Predictability of the neurodevelopmental assessment based on the Kyoto Scale of Psychological Development 2001 at 18-24 months of corrected age and 3 years of age in identifying cognitive impairment at 6 years of age in very preterm infants: A retrospective study at a Japanese tertiary center.

BACKGROUND: It is unknown how accurately the current Japanese classification system for neurodevelopmental delay based on the assessment with the Kyoto Scale of Psychological Development (KSPD) at toddlerhood and pre-school periods predicts cognitive impairment at school age. METHODS: This single-center retrospective cohort study enrolled infants born at 22-29 weeks of gestational age. At 18-24 months of corrected age and 3 years of age, the patients were categorized according to the current Japanese criteria for neurodevelopmental delay based on their overall developmental quotient calculated using the KSPD-2001. Cognitive impairment at 6 years of age was classified according to the calculated or estimated full-scale intelligence quotient. The predictability of the current Japanese classification of neurodevelopmental delay for cognitive impairment at 6 years of age was investigated. RESULTS: Of 566 eligible patients, 364 (64 %) completed the protocol. The current classification for the neurodevelopmental delay showed significant agreement with the severity of cognitive impairment at 6 years of age. The sensitivity and specificity of the KSPD-2001-based assessment for any cognitive impairment at 6 years of age were 0.64 and 0.74 at 18-24 months of corrected age and 0.83 and 0.70 at 3 years of age. The corresponding sensitivity and specificity for moderate/severe cognitive impairment were 0.51 and 0.96 at 18-24 months of corrected age and 0.68 and 0.95 at 3 years of age. CONCLUSION: The KSPD-2001 is a useful tool to predict the severity of cognitive impairment at school age.

Effects of Catecholamines on Blood Flow in Preterm Infants: A Subanalysis of PICC-MBF Trial.

INTRODUCTION: This study evaluated the correlation between skin blood flow and systemic blood flow and whether skin blood flow can determine the circulatory effects of dopamine and dobutamine on blood flow in very low birth weight (VLBW) infants. METHODS: This study was a subanalysis of the PICC-MBF randomized controlled trial. The correlation between skin blood flow and echocardiographic findings was examined. Changes in skin blood flow and blood pressure before and after initiation or dose increase of dopamine and dobutamine were also evaluated. RESULTS: Two hundred and thirty-four participants underwent echocardiography. Skin blood flow was significantly correlated with supra vena cava (SVC) flow (r = 0.31, p < 0.001). Receiver operator characteristic analysis revealed that skin blood flow <17 mL/min effectively detected SVC flow <41 mL/min (area under the curve = 0.83, p < 0.001). Dobutamine significantly increased skin blood flow after initiation or dose increase (p = 0.033) without increasing blood pressure. However, dopamine significantly increased both skin blood flow (p = 0.010) and blood pressure (p < 0.001). CONCLUSIONS: Our findings indicated that skin blood flow could be used as a surrogate marker of systemic blood flow in VLBW infants and revealed differences in the effects of dopamine and dobutamine on circulation.

Elongating, entwining, and dragging: mechanism for adaptive locomotion of tubificine worm blobs in a confined environment.

Worms often aggregate through physical connections and exhibit remarkable functions such as efficient migration, survival under environmental changes, and defense against predators. In particular, entangled blobs demonstrate versatile behaviors for their survival; they form spherical blobs and migrate collectively by flexibly changing their shape in response to the environment. In contrast to previous studies on the collective behavior of worm blobs that focused on locomotion in a flat environment, we investigated the mechanisms underlying their adaptive motion in confined environments, focusing on tubificine worm collectives. We first performed several behavioral experiments to observe the aggregation process, collective response to aversive stimuli, the motion of a few worms, and blob motion in confined spaces with and without pegs. We found the blob deformed and passed through a narrow passage using environmental heterogeneities. Based on these behavioral findings, we constructed a simple two-dimensional agent-based model wherein the flexible body of a worm was described as a cross-shaped agent that could deform, rotate, and translate. The simulations demonstrated that the behavioral findings were well-reproduced. Our findings aid in understanding how physical interactions contribute to generating adaptive collective behaviors in real-world environments as well as in designing novel swarm robotic systems consisting of soft agents.

An Extremely Preterm Infant Born at 23 Weeks' Gestation With an Interrupted Aortic Arch Complex: A Case Report.

We present a case of an infant male born at 23 weeks' gestation with an interrupted aortic arch (IAA) complex. We treated the patient with hypoxic gas ventilation to address developing systemic undercirculation in the acute postnatal phase. As the symptoms of bronchopulmonary dysplasia evolved, hypoxic gas ventilation was no longer required to stabilize the hemodynamics. The patient was discharged home after undergoing the palliative surgical procedure of bilateral pulmonary artery banding and ductus arteriosus stent implantation. Although he suffered from pulmonary hypertension, it was controllable with oxygen supplementation and pulmonary vasodilators. There are limited therapeutic options available for extremely preterm infants with critical congenital heart defects (CHDs). Hypoxic gas ventilation might be considered as one of the options, with its risks taken into account, to manage extremely preterm infants with CHDs with pulmonary overcirculation before performing surgical interventions.

Transient Recovery of Complete Atrioventricular Block Due to Maternal Anti-SS-A Antibody Through Antenatal Steroid Administration After 27 Weeks of Gestation.

Maternal anti-SS-A antibodies may cause complete atrioventricular block or myocardial damage in a fetus. Effective treatment for this has not been established. Although antenatal steroids may be a treatment option for anti-SS-A antibody-related myocarditis or atrioventricular block, a complete atrioventricular block is usually considered irreversible once established. Previous reports have indicated that, in cases where antenatal steroids were effective for atrioventricular block, they were administered earlier in the pregnancy. Here we present a case where maternal steroid administration initiated from 27 weeks, which is beyond the recommended optimal treatment period, was effective in altering a complete atrioventricular block to a grade I atrioventricular block.

Changes in In-Hospital Survival and Long-Term Neurodevelopmental Outcomes of Extremely Preterm Infants: A Retrospective Study of a Japanese Tertiary Center.

OBJECTIVES: The objective of this study was to elucidate whether the survival and long-term neurodevelopmental outcomes of extremely preterm infants have improved in a Japanese tertiary center with an active treatment policy for infants born at 22-23 weeks of gestation. STUDY DESIGN: This single-centered retrospective cohort study enrolled extremely preterm infants treated at Saitama Medical Center, Saitama Medical University, from 2003 to 2014. Patients with major congenital abnormalities were excluded. Primary outcomes were in-hospital survival and severe neurodevelopmental impairment (NDI) at 6 years of age, which was defined as having severe cerebral palsy, severe cognitive impairment, severe visual impairment, or deafness. We assessed the changes in primary outcomes between the first (period 1; 2003-2008) and the second half (period 2; 2009-2014) of the study period and evaluated the association between birth-year and primary outcomes using multivariate logistic regression models. RESULTS: Of the 403 eligible patients, 340 (84%) survived to discharge. Among 248 patients available at 6 years of age, 43 (14%) were classified as having severe NDI. Between the 2 periods, in-hospital survival improved from 155 of 198 (78%) to 185 of 205 (90%), but severe NDI increased from 11 of 108 (10%) to 32 of 140 (23%). In multivariate logistic regression models adjusted for gestational age, birthweight, sex, singleton birth, and antenatal corticosteroids, the aOR (95% CI) of birth-year for in-hospital survival and severe NDI was 1.2 (1.1-1.3) and 1.1 (1.0-1.3), respectively. CONCLUSION: Mortality among extremely preterm infants has improved over the past 12 years; nevertheless, no significant improvement was observed in the long-term neurodevelopmental outcomes.

Paradoxical Continuous Left-to-Right Ductal Shunt during Circulatory Collapse due to Ductal Closure in an Infant with Duct-Dependent Systemic Circulation.

Duct-dependent systemic circulation is accompanied by a right-to-left ductal shunt, at least during systole. Although observations of paradoxical continuous left-to-right shunts in duct-dependent systemic circulation have been reported, the mechanism remains unclear. We report a continuous left-to-right ductal shunt throughout the cardiac cycle during the initial recovery phase from circulatory collapse and right ventricular (RV) dysfunction due to ductal closure in an infant with hypoplastic left heart and severe aortic coarctation. Further recovery improved his RV function and changed the ductal flow from continuous left-to-right to bidirectional, which is usually seen in duct-dependent systemic circulation. Marked RV dysfunction may contribute to the continuous left-to-right ductal shunt. A continuous left-to-right ductal shunt should not be used to rule out duct-dependent systemic circulation.

Active-sensing-based decentralized control of autonomous mobile agents for quick and smooth collision avoidance.

There is an increasing demand for multi-agent systems in which each mobile agent, such as a robot in a warehouse or a flying drone, moves toward its destination while avoiding other agents. Although several control schemes for collision avoidance have been proposed, they cannot achieve quick and safe movement with minimal acceleration and deceleration. To address this, we developed a decentralized control scheme that involves modifying the social force model, a model of pedestrian dynamics, and successfully realized quick, smooth, and safe movement. However, each agent had to observe many nearby agents and predict their future motion; that is, unnecessary sensing and calculations were required for each agent. In this study, we addressed this issue by introducing active sensing. In this control scheme, an index referred to as the "collision risk level" is defined, and the observation range of each agent is actively controlled on this basis. Through simulations, we demonstrated that the proposed control scheme works reasonably while reducing unnecessary sensing and calculations.

Oxidative and Inflammatory Markers Are Higher in Full-Term Newborns Suffering Funisitis, and Higher Oxidative Markers Are Associated with Admission.

The aim of this study was to assess whether oxidative and inflammatory mediators in the cord blood of newborns with funisitis and chorioamnionitis can serve as indicators of their inflammatory status, and whether there is a positive association between higher mediator levels and an increased risk of admission to the neonatal intensive care unit (NICU). This study was conducted prospectively in a neonatology department of a university hospital. In total, 52 full-term newborns were evaluated, including 17 funisitis cases, 13 chorioamnionitis cases, and 22 control newborns without funisitis or chorioamnionitis. Cord blood samples were measured for oxidative stress and inflammatory status markers. The oxidative stress markers included the total nitric oxide (NO), total hydroperoxide (TH), biological antioxidant potential (BAP), and TH/BAP ratio, comprising the oxidative stress index (OSI). Inflammatory markers included interleukin (IL)-1b, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNFα), interferon γ (IFNγ), and complement component C5a. TH, OSI, IL-1b, IL-6, and IL-8 concentrations were higher in the funisitis group than in the chorioamnionitis and control groups. C5a was higher in the funisitis and chorioamnionitis groups than in the control group. Among all enrolled newborns, 14 were admitted to the NICU. Multiple logistic regression analysis showed that elevated umbilical cord blood levels of OSI and TH were associated with a higher risk of admission to the NICU (OSI: R = 2.3, 95% CI 1.26-4.29, p = 0.007 and TH: R = 1.02, 95%CI = 1.004-1.040, p = 0.015). In conclusion, OSI and TH in cord blood from full-term newborns can provide an index of inflammatory status, and higher levels are associated with the risk of admission to the NICU and, therefore, could serve as an early indicator of inflammatory conditions in newborns.

Adaptive Centipede Walking via Synergetic Coupling Between Decentralized Control and Flexible Body Dynamics.

Multi-legged animals such as myriapods can locomote on unstructured rough terrain using their flexible bodies and legs. This highly adaptive locomotion emerges through the dynamic interactions between an animal's nervous system, its flexible body, and the environment. Previous studies have primarily focused on either adaptive leg control or the passive compliance of the body parts and have shown how each enhanced adaptability to complex terrains in multi-legged locomotion. However, the essential mechanism considering both the adaptive locomotor circuits and bodily flexibility remains unclear. In this study, we focused on centipedes and aimed to understand the well-balanced coupling between the two abovementioned mechanisms for rough terrain walking by building a neuromechanical model based on behavioral findings. In the behavioral experiment, we observed a centipede walking when part of the terrain was temporarily removed and thereafter restored. We found that the ground contact sense of each leg was essential for generating rhythmic leg motions and also for establishing adaptive footfall patterns between adjacent legs. Based on this finding, we proposed decentralized control mechanisms using ground contact sense and implemented them into a physical centipede model with flexible bodies and legs. In the simulations, our model self-organized the typical gait on flat terrain and adaptive walking during gap crossing, which were similar to centipedes. Furthermore, we demonstrated that the locomotor performance deteriorated on rough terrain when adaptive leg control was removed or when the body was rigid, which indicates that both the adaptive leg control and the flexible body are essential for adaptive locomotion. Thus, our model is expected to capture the possible essential mechanisms underlying adaptive centipede walking and pave the way for designing multi-legged robots with high adaptability to irregular terrain.

Adaptive Interlimb Coordination Mechanism for Hexapod Locomotion Based on Active Load Sensing.

Insects can flexibly coordinate their limbs to adapt to various locomotor conditions, e.g., complex environments, changes in locomotion speed, and leg amputation. An interesting aspect of insect locomotion is that the gait patterns are not necessarily stereotypical but are often highly variable, e.g., searching behavior to obtain stable footholds in complex environments. Several previous studies have focused on the mechanism for the emergence of variable limb coordination patterns. However, the proposed mechanisms are complicated and the essential mechanism underlying insect locomotion remains elusive. To address this issue, we proposed a simple mathematical model for the mechanism of variable interlimb coordination in insect locomotion. The key idea of the proposed model is "decentralized active load sensing," wherein each limb actively moves and detects the reaction force from the ground to judge whether it plays a pivotal role in maintaining the steady support polygon. Based on active load sensing, each limb stays in the stance phase when the limb is necessary for body support. To evaluate the proposed model, we conducted simulation experiments using a hexapod robot. The results showed that the proposed simple mechanism allows the hexapod robot to exhibit typical gait patterns in response to the locomotion speed. Furthermore, the proposed mechanism improves the adaptability of the hexapod robot for leg amputations and lack of footholds by changing each limb's walking and searching behavior in a decentralized manner based on the physical interaction between the body and the environment.

Randomized Trial of Perfusion-Based Circulatory Management in Infants of Very Low Birth Weight.

OBJECTIVE: To establish the superiority of blood flow (BF)-based circulatory management over conventional blood pressure (BP)-based management strategies used for preventing intraventricular hemorrhage (IVH) in infants of very low birth weight (VLBW). STUDY DESIGN: We conducted a nonblinded, single-centered randomized trial with the aim to prevent IVH by managing BF. Infants with VLBW were assigned randomly to a BF-based group or BP-based (BP group) circulatory management group. The incidence of IVH was the outcome of interest. The IVH also data were compared among healthy patients and patients responsive and unresponsive to the intervention. RESULTS: A total of 219 and 220 infants with VLBW were assigned to the BF and BP groups, respectively. The IVH incidence rate was lower in the BF group, but the difference was not statistically significant (BF group, 6.8% vs BP group, 10.9%; P = .14). In 21% of patients of the BP group and 20% of the BF group, the intervention failed. In BF group, the IVH incidence rate was significantly greater in infants with unsuccessful intervention when compared with healthy individuals (6% vs 23%, P = .001). Multivariate logistic regression analysis revealed a correlation between low blood flow and IVH (aOR 3.24; 95% CI 1.49-7.08, P = .003) but not between low BP and IVH (P = .73). CONCLUSIONS: The BF management protocol did not significantly decrease the incidence of IVH. However, after further optimization, we speculate the treatment strategy holds promise in decreasing the incidence of IVH. Trial registration UMIN-CTR: UMIN000013296.

Simple decentralized control mechanism that enables limb adjustment for adaptive quadruped running.

Quadrupeds exhibit versatile and adaptive running by exploiting the flying phase during the stride cycle. Various interlimb coordination mechanisms focusing on mechanical loads during the stance phase have been proposed to understand the underlying control mechanism, and various gait patterns have been reproduced. However, the essential control mechanism required to achieve both steady running patterns and non-steady behaviours, such as jumping and landing, remains unclear. Therefore, we focus on the vertical motions of the body parts and propose a new decentralized interlimb coordination mechanism. The simulation results demonstrate that the robot can generate efficient and various running patterns in response to the morphology of the body. Furthermore, the proposed model allows the robot to smoothly change its behaviour between steady running and non-steady landing depending on the situation. These results suggest that the steady and non-steady behaviours in quadruped adaptive running may share a common simple control mechanism based on the mechanical loads and vertical velocities of the body parts.

Emergence of robust self-organized undulatory swimming based on local hydrodynamic force sensing.

Undulatory swimming represents an ideal behavior to investigate locomotion control and the role of the underlying central and peripheral components in the spinal cord. Many vertebrate swimmers have central pattern generators and local pressure-sensitive receptors that provide information about the surrounding fluid. However, it remains difficult to study experimentally how these sensors influence motor commands in these animals. Here, using a specifically designed robot that captures the essential components of the animal neuromechanical system and using simulations, we tested the hypothesis that sensed hydrodynamic pressure forces can entrain body actuation through local feedback loops. We found evidence that this peripheral mechanism leads to self-organized undulatory swimming by providing intersegmental coordination and body oscillations. Swimming can be redundantly induced by central mechanisms, and we show that, therefore, a combination of both central and peripheral mechanisms offers a higher robustness against neural disruptions than any of them alone, which potentially explains how some vertebrates retain locomotor capabilities after spinal cord lesions. These results broaden our understanding of animal locomotion and expand our knowledge for the design of robust and modular robots that physically interact with the environment.

Spontaneous Gait Transitions of Sprawling Quadruped Locomotion by Sensory-Driven Body-Limb Coordination Mechanisms.

Deciphering how quadrupeds coordinate their legs and other body parts, such as the trunk, head, and tail (i.e., body-limb coordination), can provide informative insights to improve legged robot mobility. In this study, we focused on sprawling locomotion of the salamander and aimed to understand the body-limb coordination mechanisms through mathematical modeling and simulations. The salamander is an amphibian that moves on the ground by coordinating the four legs with lateral body bending. It uses standing and traveling waves of lateral bending that depend on the velocity and stepping gait. However, the body-limb coordination mechanisms responsible for this flexible gait transition remain elusive. This paper presents a central-pattern-generator-based model to reproduce spontaneous gait transitions, including changes in bending patterns. The proposed model implements four feedback rules (feedback from limb-to-limb, limb-to-body, body-to-limb, and body-to-body) without assuming any inter-oscillator coupling. The interplay of the feedback rules establishes a self-organized body-limb coordination that enables the reproduction of the speed-dependent gait transitions of salamanders, as well as various gait patterns observed in sprawling quadruped animals. This suggests that sensory feedback plays an essential role in flexible body-limb coordination during sprawling quadruped locomotion.

Tegotae-Based Control Produces Adaptive Inter- and Intra-limb Coordination in Bipedal Walking.

Despite the appealing concept of central pattern generator (CPG)-based control for bipedal walking robots, there is currently no systematic methodology for designing a CPG-based controller. To remedy this oversight, we attempted to apply the Tegotae approach, a Japanese concept describing how well a perceived reaction, i.e., sensory information, matches an expectation, i.e., an intended motor command, in designing localised controllers in the CPG-based bipedal walking model. To this end, we developed a Tegotae function that quantifies the Tegotae concept. This function allowed incorporating decentralised controllers into the proposed bipedal walking model systematically. We designed a two-dimensional bipedal walking model using Tegotae functions and subsequently implemented it in simulations to validate the proposed design scheme. We found that our model can walk on both flat and uneven terrains and confirmed that the application of the Tegotae functions in all joint controllers results in excellent adaptability to environmental changes.

An agent-based model of the interrelation between the COVID-19 outbreak and economic activities.

As of July 2020, COVID-19 caused by SARS-COV-2 is spreading worldwide, causing severe economic damage. While minimizing human contact is effective in managing outbreaks, it causes severe economic losses. Strategies to solve this dilemma by considering the interrelation between the spread of the virus and economic activities are urgently needed to mitigate the health and economic damage. Here, we propose an abstract agent-based model of the COVID-19 outbreak that accounts for economic activities. The computational simulation of the model recapitulates the trade-off between the health and economic damage associated with voluntary restraint measures. Based on the simulation results, we discuss how the macroscopic dynamics of infection and economics emerge from individuals' behaviours. We believe our model can serve as a platform for discussing solutions to the above-mentioned dilemma.

Leg amputation modifies coordinated activation of the middle leg muscles in the cricket Gryllus bimaculatus.

Insects alter their walking pattern in order to respond to demands of an ever-changing environment, such as varying ground surface textures. They also exhibit resilient and flexible ability to retain the capacity to walk even after substantial changes in their body properties, e.g. leg amputation. While the motor control paradigm governing the inter-leg coordination in such adaptive walking has been extensively described in past studies, the mechanism remains unknown. Here, we examined this question by using the cricket (Gryllus bimaculatus), which shows a tetrapod/tripod gait on a flat surfaces, like many other insects. We performed leg amputation experiments to investigate modifications of leg movements and coordination of muscle activities. We simultaneously recorded (1) the leg movements, locomotion velocity, and body rotation and (2) the leg movements and leg muscles activities before and after leg amputation. Crickets displayed adaptive coordination of leg movement patterns in response to amputations. The activation timings of levator muscles in both middle legs tended to synchronize in phase when both legs were amputated at the coxatrochanteral joint. This supports the hypothesis that an intrinsic contralateral connection within the mesothoracic ganglion exists, and that mechanosensory feedback from the legs override this connection, resulting in the anti-phase movement of a normal gait.

Wearable Vibration Sensor for Measuring the Wing Flapping of Insects.

In this study, we fabricated a novel wearable vibration sensor for insects and measured their wing flapping. An analysis of insect wing deformation in relation to changes in the environment plays an important role in understanding the underlying mechanism enabling insects to dynamically interact with their surrounding environment. It is common to use a high-speed camera to measure the wing flapping; however, it is difficult to analyze the feedback mechanism caused by the environmental changes caused by the flapping because this method applies an indirect measurement. Therefore, we propose the fabrication of a novel film sensor that is capable of measuring the changes in the wingbeat frequency of an insect. This novel sensor is composed of flat silver particles admixed with a silicone polymer, which changes the value of the resistor when a bending deformation occurs. As a result of attaching this sensor to the wings of a moth and a dragonfly and measuring the flapping of the wings, we were able to measure the frequency of the flapping with high accuracy. In addition, as a result of simultaneously measuring the relationship between the behavior of a moth during its search for an odor source and its wing flapping, it became clear that the frequency of the flapping changed depending on the frequency of the odor reception. From this result, a wearable film sensor for an insect that can measure the displacement of the body during a particular behavior was fabricated.

Is ibuprofen superior to indomethacin for patent ductus arteriosus in Japanese preterm infants?

BACKGROUND: Many clinical trials have indicated that ibuprofen (IBU) has similar effects to indomethacin (IND) on the closure of patent ductus arteriosus (PDA) with fewer adverse effects. Owing to the scarce evidence on IBU use in Japan because of its recent approval we performed this observational study to compare the efficacy and safety of IBU with the efficiency and safety of IND. METHODS: We included infants (gestational age < 30 weeks) with hemodynamically significant PDA under a prophylactic IND protocol for intraventricular hemorrhage who were treated with either IND (n = 30) or IBU (n = 30). We compared a PDA closing effect, changes in ultrasonography findings, and adverse effects between the groups. RESULTS: There was no significant difference in the rates of PDA closure in the first treatment course (IND vs IBU: 46.7% vs 50.0%, P = 0.796) and surgical closure (IND vs IBU: 20.0% vs 20.0%, P = 1.000) between the groups. Both groups showed significant oliguria (IND vs IBU: 30.0% vs 23.3%, P = 0.559) and increased serum creatinine levels after treatment. However, an increase in serum creatinine level by >0.3 mg/dL, a criterion for acute kidney injury, was less frequent in the IBU group (35.7%) compared with that in the IND group (84.2%, P = 0.004). There were no significant differences in echocardiographic changes and jaundice and hypoglycemia incidence rates between the groups. CONCLUSIONS: Except for an increase in serum creatinine levels by >0.3 mg/dL, which was less frequent with IBU, IBU had similar efficacy and safety as IND for preterm PDA. Ibuprofen and IND should be cautiously administered.