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Although many studies have supported the efficacy of transplacental treatment for fetal supraventricular tachyarrhythmia, the long-term neurodevelopmental outcome after antenatal antiarrhythmic treatment is not well understood. The aim of this study was to investigate the prognosis and neurodevelopmental outcome at 36 months of corrected age and the incidence of tachyarrhythmia after birth, following protocol-defined antenatal therapy for fetal supraventricular tachyarrhythmia.This was a 3-year follow-up study of a multicenter trial that evaluated the efficacy and safety of protocol-defined transplacental treatment for fetal supraventricular tachycardia (SVT) and atrial flutter (AFL). The primary endpoints were mortality and neurodevelopmental impairment (NDI) at 36 months of corrected age. NDI was defined as any of the following outcomes: cerebral palsy, bilateral blindness, bilateral deafness or neurodevelopmental delay. Neurodevelopmental delay was evaluated using appropriate developmental quotient scales, mainly the Kyoto Scale of Psychological Development, or examination by pediatric neurologists. The detection rate of tachyarrhythmia at birth and at 18 and 36 months of corrected age was also evaluated as the secondary endpoint. In addition, the association of NDI at 36 months with perinatal and postnatal factors was analyzed.Of 50 patients enrolled in the original trial, one withdrew consent and in two there was fetal death, leaving 47 patients available for enrollment in this follow-up study. Of these, 45 cases were available for analysis after two infants were lost to follow-up. The mortality rate was 2.2% (1/45) during a median follow-up of 3.2 (range, 2.1-9.4) years. The infant died at the age of 2.1 years. Another infant had missing neurodevelopmental assessment data. In the remaining 43 infants, at 36 months of corrected age, NDI was detected in 9.3% (4/43) overall and in two of three (66.7%) cases with fetal hydrops with subcutaneous edema. Cerebral palsy was noted in two infants with severe subcutaneous edema or ascites at an early gestational age. Neurodevelopmental delay was found in two infants with severe congenital abnormalities (one with tuberous sclerosis and the other with heterotaxy syndrome). Tachyarrhythmia was present in 31.9% (15/47) cases in the neonatal period and decreased to 8.9% (4/45) and 4.5% (2/44) at 18 and 36 months of corrected age, respectively. The median ventricular rate at diagnosis was significantly higher in infants with NDI compared to those without (265 vs 229 bpm; P = 0.003). In infants with NDI, compared to those without, fetal hydrops with subcutaneous edema at diagnosis was more common (50.0% vs 2.6%; P = 0.019) and the duration of fetal effusion was longer (median, 10.5 vs 0 days; P = 0.013). Postnatal arrhythmia and physical development abnormalities were not associated with NDI.This multicenter 3-year follow-up study is the first to demonstrate the long-term mortality and morbidity of infants born following protocol-defined transplacental treatment for fetal SVT and AFL. NDI was associated with the presence of fetal hydrops with subcutaneous edema at diagnosis and longer duration of fetal effusion. Neurodevelopmental delay was detected only in infants with severe congenital abnormalities. Therefore, in infants that have undergone antenatal treatment for fetal tachyarrhythmia and in which there are no comorbidities, the risk of NDI is low. However, in those with fetal hydrops with subcutaneous edema and/or associated severe congenital abnormalities, the risk for long-term neurologic morbidity might be considered somewhat increased. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Abstract One of the important requirements of foundation rock mass under dam is resistance to leakage of water. The mechanism of water leakage depends on the hydraulic properties of rock mass. When considering water leakage in fracture-dominant rock mass, the pathway of the flow is controlled by distributions and connectivity of permeable fractures. In such case, a use of discrete fracture network (DFN) models is effective to simulate the groundwater flow, as DFN approach can express fractures stochastically in three-dimension based on statistical distribution of fracture parameters. One of the key challenges when building a DFN model for dam foundation rock mass is hydraulic characterization of fractures. Hydraulic characterization in this context refers to the process of assigning hydraulic properties to the fractures generated from the geometric information. In this paper, an approach to construct a DFN model for dam foundation rock mass is proposed, with a focus on hydraulic characterization of fractures, along with a case study of foundation rock mass of an embankment dam in Japan to demonstrate the application of proposed approach.

We present the first ever real-time numerical weather prediction system with 30-s update cycles at a 500-m grid spacing for the prediction of convective precipitation in the subsequent 30 min using a new-generation multi-parameter phased array weather radar. The system comprises a regional atmospheric model known as the SCALE and the local ensemble transform Kalman filter (LETKF). To accelerate the SCALE-LETKF system, data transfer between the two aforementioned components is performed using a memory copy instead of a file I/O. A complete real-time workflow including domain nesting and observational data transfer is constructed. A real-time test in July and August 2020 showed that the system is fast enough for a real-time application of 30-s forecast-analysis cycles and 30-min prediction. The development includes a new thinning method considering the spatially correlated observation errors in the dense radar data. This new thinning method is effective in two past case studies in the summer of 2019.

The objective of this study is to evaluate the spectral difference between and within 11 tree species belonging to Brazilian Atlantic Forest located in the countryside of São Paulo State, Brazil. Tree species with different development stages may have different reflectance spectra because of the structural and phenological influence on it. Tree structure can affect the crown spectra due to the differences in geometry of view and density of shadow and sunlight pixels. Additionally, reflectance spectra can be similar between tree species belonging from different species, which affect the classification accuracy of these targets. In this sense, we evaluate the spectral difference between highly diverse Atlantic Forest using two different features extracted from individual tree crowns (ITCs). Mean reflectance spectra and mean normalized reflectance spectra of each ITC were used. They were computed from hyperspectral images acquired with sensor onboard unmanned aerial vehicle. Differences between tree species and within-species were calculated. Wilcoxon-Mann-Whitney test was applied in order to statistically evaluate whether the reflectance spectra were different. Results showed that the normalized values are more propense to increase the classification accuracies than using the mean values since it reduces the variability within-species and present a higher number of different values between-species.

Rock mass surface colour is crucial for weathering assessment. CIELAB colour space and Munsell chart are methods to express the surface colour of rock masses. This study analysed the L*a*b* value from both approaches and examined the effectiveness and reliability of rock slope weathering assessment method. The Munsell Rock chart is a conventional method primarily used in practice. However, due to the constraint of individual vision and variation in the optical environment, errors and bias in rock surface colour can easily occur using the conventional method. The colourimeter was used to determine the CIELAB colour values of the samples, while the rock colour chart determined the colour coordinates and Munsell values. The Munsell hue and chroma were assigned using linear interpolation by Munsell conversion software CMC 2.1 to convert Munsell colour systems to L*a*b* value. A total of six granitic rock slopes were investigated. For quantitatively method, the Munsell optical system was less effective in assessing the rock mass surface colour. The positive correlation of a* and b* with R2=0.9407 demonstrated the efficiency of CIELAB system. The a*b* result of the rock slope indicated that most of the slopes were considered medium to strong with a moderately weathered surface. This result is strongly supported by a geomechanical test of Schmidt-UCS and index properties (Id2) with a range of 50-100 MPa and 2-4 MPa respectively. The finding verified mineralogical assessment which showed the correlation of rock mass surface colour to mineral composition. The study recommended any geotechnical and technical purpose in enhancing the method of weathering assessment by using the CIELAB colour space to rapidly and efficiently measure the rock surface colour.

Background Patients with diabetes mellitus are at very high risk for obstructive coronary artery disease; however, invasive coronary angiography is not allowed to apply in all patients. Cardio-ankle vascular index (CAVI), a marker of arterial stiffness has been reported to reflect atherosclerotic burden. Purpose To assess the diagnostic performance of CAVI vs. coronary calcium score for detecting obstructive coronary artery disease determined by Coronary CT angiography (CCTA) in asymptomatic diabetes patients. Methods During May 2015 to December 2019, 816 patients with diabetes mellitus were evaluated. First, intima-media thickness of carotid artery was measured in all subjects. Then, patients with intima-media thickness over 11mm underwent CAVI. Finally, 209 patients who have one or more cardiovascular risk factors other than diabetes mellitus were enrolled (68±11 years, 68% men). Patients were excluded if they had a disorder of the kidney, a prior history of coronary artery revascularization, atrial fibrillation, LV ejection fraction 50% by CCTA. Results CAVI, Agatston score, and intima-media thickness of carotid artery were 9.2±1.3, 396±621 and 2.0±0.7mm, respectively. CAVI was significantly correlated with age (r=0.530, p Conclusion CAVI could be informative to select patients having obstructive coronary artery disease in asymptomatic diabetes patients with thick intima-media thickness. Funding Acknowledgement Type of funding sources: None.

Background Doxorubicin (DOX)-based chemotherapy induces cardiotoxicity, which is considered the main limitation of its clinical application. Purpose The present study investigated the potential protective effect of sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, against DOX-induced cardiotoxicity in rats and H9c2 cells, and whether the underlying mechanism for any such protection involves its antioxidant activity. Methods Male Sprague-Dawley rats were randomly divided into four groups: DOX (1.5 mg/kg/day intraperitoneally for 10 days), DOX+valsartan (31 mg/kg/day by gavage from day 1 to day 18), DOX+sacubitril/valsartan (68 mg/kg/day by gavage from day 1 to day 18), and control (saline intraperitoneally for 10 days). There were 15 rats in each group. At the end of the treatment period, samples were collected and analysed. Cardiac function, tissue morphology, and reactive oxygen species (ROS) were evaluated in rats. Serum levels of Malondialdehyde (MDA) and cardiac troponin T were also measured. Mitochondrial ROS production and cell viability were evaluated in H9c2 cells. Results DOX-induced cardiac dysfunction was not prevented by valsartan and sacubitril/valsartan in this model. However, the serum level of cardiac troponin T on day 18 was increased in the DOX group (0.046±0.006 ng/mL, p Conclusions Sacubitril/valsartan protected rat hearts from DOX-induced cardiotoxicity in vivo and in vitro by decreasing oxidative stress. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This work was supported by Novartis Pharma K.K.

Background Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular (CV) events, therefore there is a need to identify T2DM patients at higher risk. A novel imaging biomarker, the peri-coronary adipose tissue (PCAT) attenuation on coronary CT angiography (CTA), reflects peri-coronary inflammation. We hypothesized that the assessment of PCAT attenuation is useful for risk stratification in T2DM patients. Purpose We aimed to investigate whether high PCAT attenuation is related to increased risk of CV events in T2DM patients. Methods This study is a post-hoc analysis of the prospective cohort study consist of T2DM patients who underwent clinically indicated coronary CTA at a Japanese University Hospital. As CT findings, coronary artery calcium score, epicardial adipose tissue volume, high-risk plaque features (positive remodeling, low density plaque, spotty calcification), significant stenosis (>50% luminal narrowing), and PCAT attenuation were examined. PCAT attenuation was assessed in Hounsfield units (HU) of proximal 40-mm segments of the left anterior descending artery. CV events was defined as CV death, acute coronary syndrome, and hospitalization for heart failure. Results In a total of 333 T2DM patients (63% male, age 66±11 years), the mean PCAT attenuation was −70.6±6.1 HU. During the follow-up period of 4.2 years, 20 CV events (2 cases of CV death, 14 of acute coronary syndrome, 4 of heart failure) were confirmed. Patients with CV events had higher PCAT attenuation than those without CV events (−67.4 vs −70.8 HU, p=0.013). Multivariate linear regression analysis revealed that the independent determinants of PCAT attenuation were male (p Conclusion High PCAT attenuation was a strong predictor of CV events in T2DM patients independent of coronary CTA findings and traditional risk factors. Our study suggested that assessment of PCAT attenuation could be a valuable tool for risk stratification in T2DM patients. Funding Acknowledgement Type of funding sources: None. Figure 1. Representative casesFigure 2. Kaplan-Meier curves

形態: カラー図版あり, Physical characteristics: Original contains color illustrations, Accepted: 2019-06-21, 資料番号: PA2010003000

Materials with strongly correlated electrons often exhibit interesting physical properties. An example of these materials is the layered oxide perovskite Sr2RuO4, which has been intensively investigated due to its unusual properties. Whilst the debate on the symmetry of the superconducting state in Sr2RuO4 is still ongoing, a deeper understanding of the Sr2RuO4 normal state appears crucial as this is the background in which electron pairing occurs. Here, by using low-energy muon spin spectroscopy we discover the existence of surface magnetism in Sr2RuO4 in its normal state. We detect static weak dipolar fields yet manifesting at an onset temperature higher than 50 K. We ascribe this unconventional magnetism to orbital loop currents forming at the reconstructed Sr2RuO4 surface. Our observations set a reference for the discovery of the same magnetic phase in other materials and unveil an electronic ordering mechanism that can influence electron pairing with broken time reversal symmetry., Strontium Ruthenate, Sr2RuO4, displays a remarkable number of intriguing physical phenomena, from superconductivity, to strain-induced ferromagnetism. Here, using low-energy muon spectroscopy, Fittipaldi et al. demonstrate the existence of unconventional magnetism at the surface of Sr2RuO4 in its normal state and without any applied strain.

We introduce an extended SEIR infectious disease model with data assimilation for the study of the spread of COVID-19. In this framework, undetected asymptomatic and pre-symptomatic cases are taken into account, and the impact of their uncertain proportion is fully investigated. The standard SEIR model does not consider these populations, while their role in the propagation of the disease is acknowledged. An ensemble Kalman filter is implemented to assimilate reliable observations of three compartments in the model. The system tracks the evolution of the effective reproduction number and estimates the unobservable subpopulations. The analysis is carried out for three main prefectures of Japan and for the entire population of Japan. For these four populations, our estimated effective reproduction numbers are more stable than the corresponding ones estimated by a different method (Toyokeizai). We also perform sensitivity tests for different values of some uncertain medical parameters, like the relative infectivity of symptomatic / asymptomatic cases. The regional analysis results suggest the decreasing efficiency of the states of emergency., Comment: 29 pages, 18 figures, 1 table

Background Previous clinical studies showed that early intravenous metoprolol before reperfusion in patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI reduced infarct size. However, intravenous beta-blockers in acute phase of STEMI can be associated with adverse effects such as cardiogenic shock and atrioventricular block. Landiolol is an ultrashort-acting beta-blocker with a half-life of 3 min that is eight times more cardioselective than esmolol. Purpose We evaluate the efficacy of intravenous infusion of landiolol on infarct size and its safety in STEMI patients undergoing primary PCI. Methods This study is a multicenter randomized control trial. A total of 47 patients with Killip class II or less STEMI undergoing PCI within 12 hours of symptoms onset were randomized to receive intravenous landiolol (n=23) or not (control, n=24). Patients allocated to landiolol group delivered an intravenous continuous dose of 3μg/min/kg before reperfusion and then continued until a total dose of 50mg. All patients started oral metoprolol or carvedilol within 12 hours. The primary end point was myocardial salvage index (MSI) on magnetic resonance imaging performed 5 to 7 days after PCI. MSI was defined as the difference between the area at risk and the area of necrosis analyzed using a commercial software. Results Magnetic resonance imaging was performed in 35 patients (17 patients in landiolol group and 18 patients in the control group), and ischemia duration time was 229 minutes in the landiolol group and the 242 minutes in control. In adjusting for confounding variables, the areas of myocardium at risk were not difference in both groups (54.4g in the landiolol group, and 46.8g in the control group; p=0.31). However, MSI in the landiolol group was significantly reduced than that in the control group (36.8% and 57.0%; p In both group blood pressure was not difference in recruitment (142mmHg in landiolol group, and 144 in control) and starting PCI (163mmHg in landiolol group, and 165 in control). Regarding safety, the composite of death, malignant ventricular arrhythmia, cardiogenic shock, and atrioventricular block at 24 hours did not differ between the landiolol and the control groups (8.7% and 8.3%, respectively, p=0.93). Conclusion Early intravenous landiolol before starting primary PCI reduced infarct size in STEMI patients without significant hemodynamic adverse effects. Funding Acknowledgement Type of funding source: None

Background The cardio-ankle vascular index (CAVI) is a non-invasive measurement that evaluates arterial stiffness using the analysis of oscillometric waveform during cuff-Inflation. Several studies reported that CAVI is associated with cardiovascular risk factors, while the clinical prognostic value of CAVI as a surrogate marker of atherosclerosis has not been fully elucidated. Meanwhile, the Framingham risk score (FRS) is an established marker of cardiovascular outcomes. Purpose To investigate whether adding CAVI to Framingham risk score improves the prediction of cardiovascular events. Methods This prospective observational study included consecutive 422 patients with cardiovascular risk factors but without known coronary artery disease (69±8 years, 63% men). CAVI was measured by the oscillometric method with VaSera vascular screening system. Patients with atrial fibrillation, left ventricular ejection fraction Results During a median follow-up of 3.1 years, cardiovascular events occurred in 12.8% (3.3%, 15.7%, and 19.1% in the low, intermediate and high-risk group of stratification by FRS, respectively). The ROC curve analysis for discriminating cardiovascular events showed that the AUC of CAVI added to Framingham risk score was the highest compared to Framingham risk score and CAVI alone (CAVI added to Framingham risk score: AUC 66.9, 95% CI 59.6–74.2, Framingham risk score alone: AUC 61.5, 95% CI 53.8–69.1, CAVI alone: AUC 62.3, 95% CI 54.1–70.6). The logistic regression analysis demonstrated that CAVI and Framingham risk score were independent predictors of cardiovascular events (CAVI: OR 1.381, 95% CI 1.164–1.597, p=0.004, Framingham risk score: OR 1.135, 95% CI 1.044–1.225, p=0.007). Next, when logistic regression analysis was performed simultaneously on Framingham risk factor and CAVI, CAVI was an independent predictor of cardiovascular events (OR 1.347, 95% CI 1.124–1.569, p=0.009). Furthermore, in the likelihood ratio test, CAVI added to Framingham risk score significantly improved the cardiovascular event prediction ability than Framingham risk factor alone. Next, when patients with intermediate risk (n=217) were divided into two groups based on CAVI of 9.0, the Kaplan-Meier estimate showed that events occurred more frequently in higher CAVI group (9.3% and 29.1%, log-rank, P=0.009) and the C-statistic was 0.662. Multiple Cox analysis showed that, in the intermediate risk group, CAVI was an independent predictor of primary outcomes (HR 1.387 per 1 index, 95% CI 1.081–1.779, p=0.010). Conclusion The measurement of CAVI could be a useful predictor for cardiovascular events. In addition, the combination of CAVI and Framingham risk score could improve the predictability compared to the Framingham risk score alone. Funding Acknowledgement Type of funding source: None

Background Recent ESC/EAS Guidelines for the management of dyslipidemia stated that the treatment goal of LDL cholesterol (LDL-C) in very high-risk patients is less than 55mg/dl. PCSK9 inhibitors in addition to strong statins could be a useful strategy for rapid and aggressive lowering of LDL-C. However, the feasibility and safety of early initiation of a PCSK9 inhibitor for AMI patients undergoing primary PCI remain unclear. Objectives We examined the effects of early initiation of a PCSK9 inhibitor, evolocumab, on lipid profile and inflammatory markers and its safety in AMI patients undergoing primary PCI. Methods This study is a single center, randomized, controlled trial involving 102 patients hospitalized for AMI. The patients were randomly assigned 1:1 to the evolocumab group and the control group. Evolocumab (140 mg) was subcutaneously injected within 24 hours after PCI and then every two weeks. All patients received pitavastatin (2mg/day) in addition to the allocated treatment. The primary endpoints were changes in lipid profile and inflammatory markers from baseline to 4 weeks. Results 102 patients were enrolled between October 2017 and December 2019. 89 patients were ST-segment elevation myocardial infarction (STEMI), 13 patients were non-STEMI. Primary PCI was successfully performed in all patients. 76 patients were statin-naïve. 2 patients were excluded from analyses because they died severe heart failure in acute phase. Finally, 100 patients (evolocumab; n=51 and control; n=49) were analyzed. Baseline LDL-C was 121.6±30.3 mg/dl in the evolocumab group and 124.7±33.6 mg in the control group. Change in LDL-C from the baseline to 4 weeks was −92.4±32.4 mg/dl (−75%) in the evolocumab group and −44.8±32.1 mg/dl (−33.1%) in the control group (mean difference; 47.6mg/dl, 95% CI; 34.8 to 60.4 mg/dl, p Conclusion In patients with AMI undergoing primary PCI, early initiation of evolocumab rapidly reduced LDL-C without no adverse event, and achieved LDL-C Funding Acknowledgement Type of funding source: None

Background For the prevention of future cardiovascular events, control of residual risks such as triglyceride rich lipoproteins and HDL-cholesterol is an emerging problem beyond LDL-cholesterol. Triglyceride to HDL-cholesterol ratio (TG/HDL ratio) has been reported to be useful for risk classification of cardiovascular diseases. Meanwhile, several studies showed that high-risk plaque characteristics evaluated with coronary CT angiography (cCTA) was associated with the incidence of acute coronary syndrome. However, the relationship of TG/HDL ratio with coronary plaque characteristics and its impact of this association on future coronary events have not been fully elucidated. Purpose The aim of this study was to evaluate the association between TG/HDL ratio and high-risk plaque detected by cCTA and its impact on future coronary events. Methods A total of 944 patients suspected stable coronary artery disease who underwent cCTA at our institution were analyzed (mean 64-year-old, 55% male). Patients were divided into two groups by the median value of TG/HDL ratio (higher TG/HDL: TG/HDL ratio ≥2.0, lower TG/HDL: TG/HDL ratio 1.1) and spotty calcification. Cardiovascular event was defined as cardiovascular death, acute coronary syndrome, and late coronary revascularization after 30 days of CT acquisition. Results The higher TG/HDL ratio was significantly associated with male gender (63% vs. 48%, P Conclusion TG/HDL ratio is involved in the vulnerability of CT-verified coronary plaque characteristics. This association may play an important role in the prognostic impact of TG/HDL ratio on future cardiovascular events. Funding Acknowledgement Type of funding source: None

Background Abdominal aortic aneurysm (AAA) is a life-threatening disease, while effective and preventive medical treatments remain unestablished. Purpose The aim of this study was to evaluate the effect of selective peroxi- some proliferator-activated receptor alpha (PPARα) modulator pemafibrate on AAA formation in mice. Methods AAA was induced by subcutaneous infusion of angiotensin II (AngII) in apolipoprotein E-deficient mice for 4 weeks. Treatment by pemafibrate or vehicle was started one week before AngII infusion. Oxidative stress was evaluated by dihydroethidium (DHE) staining. Results Prognosis after AngII infusion in pemafibrate-treated mice was significantly better than that in vehicle-treated mice (log-rang test, p=0.035) by reducing the occurrence of fatal AAA rupture. Meanwhile pemafibrate did not significantly reduce maximal diameter of the aorta. Histological findings demonstrated that the expression of collagen in adventitia in pemafibrate-treated mice was significantly greater than that in vehicle-treated mice (p Conclusion Pemafibrate reduced the rupture of AAA in this murine model, which is associated with anti-oxidative stress via catalase induction. Funding Acknowledgement Type of funding source: None

The objective of this study was to evaluate the impact of reducing the radiometric information of hyperspectral images. The image data was collected originally with 32 bits and rescaled to 8 and 16 bit/pixel. The images were acquired with a Rikola Hyperspectral Camera attached to an Unmanned Aerial Vehicle (UAV). After the geometric and radiometric processing of the images, a mosaic was obtained with pixels representing reflectance factor coded in 32 bits. Using the minimum and maximum values of each spectral band, a linear equation was thus applied to reduce the radiometric resolution of the original mosaic, from 32 bits to 8 bits and from 32 bits to 16 bits. Following, the Normalized Root Mean Square Error (NRMSE %) and the Mean Absolute Percentage Error (MAPE %) were used to evaluate the results, showing that for the 8 bits mosaic, the loss of information was higher. For this radiometric resolution rescaling, the MAPE % achieved values until 22.486 % and the highest NRMSE % value was 0.455 % while, for the 16 bits mosaics, the highest MAPE % and NRMSE % values were 0.069 % and 0.002 %, respectively. Finally, it can be inferred that the impact of radiometric transformation can be considered as negligible for the hyperspectral mosaic with 16 bits of radiometric resolution, which presented lower values of NRMSE % and MAE % and could not affect the mosaic analysis.

This study investigated the performance of a hybrid membrane filtration system to produce industrial water from highly-colored surface water. The system consists of a membrane filtration process with appropriate pretreatments, including coagulation, pre-chlorination, and anion exchange (IE) process. The results of the pilot-scale experiments revealed that the hybrid system can produce treated water with color of around 5 Pt-Co, dissolved manganese concentration of no more than 0.05 mg/L, and a silt density index (SDI) of no more than 5 when sufficient coagulant and sodium hypochlorite were dosed. Although the IE process effectively reduced the color of the water, a moderate increase in the color of the IE effluent was observed when there was a significant increase in the color of the raw water. This resulted in a severe membrane fouling, which was likely to be attributed to the excess production of inorganic sludge associated with the increased coagulant dosage required to achieve sufficient reduction of color. Such severe membrane fouling can be controlled by optimising the backwashing and relaxation frequencies during the membrane filtration. These results indicate that the hybrid system proposed is a suitable technology for treating highly-colored surface water.

Introduction As a residual cardiovascular risk, high-density lipoprotein (HDL) is of great interest in lipid management. Native HDL has an anti-atherogenic role, while oxidized HDL (oxHDL) has atherogenic property because of reduced anti-inflammatory properties compared with native HDL. Meanwhile, recent studies showed that rapid progression of coronary artery calcification (CAC), a marker of subclinical atherosclerosis, was associated with greater incidence of cardiovascular events. However, the role of oxHDL in the pathogenesis of CAC remains unclear. Purpose The purpose of this study was to examine the association between the annual change in oxHDL and the progression of CAC (Agatston score) in a substudy of prospective multicenter randomized study. Methods In the principal study, patients with a CAC score of 1 to 999 were treated with pitavastatin with/without eicosapentaenoic acid. Measurement of CAC with MDCT and a blood test were performed at baseline and at the 1-year follow-up. The principal study showed 30–40% of annual change in CAC in all patients and no difference in the progression of CAC among treatment groups. In this substudy (n=140), patients were divided into 2 groups: CAC progression (change in Agatston score of >0, n=103) and no CAC progression (n=37). The serum concentration of oxHDL was measured using an antibody against oxidized human apoA-I with ELISA. The difference in oxHDL between patients with hypercholesterolemia and healthy subjects (n=30) was also evaluated. Results OxHDL levels were significantly lower in healthy subjects than in patients with hypercholesterolemia (150 [107–176] and 167 [132–246], respectively; median [25th-75th percentile], U/ml) (p=0.006). The baseline log-transformed oxHDL level was correlated with total cholesterol (r=0.21, p=0.01), HDL-cholesterol (r=0.33, p Conclusion The decrease in oxHDL is associated with the attenuation of CAC progression, suggesting that oxHDL is a potential target for preventing atherosclerosis.

Introduction Development of chemoradiation therapy (CRT) has improved mortality in patients with cancer. Whereas, it is emerging problem that cancer-survivors suffer from cardiovascular diseases, and the association between modern CRT and the increase in future cardiovascular events is suggested. Meanwhile, previous studies showed that thoracic aortic calcification (TAC) detected by computed tomography (CT), a marker of atherosclerosis, was associated with all-cause mortality and cardiovascular events. However, the influence of CRT on TAC progression remains unclear. Purpose The purpose of this study was to evaluate whether CRT would exacerbate TAC. Methods A total of 68 patients who treated lung cancer at our hospital between 2011 and 2015 were retrospectively analyzed (mean 62 year-old, male 78%): 35 patients underwent surgical treatment after induction CRT (CRT group) and 33 patients underwent surgical treatment alone (control group), extracted by propensity score matching by age, sex, smoking status, and diseased side. The volume of TAC between 2nd and 12th thoracic vertebrae was quantitatively measured with CT imaging, at baseline and at 1 year follow-up. The annual percent change in TAC was compared between the CRT and the control group. Moreover, the independent relationship between implementation of CRT and the progression of TAC was assessed by multivariate logistic regression analysis, adjusting for age, gender, conventional atherosclerotic risk factors and baseline aortic calcification volume. Results Patients in the CRT group received radiation (mean 47.3±4.0 Gy) and chemotherapy: 2 courses of cisplatin with docetaxel (34 cases) or vinorelbine (1 case). The prevalence of dyslipidemia, taking statins and diabetes drugs were significantly higher in the control groups (17% vs. 39%; p=0.041, 11% vs. 33%; p=0.029, 3% vs. 18%; p=0.044, respectively). Baseline C-reactive protein level was significantly higher in the CRT group (0.255 vs. 0.115; p=0.034). In univariate analysis, the annual percent change in TAC volume was significantly increased in the CRT group compared with the control group (37.6% vs. 23.3%; p=0.006). Multivariate logistic regression analysis demonstrated that CRT was an independent factor associated with the progression of TAC volume, even after adjustment for baseline calcification volume and coronary risk factors (OR, 3.90; 95% CI, 1.32–11.47; p=0.014). Conclusion CRT to patients with lung cancer exacerbates thoracic aortic calcification, which may result in future cardiovascular events.

Background Recent randomized, placebo-controlled trial in patients with type 2 diabetes demonstrated that the sodium-glucose cotransporter 2 inhibitors reduced mortality, cardiovascular events and hospitalization for heart failure. However, those trials were not specialized design to investigate the effect of sodium-glucose cotransporter 2 inhibitors in patients with heart failure, in particular with heart failure with preserved ejection fraction. Purpose The aim of this study was to evaluate the drug efficacy of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, compared with voglibose, an alpha-glucosidase inhibitor, using brain natriuretic peptide (BNP) in type 2 diabetes patients with heart failure with preserved ejection fraction. Methods This study was a prospective, multicenter, open-label, randomized-controlled trial, comparing luseogliflozin 2.5 mg once daily or voglibose 0.2 mg three times daily in patients with type 2 diabetes suffering from heart failure with preserved ejection fraction (left ventricular ejection fraction >45% and BNP ≥35 pg/ml2) in a 1:1 randomization fashion. Randomization was undertaken using a computer-generated random sequence web response system. The primary outcome was the difference from baseline in BNP after 12 weeks of treatment between two drugs. The key secondary outcomes were the change from baseline in left ventricular ejection fraction and E/e' in echocardiographic parameters, body weight, glycohemoglobin level after 12 weeks of treatment. The safety outcomes included the incidence of major adverse cardiovascular events, hypoglycemic adverse events, and urinary tract infection. Results Between December 2015 and September 2018, 173 patients from 16 hospitals and clinics have been included in this study. Of those, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in the BNP concentration after 12 weeks from baseline between the two groups; the ratio of the average values at week 12 to the baseline value was 0.91 in the luseoglifllzin group as compared with 0.98 in the voglibose group (percent change, −9.0% vs. −1.9%, ratio of change with luseogliflozin vs. voglibose, 0.93; 95% confidence interval, 0.78 to 1.10; p=0.26). The key secondary outcomes including left ventricular ejection fraction, E/e', body weight, glycohemoglobin level and the safety outcomes did not differ significantly between the two groups. Conclusions In type 2 diabetes patients with heart failure with preserved ejection fraction, the administration of luseogliflozin did not lead to a significant reduction in the BNP concentration than that of voglibose. Left ventricular ejection fraction, E/e', body weight and glycohemoglobin level after 12 weeks of treatment, comparing with at baseline did not differ significantly between the two groups. (UMIN Clinical Trial Registry number, UMINehz748.005618395) Acknowledgement/Funding Novartis

Background Fractional flow reserve derived from CT-coronary angiography (FFRCT) accurately identifies ischaemic vessels which may be associated with clinical outcomes. Its predictive value in grey zone FFRCT values between 0.7–0.8 is not defined. The technique permits estimation of burden of ischaemic myocardium subtended by FFRCT significant vessels. Purpose To evaluate the prognostic value and incremental benefit of FFRCT defined ischaemic myocardial burden when compared to FFRCT alone. Methods This is a subanalysis of NXT (Analysis of Coronary Blood-Flow Using CTA:Next-Steps), a prospective study of stable coronary artery disease (CAD) patients referred for invasive angiography (ICA) undergoing invasive FFR, CTA and FFRCT in whom treating physicians had been blinded to FFRCT results. Primary endpoint, defined as a composite of non-fatal myocardial infarction and any revascularisation, was determined in 206 patients (age 64±9.5 years, 64% male) and 618 vessels. Burden of ischaemic myocardium was defined as percentage of myocardium subtended beyond the point at which a vessel's FFRCT becomes ≤0.8 as estimated by APPROACH score (FFRCT-APPROACH). In significant FFRCT vessels, the predictive value and incremental benefit of FFRCT-APPROACH was compared with significant FFRCT (≤0.8) for primary endpoint as measured by area under the receiver operator characteristic curve (AUC). Significant ischaemic myocardial burden was defined as >10%. The incidence and relationship between the primary endpoint with each 10% increase in FFRCT-APPROACH and 0.05-unit decrease in FFRCT values ≤0.8 was determined. Results Significant FFRCT was identified in 52.9% of patients (109/206) and 29.3% of vessels (181/618). At 4.7 years median follow-up the incidence of the primary endpoint in vessels with significant FFRCT-APPROACH was 58.9% (96/163) which was comparable with vessels with significant FFRCT (55.2%,100/181; P=0.50). The predictive value of FFRCT-APPROACH for the primary endpoint was comparable with FFRCT (AUC 0.72 [95% CI 0.65–0.79] vs 0.71 [0.63–0.78], P=0.79). When combined, there was significant predictive improvement compared with FFRCT alone (AUC 0.77 [0.70–0.84]; P=0.01). The largest incremental benefit upon FFRCT was observed in vessels with FFRCT values in the grey zone between 0.70–0.80 (AUC 0.76 [0.65–0.86] vs 0.62 [0.48–0.74]; P Conclusion In patients with stable CAD referred for ICA, the burden of ischaemic myocardium subtended by FFRCT significant vessels predicted non-fatal myocardial infarction and future revascularisation. This provided significant incremental benefit when used in combination with FFRCT particularly at FFRCT values in the grey zone between 0.7 to 0.8.

Disease outbreaks caused by yellow head virus (YHV) can result in significant economic losses for shrimp aquaculture; however, little is known about how YHV is transmitted. Here we evaluate the role of direct and indirect contact with YHV among Penaeus monodon . One in 3 specimens released into 5 experimental tanks was inoculated with the virus, and 100 μm-filtered water from each tank was allowed to circulate through another tank containing an additional set of 3 naive P. monodon . All of the injected shrimps died within 4 d; 9 of the 10 shrimps cohabitating with them died within 10 d. Only 5 of the 15 shrimps in the water-exposed tanks died within 14 d. As determined by RT-nested PCR, YHV infection was also lower among shrimp exposed to water. To assess the potential of moribund shrimp to transmit disease, gill samples from individuals inoculated with YHV at either 12 h or 24 h after the onset of the first obvious signs of morbidity were injected into naive P. monodon housed in individual tanks. Over a 30-d period following inoculation, the mortality rate was higher among shrimps injected with 12 h gill extracts than in those injected with 24 h gill extracts. Taken together, these data suggest that cannibalism of moribund shrimps presents a far greater potential to transmit the yellow head disease than does water exposure alone. Removing moribund shrimps as soon as morbidity becomes evident could represent an efficient measure to reduce YHV transmission and disease outbreaks.

To successfully assimilate data from a new observing system, it is necessary to develop appropriate data selection strategies, assimilating only the generally useful data. This development work is usually done by trial and error using observing system experiments (OSEs), which are very time and resource consuming. This study proposes a new, efficient methodology to accelerate the development using ensemble forecast sensitivity to observations (EFSO). First, non-cycled assimilation of the new observation data is conducted to compute EFSO diagnostics for each observation within a large sample. Second, the average EFSO conditionally sampled in terms of various factors is computed. Third, potential data selection criteria are designed based on the non-cycled EFSO statistics, and tested in cycled OSEs to verify the actual assimilation impact. The usefulness of this method is demonstrated with the assimilation of satellite precipitation data. It is shown that the EFSO-based method can efficiently suggest data selection criteria that significantly improve the assimilation results.

The NIRS has carried out carbon-ion radiotherapy (RT) with HIMAC since 1994. On the basis of their ten-year HIMAC experience, NIRS has developed a standard-type CIRT facility in order to boost availability of carbon-ion RT in Japan. Work has been carried out at its pilot facility at Gunma University since 2010. The current projects of the pilot facility include Saga-HIMAT and i-ROCK, promoted by the Kanagawa prefectural cancer center. Toward the further sophisticated conformal carbon-ion RT with HIMAC, the NIRS has since 2006 been developing new treatment technologies, such as a fast 3D rescanning with a pencil beam and a compact rotating gantry.

A tsunami coda lasting more than 5 days was clearly recorded across the Pacific Ocean following the 2011 Tohoku‐Oki earthquake. We found that the coda energy per unit area (elapsed time of 60–96 hr from the earthquake origin time) does not show a systematic variation with respect to the travel distance at the stations located at sea depths deeper than 2000 m, whereas the maximum amplitude near the source is significantly larger than those of the far‐field stations. This feature is similar to that of a seismic coda in the sense that the coda energy is distributed uniformly in space. The average tsunami coda decays with a decay time of ∼24 hr. When we carefully examined the tsunami waveform near Japan, a large‐amplitude wave was identified at an elapsed time of ∼48 hr, which corresponds to the round‐trip travel time for waves reflected from Chile. To investigate the excitation mechanisms of the tsunami coda, we conducted a tsunami simulation using a global model. Although linear long‐wave tsunami equations were found to overestimate the observed coda amplitude, the equations including an intrinsic energy loss could successfully simulate the observed coda decay if a bottom friction coefficient of 10 −5 was assumed. This indicates that not only wave scattering but also intrinsic energy loss plays an important role in the tsunami coda excitation and decay process.

We newly developed a data assimilation system based on a particle filter approach with the Spatially Explicit Individual-Based Dynamic Global Vegetation Model (SEIB-DGVM). We first performed an idealized observing system simulation experiment to evaluate the impact of assimilating the leaf area index (LAI) data every 4 days, assuming the satellite-based LAI. Although we assimilated only LAI as a whole, the forest and grass LAIs were estimated separately with high accuracy. Uncertain model parameters and other state variables were also estimated accurately. Therefore, we extended the experiment to the real world using the real Moderate Resolution Imaging Spectroradiometer (MODIS) LAI data, and obtained promising results.

In this paper, we propose the design and implementation of an ensemble data assimilation (DA) framework for weather prediction at a high resolution and with a large ensemble size. We consider the deployment of this framework on the data throughput of file input/output (I/O) and multi-node communication. As an instance of the application of the proposed framework, a Local Ensemble Transform Kalman Filter (LETKF) was used with a Non-hydrostatic Icosahedral Atmospheric Model (NICAM) for the DA system. Benchmark tests were performed using the K computer, a massive parallel supercomputer with distributed file systems. The results showed an improvement in total time required for the workflow as well as satisfactory scalability of up to 10 K nodes (80 K cores). With regard to high-performance computing systems, where data throughput performance increases at a slower rate than computational performance, our new framework for ensemble DA systems promises drastic reduction of total execution time.

BACKGROUND AND PURPOSE: Volumetry may be useful for evaluating treatment response and prognosis of intraocular lesions. Phantom, volunteer, and patient studies were performed to determine whether ocular MR volumetry is reproducible. MATERIALS AND METHODS: Half-Fourier single-shot RARE and FSPGR sequences at 1.5T with a 76-mm-diameter surface coil were optimized to obtain still ocular images. Volumetry accuracies of each sequence were compared with simulated subretinal phantom volumes. Ocular volumetry was performed in 15 volunteers twice in 1 week by using contiguous axial images of the globes while the subjects stared at a target, and images were acquired in 2 seconds before the subjects were instructed to blink, with this process repeated as necessary. Imaging, intraobserver, and interobserver reproducibility for volumes of the whole eyeball and anterior chamber were assessed. Ocular volumetry was also performed in 6 patients with intraocular tumors before and after treatment. RESULTS: The phantom study demonstrated that measurement error rates with RARE were significantly lower than with FSPGR (P < .01). The volunteer study demonstrated excellent imaging and intraobserver reproducibility of RARE volumetry for whole eyeballs and anterior chambers (P < .01). Although no interobserver differences were observed in anterior chamber volume measurement (P = .33), there was a significant difference between the 2 observers in eyeball volume measurement (P < .01). Follow-up volumetric data were useful for treatment decisions in all patients. CONCLUSIONS: Ocular volumetry from contiguous ultrafast RARE images obtained during visual fixation is feasible in volunteer and patient studies and is superior to FSPGR images.

The superlattice structure (phase III) of {N(CH3)4}2MnCl4 was analyzed from the X-ray diffraction data by using Fourier synthesis method based on maximum entropy algorithm. The partially disordered MnCl4 was found without assuming a specified structural model. As the occupation probability of Cl changes, the mean position of the atom deviates continuously from the c-glide plane, which explains the temperature dependence of the superlattice reflection intensity with decreasing temperature in the commensurate phase III. The ordering of N(CH3)4 is also found to be similar with the behavior of MnCl4.

On the basis of more than 10 years of experience with HIMAC, we proposed and designed a new treatment research facility, as an extension of the existing facility, for the further development of radiotherapy with HIMAC. The new facility employs a 3D rescanning technique developed at NIRS. Its building construction was completed in March 2010 and the devices are being installed. A beam commissioning and a pre-clinical study will be initiated from this October. Here, we report recent progress for this new treatment facility project at HIMAC.

Based on more than 10 years of experience with HIMAC, we have proposed a new treatment facility for the further development of therapy with HIMAC. The new facility, as an extension of the existing one, has been designed and the related R&D work has been carried out. The following descriptions give a summary account of the design study and the related R&D work for this new treatment facility at HIMAC.

New experimental data on the charge-state (q) evolution fractions Fq(D) and equilibrium charge-state fractions F q ∞ are presented when 2.65 MeV/u C2+, O3+, Ne4+ and Si5+ projectile ions passed through carbon foils with thickness of D = 10–200 μg/cm2. The equilibrium fractions F q ∞ for Si + C collisions (i.e. for silicon ions colliding with carbon foils) are compared with the data at 4.3 and 6.0 MeV/u previously reported, and the observed significant difference is explained by different energy dependencies of the electron-capture and projectile-ionization cross sections. Detailed information about nl-state distribution functions Nq(nl) of exit silicon ions is obtained for these three energies by solving linear balance equations for Nq(nl) values where n and l are the principal and orbital quantum numbers, respectively, and ∑ nl N q ( nl ) = F q ∞ . The collision cross sections and radiative decay rates as the coefficients of these balance equations are calculated for each ion-beam energy. Based upon the present method, it is found that the fractions of excited Si ions after the carbon foil are about 57%, 33% and 15% at energies of 2.65, 4.3 and 6.0 MeV/u, respectively, clearly indicating the significant reduction of the excited-ion component with the collision energy increasing. The calculated equilibrium charge-state fractions F q ∞ for Si ions are in good agreement with available experimental data.

The effect of Ti and C additions on the microstructures and the magnetic properties of Nd–Fe–B isotropic nanocomposite processed from Nd 9 Fe 77 B 14 , Nd 9 Fe 73 B 14 Ti 4 and Nd 9 Fe 73 B 12.6 C 1.4 Ti 4 (numbers indicate at.%) alloys has been investigated by transmission electron microscopy and three-dimensional atom probe techniques. The grain size was substantially refined by the addition of Ti due to the formation of Ti-enriched amorphous grain boundary. Further addition of C enhanced the enrichment of Ti in the grain boundary phase, which led to the increase of coercivity and maximum energy product.