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Neurologic adverse events (NAEs) are a major complication after pulmonary endarterectomy (PEA) performed under periods of deep hypothermic circulatory arrest (HCA) for chronic thromboembolic pulmonary hypertension. We modified the PEA strategy to prevent NAEs and evaluated the effectiveness of these modifications.We reviewed the surgical outcomes of 87 patients divided into the following three groups based on the surgical strategy used: group S (n = 49), periods of deep HCA with alpha-stat strategy; group M1 (n = 19), deep HCA with modifications of slower cooling and rewarming rates and the pH-stat strategy for cooling: and group M2 (n = 13), multiple short periods of moderate HCA.PEA provided significant improvement of pulmonary hemodynamics in each group. Sixteen (29%) of the 49 group S patients suffered NAEs, associated with total circulatory arrest time (cutoff, 57 min) and Jamieson type I disease. The Group M1 and M2 patients did not suffer NAEs, although the group M1 patients had prolonged cardiopulmonary bypass (CPB) and more frequent respiratory failure.NAEs were common after PEA performed under periods of deep HCA. The modified surgical strategy could decrease the risk of NAEs but increase the risk of respiratory failure. Multiple short periods of moderate HCA may be useful for patients at risk of NAEs.

Background Homebound status is one of the most important risk factors associated with functional decline and long-term care in older adults. Studies show that neighborhood built environment and community social capital may be related to homebound status. This study aimed to clarify the association between homebound status for community-dwelling older adults and community environment-including social capital and neighborhood built environment-in rural and urban areas. Methods We surveyed people aged 65 years and older residing in three municipalities of Niigata Prefecture, Japan, who were not certified as requiring long-term care. The dependent variable was homebound status; explanatory variables were community-level social capital and neighborhood built environment. Covariates were age, sex, household, marital status, socioeconomic status, instrumental activities of daily living, the Geriatric Depression Scale-15, self-rated health, number of diseases under care, and individual social capital. The association between community social capital or neighborhood built environment and homebound status, stratified by rural/urban areas, was investigated using multilevel logistic regression analysis. Results Among older adults (n = 18,099), the homebound status prevalence rate was 6.9% in rural areas and 4.2% in urban areas. The multilevel analysis showed that, in rural areas, fewer older adults were homebound in communities with higher civic participation and with suitable parks or pavements for walking and exercising. However, no significant association was found between community social capital or neighborhood built environment and homebound status for urban older adults. Conclusions Community social capital and neighborhood built environment were significantly associated with homebound status in older adults in rural areas.

Vagal afferents regulate numerous physiological functions including arterial blood pressure, heart rate, breathing, and nociception. Cell bodies of vagal afferents reside in the inferior vagal (nodose) ganglia and their stimulation by various means is being considered as a way to regulate cardiorespiratory responses and control pain sensations. Stimulation of the nodose by exposure to infrared light is recently being considered as a precise way to elicit responses. These responses would likely involve the activity of temperature-sensitive membrane-bound channels. While papers have been published to track the expression of these transient receptor potential ion channels (TRPs), further studies are warranted to determine the in situ expression of the endogenous TRP proteins in the nodose ganglia to fully understand their pattern of expression, subcellular locations, and functions in this animal model. TRP ion channels are a superfamily of Na

Retinoic acid, an active form of vitamin A, plays very important roles in mammalian embryogenesis. The concentration of retinoic acid is extremely low and strictly regulated by enzymes of cytochrome P450 (CYP) family, CYP26s (CYP26A1, CYP26B1 and CYP26C1) in the cells. Therefore, it is thought that changes in CYP26s activities due to exposure to a wide variety of drugs and chemicals exhibit teratogenicity. In this study, to easily detect the changes in retinoic acid level, we constructed an adenovirus-mediated reporter assay system using the promoter region of the CYP26A1 gene and inserting retinoic acid response element (RARE) and retinoid X response element (RXRE) into the downstream of the luciferase gene of reporter plasmid, which highly increased the response to retinoic acid. Reporter activity significantly increased in a concentration-dependent manner with retinoic acid; this increase was also observed at least after treatment with a very low concentration of 1 nM retinoic acid. This increase was suppressed by the accelerated metabolism of retinoic acid due to the overexpression of CYP26A1; however, this suppression was almost completely suspended by treatment with talarozole, a CYP26 inhibitor. In conclusion, the reporter assay system constructed using the induction of CYP26A1 expression is a risk assessment system that responds to extremely low concentrations of retinoic acid and is useful for assessing the excess vitamin A mediated teratogenicity caused by various chemicals at the cellular level.

Optical coherence tomography (OCT) has been used to investigate heart development because of its capability to image both structure and function of beating embryonic hearts. Cardiac structure segmentation is a prerequisite for quantification of embryonic heart motion and function using OCT. Since manual segmentation is time-consuming and labor-intensive, an automatic method is needed to facilitate high-throughput studies. The purpose of this study is to develop an image processing pipeline to facilitate the segmentation of beating embryonic heart structures from a 4-D OCT dataset. Sequential OCT images were obtained at multiple planes of a beating quail embryonic heart and reassembled to a 4-D dataset using image-based retrospective gating. Multiple image volumes at different time points were selected as key-volumes and their cardiac structures including myocardium, cardiac jelly, and lumen were manually labeled. Registration-based data augmentation was used to synthesize additional labeled image volumes by learning transformations between key-volumes and other unlabeled volumes. The synthesized labeled images were then used to train a fully convolutional network (U-Net) for heart structure segmentation. The proposed deep learning-based pipeline achieved high segmentation accuracy with only two labeled image volumes and reduced the time cost of segmenting one 4-D OCT dataset from a week to two hours. Using this method, one could carry out cohort studies that quantify complex cardiac motion and function in developing hearts.

A 61-year-old man presented with retroperitoneal hemorrhage caused by an aneurysm rupture of the pancreaticoduodenal arcade (PDA), and acute celiac artery dissection distal to celiac axis stenosis. Owing to the gradual growth of the false lumen, we planned to deploy a stent to the celiac artery dissection and embolize the PDA aneurysm. Prior to stent placement, we assessed the acute celiac artery dissection distal to the stenosis using four-dimensional computed tomography (CT) angiography through expiration/inspiration/expiration cycle. We diagnosed median arcuate ligament syndrome considering that the celiac axis showed a hooked narrowing at end-expiration, and the compression decreased at end-inspiration. Additionally, the true lumen distal to the stretched axis dilated in the inspiration phase. Therefore, we could advance a catheter into the true lumen during inspiration and successfully deploy a stent. Subsequently, laparoscopic median arcuate ligament release was performed after the stent deployment. A postoperative CT scan showed good patency in the stent, with disappearance of the blood filling the false lumen and with reduced celiac axis stenosis.

Increased regurgitant blood flow has been linked to endocardial cushion defects and resultant congenital heart diseases (CHDs). Prenatal alcohol exposure (PAE) has been shown to alter early blood flow resulting in abnormal endocardial cushions and CHDs. Compounds, including folic acid (FA), mitigate PAE effects and prevent CHDs, but few studies have assessed their effects on blood flow. We modeled binge drinking in quail embryos at gastrulation. Embryos were exposed to ethanol alone, FA (3.2 μg/egg) alone, and the two simultaneously. We quantified in cardiac looping stages (equivalent to 4 wk of human gestation), the regurgitant blood flow with Doppler optical coherence tomography (OCT) and endocardial cushion volumes using OCT imaging. Incidences of abnormal body curvature and heart rates were also measured. Embryos exposed to ethanol showed significantly increased regurgitant blood flow compared with controls, whereas embryos given FA with ethanol had significantly reduced regurgitant blood flow but without returning to control levels. Ethanol exposure led to significantly smaller, abnormal endocardial cushions, and the addition of FA improved their size, but they remained smaller than controls. Abnormal body curvatures after PAE were reduced in incidence but not fully prevented by FA. FA supplementation partially alleviated PAE-induced abnormal cardiovascular function and morphology. Normal blood flow and endocardial cushions are both required to produce a healthy four-chambered heart. These findings support that FA supplementation should begin early in pregnancy to prevent heart as well as neural tube defects. Investigations into the efficacy of combinations of compounds to prevent PAE-induced defects are warranted. NEW & NOTEWORTHY State-of-the-art biophotonic tools captured blood flow and endocardial cushion volumes in tiny beating quail embryo hearts, an accessible model for studying four-chambered heart development. Both hemodynamic flow and endocardial cushion volumes were altered with ethanol exposure but normalized when folic acid was introduced with ethanol. Folic acid supplementation preserved hemodynamic function that is intimately involved in sculpting the heart from the earliest stages of heart development.

Optical coherence tomography (OCT) has been used to investigate heart development because of its capability to image both structure and function of beating embryonic hearts. Cardiac structure segmentation is a prerequisite for the quantification of embryonic heart motion and function using OCT. Since manual segmentation is time-consuming and labor-intensive, an automatic method is needed to facilitate high-throughput studies. The purpose of this study is to develop an image-processing pipeline to facilitate the segmentation of beating embryonic heart structures from a 4-D OCT dataset. Sequential OCT images were obtained at multiple planes of a beating quail embryonic heart and reassembled to a 4-D dataset using image-based retrospective gating. Multiple image volumes at different time points were selected as key-volumes, and their cardiac structures including myocardium, cardiac jelly, and lumen, were manually labeled. Registration-based data augmentation was used to synthesize additional labeled image volumes by learning transformations between key-volumes and other unlabeled volumes. The synthesized labeled images were then used to train a fully convolutional network (U-Net) for heart structure segmentation. The proposed deep learning-based pipeline achieved high segmentation accuracy with only two labeled image volumes and reduced the time cost of segmenting one 4-D OCT dataset from a week to two hours. Using this method, one could carry out cohort studies that quantify complex cardiac motion and function in developing hearts.

Drug-induced liver injury (DILI) is one of the major causes for the discontinuation of drug development and withdrawal of drugs from the market. Since it is known that reactive metabolite formation and being substrates or inhibitors of cytochrome P450s (P450s) are associated with DILI, we systematically investigated the association between human P450 inhibition and DILI. The inhibitory activity of 266 DILI-positive drugs (DILI drugs) and 92 DILI-negative drugs (no-DILI drugs), which were selected from Liver Toxicity Knowledge Base (US Food and Drug Administration), against 8 human P450 forms was assessed using recombinant enzymes and luminescent substrates, and the threshold values showing the highest balanced accuracy for DILI discrimination were determined for each P450 enzyme using receiver operating characteristic analyses. The results showed that among the P450s tested, CYP1A1 and CYP1B1 were inhibited by DILI drugs more than no-DILI drugs with a statistical significance. We found that 91% of drugs that showed inhibitory activity greater than the threshold values against CYP1A1 or CYP1B1 were DILI drugs. The results of internal 5-fold cross-validation confirmed the usefulness of CYP1A1 and CYP1B1 inhibition data for the threshold-based discrimination of DILI drugs. Although the contribution of these P450s to drug metabolism in the liver is considered minimal, our present findings suggest that the assessment of CYP1A1 and CYP1B1 inhibition is useful for screening DILI risk of drug candidates at the early stage of drug development.

Autonomous mobile robots are being used to automate many tasks such as cleaning, delivering items, and surveillance. Such tasks often require uninterrupted and continuous service. However, robots have limited battery power and must be recharged frequently. Since manually charging each robot is not always feasible, automatic charging (docking) stations have been developed to automate the process of charging. In a multi-robot system, the tasks are generally distributed between the robots, and different robots have different amounts of remaining battery power. Since the charging stations are expensive, a limited number of charging points are generally available. Hence, an intelligent planner to manage a limited number of charging points for a large number of robots is essential. In this work, we propose a multi-robot path planner for intelligently accessing a limited number of charging points distributed on the map. Unlike traditional path planners, which mainly consider the shortest path criterion to generate paths, the proposed planner also considers the remaining battery power of the robots, task priority, and robot’s location in the map. It allocates the most appropriate charging station to the robots, which require recharging. Simulation results show that the proposed planner can reduce trajectory re-planning, and plan efficient paths to the available charging points.

Pulmonary embolectomy is an effective treatment of acute pulmonary embolism (APE) but not for chronic pulmonary thromboembolism. We described surgical experience of two patients with APE in preexistent unidentified chronic pulmonary thromboembolism. One patient who presented with severe hypoxia but stable hemodynamics underwent successful pulmonary endarterectomy for proximal organized thrombus instead of pulmonary embolectomy. The other patient who required extracorporeal membrane oxygenation for severe hypoxia developed right heart failure because of residual distal organized thrombus after pulmonary embolectomy. Clinical and radiographical presentation of APE in chronic pulmonary thromboembolism mimics APE, and thus, candidates of pulmonary embolectomy should be carefully selected.

Safe robot navigation in human-centered environments is important to avoid collisions. A major limitation of the traditional path planning algorithms is that the global path is planned only with the knowledge of static obstacles in the map. This paper presents a novel ‘HMRP (heat map-based robot path planner)’ which uses fixed external cameras to generate a heat map of different passages based on congestion, so that robots can generate congestion-free paths at the global planning stage itself. The congestion values are maintained in a database and the paths are classified into hot and cold regions. Robot navigation is affected by the direction of movement of people. Hence, in this work, the HMRP-based planner also considers the direction of movement of people in passages which improves robot navigation. The proposed HMRP is compared with traditional path planning algorithms in real environment. Results show that the proposed HMRP algorithm generates congestion-free paths for safe robot navigation.

Left ventricular assist device (LVAD) is an established therapy for patients with severe heart failure. Because the incidence of cardiotoxicity owing to anticancer agents is low, it is difficult to predict the recovery prospects when the cause of heart failure is due to anticancer agents. In this context, cancer patients who present with severe symptoms of heart failure and who fail medical therapy for heart failure may pose a dilemma, especially in countries such as Japan where implantable LVADs are not approved for purposes other than bridging to transplant. Recently, we encountered a 32-year-old woman with chemotherapy-related cardiomyopathy that developed after anticancer treatment using trastuzumab and anthracycline. LVAD therapy was the only option to save the young woman. The patient received an extracorporeal LVAD, her cardiac function gradually recovered while on support, and the device was successfully removed.

BACKGROUND Some attempts have been made to detect atrial fibrillation with a wearable device equipped with photoelectric volumetric pulse wave technology, and it is expected to be applied under real clinical conditions. OBJECTIVE This study is the second part of a two-phase study aimed at developing a method for immediate detection of paroxysmal atrial fibrillation (AF) using a wearable device with built-in PPG. The objective of this study is to develop an algorithm to immediately diagnose atrial fibrillation by wearing an Apple Watch equipped with a photoplethysmography (PPG) sensor on patients undergoing cardiac surgery and using machine learning of the pulse data output from the device. METHODS A total of 80 subjects who underwent cardiac surgery at a single institution between June 2020 and March 2021 were monitored for postoperative atrial fibrillation using telemetry monitored ECG and Apple Watch. Atrial fibrillation was diagnosed by qualified physicians from telemetry-monitored ECGs and 12-lead ECGs; a diagnostic algorithm was developed using machine learning on pulse rate data output from the Apple Watch. RESULTS One of the 80 patients was excluded from the analysis due to redness of the Apple Watch wearer. 27 (34.2%) of the 79 patients developed AF, and 199 events of AF, including brief AF, were observed. 18 events of AF lasting longer than 1 hour were observed, and Cross-correlation analysis (CCF) showed that pulse rate measured by Apple Watch was strongly correlated (CCF 0.6-0.8) with 8 events and very strongly correlated (CCF >0.8) with 3 events. The diagnostic accuracy by machine learning was 0.7952 (sensitivity 0.6312, specificity 0.8605 at the point closest to the top-left) for the AUC of the ROC curve. CONCLUSIONS We were able to safely monitor pulse rate in patients after cardiac surgery by wearing an Apple Watch. Although the pulse rate from the PPG sensor does not follow the heart rate of the telemetry monitoring ECG in some parts, which may reduce the accuracy of the diagnosis of atrial fibrillation by machine learning, we have shown the possibility of clinical application of early detection of atrial fibrillation using only the pulse rate collected by the PPG sensor. CLINICALTRIAL The use of wristband type continuous pulse measurement device with artificial intelligence for early detection of paroxysmal atrial fibrillation Clinical Research Protocol No. jRCTs032200032 https://jrct.niph.go.jp/latest-detail/jRCTs032200032

Using Functional Independence Measure (FIM) records, this study used latent class analysis (LCA) to clarify the structure of activities of daily living (ADL) status in patients following stroke.In this retrospective, single-center study, we extracted the medical records of patients with stroke who were admitted to a rehabilitation hospital in Japan between April 2018 and March 2020. LCA was used to determine classes of ADL status based on response patterns in FIM items converted from the original seven levels to three levels: Complete Dependence, FIM1-2; Modified Dependence, FIM3-5; Independence, FIM6-7. We compared the length of stay and discharge destinations among subgroups of patients with different ADL status at admission.From 373 patients, 1592 FIM records were analyzed. These were classified into six ADL status classes based on "Complete Dependence," "Modified Dependence," and "Independence" in the motor and cognitive domains. Significant differences were observed among the six admission ADL subgroups for the length of stay (median values in patient subgroups based on admission ADL status: 126, 146, 90, 65, 44, and 29 days in the Motor Complete/Cognitive Complete, Motor Complete/Cognitive Modified, Motor Modified/Cognitive Modified, Motor Modified/Cognitive Independent, Motor Independent/Cognitive Modified, and Motor Independent/Cognitive Independent groups, respectively) and discharge destinations (patients discharged home: 27%, 62%, 81%, 92%, 95%, and 98%, respectively, and to acute care hospitals: 18%, 14%, 8%, 8%, 2%, and 2%, respectively).LCA successfully stratified ADL status in patients with stroke undergoing rehabilitation and may aid in determining an appropriate treatment regimen.

Of all congenital heart defects (CHDs), anomalies in heart valves and septa are among the most common and contribute about fifty percent to the total burden of CHDs. Progenitors to heart valves and septa are endocardial cushions formed in looping hearts through a multi-step process that includes localized expansion of cardiac jelly, endothelial-to-mesenchymal transition, cell migration and proliferation. To characterize the development of endocardial cushions, previous studies manually measured cushion size or cushion cell density from images obtained using histology, immunohistochemistry, or optical coherence tomography (OCT). Manual methods are time-consuming and labor-intensive, impeding their applications in cohort studies that require large sample sizes. This study presents an automated strategy to rapidly characterize the anatomy of endocardial cushions from OCT images. A two-step deep learning technique was used to detect the location of the heart and segment endocardial cushions. The acellular and cellular cushion regions were then segregated by K-means clustering. The proposed method can quantify cushion development by measuring the cushion volume and cellularized fraction, and also map 3D spatial organization of the acellular and cellular cushion regions. The application of this method to study the developing looping hearts allowed us to discover a spatial asymmetry of the acellular cardiac jelly in endocardial cushions during these critical stages, which has not been reported before.

The etiology of ethanol-related congenital heart defects has been the focus of much study, but most research has concentrated on cellular and molecular mechanisms. We have shown with optical coherence tomography (OCT) that ethanol exposure led to increased retrograde flow and smaller atrioventricular (AV) cushions compared with controls. Since AV cushions play a role in patterning the conduction delay at the atrioventricular junction (AVJ), this study aims to investigate whether ethanol exposure alters the AVJ conduction in early looping hearts and whether this alteration is related to the decreased cushion size. Quail embryos were exposed to a single dose of ethanol at gastrulation, and Hamburger–Hamilton stage 19–20 hearts were dissected for imaging. Cardiac conduction was measured using an optical mapping microscope and we imaged the endocardial cushions using OCT. Our results showed that, compared with controls, ethanol-exposed embryos exhibited abnormally fast AVJ conduction and reduced cushion size. However, this increased conduction velocity (CV) did not strictly correlate with decreased cushion volume and thickness. By matching the CV map to the cushion-size map along the inflow heart tube, we found that the slowest conduction location was consistently at the atrial side of the AVJ, which had the thinner cushions, not at the thickest cushion location at the ventricular side as expected. Our findings reveal regional differences in the AVJ myocardium even at this early stage in heart development. These findings reveal the early steps leading to the heterogeneity and complexity of conduction at the mature AVJ, a site where arrhythmias can be initiated. NEW & NOTEWORTHY To the best of our knowledge, this is the first study investigating the impact of ethanol exposure on the early cardiac conduction system. Our results showed that ethanol-exposed embryos exhibited abnormally fast atrioventricular conduction. In addition, our findings, in CV measurements and endocardial cushion thickness, reveal regional differences in the AVJ myocardium even at this early stage in heart development, suggesting that the differentiation and maturation at this site are complex and warrant further studies.

Significant recurrence of atrial tachyarrhythmias are observed after the surgical Cox Maze procedure (CMP). We retrospectively enrolled 11 consecutive patients who had atrial tachyarrhythmias (ATAs) that recurred after a biatrial CMP and underwent catheter ablation. Information including the site of any incomplete lesions and the etiology of the clinical ATAs was shared with the surgical team as feedback. In a total of 11 patients, 12 clinical ATAs were identified. They consisted of 2 atrial fibrillations and 10 atrial tachycardias (ATs). In 6 patients, the CMP was performed after the beginning of this investigation. In a total of 10 ATs, we diagnosed 5 mitral annular flutters, 2 roof-dependent flutters, 1 pulmonary vein (PV)-reentrant AT, and 1 localized reentrant AT. A total of 6 patients had reconnected perimitral block lines. PV reconnections were observed in 3 and posterior wall (PW) residual conduction was also observed in 3 cases. However, no residual conduction of the pulmonary vein isolation (PVI) and only 1 residual conduction of the PW were observed in 5 patients who underwent their index surgery after the beginning of this investigation. This fact may implicate that sharing the information from the electrophysiological study of postsurgical ATAs with the surgical team may contribute to the refinement of the CMP in each facility.

National Institute for Japanese Language and Linguistics, The University of Tokyo, 会議名: 言語資源活用ワークショップ2019, 開催地: 国立国語研究所, 会期: 2019年9月2日−4日, 主催: 国立国語研究所 コーパス開発センター, 「エー」「アノー」「マー」はインフォーマルなスピーチに最もよく出現するフィラーである。これらの使用に関係する要因に違いはあるだろうか。本研究では、これらの出現に関係すると思われる以下の5つの要因の影響力を、ロジスティック回帰分析を用いて検討した。(1)当該節直前の境界の種類、(2)節中語数、(3)話者の性別、(4)年齢、(5)講演経験。『日本語話し言葉コーパス（CSJ）』コア中の107模擬講演を対象に調べた。分析の結果、境界の種類と節中語数はどのタイプのフィラーの出現確率とも関係していることがわかった。語数との関連は節頭よりも節中のフィラーで大きかった。年齢と講演経験の影響は「アノー」にのみ観察された。一方で、性別の影響は「エー」と「マー」にのみ観察され、「アノー」には観察されなかった。フィラーの種類によって、出現確率に深く関わっている要因に違いのあることが明らかになった。

Drug-induced liver injury (DILI) is one of the major causes for the discontinuation of drug development and withdrawal of drugs from the market. Since it is known that reactive metabolite formation and being substrates or inhibitors of cytochrome P450s (P450s) are associated with DILI, we systematically investigated the association between human P450 inhibition and DILI. The inhibitory activity of 266 DILI-positive drugs (DILI drugs) and 92 DILI-negative drugs (no-DILI drugs), which were selected from Liver Toxicity Knowledge Base (US Food and Drug Administration), against 8 human P450 forms was assessed using recombinant enzymes and luminescent substrates, and the threshold values showing the highest balanced accuracy for DILI discrimination were determined for each P450 enzyme using receiver operating characteristic analyses. The results showed that among the P450s tested, CYP1A1 and CYP1B1 were inhibited by DILI drugs more than no-DILI drugs with a statistical significance. We found that 91% of drugs that showed inhibitory activity greater than the threshold values against CYP1A1 or CYP1B1 were DILI drugs. The results of internal 5-fold cross-validation confirmed the usefulness of CYP1A1 and CYP1B1 inhibition data for the threshold-based discrimination of DILI drugs. Although the contribution of these P450s to drug metabolism in the liver is considered minimal, our present findings suggest that the assessment of CYP1A1 and CYP1B1 inhibition is useful for screening DILI risk of drug candidates at the early stage of drug development.

Latent Dirichlet allocation (LDA) is a popular topic model for extracting common patterns from discrete datasets. It is extended to the pachinko allocation model (PAM) with a hierarchical topic structure. This paper presents a combination meal allocation (CMA) model, which is a further enhanced topic model from the PAM that has both hierarchical categories and hierarchical topics. We consider count datasets in multiway arrays, i.e., tensors, and introduce a set of topics to each mode of the tensors. The topics in each mode are interpreted as patterns in the topics and categories in the next mode. Despite there being a vast number of combinations in multilevel categories, our model provides simple and interpretable patterns by sharing the topics in each mode. Latent topics and their membership are estimated using Markov chain Monte Carlo (MCMC) methods. We apply the proposed model to step-count data recorded by activity monitors to extract some common activity patterns exhibited by the users. Our model identifies four daily patterns of ambulatory activities (commuting, daytime, nighttime, and early-bird activities) as sub-topics, and six weekly activity patterns as super-topics. We also investigate how the amount of activity in each pattern dynamically affects body weight changes.

BACKGROUND Fetal alcohol spectrum disorder (FASD) is caused by prenatal alcohol exposure (PAE), the intake of ethanol (C2 H5 OH) during pregnancy. Features of FASD cover a range of structural and functional defects including congenital heart defects (CHDs). Folic acid and choline, contributors of methyl groups to one-carbon metabolism (OCM), prevent CHDs in humans. Using our avian model of FASD, we have previously reported that betaine, another methyl donor downstream of choline, prevents CHDs. The CHD preventions are substantial but incomplete. Ethanol causes oxidative stress as well as depleting methyl groups for OCM to support DNA methylation and other epigenetic alterations. To identify more compounds that can safely and effectively prevent CHDs and other effects of PAE, we tested glutathione (GSH), a compound that regulates OCM and is known as a "master antioxidant." METHODS/RESULTS Quail embryos injected with a single dose of ethanol at gastrulation exhibited congenital defects including CHDs similar to those identified in FASD individuals. GSH injected simultaneously with ethanol not only prevented CHDs, but also improved survival and prevented other PAE-induced defects. Assays of hearts at 8 days (HH stage 34) of quail development, when the heart normally has developed 4-chambers, showed that this single dose of PAE reduced global DNA methylation. GSH supplementation concurrent with PAE normalized global DNA methylation levels. The same assays performed on quail hearts at 3 days (HH stage 19-20) of development, showed no difference in global DNA methylation between controls, ethanol-treated, GSH alone, and GSH plus ethanol-treated cohorts. CONCLUSIONS GSH supplementation shows promise to inhibit effects of PAE by improving survival, reducing the incidence of morphological defects including CHDs, and preventing global hypomethylation of DNA in heart tissues.

While major coronary artery development and pathologies affecting them have been extensively studied, understanding the development and organization of the coronary microvasculature beyond the earliest developmental stages requires new tools. Without techniques to image the coronary microvasculature over the whole heart, it is likely we are underestimating the microvasculature’s impact on normal development and diseases. We present a new imaging and analysis toolset to visualize the coronary microvasculature in intact embryonic hearts and quantify vessel organization. The fluorescent dyes DiI and DAPI were used to stain the coronary vasculature and cardiomyocyte nuclei in quail embryo hearts during rapid growth and morphogenesis of the left ventricular wall. Vessel and cardiomyocytes orientation were automatically extracted and quantified, and vessel density was calculated. The coronary microvasculature was found to follow the known helical organization of cardiomyocytes in the ventricular wall. Vessel density in the left ventricle did not change during and after compaction. This quantitative and automated approach will enable future cohort studies to understand the microvasculature’s role in diseases such as hypertrophic cardiomyopathy where misalignment of cardiomyocytes has been observed in utero.

Background Little is known regarding the association between adverse events (AEs) and psychiatric medications administered to pregnant women in clinical trials during the pre-marketing period. This study analyzes reports of AE association with psychiatric medication administrated during pregnancy using post-marketing spontaneous reports of AE from the Japanese Adverse Drug Event Report (JADER) database and Food and Drug Administration Adverse Event Reporting System in the United States (FAERS-US). Methods We summarized AE reports of psychiatric medication administrated during pregnancy by comparing data obtained from JADER and FAERS-US databases with medication patterns determined as classes via latent class analysis. The odds ratios (ORs) of AE reports categorized into system organ classes in which each class was compared with those without psychiatric medications. Results The proportions of AE reports under psychiatric medication in pregnancy among all AE reports were 22.0% and 16.6% in JADER and FAERS-US, respectively. The 10,389 reports of psychiatric medication during pregnancy were classified into 11 classes. The proportion of patients receiving four or more psychiatric drugs in JADER was larger than that in FAERS-US. The maximum number of reports in combinations of AE and medication pattern in JADER was 169, for ‘general disorders and administration site conditions’ from the class of four or more medications (OR = 9.1), while that in FAERS-US was 1,654, for ‘injury, poisoning, and procedural complications’ from the class of single psychiatric medication (OR = 2.8). Conclusions The main AE reports and associated AE differed depending on medication patterns in pregnant women taking psychiatric medication. This study may provide a prediction of AEs that are likely to be reported with each medication pattern. Our findings of the association between AE reports and medication patterns could help improve the administration of psychiatric medications during pregnancy, though further research on additional datasets is needed to clarify these results.

Very few studies have investigated the efficacy of ganglionated plexus ablation during the conventional maze procedure. In this study, we sought to evaluate its additive effect in reducing recurrent atrial fibrillation after concomitant maze surgery. A retrospective study was conducted of 79 patients who underwent Cox maze IV concomitantly with open-heart surgery with (GP group) or without (Maze group) ganglionated plexus mapping. All active ganglionated plexuses were ablated. The two groups were compared and their follow-up data were analyzed. Active ganglionated plexuses were found in 81% of patients who underwent ganglionated plexus mapping. The rates of freedom from atrial fibrillation at 1 year in the GP and Maze groups were 77 and 75%, respectively. The cumulative freedom from atrial fibrillation at follow-up (27.7 ± 17.3 months) was comparable in the two groups (p = 0.427). A multivariate analysis revealed that persistent atrial fibrillation for more than 90 months was an independent predictor of recurrent atrial fibrillation. Ganglionated plexus ablation with Cox maze IV did not reduce the incidence of recurrent atrial fibrillation in comparison to Maze alone.

National Institute for Japanese Language and Linguistics, The University of Tokyo, 会議名: 言語資源活用ワークショップ2018, 開催地: 国立国語研究所, 会期: 2018年9月4日-5日, 主催: 国立国語研究所 コーパス開発センター, 文境界，節境界にはフィラーがよく観察される。これは，文や節などの談話の切れ目では，その先の発話内容や表現を考えるのに時間が必要なためと考えられる。本研究では，文頭，節頭でのフィラーの使用に影響する要因を，節頭フィラー全体ならびに頻度の高い「エー」「アノ」「マー」についてCSJコア中の模擬講演を対象に調べた。考察対象とした要因は，①話者の性別，②年齢，③学歴，④講演経験，⑤直前の境界の種類，⑥節中語数，⑦節頭の接続詞の有無，の7つである。節頭フィラーの出現確率との間に有意な関連が見られたのは要因①，⑤，⑥のみであった。フィラーの出現確率は男性話者の方が女性話者よりも高く，強い節境界の方が文境界よりも高かった。頻度の高い3種類のフィラーを個別に見ると，エーのみ，文境界の方が強い節境界よりも出現確率が高かった。エーは，アノ，マーよりも，深い談話境界で用いられる傾向のあることが明らかになった。