperpolarized biomedical contrast-agent compounds and hyperpolarization procedures that are used near zero field.

Autoheterodyne Characterization of Narrow-Band Photon Pairs.

We describe a technique to measure photon pair joint spectra by detecting the time-correlation beat note when nondegenerate photon pairs interfere at a beam splitter. The technique implements a temporal analog of the Ghosh-Mandel effect with one photon counter and a time-resolved Hong-Ou-Mandel interference with two. It is well suited to characterize pairs of photons, each of which can interact with a single atomic species, as required to study recently predicted photon-photon interaction in subwavelength atomic arrays. With this technique, we characterize photon pairs from cavity-enhanced parametric down-conversion with a bandwidth ≈ 5 MHz and frequency separation of ∼200 MHz near the D_{1} line of atomic Rb.

Fast-field-cycling ultralow-field nuclear magnetic relaxation dispersion.

Optically pumped magnetometers (OPMs) based on alkali-atom vapors are ultra-sensitive devices for dc and low-frequency ac magnetic measurements. Here, in combination with fast-field-cycling hardware and high-resolution spectroscopic detection, we demonstrate applicability of OPMs in quantifying nuclear magnetic relaxation phenomena. Relaxation rate dispersion across the nT to mT field range enables quantitative investigation of extremely slow molecular motion correlations in the liquid state, with time constants > 1 ms, and insight into the corresponding relaxation mechanisms. The 10-20 fT/[Formula: see text] sensitivity of an OPM between 10 Hz and 5.5 kHz 1H Larmor frequency suffices to detect magnetic resonance signals from ~ 0.1 mL liquid volumes imbibed in simple mesoporous materials, or inside metal tubing, following nuclear spin prepolarization adjacent to the OPM. High-resolution spectroscopic detection can resolve inter-nucleus spin-spin couplings, further widening the scope of application to chemical systems. Expected limits of the technique regarding measurement of relaxation rates above 100 s-1 are discussed.

Three-Dimensionally Printed Skin Substitute Using Human Dermal Fibroblasts and Human Epidermal Keratinocytes.

INTRODUCTION: Wound healing affects millions of people annually. After injury, keratinocytes from the wound edge proliferate, migrate, and differentiate to recapitulate the 3-dimensional (3D) structure needed to provide a barrier function. If the wound is too large, skin grafting may be required. We are interested in discovering novel strategies to enhance the wound healing process. It may be possible to recreate a viable and histologically accurate skin tissue using 3D printing. We hypothesize that keratinocytes and dermal fibroblasts can be bioprinted into a viable skin substitute. METHODS: Adult human dermal fibroblasts (HDFa) and adult human epidermal keratinocytes (HEKa) were cultured and subsequently printed with a 3D bioprinter within a hydrogel scaffold. After printing the HDFa and HEKa separately, cell viability and histological appearance were determined by sectioning the printed tissue and performing hematoxylin and eosin staining. The stained histological sections were analyzed for tissue morphology. RESULTS: The HEKa and HDFa cells suspended in the hydrogel were successfully printed into 3D scaffolds that resembled skin with hematoxylin and eosin staining. CONCLUSIONS: The HEKa and HDFa cells can be grown on 3D-printed hydrogels successfully. In addition, HEKa and HDFa cells can survive and grow when suspended in a hydrogel and 3D printed. Future potential applications of these results could lead to the creation of viable skin tissue for wound healing and surgical repair.

Manipulating and measuring single atoms in the Maltese cross geometry.

Background: Optical microtraps at the focus of high numerical aperture (high-NA) imaging systems enable efficient collection, trapping, detection and manipulation of individual neutral atoms for quantum technology and studies of optical physics associated with super- and sub-radiant states.  The recently developed "Maltese cross" geometry (MCG) atom trap uses four in-vacuum lenses to achieve four-directional high-NA optical coupling to single trapped atoms and small atomic arrays. This article presents the first extensive characterisation of atomic behaviour in a MCG atom trap. Methods: We employ a MCG system optimised for high coupling efficiency and characterise the resulting properties of the trap and trapped atoms.  Using current best practices, we measure occupancy, loading rate, lifetime, temperature, fluorescence anti-bunching and trap frequencies. We also use the four-directional access to implement a new method to map the spatial distribution of collection efficiency from high-NA optics:  we use the two on-trap-axis lenses to produce a 1D optical lattice, the sites of which are stochastically filled and emptied by the trap loading process. The two off-trap-axis lenses are used for imaging and single-mode collection.  Correlations of single-mode and imaging fluorescence signals are then used to map the single-mode collection efficiency. Results: We observe trap characteristics comparable to what has been reported for single-atom traps with one- or two-lens optical systems. The collection efficiency distribution in the axial and transverse directions is directly observed to be in agreement with expected collection efficiency distribution from Gaussian beam optics. Conclusions: The multi-directional high-NA access provided by the Maltese cross geometry enables complex manipulations and measurements not possible in geometries  with fewer  directions of  access,  and can  be  achieved  while  preserving other trap characteristics such as lifetime, temperature, and trap size.

Measurement-induced, spatially-extended entanglement in a hot, strongly-interacting atomic system.

Quantum technologies use entanglement to outperform classical technologies, and often employ strong cooling and isolation to protect entangled entities from decoherence by random interactions. Here we show that the opposite strategy-promoting random interactions-can help generate and preserve entanglement. We use optical quantum non-demolition measurement to produce entanglement in a hot alkali vapor, in a regime dominated by random spin-exchange collisions. We use Bayesian statistics and spin-squeezing inequalities to show that at least 1.52(4) × 1013 of the 5.32(12) × 1013 participating atoms enter into singlet-type entangled states, which persist for tens of spin-thermalization times and span thousands of times the nearest-neighbor distance. The results show that high temperatures and strong random interactions need not destroy many-body quantum coherence, that collective measurement can produce very complex entangled states, and that the hot, strongly-interacting media now in use for extreme atomic sensing are well suited for sensing beyond the standard quantum limit.

Bose-Einstein Condensate Comagnetometer.

We describe a comagnetometer employing the f=1 and f=2 ground state hyperfine manifolds of a ^{87}Rb spinor Bose-Einstein condensate as colocated magnetometers. The hyperfine manifolds feature nearly opposite gyromagnetic ratios and thus the sum of their precession angles is only weakly coupled to external magnetic fields, while being highly sensitive to any effect that rotates both manifolds in the same way. The f=1 and f=2 transverse magnetizations and azimuth angles are independently measured by nondestructive Faraday rotation probing, and we demonstrate a 44.0(8) dB common-mode rejection in good agreement with theory. We show how the magnetometer coherence time can be extended to ∼1 s, by using spin-dependent interactions to inhibit hyperfine relaxing collisions between f=2 atoms. The technique could be used in high sensitivity searches for new physics on submillimeter length scales, precision studies of ultracold collision physics, and angle-resolved studies of quantum spin dynamics.

Experimental Low-Latency Device-Independent Quantum Randomness.

Applications of randomness such as private key generation and public randomness beacons require small blocks of certified random bits on demand. Device-independent quantum random number generators can produce such random bits, but existing quantum-proof protocols and loophole-free implementations suffer from high latency, requiring many hours to produce any random bits. We demonstrate device-independent quantum randomness generation from a loophole-free Bell test with a more efficient quantum-proof protocol, obtaining multiple blocks of 512 random bits with an average experiment time of less than 5 min per block and with a certified error bounded by 2^{-64}≈5.42×10^{-20}.

Narrowband photon pairs with independent frequency tuning for quantum light-matter interactions.

We describe a cavity-enhanced spontaneous parametric down-conversion (CE-SPDC) source for narrowband photon pairs with filters designed such that 97.7% of the correlated photons are in a single mode of 4.3(4) MHz bandwidth. Type-II phase matching, a tuneable-birefringence resonator, MHz-resolution pump tuning, and tuneable Fabry-Perot filters are used to achieve independent signal and idler tuning. We map the CE-SPDC spectrum using difference frequency generation to precisely locate the emission clusters, demonstrate CE-SPDC driven atomic spectroscopy, and measure a contribution from unwanted modes of 7.7%. The generated photon pairs efficiently interact with neutral rubidium, a well-developed system for quantum networking and quantum simulation. The techniques are readily extensible to other material systems.

Maltese cross coupling to individual cold atoms in free space.

We report on the simultaneous observation from four directions of the fluorescence of single 87Rb atoms trapped at the common focus of four high numerical aperture (NA=0.5) aspheric lenses. We use an interferometrically-guided pick-and-place technique to precisely and stably position the lenses along the four cardinal directions with their foci at a single central point. The geometry gives right angle access to a single quantum emitter, and will enable new trapping, excitation, and collection methods. The fluorescence signals indicate both sub-Poissonian atom number statistics and photon anti-bunching, showing suitability for cold atom quantum optics.

Signal Tracking Beyond the Time Resolution of an Atomic Sensor by Kalman Filtering.

We study causal waveform estimation (tracking) of time-varying signals in a paradigmatic atomic sensor, an alkali vapor monitored by Faraday rotation probing. We use Kalman filtering, which optimally tracks known linear Gaussian stochastic processes, to estimate stochastic input signals that we generate by optical pumping. Comparing the known input to the estimates, we confirm the accuracy of the atomic statistical model and the reliability of the Kalman filter, allowing recovery of waveform details far briefer than the sensor's intrinsic time resolution. With proper filter choice, we obtain similar benefits when tracking partially known and non-Gaussian signal processes, as are found in most practical sensing applications. The method evades the trade-off between sensitivity and time resolution in coherent sensing.