Neonatal-onset pulmonary alveolar proteinosis is a phenotype associated with poor outcomes in surfactant protein-C disorder.

BACKGROUND: Surfactant protein C (SP-C) disorder is a major component of hereditary interstitial lung disease (HILD) among Japanese. The correlation between clinical outcomes and the phenotype/genotype of SP-C disorder has not been evaluated comprehensively. The current study aimed to evaluate the phenotype/genotype correlated with poor outcomes in patients with SP-C disorder. METHODS: Sequencing analysis of SFTPC in 291 candidates with HILD was performed. The phenotype and genotype correlated with poor outcomes were examined. The log-rank test was used to compare the probability of good outcomes between two patient groups. RESULTS: Twenty patients were diagnosed with SP-C disorder. Of nine patients with neonatal-onset disease, four and five presented with pulmonary alveolar proteinosis (PAP) and interstitial pneumonitis (IP), respectively. The remaining 11 patients with late-onset disease had IP. In total, four and 16 patients had PAP and IP phenotypes, respectively. Four of nine patients with neonatal-onset disease died, and one survived after lung transplant. Further, 1 of 11 patients with late-onset disease died. Four patients with neonatal-onset PAP had a significantly lower probability of good outcomes than the remaining patients. Two patients with neonatal-onset PAP had the p.Leu45Arg variant, one died and the another survived after lung transplant. Of eight patients with variants in the BRICHOS domain, one with frame shift variant located in exon 4, one with variant located at the splicing acceptor site of exon 4, and one with variant located at the splicing donor site of exon 4 died. CONCLUSION: Neonatal-onset PAP was a phenotype predicting poor outcomes in patients with SP-C disorder. The p.Leu45Arg variant and splicing disorder of exon 4 might be genotypes predicting poor outcomes in patients with SP-C disorder.

Cortical oscillations and interareal synchronization as a preparatory activity for postural response.

Neural mechanisms of human standing are expected to be elucidated for preventing fallings. Postural response evoked by sudden external perturbation originates from various areas in the central nervous system. Recent studies have revealed that the corticospinal pathway is one of the key nodes for an appropriate postural response. The corticospinal pathway that mediates the early part of the electromyographic response is modulated with prediction before a perturbation occurs. Temporal prediction explicitly exhibiting an onset timing contributes to enhancing corticospinal excitability. However, how the cortical activities in the sensorimotor area with temporal prediction are processed before the corticospinal pathway enhancement remains unclear. In this study, using electroencephalography, we investigated how temporal prediction affects both neural oscillations and synchronization between sensorimotor and distal areas. Our results revealed that desynchronization of cortical oscillation at α- and ß-bands was observed in the sensorimotor and parietooccipital areas (Cz, CPz, Pz and POz), and those are nested in the phase at θ-band frequency. Furthermore, a reduction in the interareal phase synchrony in the α-band was induced after the timing cue for the perturbation onset. The phase synchrony at the low frequency can relay the temporal prediction among the distant areas and initiate the modulation of the local cortical activities. Such modulations contribute to the preparation for sensory processing and motor execution that are necessary for optimal responses.

The damage and reconstruction of the Kumamoto earthquake: an analysis on the impact of changes in expenditures with multi-regional input-output table for Kumamoto Prefecture.

The Kumamoto earthquake which occurred in April 2016 measured twice the maximum seismic intensity of 7, causing serious damage to the Kumamoto Prefecture. This study mainly focuses on the demand side of expenditures, estimating the monthly expenditures for 1 year before and after the earthquake. Then, using the multi-regional input-output table for Kumamoto Prefecture, we analyzes the ripple effects by region of the changes in monthly expenditures due to the earthquake. Expenditures in the prefecture in fiscal year 2016 by month decreased by a cumulative total of 592 billion yen because of the earthquake, which generated a value-added loss of 348 billion yen. On the other hand, expenditures increased by a cumulative total of 648 billion yen caused by reconstruction demand, inducing 375 billion yen in value-added gains. Thus, net increase of the value-added of 27 billion yen occupied 10.9% of net increase of the gross prefectural domestic product between fiscal years 2015-2016. The fluctuation of expenditures, induced production, and induced value-added caused by the earthquake is huge. Although the damage to the prefectural economy was severe, reconstruction demand exceeded it, resulting in a quick recovery. However, at the same time, there was a confirmed delay in restoration in industries that were almost unrelated to reconstruction and in regions with a heavy concentration of damage.

A shuttling-based two-qubit logic gate for linking distant silicon quantum processors.

Control of entanglement between qubits at distant quantum processors using a two-qubit gate is an essential function of a scalable, modular implementation of quantum computation. Among the many qubit platforms, spin qubits in silicon quantum dots are promising for large-scale integration along with their nanofabrication capability. However, linking distant silicon quantum processors is challenging as two-qubit gates in spin qubits typically utilize short-range exchange coupling, which is only effective between nearest-neighbor quantum dots. Here we demonstrate a two-qubit gate between spin qubits via coherent spin shuttling, a key technology for linking distant silicon quantum processors. Coherent shuttling of a spin qubit enables efficient switching of the exchange coupling with an on/off ratio exceeding 1000, while preserving the spin coherence by 99.6% for the single shuttling between neighboring dots. With this shuttling-mode exchange control, we demonstrate a two-qubit controlled-phase gate with a fidelity of 93%, assessed via randomized benchmarking. Combination of our technique and a phase coherent shuttling of a qubit across a large quantum dot array will provide feasible path toward a quantum link between distant silicon quantum processors, a key requirement for large-scale quantum computation.

Quantum error correction with silicon spin qubits.

Future large-scale quantum computers will rely on quantum error correction (QEC) to protect the fragile quantum information during computation1,2. Among the possible candidate platforms for realizing quantum computing devices, the compatibility with mature nanofabrication technologies of silicon-based spin qubits offers promise to overcome the challenges in scaling up device sizes from the prototypes of today to large-scale computers3-5. Recent advances in silicon-based qubits have enabled the implementations of high-quality one-qubit and two-qubit systems6-8. However, the demonstration of QEC, which requires three or more coupled qubits1, and involves a three-qubit gate9-11 or measurement-based feedback, remains an open challenge. Here we demonstrate a three-qubit phase-correcting code in silicon, in which an encoded three-qubit state is protected against any phase-flip error on one of the three qubits. The correction to this encoded state is performed by a three-qubit conditional rotation, which we implement by an efficient single-step resonantly driven iToffoli gate. As expected, the error correction mitigates the errors owing to one-qubit phase-flip, as well as the intrinsic dephasing mainly owing to quasi-static phase noise. These results show successful implementation of QEC and the potential of a silicon-based platform for large-scale quantum computing.

Fast universal quantum gate above the fault-tolerance threshold in silicon.

Fault-tolerant quantum computers that can solve hard problems rely on quantum error correction1. One of the most promising error correction codes is the surface code2, which requires universal gate fidelities exceeding an error correction threshold of 99 per cent3. Among the many qubit platforms, only superconducting circuits4, trapped ions5 and nitrogen-vacancy centres in diamond6 have delivered this requirement. Electron spin qubits in silicon7-15 are particularly promising for a large-scale quantum computer owing to their nanofabrication capability, but the two-qubit gate fidelity has been limited to 98 per cent owing to the slow operation16. Here we demonstrate a two-qubit gate fidelity of 99.5 per cent, along with single-qubit gate fidelities of 99.8 per cent, in silicon spin qubits by fast electrical control using a micromagnet-induced gradient field and a tunable two-qubit coupling. We identify the qubit rotation speed and coupling strength where we robustly achieve high-fidelity gates. We realize Deutsch-Jozsa and Grover search algorithms with high success rates using our universal gate set. Our results demonstrate universal gate fidelity beyond the fault-tolerance threshold and may enable scalable silicon quantum computers.

Enhanced loading dose of teicoplanin for three days is required to achieve a target trough concentration of 20 µg/mL in patients receiving continuous venovenous haemodiafiltration with a low flow rate.

INTRODUCTION: Because of its lower risk of renal toxicity than vancomycin, teicoplanin is the preferred treatment for methicillin-resistant Staphylococcus aureus infection in patients undergoing continuous venovenous haemodiafiltration (CVVHDF) in whom renal function is expected to recover. The dosing regimen for achieving a trough concentration (Cmin) of ≥20 µg/mL remains unclear in patients on CVVHDF using the low flow rate adopted in Japan. METHODS: The study was conducted in patients undergoing CVVHDF with a flow rate of <20 mg/kg/h who were treated with teicoplanin. We adopted three loading dose regimens for the initial 3 days: the conventional regimen, a high-dose regimen (four doses of 10 mg/kg), and an enhanced regimen (four doses of 12 mg/kg). The initial Cmin was obtained at 72 h after the first dose. RESULTS: Overall, 60 patients were eligible for study inclusion. The proportion of patients achieving the Cmin target was significantly higher for the enhanced regimen than for the high-dose regimen (52.9% versus 8.3%, p = 0.003). In multivariate analysis, the enhanced regimen (odds ratio [OR] = 39.93, 95% confidence interval [CI] = 5.03-317.17) and hypoalbuminaemia (OR = 0.04, 95% CI = 0.01-0.44) were independent predictors of the achievement of Cmin ≥ 20 µg/mL. CONCLUSIONS: An enhanced teicoplanin regimen was proposed to treat complicated or invasive infections by methicillin-resistant Staphylococcus aureus in patients receiving CVVHDF even with a low flow rate.

Designs for a two-dimensional Si quantum dot array with spin qubit addressability.

Electron spins in Si are an attractive platform for quantum computation, backed with their scalability and fast, high-fidelity quantum logic gates. Despite the importance of two-dimensional integration with efficient connectivity between qubits for medium- to large-scale quantum computation, however, a practical device design that guarantees qubit addressability is yet to be seen. Here, we propose a practical 3 × 3 quantum dot device design and a larger-scale design as a longer-term target. The design goal is to realize qubit connectivity to the four nearest neighbors while ensuring addressability. We show that a 3 × 3 quantum dot array can execute four-qubit Grover's algorithm more efficiently than the one-dimensional counterpart. To scale up the two-dimensional array beyond 3 × 3, we propose a novel structure with ferromagnetic gate electrodes. Our results showcase the possibility of medium-sized quantum processors in Si with fast quantum logic gates and long coherence times.

Quantum tomography of an entangled three-qubit state in silicon.

Quantum entanglement is a fundamental property of coherent quantum states and an essential resource for quantum computing1. In large-scale quantum systems, the error accumulation requires concepts for quantum error correction. A first step toward error correction is the creation of genuinely multipartite entanglement, which has served as a performance benchmark for quantum computing platforms such as superconducting circuits2,3, trapped ions4 and nitrogen-vacancy centres in diamond5. Among the candidates for large-scale quantum computing devices, silicon-based spin qubits offer an outstanding nanofabrication capability for scaling-up. Recent studies demonstrated improved coherence times6-8, high-fidelity all-electrical control9-13, high-temperature operation14,15 and quantum entanglement of two spin qubits9,11,12. Here we generated a three-qubit Greenberger-Horne-Zeilinger state using a low-disorder, fully controllable array of three spin qubits in silicon. We performed quantum state tomography16 and obtained a state fidelity of 88.0%. The measurements witness a genuine Greenberger-Horne-Zeilinger class quantum entanglement that cannot be separated into any biseparable state. Our results showcase the potential of silicon-based spin qubit platforms for multiqubit quantum algorithms.

Development of temporal and spatial characteristics of anticipatory postural adjustments during gait initiation in children aged 3-10 years.

This study aimed to analyze the development of direction specificities of temporal and spatial control and the coordination pattern of anticipatory postural adjustment (APA) along the anteroposterior (AP) and mediolateral (ML) directions during gait initiation (GI) in children aged 3-10 years. This study included 72 healthy children aged 3-10 years and 14 young adults. The child population was divided into four groups by age: 3-4, 5-6, 7-8, and 9-10 years. The GI task included GI using the dominant limb. The peak center of feet pressure (COP) shifts during APAs (APApeak), initiation time of COP shifts (APAonset), and the COP vectors in the horizontal plane were calculated to evaluate the direction specificity of spatial, temporal, and coordination control, respectively. A difference in direction specificity development was found for the APApeak. The APApeak in the mediolateral axis, but not in the anteroposterior axis, was significantly higher in the 7-8 years age group than in other groups. Although APAonset was not found for direction specificity, a significant difference between the adult and children groups (5-6 years, 7-8 years, and 9-10 years) was observed in the direction of the COP vector. In conclusion, the developmental process of the spatial, temporal, and coordination control of APAs during GI varied with age. Furthermore, the spatial control and coordination pattern of APAs was found to be direction specific. All components of APAs, namely temporal and spatial control, coordination pattern, and direction specificities, should be analyzed to capture the developmental process of anticipatory postural control.

Differential effects of visual versus auditory biofeedback training for voluntary postural sway.

Augmented sensory biofeedback training is often used to improve postural control. Our previous study showed that continuous auditory biofeedback was more effective than continuous visual biofeedback to improve postural sway while standing. However, it has also been reported that both discrete visual and auditory biofeedback training, presented intermittently, improves bimanual task performance more than continuous visual biofeedback training. Therefore, this study aimed to investigate the relative effectiveness of discrete visual biofeedback versus discrete auditory biofeedback to improve postural control. Twenty-two healthy young adults were randomly assigned to either a visual or auditory biofeedback group. Participants were asked to shift their center of pressure (COP) by voluntary postural sway forward and backward in line with a hidden target, which moved in a sinusoidal manner and was displayed intermittently. Participants were asked to decrease the diameter of a visual circle (visual biofeedback) or the volume of a sound (auditory biofeedback) based on the distance between the COP and the target in the training session. The feedback and the target were given only when the target reached the inflection points of the sine curves. In addition, the perceptual magnitudes of visual and auditory biofeedback were equalized using Stevens' power law. Results showed that the mean and standard deviation of the distance between COP and the target were reduced int the test session, removing the augmented sensory biofeedback, in both biofeedback training groups. However, the temporal domain of the performance improved in the test session in the auditory biofeedback training group, but not in the visual biofeedback training group. In conclusion, discrete auditory biofeedback training was more effective for the motor learning of voluntarily postural swaying compared to discrete visual biofeedback training, especially in the temporal domain.

The role of the ventromedial prefrontal cortex in automatic formation of impression and reflected impression.

Previous neuroimaging studies demonstrated that ventromedial prefrontal cortex (vmPFC) activity reflects how much an individual positively views each person (impression). Here, we investigated whether the degree to which individuals think others positively view them (reflected impression) is similarly tracked by activity in the vmPFC by using fMRI and speed-dating events. We also examined whether activity of the vmPFC in response to the faces of others would predict the impression formed through direct interactions with them. The task consisted of three sessions: pre-speed-dating fMRI, speed-dating events, and post-speed-dating fMRI (not reported here). During the pre-speed-dating fMRI, each participant passively viewed the faces of others whom they would meet in the subsequent speed-dating events. After the fMRI, they rated the impression and reflected impression of each face. During the speed-dating events, the participants had 3-min conversations with partners whose faces were presented during the fMRI task, and they were asked to choose the partners whom they preferred at the end of the events. The results revealed that the value of both the impression and reflected impression were automatically represented in the vmPFC. However, the impression fully mediated the link between the reflected impression and vmPFC activity. These results highlight a close link between reflected appraisal and impression formation and provide important insights into neural and psychological models of how the reflected impression is formed in the human brain.

Focused attention meditation training modifies neural activity and attention: longitudinal EEG data in non-meditators.

Focused attention meditation (FAM) is a basic meditation practice that cultivates attentional control and monitoring skills. Cross-sectional studies have highlighted high cognitive performance and discriminative neural activity in experienced meditators. However, a direct relationship between neural activity changes and improvement of attention caused by meditation training remains to be elucidated. To investigate this, we conducted a longitudinal study, which evaluated the results of electroencephalography (EEG) during three-stimulus oddball task, resting state and FAM before and after 8 weeks of FAM training in non-meditators. The FAM training group (n = 17) showed significantly higher P3 amplitude during the oddball task and shorter reaction time (RT) for target stimuli compared to that of the control group (n = 20). Furthermore, a significant negative correlation between F4-Oz theta band phase synchrony index (PSI) during FAM and P3 amplitude during the oddball task and a significant positive correlation between F4-Pz theta band PSI during FAM and P3 amplitude during the oddball task were observed. In contrast, these correlations were not observed in the control group. These findings provide direct evidence of the effectiveness of FAM training and contribute to our understanding of the mechanisms underpinning the effects of meditation on brain activity and cognitive performance.

Radio-Frequency-Detected Fast Charge Sensing in Undoped Silicon Quantum Dots.

Spin qubits in silicon quantum dots offer a promising platform for a quantum computer as they have a long coherence time and scalability. The charge sensing technique plays an essential role in reading out the spin qubit as well as tuning the device parameters, and therefore, its performance in terms of measurement bandwidth and sensitivity is an important factor in spin qubit experiments. Here we demonstrate fast and sensitive charge sensing by radio frequency reflectometry of an undoped, accumulation-mode Si/SiGe double quantum dot. We show that the large parasitic capacitance in typical accumulation-mode gate geometries impedes reflectometry measurements. We present a gate geometry that significantly reduces the parasitic capacitance and enables fast single-shot readout. The technique allows us to distinguish between the singly- and doubly occupied two-electron states under the Pauli spin blockade condition in an integration time of 0.8 µs, the shortest value ever reported in silicon, by the signal-to-noise ratio of 6. These results provide a guideline for designing silicon spin qubit devices suitable for the fast and high-fidelity readout.

Avoidance Behavioral Difference in Acquisition and Extinction of Pain-Related Fear.

Fear of movement-related pain leads to two types of avoidance behavior: excessive avoidance and pain-inhibited movement. Excessive avoidance is an absence of movement by fear, and pain-inhibited movements involve a change in motor behavior for the purpose of protecting the painful part. Here, we sought to clarify the acquisition process and adaptation of fear for each avoidance behavior. Thirty-one female and 13 male (age 20.9 ± 2.1 years) subjects could decide persistent behaviors: approach with an intense pain stimulus, pain-inhibited movement with weak pain stimulus, or excessive avoidance with no pain in acquisition and test phases. In the subsequent extinction phase, the pain stimulus was omitted. Subjects were divided into an approach group (n = 24), a pain-inhibited movement group (n = 10), and an excessive avoidance group (n = 10) by cluster analysis. The response latencies in approach and pain-inhibited movement groups were not affected by conditioned pain. The subjects in the excessive avoidance group exhibited delayed response latencies, and their high-fear responses remained in the acquisition, test, and extinction phases. In addition, the excessive avoidance group showed high harm avoidance and high trait anxiety. This study demonstrated that differences in pain-related avoidance behaviors are affected by psychological traits. Pain-related excessive avoidance behavior indicated a maladaptive fear, but pain-inhibited movement did not.

Quantum non-demolition measurement of an electron spin qubit.

Measurements of quantum systems inevitably involve disturbance in various forms. Within the limits imposed by quantum mechanics, there exists an ideal projective measurement that does not introduce a back action on the measured observable, known as a quantum non-demolition (QND) measurement1,2. Here we demonstrate an all-electrical QND measurement of a single electron spin in a gate-defined quantum dot. We entangle the single spin with a two-electron, singlet-triplet ancilla qubit via the exchange interaction3,4 and then read out the ancilla in a single shot. This procedure realizes a disturbance-free projective measurement of the single spin at a rate two orders of magnitude faster than its relaxation. The QND nature of the measurement protocol5,6 enables enhancement of the overall measurement fidelity by repeating the protocol. We demonstrate a monotonic increase of the fidelity over 100 repetitions against arbitrary input states. Our analysis based on statistical inference is tolerant to the presence of the relaxation and dephasing. We further exemplify the QND character of the measurement by observing spontaneous flips (quantum jumps)7 of a single electron spin. Combined with the high-fidelity control of spin qubits8-13, these results will allow for various measurement-based quantum state manipulations including quantum error correction protocols14.

Development of postural control during single-leg standing in children aged 3-10 years.

BACKGROUND: The ability to control the center of mass (COM) during single-leg standing (SLS) is imperative for individuals to walk independently. However, detailed biomechanical features of postural control during SLS performed by children remain to be comprehensively investigated. RESEARCH QUESTION: We aimed to investigate the development of postural control during SLS in children aged 3-10 years. METHODS: Forty-eight healthy children (26 boys and 22 girls) aged 3-10 years and 11 young adults participated in this experiment. The child population was divided into four groups by age: 3-4, 5-6, 7-8, and 9-10 years. The SLS task included standing on a single leg as long and as steady as possible for up to 30 s. A three-dimensional motion capture system and two force plates were used for calculating the COM and center of pressure (COP). The task was divided into three phases (accelerated, decelerated, and steady) on the basis of the relationship between COM and COP. RESULTS: COP-COM distances in the 5-6 years' and 7-8 years' groups were significantly increased during the acceleration phase when compared with those in the adult group. Furthermore, COP-COM distances during the decelerated phase were significantly higher in all children's groups compared with those in the adult group. Lastly, COP-COM distance during the steady phase was significantly higher in the 3-4 year age group than in the 9-10 year age and adults groups. SIGNIFICANCE: These results suggest that postural control during the acceleration and steady phases mature by 9 years. Conversely, children ∼10 years did not attain adult-like levels of postural control during the decelerated phase. The developmental process for postural control at each phase possibly plays a significant role in the basic biomechanics of movement and does not display a monotonic pattern.

Coherent transfer of electron spin correlations assisted by dephasing noise.

Quantum coherence of superposed states, especially of entangled states, is indispensable for many quantum technologies. However, it is vulnerable to environmental noises, posing a fundamental challenge in solid-state systems including spin qubits. Here we show a scheme of entanglement engineering where pure dephasing assists the generation of quantum entanglement at distant sites in a chain of electron spins confined in semiconductor quantum dots. One party of an entangled spin pair, prepared at a single site, is transferred to the next site and then adiabatically swapped with a third spin using a transition across a multi-level avoided crossing. This process is accelerated by the noise-induced dephasing through a variant of the quantum Zeno effect, without sacrificing the coherence of the entangled state. Our finding brings insight into the spin dynamics in open quantum systems coupled to noisy environments, opening an avenue to quantum state manipulation utilizing decoherence effects.