Pediatric hemolysis in emergency departments: Prevalence, risk factors, and clinical implications.

OBJECTIVE: This study aimed to analyze the prevalence, risk factors, and clinical implications of hemolyzed laboratory samples in the pediatric emergency department (ED), a subject on which existing data remains scarce. METHODS: We conducted a multi-site observational cohort analysis of pediatric ED encounters in Metro Detroit, Michigan, United States. The study included participants below 18 years of age who had undergone peripheral intravenous catheter (PIVC) placement and laboratory testing. The primary outcome was the presence of hemolysis, and secondary outcomes included identifying risk factors for hemolysis and assessing the impact of hemolysis on PIVC failure. RESULTS: Between January 2021 and May 2022, 10,462 ED encounters met inclusion criteria, of which 14.0% showed laboratory evidence of hemolysis. The highest proportion of hemolysis occurred in the infant (age 0-1) population (20.1%). Multivariable regression analysis indicated higher odds of hemolysis for PIVCs placed in the hand/wrist in the toddler (age 2-5) and child (age 6-11) subgroups. PIVCs placed in the hand/wrist also demonstrated higher odds of failure in infants. CONCLUSIONS: Hemolysis in the pediatric ED population is a frequent complication that occurs at similar rates as in adults. PIVCs placed in the hand/wrist were associated with higher odds of hemolysis compared to those placed in the antecubital fossa. Clinicians should consider alternative locations for PIVC placement if clinically appropriate. Further research is needed to better understand the clinical implications of pediatric hemolysis.

Enhancement of mediodorsal thalamus rescues aberrant belief dynamics in a mouse model with schizophrenia-associated mutation.

Optimizing behavioral strategy requires belief updating based on new evidence, a process that engages higher cognition. In schizophrenia, aberrant belief dynamics may lead to psychosis, but the mechanisms underlying this process are unknown, in part, due to lack of appropriate animal models and behavior readouts. Here, we address this challenge by taking two synergistic approaches. First, we generate a mouse model bearing patient-derived point mutation in Grin2a (Grin2aY700X+/-), a gene that confers high-risk for schizophrenia and recently identified by large-scale exome sequencing. Second, we develop a computationally trackable foraging task, in which mice form and update belief-driven strategies in a dynamic environment. We found that Grin2aY700X+/- mice perform less optimally than their wild-type (WT) littermates, showing unstable behavioral states and a slower belief update rate. Using functional ultrasound imaging, we identified the mediodorsal (MD) thalamus as hypofunctional in Grin2aY700X+/- mice, and in vivo task recordings showed that MD neurons encoded dynamic values and behavioral states in WT mice. Optogenetic inhibition of MD neurons in WT mice phenocopied Grin2aY700X+/- mice, and enhancing MD activity rescued task deficits in Grin2aY700X+/- mice. Together, our study identifies the MD thalamus as a key node for schizophrenia-relevant cognitive dysfunction, and a potential target for future therapeutics.

Microstimulation of human somatosensory cortex evokes task-dependent, spatially patterned responses in motor cortex.

The primary motor (M1) and somatosensory (S1) cortices play critical roles in motor control but the signaling between these structures is poorly understood. To fill this gap, we recorded - in three participants in an ongoing human clinical trial (NCT01894802) for people with paralyzed hands - the responses evoked in the hand and arm representations of M1 during intracortical microstimulation (ICMS) in the hand representation of S1. We found that ICMS of S1 activated some M1 neurons at short, fixed latencies consistent with monosynaptic activation. Additionally, most of the ICMS-evoked responses in M1 were more variable in time, suggesting indirect effects of stimulation. The spatial pattern of M1 activation varied systematically: S1 electrodes that elicited percepts in a finger preferentially activated M1 neurons excited during that finger's movement. Moreover, the indirect effects of S1 ICMS on M1 were context dependent, such that the magnitude and even sign relative to baseline varied across tasks. We tested the implications of these effects for brain-control of a virtual hand, in which ICMS conveyed tactile feedback. While ICMS-evoked activation of M1 disrupted decoder performance, this disruption was minimized using biomimetic stimulation, which emphasizes contact transients at the onset and offset of grasp, and reduces sustained stimulation.

Mindfulness-based real-time fMRI neurofeedback: a randomized controlled trial to optimize dosing for depressed adolescents.

BACKGROUND: Adolescence is characterized by a heightened vulnerability for Major Depressive Disorder (MDD) onset, and currently, treatments are only effective for roughly half of adolescents with MDD. Accordingly, novel interventions are urgently needed. This study aims to establish mindfulness-based real-time fMRI neurofeedback (mbNF) as a non-invasive approach to downregulate the default mode network (DMN) in order to decrease ruminatory processes and depressive symptoms. METHODS: Adolescents (N = 90) with a current diagnosis of MDD ages 13-18-years-old will be randomized in a parallel group, two-arm, superiority trial to receive either 15 or 30 min of mbNF with a 1:1 allocation ratio. Real-time neurofeedback based on activation of the frontoparietal network (FPN) relative to the DMN will be displayed to participants via the movement of a ball on a computer screen while participants practice mindfulness in the scanner. We hypothesize that within-DMN (medial prefrontal cortex [mPFC] with posterior cingulate cortex [PCC]) functional connectivity will be reduced following mbNF (Aim 1: Target Engagement). Additionally, we hypothesize that participants in the 30-min mbNF condition will show greater reductions in within-DMN functional connectivity (Aim 2: Dosing Impact on Target Engagement). Aim 1 will analyze data from all participants as a single-group, and Aim 2 will leverage the randomized assignment to analyze data as a parallel-group trial. Secondary analyses will probe changes in depressive symptoms and rumination. DISCUSSION: Results of this study will determine whether mbNF reduces functional connectivity within the DMN among adolescents with MDD, and critically, will identify the optimal dosing with respect to DMN modulation as well as reduction in depressive symptoms and rumination. TRIAL REGISTRATION: This study has been registered with clinicaltrials.gov, most recently updated on July 6, 2023 (trial identifier: NCT05617495).

Identifying Membrane Protein-Lipid Interactions with Lipidomic Lipid Exchange-Mass Spectrometry.

Lipids can play important roles in modulating membrane protein structure and function. However, it is challenging to identify natural lipids bound to membrane proteins in complex bilayers. Here, we developed lipidomic lipid exchange-mass spectrometry (LX-MS) to study the lipid affinity for membrane proteins on a lipidomic scale. We first mix membrane protein nanodiscs with empty nanodiscs that have no embedded membrane proteins. After allowing lipids to passively exchange between the two populations, we separate the two types of nanodiscs and perform lipidomic analysis on each with liquid chromatography and MS. Enrichment of lipids in the membrane protein nanodiscs reveals the affinity of individual lipids for binding the target membrane protein. We apply this approach to study three membrane proteins. With the Escherichia coli ammonium transporter AmtB and aquaporin AqpZ in nanodiscs with E. coli polar lipid extracts, we detected binding of cardiolipin and phosphatidyl-glycerol lipids to the proteins. With the acetylcholine receptor in nanodiscs with brain polar lipid extracts, we discovered a complex set of lipid interactions that depended on the head group and tail composition. Overall, lipidomic LX-MS provides a detailed understanding of the lipid-binding affinity and thermodynamics for membrane proteins in complex bilayers and provides a unique perspective on the chemical environment surrounding membrane proteins.

Interplay between intensity-dependent dispersion and Kerr nonlinearity on the soliton formation.

A generalized nonlinear Schrödinger equation is studied with the interplay between Kerr nonlinearity and intensity-dependent dispersion. The supported soliton solutions are characterized analytically in different families by the pseudo-potential method, in terms of Maimistov and Cuspon solitons for different ratio between the intensity-dependent dispersion and Kerr nonlinearity. Direct numerical simulations also agree with our analytical formulas. In addition to the well-studied Kerr-type nonlinearity, our results reveal an unexplored scenario with the introduction of the nonlinear corrections to wave dispersion.

Tessellation of artificial touch via microstimulation of human somatosensory cortex.

When we interact with objects, we rely on signals from the hand that convey information about the object and our interaction with it. A basic feature of these interactions, the locations of contacts between the hand and object, is often only available via the sense of touch. Information about locations of contact between a brain-controlled bionic hand and an object can be signaled via intracortical microstimulation (ICMS) of somatosensory cortex (S1), which evokes touch sensations that are localized to a specific patch of skin. To provide intuitive location information, tactile sensors on the robotic hand drive ICMS through electrodes that evoke sensations at skin locations matching sensor locations. This approach requires that ICMS-evoked sensations be focal, stable, and distributed over the hand. To systematically investigate the localization of ICMS-evoked sensations, we analyzed the projected fields (PFs) of ICMS-evoked sensations - their location and spatial extent - from reports obtained over multiple years from three participants implanted with microelectrode arrays in S1. First, we found that PFs vary widely in their size across electrodes, are highly stable within electrode, are distributed over large swaths of each participant's hand, and increase in size as the amplitude or frequency of ICMS increases. Second, while PF locations match the locations of the receptive fields (RFs) of the neurons near the stimulating electrode, PFs tend to be subsumed by the corresponding RFs. Third, multi-channel stimulation gives rise to a PF that reflects the conjunction of the PFs of the component channels. By stimulating through electrodes with largely overlapping PFs, then, we can evoke a sensation that is experienced primarily at the intersection of the component PFs. To assess the functional consequence of this phenomenon, we implemented multichannel ICMS-based feedback in a bionic hand and demonstrated that the resulting sensations are more localizable than are those evoked via single-channel ICMS.

Hemolyzed Laboratory Specimens in the Emergency Department: An Underappreciated, but Frequent Problem.

INTRODUCTION: Hemolysis of blood samples from emergency department (ED) patients leads to delays in treatment and disposition. The aim of this study is to determine the frequency of hemolysis and variables predictive of hemolysis. METHODS: This observational cohort study was conducted among three institutions: academic tertiary care center and two suburban community EDs, with an annual census of over 270,000 ED visits. Data were obtained from the electronic health record. Adults requiring laboratory analysis with at least one peripheral intravenous catheter (PIVC) inserted within the ED were eligible. Primary outcome was hemolysis of lab samples and secondary outcomes included variables related to PIVC failure. RESULTS: Between January 8, 2021 and May 9, 2022, 141,609 patient encounters met inclusion criteria. The average age was 55.5 and 57.5% of patients were female. Hemolysis occurred in 24,359 (17.2%) samples. In a multivariate analysis, when compared to 20-gauge catheters, smaller 22-gauge catheters had an increased odds of hemolysis (OR 1.78, 95% confidence interval (CI) 1.65-1.91; P < .001), while larger 18-gauge catheters had a lower odds of hemolysis (OR 0.94; 95% CI 0.90-0.98; P = .0046). Additionally, when compared to antecubital placement, hand/wrist placement demonstrated increased odds of hemolysis (OR 2.06; 95% CI 1.97-2.15; P < .001). Finally, hemolysis was associated with a higher rate of PIVC failure (OR 1.06; 95%CI 1.00-1.13; P = 0.043). DISCUSSION: This large observational analysis demonstrates that lab hemolysis of is a frequent occurrence among ED patients. Given the added risk of hemolysis with certain placement variables, clinicians should consider catheter gauge/placement location to avoid hemolysis that may result in patient care delays and prolonged hospital stays.

Quantum walk processes in quantum devices.

Simulation and programming of current quantum computers as Noisy Intermediate-Scale Quantum (NISQ) devices represent a hot topic at the border of current physical and information sciences. The quantum walk process represents a basic subroutine in many quantum algorithms and plays an important role in studying physical phenomena. Simulating quantum walk processes is computationally challenging for classical processors. With an increasing improvement in qubits fidelity and qubits number in a single register, there is a potential to improve quantum walks simulations substantially. However, efficient ways to simulate quantum walks in qubit registers still have to be explored. Here, we explore the relationship between quantum walk on graphs and quantum circuits. Firstly, we discuss ways to obtain graphs provided quantum circuit. We then explore techniques to represent quantum walk on a graph as a quantum circuit. Specifically, we study hypercube graphs and arbitrary graphs. Our approach to studying the relationship between graphs and quantum circuits paves way for the efficient implementation of quantum walks algorithms on quantum computers.

Biomimetic multi-channel microstimulation of somatosensory cortex conveys high resolution force feedback for bionic hands.

Manual interactions with objects are supported by tactile signals from the hand. This tactile feedback can be restored in brain-controlled bionic hands via intracortical microstimulation (ICMS) of somatosensory cortex (S1). In ICMS-based tactile feedback, contact force can be signaled by modulating the stimulation intensity based on the output of force sensors on the bionic hand, which in turn modulates the perceived magnitude of the sensation. In the present study, we gauged the dynamic range and precision of ICMS-based force feedback in three human participants implanted with arrays of microelectrodes in S1. To this end, we measured the increases in sensation magnitude resulting from increases in ICMS amplitude and participant's ability to distinguish between different intensity levels. We then assessed whether we could improve the fidelity of this feedback by implementing "biomimetic" ICMS-trains, designed to evoke patterns of neuronal activity that more closely mimic those in natural touch, and by delivering ICMS through multiple channels at once. We found that multi-channel biomimetic ICMS gives rise to stronger and more distinguishable sensations than does its single-channel counterpart. Finally, we implemented biomimetic multi-channel feedback in a bionic hand and had the participant perform a compliance discrimination task. We found that biomimetic multi-channel tactile feedback yielded improved discrimination over its single-channel linear counterpart. We conclude that multi-channel biomimetic ICMS conveys finely graded force feedback that more closely approximates the sensitivity conferred by natural touch.

Affective mirror and anti-mirror neurons relate to prosocial help in rats.

Although empathic emotion is closely related to prosocial behavior, neuronal substrate that accounts for empathy-associated prosocial action remains poorly understood. We recorded neurons in the anterior cingulate cortex (ACC) and insular cortex (InC) in rats when they observed another rat in pain. We discovered neurons with anti-mirror properties in the ACC and InC, in addition to those with mirror properties. ACC neurons show higher coupling between activation of self-in-pain and others-in-pain, whereas the InC has a higher ratio of neurons with anti-mirror properties. During others-in-pain, ACC neurons activated more when actively nose-poking toward others and InC neurons activated more when freezing. To further illustrate prosocial function, we examined neuronal activities in the helping behavior test. Both ACC and InC neurons showed specific activation to rat rescuing which is contributed by mirror, but not anti-mirror neurons. Our work indicates the functional involvement of mirror neuron system in prosocial behaviors.

Hybrid active and passive local shimming (HAPLS) for two-region MRI.

PURPOSE: An MRI scanner is equipped with global shim systems for shimming one region of interest (ROI) only. However, it often fails to reach state-of-the-art when shimming two isolated regions of interest simultaneously, even though the two-area shimming can be essential in scan scenarios, such as bilateral breasts or dyadic brains. To address these challenges, a hybrid active and passive local shimming technique is proposed to simultaneously shim two isolated region-of-interest areas within the whole FOV. METHODS: A local passive shimming system is constructed by optimized bilateral ferromagnetic chip arrays to compensate for the magnet's significant high-order B0 inhomogeneities at the boundary of the manufacturer's specified homogeneous volume, thus locally improving the available FOV. The local active shimming consists of 40-channel DC loops powered by 64-channel current amplifiers. With the optimized current distribution, active shimming can correct the residual low-order B0 inhomogeneities and subject-specific field inhomogeneities. In addition, active shimming is used to homogenize the center frequencies of the two regions. RESULTS: With the implementation of the hybrid active and passive local shimming, the 95% peak-to-peak was reduced from 1.92 to 1.12 ppm by 41.7%, and RMS decreased from 0.473 to 0.255 ppm by 46.1% in a two-phantom experiment. The volume ratio containing MR voxels within a 0.5-ppm frequency span increased from 64.3% to 81.3% by 26.3%. CONCLUSION: The proposed hybrid active and passive local shimming technique uses both passive and active local shimming, and it can efficiently shim two areas simultaneously, which is an unmet need for a commercial MRI scanner.

Social Relationship as a Factor for the Development of Stress Incubation in Adult Mice.

While stress reactions can emerge long after the triggering event, it remains elusive how they emerge after a protracted, seemingly stress-free period during which stress incubates. Here, we study the behavioral development in mice isolated after observing an aggressive encounter inflicted upon their pair-housed partners. We developed a spatially resolved fine-scale behavioral analysis and applied it to standard behavioral tests. It reveals that the seemingly sudden behavioral changes developed gradually. These behavioral changes were not observed if the aggressive encounter happened to a stranger mouse, suggesting that social bonding is a prerequisite for stress incubation in this paradigm. This finding was corroborated by hemisphere-specific morphological changes in cortex regions centering at the anterior cingulate cortex, a cognitive and emotional center. Our non-invasive analytical methods to capture informative behavioral details may have applications beyond laboratory animals.

Extract the Degradation Information in Squeezed States with Machine Learning.

In order to leverage the full power of quantum noise squeezing with unavoidable decoherence, a complete understanding of the degradation in the purity of squeezed light is demanded. By implementing machine-learning architecture with a convolutional neural network, we illustrate a fast, robust, and precise quantum state tomography for continuous variables, through the experimentally measured data generated from the balanced homodyne detectors. Compared with the maximum likelihood estimation method, which suffers from time-consuming and overfitting problems, a well-trained machine fed with squeezed vacuum and squeezed thermal states can complete the task of reconstruction of the density matrix in less than one second. Moreover, the resulting fidelity remains as high as 0.99 even when the antisqueezing level is higher than 20 dB. Compared with the phase noise and loss mechanisms coupled from the environment and surrounding vacuum, experimentally, the degradation information is unveiled with machine learning for low and high noisy scenarios, i.e., with the antisqueezing levels at 12 dB and 18 dB, respectively. Our neural network enhanced quantum state tomography provides the metrics to give physical descriptions of every feature observed in the quantum state with a single scan measurement just by varying the local oscillator phase from 0 to 2π and paves a way of exploring large-scale quantum systems in real time.

Optical nonreciprocity and nonreciprocal photonic devices with directional four-wave mixing effect.

A scheme for magnetic-free optical nonreciprocity in an ensemble of four-level cold atoms is proposed by exploiting the directional four-wave mixing effect. Using experimentally achievable parameters, the nonreciprocal optical responses of the system can be observed and the conversion on nonreciprocal transmission and nonreciprocal phase shift can be implemented. These nonreciprocal phenomena originate from the directional phase matching, which breaks the time-reversal symmetry and dynamic reciprocity of the cold atomic system. Moreover, by embedding the cold atoms into a Mach-Zehnder interferometer and choosing proper parameters, a two-port optical isolator with an isolation ratio of 79.70 dB and an insertion loss of 0.35 dB and a four-port optical circulator with a fidelity of 0.9985 and a photon survival probability of 0.9278 can be realized, which shows the high performance of isolation and circulation. The proposal may enable a new class of optically controllable cavity-free nonreciprocal devices in optical signal processing at the low light level.

Bose-Einstein condensate soliton qubit states for metrological applications.

We propose a novel platform for quantum metrology based on qubit states of two Bose-Einstein condensate solitons, optically manipulated, trapped in a double-well potential, and coupled through nonlinear Josephson effect. We describe steady-state solutions in different scenarios and perform a phase space analysis in the terms of population imbalance-phase difference variables to demonstrate macroscopic quantum self-trapping regimes. Schrödinger-cat states, maximally path-entangled (N00N) states, and macroscopic soliton qubits are predicted and exploited to distinguish the obtained macroscopic states in the framework of binary (non-orthogonal) state discrimination problem. For an arbitrary frequency estimation we have revealed these macroscopic soliton states have a scaling up to the Heisenberg and super-Heisenberg (SH) limits within linear and nonlinear metrology procedures, respectively. The examples and numerical evaluations illustrate experimental feasibility of estimation with SH accuracy of angular frequency between the ground and first excited macroscopic states of the condensate in the presence of moderate losses, which opens new perspectives for current frequency standard technologies.

Generation of quantum entanglement based on electromagnetically induced transparency media.

Quantum entanglement is an essential ingredient for the absolute security of quantum communication. Generation of continuous-variable entanglement or two-mode squeezing between light fields based on the effect of electromagnetically induced transparency (EIT) has been systematically investigated in this work. Here, we propose a new scheme to enhance the degree of entanglement between probe and coupling fields of coherent-state light by introducing a two-photon detuning in the EIT system. This proposed scheme is more efficient than the conventional one, utilizing the ground-state relaxation (population decay or dephasing) rate to produce entanglement or two-mode squeezing which adds far more excess fluctuation or noise to the system. In addition, maximum degree of entanglement at a given optical depth can be achieved with a wide range of the coupling Rabi frequency and the two-photon detuning, showing our scheme is robust and flexible. It is also interesting to note that while EIT is the effect in the perturbation limit, i.e. the probe field being much weaker than the coupling field and treated as a perturbation, there exists an optimum ratio of the probe to coupling intensities to achieve the maximum entanglement. Our proposed scheme can advance the continuous-variable-based quantum technology and may lead to applications in quantum communication utilizing squeezed light.

Synthesizing quantum spin Hall phase for ultracold atoms in bichromatic chiral optical ladders.

Realizing the topological bands of helical states poses a challenge in studying ultracold atomic gases. Motivated by the recent experimental success in realizing chiral optical ladders, here we present a scheme for synthesizing topological quantum matter, especially the quantum spin Hall phase, in the chiral optical ladders. More precisely, we first establish the synthetic pseudo-spin-orbit coupling and Zeeman splitting in the chiral ladders. After analyzing the band structure of the ladders exposed to the bichromatic optical potentials, we report the existence of quantum spin Hall phase. We further identify a rich phase diagram of the bichromatic chiral ladders, illustrating that our proposal features a large space of system parameters exhibiting quantum phase transitions. Our scheme is within reach of the existing ladder optical lattices and hence provides a new method to engineer the elaborate topological bands for cold atomic gases.

Frequency-Dependent Squeezed Vacuum Source for Broadband Quantum Noise Reduction in Advanced Gravitational-Wave Detectors.

The astrophysical reach of current and future ground-based gravitational-wave detectors is mostly limited by quantum noise, induced by vacuum fluctuations entering the detector output port. The replacement of this ordinary vacuum field with a squeezed vacuum field has proven to be an effective strategy to mitigate such quantum noise and it is currently used in advanced detectors. However, current squeezing cannot improve the noise across the whole spectrum because of the Heisenberg uncertainty principle: when shot noise at high frequencies is reduced, radiation pressure at low frequencies is increased. A broadband quantum noise reduction is possible by using a more complex squeezing source, obtained by reflecting the squeezed vacuum off a Fabry-Perot cavity, known as filter cavity. Here we report the first demonstration of a frequency-dependent squeezed vacuum source able to reduce quantum noise of advanced gravitational-wave detectors in their whole observation bandwidth. The experiment uses a suspended 300-m-long filter cavity, similar to the one planned for KAGRA, Advanced Virgo, and Advanced LIGO, and capable of inducing a rotation of the squeezing ellipse below 100 Hz.