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Aim Women who inevitably underwent surgical hysterectomy before natural menopause may have an earlier increase in hematocrit and storage iron than women who continue menstruation, thereby increasing the risk of cardiovascular disease (CVD) early. We aimed to evaluate the association of women with hysterectomy vs. without hysterectomy before their 50s with the risk of incident CVD. Methods This was a retrospective-cohort study, 135,575 women aged 40 to 50 years in 2011–2014 were extracted from the Korean Health Insurance Review and Assessment Service data and after propensity score matching, 55,539 pairs were included in hysterectomy and non-hysterectomy group respectively. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of cardiovascular death, myocardial infarction (MI), stroke, and coronary artery revascularization. Results After adjustment for confounding factors, hysterectomy group had an increased risk of MACCE compared with non-hysterectomy group (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.09–1.44). Regarding individual outcomes, cardiovascular death, MI, and coronary revascularization were comparable between the groups, whereas, the risk of stroke was significantly higher in hysterectomy group than non-hysterectomy group (HR, 1.31; 95% CI, 1.12–1.53). Even after excluding women who underwent oophorectomy, hysterectomy group had a higher risk of MACCE than non-hysterectomy group (HR, 1.24; 95% CI 1.06–1.44). Conclusions Early surgical menopause due to hysterectomy, not hormonal menopause, was associated with an increased risk for a composite of CVD, especially stroke. This suggest that the role of “uterus” as well as sex hormones may be important for the sharp increase in the risk of CVD in women after menopause. Funding Acknowledgement Type of funding sources: None.

Background Relationship between the level of antiplatelet effect and clinical event appears weak in East Asian patients. In addition prognostic implication of platelet reactivity may differ according to index presentation of disease entity (AMI vs. non-AMI). Methods PTRG-PFT consortium was established to determine the linkage of platelet function with long-term clinical outcome during DAPT (aspirin+clopidogrel) in DES-treated East Asian patients (n=11,714). Platelet reactivity was measured using the VerifyNow P2Y12 assay and its level was divided according to quartile distribution (≤168, 169–220, 221–271, ≥272 P2Y12 reaction unit [PRU]). Primary endpoints were incidences of major adverse cardiac and cerebrovascular events (MACCE) post-PCI. Results Impact of platelet reactivity on MACCE occurrence appeared proportionally increased irrespective of type of disease entity, but their relationship was relatively stronger in the AMI vs. non-AMI group (Figure 1A and B). The cutoff of high-risk platelet reactivity was lower in the AMI group compared with the non-AMI group (225 vs. 245 PRU), and the cutoff of low-risk platelet reactivity (immunity zone) was similar between the groups (175 vs. 170 PRU). In the AMI patients (28.5%), 3rd and 4th quartiles significantly increased MACCE rate (HRadjusted 2.19 and 2.24) (Figure 1C and D). However, 4th quartile only was significantly associated with increased risk of MACCE among the non-AMI patients (71.5%) (HRadjusted 2.19). Conclusion Close associations between platelet reactivity and MACCE occurrence were observed irrespective of type of disease entity. In addition, the targeted antiplatelet level to prevent platelet-centric events appeared similar between the AMI and non-AMI patients. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Korean Society of Intervention Cardiology

Background Although active rhythm control by atrial fibrillation (AF) catheter ablation (AFCA) reduces left atrial (LA) dimension, blunted atrial reverse remodeling can be observed in patients with significant atrial myopathy. We explored the characteristics and long-term outcomes of AF patients who showed blunted atrial reverse remodeling despite no AF recurrence within a year after AFCA. Methods Among a total of 2,756 patients with AFCA, we included 1,685 patients (74.8% male, 60.2±10.1 years old, 54.5% paroxysmal AF) who underwent both baseline and 1-year follow-up echocardiogram, baseline LA>40mm, and did not recur within a year. We divided them into tertile groups (T1–T3) based on one-year percent change of LA dimension after propensity matching for age, sex, AF type, and baseline LA dimension. We also investigated the patients' genetic characteristics with blunted LA reverse remodeling (T1) using a genome-wide association study (GWAS). Results Patients with blunted LA reverse remodeling (T1, n=424) were independently associated with body mass index (OR 1.082 [1.010–1.160], p=0.025), LA peak pressure (OR 1.010 [1.002–1.019], p=0.019), LA wall thickness (OR 0.448 [0.252–0.789], p=0.006), LA voltage (OR 0.651 [0.463–0.907], p=0.012), and pericardial fat volume (OR 1.004 [1.001–1.008], p=0.014). Throughout 65.9±37.4 months of follow-up, the incidence of AF recurrence a year after the procedure was significantly higher in the T1 group than in T2 or T3 groups (Log-rank p Conclusions Patients with blunted LA reverse remodeling after AFCA were independently associated with low LA voltage, thin wall thickness, high LA pressure, and fat volume, and have a genetic background. Long-term clinical recurrence a year after AFCA was higher in this patient group with suspicious atrial myopathy. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health and WelfareNational Research Foundation of Korea

OBJECTIVE The current grading system for moyamoya disease (MMD) is focused on angiographic studies with limited clinical application. The authors aimed to determine relevant factors that may impact postoperative outcome and establish a scoring system to predict the functional outcome. METHODS Adult patients with MMD who underwent treatment between 1998 and 2016 were included. Factors such as age, sex, comorbidity, smoking, MMD family history, initial presentation, multimodal imaging modalities, and types of surgical revascularization were thoroughly reviewed. These factors were analyzed to determine possible risk factors related to unfavorable 6-month postoperative outcomes using the modified Rankin Scale (mRS) (unfavorable: mRS score ≥ 3). A scoring system was developed using these independent risk factors to predict the outcome and validated using prospectively collected data from multiple centers between 2017 and 2018. RESULTS Of 302 patients for whom applications were submitted, 260 patients (321 hemispheres) met the diagnostic criteria. In multivariate analysis, hyperlipidemia, smoking, cerebral infarction on preoperative CT or MRI, and moderately to severely reduced regional cerebrovascular reserve results from Diamox SPECT were significantly related to unfavorable outcome. The authors developed a scoring system and stratified patients into risk groups according to their scores: low-risk (score 0–3), intermediate-risk (score 4–6), and high-risk (score 7–9) groups. This model demonstrated both good discrimination and calibration using C-statistics and the Hosmer-Lemeshow goodness-of-fit test showing 0.812 (95% CI 0.743–0.881) (p = 0.568) for the development and 0.954 (95% CI 0.896–1) (p = 0.097) for the temporal and external validation cohort. CONCLUSIONS The authors’ scoring system is readily adoptable to predict the postoperative outcome for MMD. Their data revealed the importance of smoking and hyperlipidemia, which were the only modifiable factors included in the scoring system. The authors validated their scoring system both internally and externally and maintained good performance, highlighting the system’s generalizability and reliability.

During bursty MHD events, transient ion cyclotron emission (ICE) is observed from deuterium plasmas in the large helical device (LHD) heliotron-stellarator. Unusually, the frequencies of the successive ICE spectral peaks are not close to integer multiples of the local cyclotron frequency of an energetic ion population in the likely emitting region. We show that this ICE is probably driven by a subset of the fusion-born protons near their birth energy E H = 3.02 MeV. This subset has a kinetic energy component parallel to the magnetic field, m H v ∥ 2 / 2 , significantly greater than its perpendicular energy m H v ⊥ 2 / 2 , for which v ⊥ ∼ V A , the Alfvén speed. First principles computations of the collective relaxation of this proton population, within a majority thermal deuterium plasma, are carried out using a particle-in-cell approach. This captures the full gyro-orbit kinetics of all ions which, together with an electron fluid, evolve self-consistently with the electric and magnetic fields under the Maxwell–Lorentz equations. The simulated ICE spectra are derived from the Fourier transform of the fields which are excited. We find substantial frequency shifts in the peaks of the simulated ICE spectra, which correspond closely to the measured ICE spectra following the resonance condition ω = k ∥ v ∥ + n Ω H for nth proton harmonic. This suggests that the transient ICE in LHD is generated by the identified subset of the fusion-born protons, relaxing under the magnetoacoustic cyclotron instability. So far as is known, this is the first report of a collective radiation signal from fusion-born ions in anon-tokamak magnetically confined plasma. Disambiguation between two or more energetic ion species that could potentially generate complex observed ICE spectra is an increasing challenge, and the results and methodology developed here will assist this. Our approach is also expected to be relevant to ICE driven by ion beams with lower parallel velocities, for example in cylindrical plasma experiments.

Background and Purpose: Patients with intracerebral hemorrhage (ICH) have oxidative stress. Oxidative stress contributes to the development and progression of perihematomal edema (PHE) in brain hemorrhage patients. We hypothesized that reactive oxygen species (ROS) scavengers might have a neuroprotective role in the acute period of patients with ICH. Methods: This prospective, multicenter, single-blind, randomized study was conducted between June 2017 and October 2019. Intracranial bleeding, including spontaneous ICH, secondary ICH due to vascular anomalies, venous thrombosis, neoplasms, or hemorrhagic infarction, were included in our study. These ROS scavengers were given for 14 days with a dose of N-acetylcysteine 2000 mg/d and selenium 1600 µg/d intravenously. Other patients received a placebo. The primary outcome was hemorrhage and PHE volume changes in 2-week follow-up computed tomography between ROS scavenger versus placebo groups. Results: In total, 448 patients were enrolled with 123 patients remaining after applying the inclusion and exclusion criteria. There were no significant differences in baseline characteristics between the ROS scavenger (n=57) and placebo (n=66) groups. No significant differences in baseline hematoma and PHE volumes were observed but 2 weeks follow-up computed tomography showed significant differences in PHE volume (21.90±17.63 versus 30.66±32.35, P P P P Conclusions: ROS scavenger showed a significantly reduced PHE volume, time to reach target Richmond Agitation Sedation Scale, and shortened length of intensive care unit stay in patients with acute ICH. Early and high doses of ROS scavengers in a combination regimen may have played a key role in obtaining a favorable outcome in our study. Registration: URL: https://cris.nih.go.kr/cris/en ; Unique identifier: KCT0004628.

Background and purpose The increased demand for donor organs has made it crucial to keep the organs of patients with impending brain death (PWIBDs) suitable for transplantation during the process of determining brain death. This study aimed to identify the time taken to determine brain death (TT-BD) in PWIBDs and the associated influencing factors. Methods This study analyzed data collected by the Korean Organ Donation Agency from 15 hospitals in the Yeongnam region of South Korea. There were 414 PWIBDs eligible for inclusion in this study. The data consisted of the TT-BD for PWIBDs and the potential variables influencing the TT-BD. Results The mean age of the 414 PWIBDs was 48.9 years, and 120 of them were female (29.0%). The mean TT-BD was 8.5 days. The presence of spontaneous movements (SMs) and craniotomy significantly affected the TT-BD. The mean TT-BDs were 13.9 and 8.2 days in the PWIBDs with and without SMs, respectively, and 9.8 and 8.0 days in the PWIBDs with and without craniotomy, respectively. Conclusions The SMs in PWIBDs and a craniotomy performed immediately before starting the process of determining brain death seem to be related to lengthening the TT-BD.

Precise understanding of hadronic interactions at high energies is a key to improve mass composition measurements of very high energy cosmic-rays and to solve the muon excess issue observed in high energy cosmic-ray experiments using an air-shower technique. The LHCf and RHICf experiments measures the differential production cross sections of very forward neutral particle as photons, neutral pions and neutrons at LHC and RHIC, respectively. These data are critically important to test and tune hadronic interaction models used for air-shower simulations. In this presentation, we introduce the recent results of both the experiments as well as our future operation plans. LHCf published an updated result of forward neutron measurement at pp, $\sqrt{s}$ = 13 TeV. From the observed neutron energy spectra, we also obtained the average inelasticity, which is one of the key parameters for air shower development, as 0.536 +0.031-0.037. In addition, several analysis are on-going; neutral pion measurement at pp, $\sqrt{s}$ = 13 TeV, central- forward correlation analysis with LHCf+ATLAS, photon measurement by RHICf. LHCf plans to have operations at $pp$ and $p$O during the LHC-Run3 period. At pp collisions, new silicon readout system will be introduced to improve the read-out speed, and 10 times more statistics of the previous operation in 2015 will be obtained. Thanks to high statistics, rare particles such as $\eta$, $K^0_s$ and $\Lambda$ will be addressed also. We also plan another operation at RHIC in 2024 with a new detector. The detector, a calorimeter composed of tungsten, Si pad and pixel layers, will have a much wider acceptance and higher sensitivity of $K^0_s$ measurement than the current detector.

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

We present the first observation by the Telescope Array Surface Detector (TASD) of the effect of thunderstorms on the development of cosmic ray single count rate intensity over a 700 km$^{2}$ area. Observations of variations in the secondary low-energy cosmic ray counting rate, using the TASD, allow us to study the electric field inside thunderstorms, on a large scale, as it progresses on top of the 700 km$^{2}$ detector, without dealing with the limitation of narrow exposure in time and space using balloons and aircraft detectors. In this work, variations in the cosmic ray intensity (single count rate) using the TASD, were studied and found to be on average at the $\sim(0.5-1)\%$ and up to 2\% level. These observations were found to be both in excess and in deficit. They were also found to be correlated with lightning in addition to thunderstorms. These variations lasted for tens of minutes; their footprint on the ground ranged from 6 to 24 km in diameter and moved in the same direction as the thunderstorm. With the use of simple electric field models inside the cloud and between cloud to ground, the observed variations in the cosmic ray single count rate were recreated using CORSIKA simulations. Depending on the electric field model used and the direction of the electric field in that model, the electric field magnitude that reproduces the observed low-energy cosmic ray single count rate variations was found to be approximately between 0.2-0.4 GV. This in turn allows us to get a reasonable insight on the electric field and its effect on cosmic ray air showers inside thunderstorms.

Background:Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are major causes of death in systemic sclerosis (SSc). Six-minute-walk test (6MWT) is a standard outcome measure for exercise capacity in cardiopulmonary diseases. However, the results of 6MWT may not reflect real cardiopulmonary function of SSc patients in whom musculoskeletal system is frequently inflicted.Objectives:This study aimed to evaluate the clinical utility of breath-holding test (BHT) in evaluating cardiopulmonary function in SSc patients, as compared with 6MWT.Methods:Seventy-two patients with SSc were prospectively enrolled and underwent BHT and 6MWT with measurement of Borg score and Scleroderma Health Assessment Questionnaire (SHAQ). Data on diffusing capacity for carbon monoxide (DLCO, %), forced vital capacity (FVC, % and liters), and ejection fraction and pulmonary arterial systolic pressure (PASP) measured by transthoracic echocardiography (TTE), were also collected. For BHT, participants were required to make a maximum expiration followed by a maximum inspiration and to hold the breath as long as possible at maximum inspiratory level. This procedure was repeated three times, with 5-minute intervals. 6MWT was performed according to the American Thoracic Society guidelines. Pearson’s correlation test was applied to demonstrate the relationship between BHT results and each clinical parameter.Results:Among 72 (66 female) patients, mean (SD) age was 57.1 (11.1) years, modified Rodnan skin score 10.6 (10.5), SHAQ 0.64 (0.61) and 6MWT distance 473.5 (95.5) m. Mean BHT time was 35.05 (14.90) sec at the first time, 38.92 (16.14) sec at the second time, and 41.11 (17.71) sec at the third time. The BHT time showed a statistically significant negative correlation with Borg scale (pre-test, r = -0.336, p = 0.002; post-test, r = -0.252, p = 0.034; Figure 1 and Table 1), while 6MWT showed a negative correlation with only post-test Borg scale (pre-test, r = -0.113 p = 0.343; post-test, r = -0.351 p = 0.002; Table 1). The BHT time was positively correlated with DLCO (%, r = 0.409, p < 0.001) and FVC (liters, r = 0.402, p < 0.001) (Table 1). We also found a statistically significant correlation between BHT time and SHAQ score (r = -0.451, p < 0.001; Table 1). However, EF and PASP by TTE showed no significant relationship with BHT time (EF, r = -0.108, p = 0.374; PASP, r = -0.246, p = 0.054; Table 1).Table 1.Pearson’s correlation coefficients (r) for the relation between BHT and clinical parameters in comparison to 6MWT.Pre-test Borg scalePost-test Borg scaleDLCO(%)FVC(L)FVC(%)FVC/DLCOEF(%)PSAP(mm Hg)SHAQ (score)BHT (sec)-0.366**-0.252*0.409***0.402**0.191-0.244***-0.108-0.246-0.451***6MWT (m)-0.113-0.351**0.297*0.321**0.063-0.250*0.137-0.354**-0.531***BHT, breath-holding test; 6MWT, 6-minute-walk test; DLCO, diffusing capacity for carbon monoxide; FVC, forced vital capacity; EF, ejection fraction estimated by transthoracic echocardiography; SHAQ, Scleroderma Health Assessment Questionnaire.* p < 0.05, ** p < 0.01, *** p < 0.001Figure 1.Association of Borg dyspnea scale with breath-holding time.Conclusion:The BHT is a simple, safe, and less time-consuming test, reflective of pulmonary parameters and SHAQ, as compared with 6MWT. Our results suggest that the BHT might be a useful surrogate marker of cardiopulmonary capacity in SSc patients.References:[1]Villalba WO, Sampaio-Barros PD, Pereira MC, Cerqueira EM, Leme CA, Jr., Marques-Neto JF, et al. Six-minute walk test for the evaluation of pulmonary disease severity in scleroderma patients. Chest. 2007;131(1):217-22.[2]Garin MC, Highland KB, Silver RM, Strange C. Limitations to the 6-minute walk test in interstitial lung disease and pulmonary hypertension in scleroderma. J Rheumatol. 2009;36(2):330-6.[3]Barnai M, Laki I, Gyurkovits K, Angyan L, Horvath G. Relationship between breath-hold time and physical performance in patients with cystic fibrosis. Eur J Appl Physiol. 2005;95(2-3):172-8.Acknowledgements:This study would not have been possible without help from research assistant, Sung-Soon Cho.Disclosure of Interests:Jina Yeo: None declared, Mi Hyeon Kim: None declared, Jun Won Park: None declared, Jin Kyun Park: None declared, Eun Bong Lee Consultant of: Pfizer, Grant/research support from: GC Pharma and Handok Inc.

Transverse single-spin asymmetries of very forward neutral pions generated in polarized p+p collisions allow us to understand the production mechanism in terms of perturbative and nonperturbative strong interactions. During 2017, the RHICf Collaboration installed an electromagnetic calorimeter in the zero-degree region of the STAR detector at the Relativistic Heavy Ion Collider (RHIC) and measured neutral pions produced at pseudorapidity larger than 6 in polarized p+p collisions at sqrt[s]=510 GeV. The large nonzero asymmetries increasing both in longitudinal momentum fraction x_{F} and transverse momentum p_{T} have been observed at low transverse momentum p_{T}

Aim Diffuse axonal injury (DAI) is an important determining factor of morbidity and mortality after traumatic brain injury (TBI). However, its clinical outcome remains a subject of debate. Material and methods A total of 992 TBI patients visited our hospital between 2011 and 2016. Thirty-seven patients diagnosed with DAI were enrolled in this study and stratified by DAI stage: stage I, 20 patients (54.1%); stage II, 4 patients (10.8%); and stage III, 13 patients (35.1%). Results The mean age and the median follow-up period were 45.43 years and 13 months, respectively. Patient demographic data and clinical findings on admission showed no differences according to DAI stage, except for the revised trauma score (RTS) (p = 0.026). In univariate analysis, stages I and II vs. III (p = 0.001) and stages I vs. II and III (p = 0.019), transfusion within 24 hours of visit (p = 0.033), shock or cardiac arrest (p = 0.006), traumatic subarachnoid hemorrhage (T-SAH) (p = 0.011), and subdural hematoma (SDH) (p = 0.009) were significantly correlated with Glasgow outcome score (GOS). In multivariate analysis, DAI stage I and II vs. III (p = 0.005) and SDH (p = 0.040) were significant. Conclusion Clinically, stage II was more correlated with stage I, rather than stage III. Stage III showed a much poorer outcome compared to stages I and II. Magnetic resonance imaging (MRI) should be promptly performed in all TBI patients when a patient's level of consciousness and cranial computed tomography (CT) does not match, as there is a possibility of stage III DAI.

Background Brain death is a clinical diagnosis that implies irreversible loss of function of the entire brain, including the brainstem and both hemispheres. Based on previous reports, it is not rare for reflex and spontaneous movements to occur in patients during the process of determining brain death. However, reports of the frequency and common types of these movements vary from study to study. Thus, we evaluated adult patients with impending brain death in Korea to determine the frequency and characteristics of reflex and spontaneous movements. Methods Brain dead patients who were admitted to 15 hospitals in the Yeongnam region (Southeast) of Korea were recruited prospectively from January 2013 to September 2016. All patients met the criteria for brain death as established by the Korea Medical Association. All body movements occurred during the process of diagnosing brain death and were assessed by physicians and trained organ transplant coordinators. The frequency and characteristics of these movements were identified and the demographic and clinical factors of impending brain dead patients with and without these movements were compared. Results A total of 436 patients who met the criteria for brain death were enrolled during the study period. Of these patients, 74 (17.0%) exhibited either reflex or spontaneous movements. Of this subset, 45 (60.8%) exhibited reflex movements only, 18 (24.3%) exhibited spontaneous movements only, and 11 (14.9%) exhibited both reflex and spontaneous movements. The most common reflex movements were the flexor/extensor plantar response and spinal myoclonus. Of the 74 patients, 52 (70.3%) exhibited one movement of the same pattern and 22 (29.7%) exhibited two or more different movement patterns. In addition, 45 (60.8%) exhibited these movements only on a limited area of the body with the leg being most common (n = 26, 57.8%). Patients with hypoxic brain damage and a higher systolic blood pressure exhibited significantly more reflex or spontaneous movements. Conclusion Movements associated with brain dead patients are not rare and thus an awareness of these movements is important to brain death diagnosis. Physicians who perform brain death examinations should understand the frequency and characteristics of these movements to reduce delays in determining brain death., Graphical Abstract

The Relativistic Heavy Ion Collider forward (RHICf) experiment aims at understanding the high-energy hadronic interaction by measuring the cross sections of very forward neutral particles in proton-proton collisions at $\sqrt{s}$ = 510 GeV. For the analysis of the photon measurement, the trigger efficiency and the particle identification performance are studied by using the Monte Carlo simulation data and the experimental data. In the RHICf operation, two kinds of trigger modes (Shower, HighEM) were implemented. The trigger efficiency of the Shower trigger is 100$\%$ for photons with the energies more than 20 GeV. The HighEM trigger is designed to detect high energy photons effectively, and the trigger efficiency of the HighEM trigger is 90$\%$ for photons with the energies more than 130 GeV. The correction factor for the photon identification is calculated by using the efficiency and purity. It is found that this correction does not make a sizeable effect on the shape of the energy spectrum because the energy dependency of the factor is small.

Introduction: Sox17 promotes endothelial migration by destabilizing endothelial adherens junctions, rearranging cytoskeletal structure and upregulates expression of a number of genes preferentially expressed in angiogenic tip cells. However, the deletion of Sox17 stabilizes endothelial junctions and decreased proliferation, vice versa. The AVM after endothelial Alk1 deletion shows uncontrolled endothelial proliferation and cytoskeletal misarrangement. Therefore, we hypothesized that deletion of Sox17 in endothelial cells are sufficient to ameliorate brain AVM via Notch pathway modulation. Methods: Alk1 2f/2f Sox17 2f/2f double transgenic mice (Alk1 exons 4-6 flanked by loxP sites) were bred with VEcad-iCreER T2 mice that express tamoxifen-inducible cre re-combinase (iCreER) in EC. EC-Alk1 and Sox17 deletion was induced by intraperitoneal injection of tamoxifen (25mg/kg, Sigma-Aldrich) with interval of 3 days. The spatiotemporal changes of blood vessel were investigated in Alk1 deletion alone and Alk1-Sox17 co-deletion mice. Vascular morphology was analyzed 9 days after tamoxifen administration. The transcripts (mRNA) and protein expression of target molecules of Notch pathway (Dll4, Hey1, Hey2, NIICD) were also evaluated. Results: The dysplastic blood vessel index of solitary Alk1 2f/2f deletion mice was higher than Alk1 2f/2f -Sox17 2f/2f double transgenic mice (P2f/2f mice was partially rescued by Sox17 co-deletion in morphologically. In addition, target molecules of Notch pathway, Dll4, Hey1, Hey2, Jag1 was increased in Alk1-Sox17 co-deletion mice rather than solitary Alk1 deletion mice. Conclusions: Collectively, our findings demonstrate that the modulation of Sox17 could restrict the Alk1-induced AVM by upregulation of Notch pathway. This work establishes the Notch-Sox17 axis as a novel regulatory mechanism underlying Notch-mediated vascular stabilization in brain AVM.

Experimental results from the J-PARC E13 experiments are summarized. A new experimental set up of E13 has established a platform for the future γ-ray hypernuclear spectroscopy at J-PARC using kaon beams. New γ rays are identified in HeΛ4 and FΛ19. The energy of 1.406 MeV for the HeΛ4(1+→0+) transition confirmed a sizable effect of Charge Symmetry Breaking (CSB) in ΛN interaction in the A=4 hypernuclear system. The identification of four γ rays in FΛ19 is made for the first time in sd shell hypernuclei. Especially, energy spacing of the ground state doublet is found to be 315.5 keV. A good agreement with two theoretical calculations suggests that the theoretical formalism used in p shell hypernuclei is also applicable to heavier hypernuclei. Lastly, an overview of the future J-PARC E63 experiment is given.

J-PARC E07 is the most complex emulsion experiment to date investigating double hypernuclei with a hybrid emulsion method. This experiment aims to detect 104 Ξ− stop events, ten times more events than the past experiments. Thus, an unequivocal identification of several new double hypernuclei is expected. The beam exposure has been completed at the K1.8 beam line of the J-PARC hadron facility in June 2017. The photographic development of all emulsion sheets has also been completed in February 2018. The emulsion sheets are presently being analyzed with dedicated optical microscopes. Current statistics is comparable to that of E373 and so far 10 events of 3-vertices topology have been detected. A typical event of double Λ hypernucleus and a twin Λ hypernucleus are introduced. We plan to complete the main part of the emulsion scanning within a year.

This study aimed to assess the association between caudal block and postoperative complications after tubularised incised plate urethroplasty. The medical records of 388 paediatric patients who underwent urethroplasty at a tertiary medical centre were analysed retrospectively. Among the 342 patients included, 216 patients received a caudal block and 72 (21.1%) patients suffered surgical complications. The number of patients having surgical complications was significantly greater among patients who received a caudal block than among patients who did not receive a caudal block (53 (24.5%) versus 19 (15.1%), respectively, p = 0.04). Based on multivariate logistic regression analysis, duration of surgery, caudal block and hypospadias types were independent risk factors for the surgical complications. Patients with caudal block had an odds ratio of 2.1 (95% CI, 1.14-3.81, p = 0.018) for the development of postoperative complications compared with patients without caudal block. This analysis demonstrates that caudal block is associated with surgical complications after tubularised incised plate urethroplasty.

A one-year-old, 2.6 kg, spayed female Maltese dog was referred with passage of faeces coming from the vulva, repeated vaginal discharge and vaginitis. Through physical examination, contrast radiograph and vaginoscopic exploration, the dog was diagnosed with rectovaginal fistula which was surgically corrected. After midline perineal incision, the rectovaginal fistula was isolated and transected. The vaginal and rectal defects were closed separately, but dehiscence of the surgical region took place three days after surgery. For the second opera- tion, the rectal segment containing the fistula was removed by transanal rectal pull-through, and anastomosis was performed. Total follow-up time was 10 months and no sign of recurrence was reported. Early postoperative complications included perineal soiling and wound dehiscence, but the long-term outcome was good. This case is the first report of surgical correction of a rectovaginal fistula in a dog with a normal anus.

Evidence for a large-scale supergalactic cosmic-ray multiplet (arrival directions correlated with energy) structure is reported for ultra-high-energy cosmic-ray (UHECR) energies above 1019 eV using 7 years of data from the Telescope Array (TA) surface detector and updated to 10 years. Previous energy–position correlation studies have made assumptions regarding magnetic field shapes and strength, and UHECR composition. Here the assumption tested is that, because the supergalactic plane is a fit to the average matter density of the local large-scale structure, UHECR sources and intervening extragalactic magnetic fields are correlated with this plane. This supergalactic deflection hypothesis is tested by the entire field-of-view (FOV) behavior of the strength of intermediate-scale energy–angle correlations. These multiplets are measured in spherical cap section bins (wedges) of the FOV to account for coherent and random magnetic fields. The structure found is consistent with supergalactic deflection, the previously published energy spectrum anisotropy results of the TA (the Hotspot and Coldspot), and toy-model simulations of a supergalactic magnetic sheet. The seven year data posttrial significance of this supergalactic structure of multiplets appearing by chance, on an isotropic sky, is found by Monte Carlo simulation to be 4.2σ. The 10 years of data posttrial significance is 4.1σ. Furthermore, the starburst galaxy M82 is shown to be a possible source of the TA Hotspot, and an estimate of the supergalactic magnetic field using UHECR measurements is presented.

Background Standardized postoperative airway management is essential for patients undergoing anterior cervical spine surgery (ACSS). The paucity of clinical series evaluating these airway complications after ACSS has been resulted in a significant limitation in statistical analyses. Methods A retrospective cohort study was performed regarding airway distress (intubation for more than 24 hours or unplanned reintubation within 7 days of operation) developed after ACSS. If prevertebral soft tissue swelling was evident after the operation, patients were managed with prolonged intubation (longer than 24 hours). Preoperative and intraoperative patient data, and postoperative outcome (time to extubation and reintubation) were analyzed. Results Between 2008 and 2016, a total of 400 ACSS were performed. Of them, 389 patients (97.25%) extubated within 24 hours of surgery without airway complication, but 11 patients (2.75%) showed postoperative airway compromise; 7 patients (1.75%) needed prolonged intubation, while 4 patients (1.00%) required unplanned reintubation. The mean time for extubation were 2.75 hours (range: 0–23 hours) and 50.55 hours (range: 0–250 hours), respectively. Age (P = 0.015), diabetes mellitus (P = 0.003), operative time longer than 5 hours (P = 0.048), and estimated blood loss (EBL) greater than 300 mL (P = 0.042) were associated with prolonged intubation or reintubation. In prolonged intubation group, all patients showed no airway distress after extubation. Conclusion In ACSS, postoperative airway compromise is related to both patients and operative factors. We recommend a prolonged intubation for patients who are exposed to these risk factors to perform a safe and effective extubation., Graphical Abstract

A double-$\Lambda$ hypernucleus, ${}_{\Lambda\Lambda}\mathrm{Be}$, was observed by the J-PARC E07 collaboration in nuclear emulsions tagged by the $(K^{-},K^{+})$ reaction. This event was interpreted as a production and decay of $ {}_{\Lambda\Lambda}^{\;10}\mathrm{Be}$, ${}_{\Lambda\Lambda}^{\;11}\mathrm{Be}$, or ${}_{\Lambda\Lambda}^{\;12}\mathrm{Be}^{*}$ via $\Xi^{-}$ capture in ${}^{16}\mathrm{O}$. By assuming the capture in the atomic 3D state, the binding energy of two $\Lambda$ hyperons$\,$($B_{\Lambda\Lambda}$) of these double-$\Lambda$ hypernuclei are obtained to be $15.05 \pm 0.11\,\mathrm{MeV}$, $19.07 \pm 0.11\,\mathrm{MeV}$, and $13.68 \pm 0.11\,\mathrm{MeV}$, respectively. Based on the kinematic fitting, ${}_{\Lambda\Lambda}^{\;11}\mathrm{Be}$ is the most likely explanation for the observed event., Comment: 11 pages, 3 figures

Asymmetric nuclear collisions of $p$$+$Al, $p$$+$Au, $d$$+$Au, and $^{3}$He$+$Au at $\sqrt{s_{_{NN}}}=200$ GeV provide an excellent laboratory for understanding particle production, as well as exploring interactions among these particles after their initial creation in the collision. We present measurements of charged hadron production $dN_{\rm ch}/d\eta$ in all such collision systems over a broad pseudorapidity range and as a function of collision multiplicity. A simple wounded quark model is remarkably successful at describing the full data set. We also measure the elliptic flow $v_{2}$ over a similarly broad pseudorapidity range. These measurements provide key constraints on models of particle emission and their translation into flow., Comment: 368 authors, 7 pages, 4 figures. v2 is the version accepted for publication by Physical Review Letters. Plain text data tables for points plotted in figures for this and other PHENIX publications are publicly available at http://www.phenix.bnl.gov/papers.html

The Relativistic Heavy Ion Collider forward (RHICf) experiment has measured neutral particles produced in the very forward direction in the √s=510 GeV proton-proton collisions at RHIC in June 2017. The production cross sections of these particles are crucial to understand the hadronic interaction relevant to the air shower development at the cosmic-ray equivalent energy of 1.4×10$^{14}$ eV, just below the energy of the knee. Together with the data at LHC, accelerator data can cover the interaction in the cosmic-ray energy of 10$^{14}$ eV to 10$^{17}$ eV. In addition, RHICf is able to improve the former measurements of single-spin asymmetry in the polarized proton- proton collisions that is sensitive to the fundamental process of the meson exchange. Common data taking with the STAR experiment will shed light on the unexplored low mass diffraction process.

Several enhancements have been implemented for the version 4 aerosol subtyping and lidar ratio selection algorithms of Cloud Aerosol Lidar with Orthogonal Polarization (CALIOP). Version 4 eliminates the confusion between smoke and clean marine aerosols seen in version 3 by modifications to the elevated layer flag definitions used to identify smoke aerosols over the ocean. To differentiate between mixtures of dust and smoke, and dust and marine aerosols, a new aerosol type will be added in the version 4 data products. In the marine boundary layer, moderately depolarizing aerosols are no longer modeled as mixtures of dust and smoke (polluted dust) but rather as mixtures of dust and seasalt (dusty marine). Some lidar ratios have been updated in the version 4 algorithms. In particular, the dust lidar ratios have been adjusted to reflect the latest measurements and model studies.

Differential cross sections at $t={t}_{\text{min}}$ and decay asymmetries for the $\ensuremath{\gamma}p\ensuremath{\rightarrow}\ensuremath{\phi}p$ reaction have been measured using linearly polarized photons in the range 1.5 to 2.9 GeV. These cross sections were used to determine the Pomeron strength factor. The cross sections and decay asymmetries are consistently described by the $t$-channel Pomeron and pseudoscalar exchange model in the ${E}_{\ensuremath{\gamma}}$ region above 2.37 GeV. In the lower energy region, an excess over the model prediction is observed in the energy dependence of the differential cross sections at $t={t}_{\text{min}}$. This observation suggests that additional processes or interference effects between Pomeron exchange and other processes appear near the threshold region.

Metabolic diseases affect various organs including the brain. Accumulation or depletion of substrates frequently leads to brain injury and dysfunction. Deficiency of aminopeptidase P1, a cytosolic proline-specific peptidase encoded by the Xpnpep1 gene, causes an inborn error of metabolism (IEM) characterized by peptiduria in humans. We previously reported that knockout of aminopeptidase P1 in mice causes neurodevelopmental disorders and peptiduria. However, little is known about the pathophysiological role of aminopeptidase P1 in the brain. Here, we show that loss of aminopeptidase P1 causes behavioral and neurological deficits in mice. Mice deficient in aminopeptidase P1 (Xpnpep1

The phase-matching condition is a key aspect in nonlinear wavelength conversion processes, which requires the momenta of the photons involved in the processes to be conserved. Conventionally, nonlinear phase matching is achieved using either birefringent or periodically poled nonlinear crystals, which requires careful dispersion engineering and is usually narrowband. In recent years, metasurfaces consisting of densely packed arrays of optical antennas have been demonstrated to provide an effective optical momentum to bend light in arbitrary ways. Here, we demonstrate that gradient metasurface structures consisting of phased array antennas are able to circumvent the phase-matching requirement in on-chip nonlinear wavelength conversion. We experimentally demonstrate phase-matching-free second harmonic generation over many coherent lengths in thin film lithium niobate waveguides patterned with the gradient metasurfaces. Efficient second harmonic generation in the metasurface-based devices is observed over a wide range of pump wavelengths (λ = 1580–1650 nm)., Phase matching is a crucial condition for nonlinear optical processes. Here, Wang et al. demonstrate that a gradient metasurface composed of phased array antennas allows phase-matching-free frequency conversion over a pump wavelength range of almost 100 nm.

Summary Background Chronic low back pain (CLBP) is one of the most common musculoskeletal disorders, and thus effective treatments are required. Recently, a real horseback riding has been reported to be beneficial for the patients. However, it has some limitations, such as limited approaches and safety issues. Objective The purpose of this study was to investigate the effect of horse simulator riding on back pain, body composition and trunk strength in the patients with CLBP. Participants Forty-seven men with CLBP (mean age 20.55 ± 1.38 years) were randomly divided into a control group (n = 23) and a horse simulator riding group (n = 24), and visual analogue scale (VAS), body composition and isokinetic trunk strength were measured after 8 weeks for which subjects in a horse simulator riding group had performed the horse simulator exercise (HSE). Results Horse simulator exercise significantly reduced pain scores of VAS and enhanced isokinetic torques of trunk at 30 and 90°/s. There were also significantly increased muscle mass and decreased fat mass in horse simulator riding group. Conclusion It can be inferred that HSE may be helpful in relief of back pain and recovery of back function through developing trunk strength and balancing the ratio of trunk flexor/extensor muscles.