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Resumen Introduccion y objetivos En la obtencion de imagenes de angiografia por cardiotomografia (ACT) es importante escoger una ubicacion adecuada para inyectar el medio de contraste (p. ej., el brazo o la pierna) a fin de evitar la formacion de artefactos que este provoca. En este estudio se comparan los valores de tomografia computarizada (TC) y las puntuaciones de visualizacion de las imagenes tridimensionales (3 D) de los lumenes de los vasos sanguineos del brazo y la pierna durante la ACT en pacientes neonatos y lactantes. Pacientes o materiales y metodos Entre los meses de enero de 2017 y enero de 2020 se evaluaron 253 pacientes de forma consecutiva para determinar su inclusion en el estudio. Se utilizaron las puntuaciones de propension estimadas en funcion de los datos demograficos, incluidos la edad, el peso corporal y la ubicacion de la inyeccion (lado derecho o izquierdo) en el brazo (n = 58) y la pierna (n = 58) de los pacientes neonatos y lactantes. A continuacion, se compararon los valores medios de TC de la arteria pulmonar, la aorta ascendente y la vena cava superior izquierda; las relaciones contraste-ruido (RCR); y las puntuaciones de visualizacion del brazo y la pierna como lugares de inyeccion. Resultados Los valores medios de TC durante la ACT para el brazo y la pierna fueron de 479,4 y 461,3 UH en la aorta ascendente, de 464,2 y 448,1 UH en la arteria pulmonar y de 232,8 y 220,1 UH en la vena cava superior izquierda, respectivamente. Los valores medios de ruido de la imagen (DE) y de RCR fueron, respectivamente, de 38,9 y 12,1 UH para el brazo y de 39,1 y 12,3 UH para la pierna. Las puntuaciones medias de visualizacion de la representacion del volumen de las imagenes 3 D fueron de 3,0 y 3,0 para los lugares de inyeccion del brazo y la pierna, respectivamente. No se observaron diferencias significativas en los valores medios de TC de la aorta ascendente, la arteria pulmonar y la vena cava superior izquierda; el valor de DE; la RCR; y las puntuaciones de visualizacion del brazo y la pierna. Conclusiones Los valores de TC del lumen de los vasos sanguineos y las puntuaciones de visualizacion de las imagenes 3 D observados durante la realizacion de una ACT en pacientes neonatos y lactantes con cardiopatias congenitas son los mismos, independientemente de si el lugar de inyeccion es el brazo o la pierna.

Obtaining CCTA images with optimal injection location such as the arm or leg is important to avoid the artifacts caused by the CM. This study compares the computed tomography (CT) numbers and visualization scores of the three-dimensional (3D) images of the lumens of the blood vessels in the arm or leg during cardiac computed tomography angiography (CCTA) in neonatal and infant patients.Between January 2017 and January 2020, 253 consecutive patients were considered for inclusion. We used the estimated propensity scores as a function of the demographic data, including age, body weight, and injection location (right or left side) in the arm (n = 58) and leg (n = 58) of neonatal and infant patients. We compared the mean CT numbers of the pulmonary artery, ascending aorta, and left superior vena cava; contrast-noise ratios (CNR); and visualization scores between the arm and leg as the injection locations.The mean CT numbers during CCTA for the arm and leg were 479.4 and 461.3 HU in the ascending aorta, 464.2 and 448.1 HU in the pulmonary artery, and 232.8 and 220.1 HU in the left superior vena cava, respectively. The mean image noise (SD) and CNR values, respectively, were 38.9 HU and 12.1 for the arm as the injection location and 39.1 HU and 12.3 for the leg as the injection location. The median visualization scores of volume rendering of the 3D images were 3.0 and 3.0 for the arm and leg injection sites, respectively. There were no significant differences in the mean CT numbers of the ascending aorta, pulmonary artery, and left superior vena cava; SD value; CNR; and visualization scores between the arm and leg injection locations.The CT numbers of the lumen of the blood vessel and visualization scores of the 3D images of the arm and leg injection locations are equal during CCTA in neonatal and infant patients with congenital heart disease.

Janus kinases (JAK) play a critical role in JAK/signal transducer and activator of transcription (STAT) signaling pathways that mediate immune response and cell growth. From high-throughput screening (HTS) hit to lead optimization, a series of pyrimidine compounds has been discovered as potent JAK1 inhibitors with selectivity over JAK2. Cell-based assays were used as primary screening methods for evaluating potency and selectivity, the results were further assessed and confirmed by biochemical and additional cellular assays for lead molecules. Also discussed is the unique correlation between a trifluomethyl group and CYP3A4 inhibition in the presence of NADPH, the activity of which was successfully decreased with the reduction of fluoro-atoms, increasing IC

To investigate how changing the injection duration at cardiac computed tomography angiography (CCTA) affects contrast enhancement in newborns and infants.Included were 142 newborns and infants with confirmed congenital heart disease who underwent CCTA between January 2015 and December 2018. In group 1 (n = 71 patients), the injection duration was 8 s; in group 2 (n = 71) it was 16 s. Our findings were assessed by one-to-one matching analysis to estimate the propensity score of each patient. We compare the CT number for the pulmonary artery (PA), ascending aorta (AAO), left superior vena cava (SVC), AAO and PA enhancement ratio, and the scores for visualization between the two groups.In group 1, median CT number and ranges was 345 (211-591) HU in the AAO, 324 (213-567) HU in the PA, and 62 (1-70) HU in the SVC. These values were 465 (308-669) HU, 467 (295-638) HU, and 234 (67-443) HU, respectively, in group 2 (p 0.05). The median score for volume-rendering visualization on 3D images of the CCTA was 2 in group 1 and 3 in group 2; the score for visualization of the left SVC of the maximum intensity projection images was 2 in group 1 and 3 in group 2 (p 0.05). The CT number for the AAO and PA enhancement ratio was 15.2 in group 1 and 9.2 in group 2 (p 0.05).The 16-sec injection protocol yielded significantly higher CT numbers for the AAO, PA, and the SVC than the 8-sec injection protocol; the visualization scores were also significantly higher in group 2.In newborns and infants, the longer injection time for CCTA yields stable and higher contrast enhancement at identical CM concentrations.

To compare the computed tomography (CT) number for paediatric cardiac computed tomography angiography (CCTA) and visualisation score of the three-dimensional (3D) images using the conventional T-shaped extended tube (T-tube) and spiral flow-generating extended tube (spiral-tube) connected between the contrast injector and cannula.In total, 108 patients suspected to have congenital heart disease (CHD) were considered for inclusion. We utilised the T-tube for intravenous contrast and spiral-tube in 54 patients each. Observers individually inspected randomized volume rendering images of the internal thoracic artery, each acquired from the with or without spiral-tube groups, using a four-point scale. We compared the mean CT number of the ascending aorta (AAO) and pulmonary artery (PA), contrast noise ratio (CNR), CT number for the AAO and PA enhancement ratio, and the visualisation scores between the groups.There were no significant differences in patient characteristics between the with or without spiral-tube groups (p 0.05). The mean CT number ±standard deviation for the AAO and PA, and the CNR without or with spiral-tube groups were 441.2 ± 89.2 and 489.8 ± 86.1 HU for the AAO, 436.3 ± 100.6 and 475.3 ± 85.2 HU for the PA, and 9.5 ± 2.2 and 10.8 ± 2.4 for the CNR, respectively (p 0.05). In the spiral-tube group, the CT number, CNR, and visualisations score of the 3D images were significantly higher for the AAO and PA than those in the T-tube group (p 0.05).The spiral-tube proved to be beneficial in improving the CT number for the AAO and PA, CNR, and visualisation score compared with the conventional T-tube during paediatric CCTA.The spiral-tube may allow the visualisation of smaller blood vessels than those visualised by the conventional T-tube for paediatric patients in CCTA.

Introduction The SYNTAX III REVOLUTION trial demonstrated that clinical decision-making between coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) based on coronary artery computed tomography (CCTA) and predicting four years mortality according to the SYNTAX score II had a high agreement with the treatment decision derived from invasive coronary angiography (ICA). The agreement of the novel SYNTAX score 2020 (SS-2020) based on CCTA and ICA has not yet been evaluated in a prospective fashion. Methods This study included 54 consecutive patients in the ongoing FASTTRACK CABG trial that investigates decision making, planning and procedural CABG guidance based solely on CCTA and FFRct. All the patients underwent CCTA and ICA, and SS-2020 was calculated based on the results of anatomical SYNTAX score derived from either CCTA or ICA, and the respective scores were compared by using paired t-test. Results The mean age was 67.3±9.7, and 48 were men (88.9%). Anatomical SYNTAX score derived from CCTA was assessed in the 54 cases (analysability 100%). Anatomical SYNTAX scores based on CCTA and ICA were 34.3±9.3, and 35.5±11.3, respectively (P=0.480). As shown in the table predicted 5 years major adverse cardiac and cerebrovascular events (MACCE) following either PCI or CABG, as well as predicted 10 years mortality following CABG differed significantly. However the absolute risk differences (ARD) in 5 years MACCE and 10 years mortality following either PCI or CABG, were comparable. Conclusions High agreements were confirmed in the calculations of anatomical SYNTAX scores with CCTA and ICA. Despite significant differences in predicted MACCE rates at 5 years and mortalities at 10 years, the ARD in MACCE rates and mortality were comparable. In terms of treatment decision-making, SS-2020 calculations based on CCTA is a non-invasive predictive tool comparable to the one based on ICA. Funding Acknowledgement Type of funding sources: None.

Backgrounds The impact on vital prognosis at very long-term of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with reduced ejection fraction (EF) remains to be elucidated. Objective To investigate the impact of left ventricular ejection fraction (LVEF) on 10-year mortality after PCI and CABG in the SYNTAX trial. Methods In the SYNTAXES study, 1,800 randomized patients were categorized into three groups according to the current guidelines; (1) reduced EF (rEF; LVEF ≤40%), (2) mildly reduced EF (mrEF; LVEF 41–49%), (3) preserved EF (pEF; LVEF ≥50%). The primary endpoint was 10-year all-cause mortality. Event rate up to 10 years was estimated according to the Kaplan-Meier method, and the log-rank test was performed to examine the differences among LVEF subgroups. The SYNTAX score 2020 (SS-2020) was compared between the patients with reduced (LVEF Results The population was stratified as rEF (n=168), mrEF (n=179), and pEF (n=1453). Ten-year all-cause mortality were 44.0% vs. 31.8% vs. 22.6% (P Conclusion LVEF could an important factor for determining the revascularization treatment in patients presenting with complex coronary artery disease. Calculation of individualized 10-year prognosis using the SS-2020 may be a viable option in decision-making. Funding Acknowledgement Type of funding sources: None.

Backgrounds Heart failure (HF) is a risk factor for new onset atrial fibrillation (AF), and the new onset AF is associated with a worse prognosis in HF patients. It has been reported that renin-angiotensin system inhibitor (RASi), β-blocker and mineral-corticoid receptor antagonist (MRA) prevent the new onset AF in HF patients. However, the effect of combined pharmacotherapy including angiotensin receptor neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitor (SGLT2i) on AF is unknown. We investigated the impact of contemporary regimen of combined pharmacotherapy for HF (RASi/ARNI+β-blocker+MRA+SGLT2i) on new onset AF. Methods and results We retrospectively studied rEF and mrEF patients without AF admitted to our hospital due to decompensated HF between 2015 and 2021 (n=366). Long-term (The mean follow-up was 635±421 days) incidence of new onset AF was investigated with regard to medical therapies. Patients were divided into 2 groups; patients with ≤2 HF drugs (n=181) and patients with ≥3 HF drugs (n=185). Patients with ≤2 HF drugs group were older (77.3 vs 67.0 years old, P Conclusion Aggressive combined pharmacotherapy for HF may be associated with fewer new onset AF in patients with HF. Funding Acknowledgement Type of funding sources: None.

Background/Introduction Atrial fibrillation (AF) and heart failure (HF) frequently coexist in the elderly people, leading to worse clinical outcomes. HF with preserved ejection fraction (HFpEF) is the most common form of HF in the elderly, particularly in women, associated with AF. Ablation of AF in younger patients with HF with reduced EF (HFrEF) has become an established treatment option. However, clinical impact of ablation for persistent AF accompanying with HF in the elderly remains unclear. Purpose This study aimed to evaluate the effect of catheter ablation of persistent AF with heart failure in the elderly. Methods Consecutive 70 patients who underwent catheter ablation of persistent AF accompanying with HF (NYHA class> II, mean LVEF 51.7%) in our institution were retrospectively analyzed with regards to their 1-year clinical outcomes, HF markers such as BNP, renal function and transthoracic echocardiographic findings. Patients were dichotomized by age of 75-year-old (31 elderly vs 39 younger subjects) and separately analyzed. Results Mean age of the studied population was 70.5 year-old; 79.6±3.8 in the elderly group and 63.2±8.5 in the younger group. The elderly patients were more frequently females (45% vs 21%). Longstanding persistent AF was observed in 32% in the elderly and 28% in the younger group. Circumferential pulmonary vein isolation (PVI) was performed in all patients, with additional ablations of liner lesions and/or non-PV foci as needed. PVI alone was observed in 54.8% in the elderly and 41% in the younger group. There were no serious complications associated with the procedure. During 1 year after ablation, recurrence of AF was observed in 15 patients [6/31 (19%) in the elderly, 9/39 (23%) in the younger]. Readmission due to HF was observed in only 1 patient in the elderly and 2 patients in the younger group (3% vs. 5%, respectively). Cardiovascular events were observed in 3 patients [2/31 (6%) in the elderly, 1/39 (3%) in the younger], but there was no death. The BNP level as well as the NYHA class significantly decreased at 1-year follow-up compared to baseline in the both groups (Figure A and B). There was no change in serum creatinine level in the both groups (Figure C). The left atrial dimension and the LA volume index decreased at 1-year follow-up in the both groups (Figure D and E). The LVEF improved only in the younger group (Figure F). Conclusions Ablation of persistent AF in the elderly with HF (mostly with preserved EF) was associated with hemodynamic and functional improvements without deteriorating renal function in a mid-term, which was mostly comparable to the results in the younger. Funding Acknowledgement Type of funding sources: None.

Aims To investigate geographic disparity in long-term mortality following revascularization in patients with complex coronary artery disease (CAD). Methods and results The SYNTAXES trial randomized 1800 patients with three-vessel and/or left main CAD to percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) and assessed their survival at 10-years. Patients were stratified according to the region of recruitment: North America (N-A, n=245), Eastern Europe (E-E: Poland, Hungary, Czech, n=189), Northern Europe (N-E: United Kingdom, Sweden, Norway, Latvia, Finland, and Denmark, n=425), Southern Europe (S-E: Spain, Portugal, and Italy, n=263), and Western Europe (W-E: Netherlands, Germany, France, Belgium, and Austria, n=678), which also served as the reference group. Compared to W-E, patients were younger in E-E (62 vs 65 years, p Discussion and conclusions The main findings of this study are: 1. Rates of crude 10-year mortality were significantly lower in E-E, N-E, and S-E compared to W-E and N-A. 2. The differences in 10-year mortality remained significantly lower with N-E and S-E even after adjustment for confounding factors. 3. However, when comparing PCI to CABG in the five geographic regions, there were no statistically significant interactions between the geographic disparity in pre- and peri-procedural characteristics and all-cause mortality. In the era of globalization, knowledge and understanding of geographic disparity are of paramount importance for the correct interpretation of global studies. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The German Foundation of Heart Research (Frankfurt am Main, Germany)

Background In patients with complex CAD, the presence of left main (LM) disease is an important prognostic factor in assessing the risk balance between PCI and CABG. Functional assessment has become standard of care to evaluate the significance of coronary stenosis and to justify the performance of PCI in the contemporary practice. FFRCT is a well-established method based on 3D reconstruction of coronary artery derived from CCTA. The Murray law-based quantitative flow reserve (μQFR) is a novel computational method of invasive angiography relying on a single angiographic view that takes into account side branches diameters to compute fractal flow division. The aim of the current analysis is to evaluate in patients with complex CAD the feasibility of μQFR in LM bifurcation and its diagnostic concordance with FFRCT. The impact of the optimal viewing angle defined by CCTA on the physiological assessment of the LM bifurcation using a single angiographic view was also evaluated. Methods In 299 consecutive patients with 3-vessel disease with or without LM coronary artery disease, up to 3 analyzable fluoroscopic projections per patient were analysed with μQFR retrospectively. FFRCT and μQFR were measured at 3 fiducial landmark points: i) point of LM bifurcation (POB); ii) proximal LAD 10 mm distal to POB; ii) proximal LCX 10 mm distal to POB. CCTA-based “optimal viewing angle” of LM bifurcation are computed by creating a 3-point closed spline involving the LM, LAD, and LCX at 5mm from the POB and subsequently by reconstructing the “en face” fluoroscopic viewing angle of the spline. The en face viewing angle provides an optimal assessment of the bifurcation geometry [1]. In terms of Rx gantry angulation, the closest angiographic projection to the optimal viewing angle derived from CCTA was defined as the “best fluoroscopic projection” for each patient. Results In 299 patients, 793 projections were analysed with μQFR and compared to FFRCT. Single view μQFR was analyzable in 100%. Correlation and agreement between μQFR and FFRCT for 793 projections in 299 patients are shown in Figure 1A, 2A. The Spearman's correlation coefficient showed moderate correlations at POB (r=0.481, p Conclusion Computation of μQFR from a single angiographic view has a high feasibility. Tailored optimal fluoroscopic view is essential for the physiological assessment of the LM bifurcation using a single angiographic view. Evaluation of diagnostic accuracy of μQFR warrants further analysis of the LMCAD after prospective planning of the optimal fluoroscopic view based on the selection of the best CCTA 3D view. Funding Acknowledgement Type of funding sources: None.

Background Percutaneous coronary intervention (PCI) of bifurcation lesions is associated with higher rates of adverse events, and currently it is unclear whether PCI or coronary artery bypass grafting (CABG) is the safer treatment for these patients at very long-term follow up. Objectives To investigate the impact of bifurcation lesions on observed all-cause 10-year mortality in the SYNTAX trial. Methods In the SYNTAX Extended Survival study, 10-year observed mortality was compared among four groups: (a) presence of ≥1 bifurcation lesion and treatment with PCI (n=649), (b) no bifurcation lesion and treatment with PCI (n=248), (c) presence of ≥1 bifurcation lesion and treatment with CABG (n=651), and (d) no bifurcation lesion and treatment with CABG (n=239). Results Compared to patients without bifurcations, those with bifurcation lesion(s) treated with PCI had a significantly higher risk of all-cause death (19.8% vs 30.1%; HR: 1.55, 95% CI: 1.12 to 2.14; p=0.007), whereas following CABG, mortality was similar in patients with or without bifurcation lesion(s) (23.3% vs 23.0%; HR: 0.81, 95% CI: 0.59 to 1.12; p=0.207). (Figure1) There was a significant interaction between bifurcation lesion(s) and treatment arm (p for interaction=0.006). In PCI patients, at 5-years there was no significant difference in mortality between 1- vs 2-stent techniques, whereas at 10-years, a 2-stent technique was associated with higher mortality (33.3% vs 25.9%; HR: 1.51, 95% CI: 1.06 to 2.14; p=0.021, Figure2). Conclusions Bifurcation lesion(s) require special attention from the heart team discussion, considering the higher 10-year all-cause mortality associated with PCI. Careful evaluation of bifurcation lesion complexity may be helpful in decision-making. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The SYNTAX Extended Survival study was supported by the German Foundation of Heart Research (Frankfurt am Main, Germany). The SYNTAX trial, during 0-5 years follow-up, was funded by Boston Scientific Corporation (Marlborough, MA, USA). Both sponsors had no role in the study design, data collection, data analyses, and interpretation of the study data, nor were involved in the decision to publish the final manuscript. The principal investigators and authors had complete scientific freedom.

Aims The purpose of the study is to assess the treatment results in the first 200 patients in the ongoing Multivessel TALENT trial and to predict the vessel-oriented endpoint by assessing the quantitative flow ratio (QFR) post PCI in a central independent core laboratory. Methods In this prospective, randomized, 1:1 balanced, multi-centre, open-label trial, de novo multivessel coronary artery disease patients without left main disease are assigned to the sirolimus-eluting stent or everolimus-eluting stent arm. The percutaneous coronary intervention (PCI) is planned based on functional lesion evaluation by QFR provided by the Core laboratory and the PCI has to be optimized by intravascular imaging, optimal pharmacological treatment and prasugrel monotherapy. Results Mean age of the population was 66.6±14.7 years, and 78.1% of them were male. This population consists of 17.4% unstable angina and of 31.8% diabetic patients. Anatomical SYNTAX score was 18.8±9.1. Total 458 lesions were treated from September 2020 to December 2021. Left anterior descending artery accounts for 40.3%, bifurcation lesion was present in 40.8%, total occlusion in 4.2%. The average stent diameter and total stent length were 3.0±0.4mm and 38.7±22.4mm, respectively. Intravascular imaging was used in 92.8% of treated vessels (intravascular ultrasound 56.5%, optical coherent tomography 36.3%). Pre-PCI QFR was analysable in 435 vessels (0.59±0.21), and 5.5% of them were treated even though the pre-PCI QFR values were more than 0.8. Post-PCI QFR has been so far analysed in 303 vessels (0.93±0.11) and 79.5% of them achieved a post-PCI QFR equal or superior to 0.91. Based on the previous study [1], Two-year vessel-oriented composite endpoint (VOCE) was estimated to become 5.4% in the present study population (3.7% in the patient group that achieved post PCI QFR equal or superior to 0.91, while 12% in the patients who could not reach the threshold), which was almost equal to what is expected in the power calculation. Conclusions In the Multivessel TALENT trial, the large majority of the vessels treated (94.5%) complied with the hemodynamic criteria of recommended PCI as provided by the QFRs of the Core laboratory. Favourable post-PCI QFR (≥0.91) obtained in 80% of the patients let expected a favourable VOCE outcome of 5.4%. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The National University of Ireland Galway

Objectives To compare the modality of revascularization selected by the local heart team to the one recommended by the core laboratory according to the SYNTAX score 2020 amongst patients with three-vessel disease (3VD) with or without left main disease (LMCAD), who were allocated to CABG planned and solely guided by coronary computerized tomographic angiography in the FASTTRACK CABG trial. Background Personalized long term vital prognosis plays a key role in deciding between PCI and coronary artery bypass grafting (CABG) in patients with complex coronary artery disease. Methods In an interim analysis requested by the Data Safety Monitoring Board the treatment recommendations according to the SYNTAX 2020 were prospectively assessed in 57 consecutive patients (half of the planned population in this First in Man) by a core laboratory and compared to the decision of the “on site” heart team. Results According to SS-2020, the predicted absolute risk difference (ARD) in mortality between the virtual PCI treatment population and the CABG treatment group, which can be considered a virtual surrogate for the average treatment effect, increased with the duration of follow up, from 4.8±3.5% at 5 years to 8.8±5.1% at 10 years (Table 1). The ARD of less than 0% in mortality at 5-year in favour of PCI was only documented in two patients while the 55 remaining patients had a predicted survival benefit over PCI if receiving CABG. However, based on a novel threshold of equipoise (ARD Conclusions According to the SYNTAX Score 2020 there was a strict observance of the CABG treatment recommendation in the first 57 consecutive patients with 3VD or LMCAD, screened on site in the FAST TRACK CABG trial. The more lenient selection criteria derived from the contemporary regitry will have to be tested propectively. Application of artificial intelligence with expanded collection of baseline characteristics, scientific endorsement and regulatory enforcement as well as further prospective evaluation are the challenges of future decision-making scores, that should be ultimately shared with the patients. Funding Acknowledgement Type of funding sources: None.

Background Epidemiology of non-pulmonary vein (PV) triggers of atrial fibrillation (AF) is not fully known. Purpose This study aimed to clarify the prevalence and distribution of non-PV triggers in real-world clinical settings of AF catheter ablation. Methods One-thousand and twenty patients undergoing AF ablations were retrospectively analyzed (mean age 65 years old, 702 males (69%), 506 paroxysmal and 514 non-paroxysmal). Induction and observation of AF triggers were attempted using intravenous isoproterenol/adenosine triphosphate and repeated direct current cardioversion during AF in each session. Documentable non-PV AF triggers were characterized in the studied population. Premature atrial contractions that did not initiate AF were excluded. Results A hundred and twenty-six non-PV triggers were documented in 108 patients (10.6%). Non-PV trigger was documented in 6.3% of 1st session cases, whereas 30.9% of recurrent cases undergoing multiple sessions (p Conclusions Prevalence of non-PV trigger in cases undergoing multiple sessions is extremely high, suggesting a particular importance of non-PV trigger targeting in patients with recurrent AF undergoing 2nd or 3rd ablation sessions. Progressive nature of AF with newly generated AF triggers should be under consideration. Distributions of non-PV triggers are largely different between paroxysmal and non-paroxysmal AF. These findings may help ablation strategy regarding non-PV trigger targeting in practice. Funding Acknowledgement Type of funding sources: None.

Background The index of microvascular resistance (IMR) is an established measurement of coronary microcirculation status. However, it has not been widely incorporated into routine practice due to need for intracoronary instrumentation (pressure wire) and hyperaemic agents. Several angiography-derived quantitative flow ratio-based indexes of microvascular resistance (angio-IMR) have been proposed rekindling the interest for the assessment and management of microvascular disease. Purpose To review the overall diagnostic accuracy of angio-IMR against wire based IMR. Methods A systematic review of the literature was performed and studies comparing angio-IMR with wire based IMR were included. Individual data was extracted using semi-automatic digitalization. Correlation of angio-IMR with IMR and its diagnostic performance against IMR were analysed. Results Six studies directly comparing angio-IMR with IMR were included. Data extraction rate was 85.1% (582/684 vessels). There was a linear correlation between angio-IMR and IMR (β=0.483, R square=0.298) (Figure 1A). Pooled sensitivity was 77%, specificity was 66%, positive predictive value was 65%, negative predictive value was 78%, and accuracy was 71.0%. Pooled area under receiver operator curve of angio-IMR for predicting IMR diagnosed coronary microvascular disease was 0.754 (95% confidential interval 0.715 to 0.793) (Figure 1B). Similar diagnostic performance was observed in subgroups of patients with or without ST-segment elevation myocardial infarction. Conclusions Currently available angio-IMR showed a clearly useful discrimination and diagnostic performance against the standard of wire based IMR. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): China Scholarship Council

Kerr parametric oscillators (KPOs), which can be implemented with superconducting parametrons possessing large Kerr nonlinearity, have been attracting much attention in terms of their applications to quantum annealing, universal quantum computation and studies of quantum many-body systems. It is of practical importance for these studies to realize fast and accurate tunable coupling between KPOs in a simple manner. We develop a simple scheme of fast tunable coupling of KPOs with high tunability in speed and amplitude using the fast transitionless rotation of a KPO in the phase space based on the shortcuts to adiabaticity. Our scheme enables rapid switching of the effective coupling between KPOs, and can be implemented with always-on linear coupling between KPOs, by controlling the phase of the pump field and the resonance frequency of the KPO without controlling the amplitude of the pump field nor using additional drive fields and couplers. We apply the coupling scheme to a two-qubit gate, and show that our scheme realizes high gate fidelity compared to a purely adiabatic one, by mitigating undesired nonadiabatic transitions.

Introduction With intra-arterial digital subtraction angiography (DSA) considered as the gold standard, we compared the diagnostic value of computed tomography angiography (CTA) and computed tomography-digital subtraction angiography (CT-DSA in hemodialysis (HD) patients suspected of having lower limb peripheral artery disease (PAD). Methods In this retrospective study, we enrolled 220 HD patients with suspected PAD. CT-DSA images were obtained by subtracting unenhanced images from enhanced images. The research team calculated the area under the curve (AUC), sensitivity, specificity, positive and negative predictive value (PPV, NPV), and recorded the diagnostic accuracy between the CTA and CT-DSA images using the DSA as gold standard. Visual evaluation of calcifications in the peripheral arteries were also compared between CTA and CT-DSA images. Results At the above-knee level, the CTA AUC [95% confidence interval (CI)] was 0.68 (CI 0.64–0.72), sensitivity and specificity were 60 and 81%, PPV and NPV were 85 and 53%, and accuracy was 67%. Below the knee, these values were 0.66 (CI 0.62–0.70), 71 and 79%, 79 and 47%, and 66%. For CT-DSA, above-knee, the AUC [95% CI] was 0.88 (CI 0.85–0.91), sensitivity and specificity were 84 and 92%, PPV and NPV were 89 and 97%, and accuracy was 93%. Below the knee, these values were 0.95 (CI 0.93–0.97), 95 and 93%, 96 and 83%, and 93%. The scores for the visualization of calcification in the peripheral arteries was significantly higher for CT-DSA than CTA (p Conclusions CT-DSA helps to assess stenotic PAD with high calcification in the lower extremities of HD patients. Implications for practice On CT-DSA images, the severity of vascular calcification can be assessed for HD patients suspected of PAD of the lower extremities.

OBJECTIVE: Syk is a cytoplasmic protein tyrosine kinase that plays a role in signaling via B cell and Fc receptors (FcR). FcR engagement and signaling via Syk is thought to be important in antineutrophil cytoplasm antibody (ANCA) IgG-mediated neutrophil activation. This study was undertaken to investigate the role of Syk in ANCA-induced myeloid cell activation and vasculitis pathogenesis. METHODS: Phosphorylation of Syk in myeloid cells from healthy controls and ANCA-associated vasculitis (AAV) patients was analyzed using flow cytometry. The effect of Syk inhibition on myeloperoxidase (MPO)-ANCA IgG activation of cells was investigated using functional assays (interleukin-8 and reactive oxygen species production) and targeted gene analysis with NanoString. Total and phosphorylated Syk at sites of tissue inflammation in patients with AAV was assessed using immunohistochemistry and RNAscope in situ hybridization. RESULTS: We identified increased phosphorylated Syk at critical activatory tyrosine residues in blood neutrophils and monocytes from patients with active AAV compared to patients with disease in remission or healthy controls. Syk was phosphorylated in vitro following MPO-ANCA IgG stimulation, and Syk inhibition was able to prevent ANCA-mediated cellular responses. Using targeted gene expression analysis, we identified up-regulation of FcR- and Syk-dependent signaling pathways following MPO-ANCA IgG stimulation. Finally, we showed that Syk is expressed and phosphorylated in tissue leukocytes at sites of organ inflammation in AAV. CONCLUSION: These findings indicate that Syk plays a critical role in MPO-ANCA IgG-induced myeloid cell responses and that Syk is activated in circulating immune cells and tissue immune cells in AAV; therefore, Syk inhibition may be a potential therapeutic option.

Speed is the key to further advances in technology. For example, quantum technologies, such as quantum computing, require fast manipulations of quantum systems in order to overcome the effect of decoherence. However, controlling the speed of quantum dynamics is often very difficult due to both the lack of a simple scaling property in the dynamics and the infinitely large parameter space to be explored. Therefore, protocols for speed control based on understanding of the dynamical properties of the system, such as non-trivial scaling property, are highly desirable. Fast-forward scaling theory (FFST) was originally developed to provide a way to accelerate, decelerate, stop and reverse the dynamics of quantum systems. FFST has been extended in order to accelerate quantum and classical adiabatic dynamics of various systems including cold atoms, internal state of molecules, spins and solid-state artificial atoms. This paper describes the basic concept of FFST and reviews the recent developments and its applications such as fast state-preparations, state protection and ion sorting. We introduce a method, called inter-trajectory travel, recently derived from FFST. We also point out the significance of deceleration in quantum technology. This article is part of the theme issue ‘Shortcuts to adiabaticity: theoretical, experimental and interdisciplinary perspectives’.

[Image: see text] IRAK4 kinase plays a key role in TLR/IL-1R signaling pathways that regulate innate immune responses, and if uncontrolled, it is responsible for various inflammatory disorders. By high-throughput screening (HTS) and hit-to-lead optimization, compounds with a 5-aryl-2,4-diaminopyrimidine core structure have been identified as potent IRAK4 inhibitors. A cocrystal structure of IRAK4 protein with an early lead molecule helped with understanding the structure–activity relationship and the design of the new compounds. Initial HTS hits from this series of compounds were also found to inhibit TAK1 kinase, which would cause liver toxicity and potentially bone marrow failure. Optimization of this series resulted in improved selectivity over TAK1 kinase. The TAK1 selectivity was found to be closely associated with different sizes and types of substituents at the 5-position of the pyrimidine. The impact of other pyrimidine substituents on the potency and selectivity was also explored. A few representative compounds were evaluated in IL-1β-induced IL-6 inhibition animal model studies and showed modest efficacy.

Drought is a serious global problem of agriculture. For this, an investigation was carried out with 25 wheat genotypes composed of cultivars and advanced lines to screen drought-tolerant bread wheat genotypes using multivariate analysis. The experiment was conducted in a split plot design with three replications and two treatments control and drought. The analysis of variance revealed significant differences among the genotypes and treatments for all the characters studied, viz. plant height, flag leaf collar height, flag leaf length, flag leaf breadth, chlorophyll a, chlorophyll b, proline content, number of tillers per plant, root fresh weight, shoot fresh weight and root–shoot ratio. High heritability was observed for all the traits except flag leaf length, flag leaf breadth and number of tillers per plant. Based on the genetic distances, all the 25 genotypes were grouped into three different clusters. In control conditions, cluster number I contained most tolerant genotypes and under drought conditions, cluster number III contained most drought-tolerant genotypes. In biplot, the genotypes SATYN-24, BARI Gom-24 and SATYN-2 contributed positively and correlated with number of tillers per plant, shoot fresh weight, flag leaf breadth, proline content and plant height under drought conditions. The drought susceptibility index (DSI) indicated that the genotypes BARI Gom-24 and SATYN-9 exhibited a highly drought-tolerant genotype in the present investigation. These genotypes might carry genes for drought tolerance and may be useful for further drought tolerance breeding.

Antibody mediated rejection is a major cause of renal allograft loss. Circulating preformed donor specific antibodies (DSA) can result as a consequence of blood transfusion, pregnancy or prior transplantation. Current treatment strategies are limited due to partial or transient efficacy, adverse side-effects or patient unsuitability. Previous in vivo studies exploring autoimmune diseases have shown that spleen tyrosine kinase (SYK) signalling is involved in the development of pathogenic autoantibody. The role of SYK in allogenic antibody production is unknown, and we investigated this in a rodent model of sensitization, established by the transfusion of F344 whole blood into LEW rats. Two-week treatment of sensitized rats with selective SYK inhibitor fostamatinib strongly blocked circulating DSA production without affecting overall total immunoglobulin levels, and inhibition was sustained up to 5 weeks post-completion of the treatment regimen. Fostamatinib treatment did not affect mature B cell subset or plasma cell levels, which remained similar between non-treated controls, vehicle treated and fostamatinib treated animals. Our data indicate fostamatinib may provide an alternative therapeutic option for patients who are at risk of sensitization following blood transfusion while awaiting renal transplant.

The JSNS^2 (J-PARC Sterile Neutrino Search at J-PARC Spallation Neutron Source) experiment aims to search for oscillations involving a sterile neutrino in the eV^2 mass-splitting range. The experiment will search for the appearance of electron antineutrinos oscillated from muon antineutrinos. The electron antineutrinos are detected via the inverse beta decay process using a liquid scintillator detector. A 1MW beam of 3 GeV protons incident on a spallation neutron target produces an intense and pulsed neutrino source from pion, muon, and kaon decay at rest. The JSNS^2 detector is located 24 m away from the neutrino source and began operation from June 2020. The detector contains 17 tonnes of gadolinium (Gd) loaded liquid scintillator (LS) in an acrylic vessel, as a neutrino target. It is surrounded by 31 tonnes of unloaded LS in a stainless steel tank. Optical photons produced in LS are viewed by 120 R7081 Hamamatsu 10-inch Photomultiplier Tubes (PMTs). In this paper, we describe the JSNS^2 detector design, construction, and operation., 41 pages, 29 figures

This study aims to predict endoleak after endovascular aneurysm repair (EVAR) using machine learning (ML) integration of patient characteristics, stent-graft configuration, and a selection of vessel lengths, diameters and angles measured using pre-operative computed tomography angiography (CTA).We evaluated 1-year follow-up CT scans (arterial and delayed phases) in patients who underwent EVAR for the presence or absence of an endoleak. We also obtained data on the patient characteristics, stent-graft selection, and preoperative CT vessel morphology (diameter, length, and angle). The extreme gradient boosting (XGBoost) for the ML system was trained on 30 patients with endoleaks and 81 patients without. We evaluated 5217 items in 111 patients with abdominal aortic aneurysms, including the patient characteristics, stent-graft configuration and vascular morphology acquired using pre-EVAR abdominal CTA. We calculated the area under the curve (AUC) of our receiver operating characteristic analysis using the ML method.The AUC, accuracy, 95% confidence interval (CI), sensitivity, and specificity were 0.88, 0.88, 0.79-0.97, 0.85, and 0.91 for ML applying XGBoost, respectively.The diagnostic performance of the ML method was useful when factors such as the patient characteristics, stent-graft configuration and vessel length, diameter and angle of the vessels were considered from pre-EVAR CTA.Based on our findings, we suggest that this is a potential application of ML for the interpretation of abdominal CTA scans in patients with abdominal aortic aneurysms scheduled for EVAR.

Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in transduction of IL-1R/TLR signaling which is responsible for innate immune response. From HTS campaign, bicyclic-pyrimidine compounds have been identified as potent IRAK4 inhibitors, exhibiting good potency in both IRAK4 biochemical and LPS induced IL-23 inhibition cell-based assays. The SAR efforts were focused on further improving on-target potency, reducing PAD activities of HTS hit molecule and improving in vivo PK profiles of early lead compounds. When different aromatic rings were fused to the pyrimidine core, and with various substituents at 2- or 4-position of the pyrimidine, the impact on potency and PK properties were observed and are discussed. Selected compounds were further evaluated in IL-1β induced IL-6 inhibition acute animal model and rodent arthritis disease model, of which compounds 33 and 39 showed good efficacy in both studies.

This study aimed to compare the correlation between the computed tomography (CT) enhancement rate of the venous to portal venous phase (VP-ER) and the extracellular volume (ECV) fraction with shear-wave ultrasound elastography (USE) findings in patients with liver fibrosis.We included 450 patients with clinically suspected liver cirrhosis who underwent triphasic dynamic CT studies and USE. We compared the USE results with the unenhanced CT phase, with enhancement in the hepatic artery phase (HAP), portal venous phase (PVP), and venous phase (VP), and with the ECV fraction and the VP-ER. We also compared the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the ECV fraction and VP-ER with that of the values obtained with USE.The VP-ER was the most highly correlated with the liver stiffness value determined with USE (Pearson's correlation coefficient: r = 0.37), followed by enhancement in the PVP (r = -0.25), CT number on unenhanced CT scans (r = -0.22), the ECV fraction (r = 0.19), enhancement in the VP (r = 0.059), and enhancement in the HAP (r = -0.023) (all p 0.01). The VP-ER showed a significantly higher AUC than the ECV fraction (0.75 vs 0.62) when the liver stiffness was15 kPa in USE studies (p = 0.04).Compared to the ECV fraction, the VP-ER is more useful for predicting all degrees of liver fibrosis on routine triphasic dynamic CT images.Although improvement is needed, the VP-ER has a higher diagnostic ability for liver fibrosis than the ECV fraction in clinical practice.

Iridium (Ir) exhibits a good efficiency for reduction of NO under excess O2 coexisting conditions at temperatures higher than 250 °C. On the other hand, the advantage is lost at lower temperatures below 250 °C under O2 existence, compared to any other platinum group metals. In this study, adsorption behavior of NO on Ir(111) single-crystal surfaces under excess O2 coexisting conditions at the temperatures from room temperature to 250 °C has been studied by in-situ X-ray Photoelectron Spectroscopy (XPS). It is revealed that the coexisting O2 induces formation of a high-density chemisorbed atomic oxygen (O) phase and the atomic O phase suppresses adsorption of NO at on-top sites significantly, which suggests that the suppression of NO adsorption causes a decrease in the ability of NO reduction at the lower temperatures.

Various applications of quantum devices call for an accurate calibration of cryogenic amplification chains. To this end, we present a convenient calibration scheme and use it to accurately measure the total gain and noise temperature of an amplification chain by employing normal-metal--insulator--superconductor (NIS) junctions. Our method is based on the radiation emitted by inelastic electron tunneling across voltage-biased NIS junctions. We derive an analytical equation that relates the generated power to the applied bias voltage which is the only control parameter of the device. After the setup has been characterized using a standard voltage reflection measurement, the total gain and the noise temperature are extracted by fitting the analytical equation to the microwave power measured at the output of the amplification chain. The 1$\sigma$ uncertainty of the total gain of 51.84 dB appears to be of the order of 0.1 dB., Comment: 5 pages, 3 figures

BackgroundKnee joint disorder is one of the factors causing frailty in the elderly, which is associated with a decrease in walking speed.ObjectivesWe measured the walking speed of patients scheduled to undergo primary total knee arthroplasty (TKA) and examined factors correlated with walking speed.MethodsThe patients with knee disorders scheduled to undergo knee arthroplasty at our hospital between July 2020 and May 2021 were included. They were assessed for basic attributes, clinical assessment including Kness Society Score (KSS), degree of pain on walking by visual analogue scale (VAS), range of motion (ROM), and also leg skeletal muscle mass index (SMI; whole-body mode DXA), quadriceps strength by dynamometer with written consent (UMIN ID: 000040940). And Japanese Cardiovascular Health Study criteria for frailty, and sarcopenia by Asian Working Group for Sarcopenia 2019 criteria were evaluated.ResultsDemographic data of 83 patients (65 women, mean age 74.9 years) included in this study was shown in Table 1. The distribution in frailty is 36.2% and that in sarcopenia is 7.3%. Most of the patients with frailty with knee disorder did not suffer from sarcopenia. A multivariate analysis was conducted with walking speed as the objective variable and the dependent variables as age, gender, pain VAS on walking, KSS, leg SMI, quadriceps strength, and ROM. The results showed that age and ROM in flexion were significantly and independently associated with walking speed (P=0.01, 0.03). Gender, pain VAS on walking, KSS, leg SMI, quadriceps strength, and ROM in extension were not significantly associated with walking speed (P=0.92, 0.11, 0.11, 0.52, 0.85, 0.52).ConclusionAmong the patients with knee disorders immediately before arthroplasty, frailty was not caused by sarcopenia. Age was found to be the most correlated factor with walking speed, and walking speed became slower with age. In addition, poor flexion angle was also the factor for delayed walking speed, but it did not correlate with lower limb skeletal muscle mass or quadriceps strength. In this study pain on walking was not significant factor for walking speed, because it was observed in most of all cases.FactorGroup disease (n)osteoarthritis78 (94%) rheumatoid arthritis5 (6.0%)body mass index (kg/m2) 25.54 (4.11)pain VAS on walking 37.08 (26.35)total Knee Society Score 77.66 (27.85)range of motion (degree)flexion119.46 (12.88) extension-9.58 (6.59)quadriceps power (N) 122.00 [53.00, 350.00]waling speed (m/sec) 0.95 (0.33)grip power (kg) 20.24 (6.97)skeletal muscle mass index (kg/m2)appendicular6.50 [4.92, 9.85] lower limb5.06 [3.76, 7.56]Frailty (n)none10 (12.5%)Pre-frail41 (51.2%) frail29 (36.2%)Sarcopenia (n)none76 (92.7%)sarcopenia4 (4.9%) severe sarcopenia2 (2.4%)mean (standard deviation); median [min max]Disclosure of InterestsNone declared

BackgroundMPO-ANCA-associated vasculitis (MPO-AAV) is a systemic small vessel vasculitis with the production of MPO-ANCA in the serum. This disease develops necrotizing and crescent glomerulonephritis (NCGN) and peritubular capillaritis-mediated interstitial damages in the kidneys, and pulmonary hemorrhage due to capillaritis in the lungs. Recent studies have revealed that neutrophil extracellular traps (NETs) induced by MPO-ANCA are critically involved in its pathogenesis,1 and neutrophil elastase (NE) plays an essential role in the formation of NETs.2 Cathepsin C (CatC) functions as a key enzyme in the activation process of several neutrophil serine proteases (NSPs) such as NE, proteinase 3 and cathepthin G by converting the inactive forms of the NSPs to the active forms by digesting dipeptides at the N-terminus of the enzymes.3ObjectivesAlthough glucocorticoids and immunosuppressive drugs used as the standard of cares can lead remission in MPO-AAV patients, there are remaining unmet medical needs such as severe side effects, resistance to the treatment and relapse. Therefore, development of new therapeutic strategies is awaited. The aim of this study is to demonstrate the efficacy of MOD06051, a novel CatC inhibitor, against MPO-AAV, using an MPO-AAV rat model established previously.4MethodsIn vitro studies: Cathpsins and NE inhibitory activity was measured using recombinant enzymes and fluorescent substrates. Cellular NE activity in the granulocytes differentiated from the primary human bone marrow-derived hematopietic stem cells under the presence or absence of MOD06051 was determined using fluorescent substrates.In vivo studies: 4-week-old Wistar Kyoto (WKY) rats were immunized with human MPO according to Little’s protocol.4 The rats were divided into three groups (n=8 in each group), and vehicle (0.5% methylcellulose) or MOD06051 (0.3 or 3 mg/kg bid) was orally administered every day for 42 days. All rats were euthanized at the end of the study for serological and histological evaluations.ResultsIn vitro studies: MOD06051 inhibited the enzymatic activity of human recombinant CatC with an IC50 value of 1.5 nM, and no other cathepsins nor NE inhibition was observed at 10 μM. The NE activity in primary human granulocytes was suppressed by MOD06051 with an IC50 value of 18 nM.In vivo studies: MPO-ANCA was induced in all groups at the same level. The percentage of affected glomeruli including those with NCGN, NET-forming neutrophils in the peripheral blood and glomeruli, and glomerular neutrophil counts were significantly suppressed by MOD06051 treatment in a dose-dependent manner. Furthermore, hematuria score, urinary NGAL (Neutrophil Gelatinase-Associated Lipocalin), tubular erythrocyte cast counts, and pulmonary hemorrhage foci were significantly decreased in the 3 mg/kg of MOD06051 treated group with the similar trends in 0.3 mg/kg group.ConclusionMOD06051 showed sepcific inhibition of CatC activity. This compound suppressed the serine proteases activation in primary human neutrophils and NET formation in the MPO-AAV model rats, resulting in amelioration of MPO-ANCA-induced tissue destruction, including NCGN and tubular interstitial damages in the kidneys, and disorder of alveolar septal capillaries in the lungs. MOD06051 appears to be a promising agent for treatment of MPO-AAV patients.References[1]Nakazawa D, et al. Nat Rev Rheumatol 15: 91-101, 2019.[2]Papayannopoulos V, et al. J Cell Biol 191: 677-691, 2010.[3]Korkmaz B, et al. Pharmacol Ther 190: 202-236, 2018.[4]Little MA, et al. Am J Pathol 174: 1212-1220, 2009.Disclosure of InterestsAkihiro Ishizu Grant/research support from: Modulus Discovery, Inc., Mai Taniguchi: None declared, Suishin Arai: None declared, Yuka Nishibata Grant/research support from: Modulus Discovery, Inc., Sakiko Masuda Grant/research support from: Modulus Discovery, Inc., Utano Tomaru: None declared, Takafumi Shimizu Shareholder of: Modulus Discovery, Inc., Employee of: Modulus Discovery, Inc., William Sinko Shareholder of: Modulus Discovery, Inc., Employee of: Modulus Discovery, Inc., Tadashi Nagakura Shareholder of: Modulus Discovery, Inc., Employee of: Modulus Discovery, Inc., Yoh Terada Shareholder of: Modulus Discovery, Inc., Employee of: Modulus Discovery, Inc.

Background Induction of atrial fibrillation (AF)/atrial tachycardia (AT) by atrial burst pacing following ablation procedure may reflect the presence of residual substrates in the atria that maintain AF. However, the relation between the inducibility and left atrial low voltage area (LVA) has not been established. Methods Fifty-nine patients (65 years old, 43 males) with persistent AF who underwent pulmonary vein isolation (PVI)-based ablation were studied. All patients underwent left atrial voltage mapping during sinus rhythm and atrial burst pacing after PVI. Atrial burst pacing was performed with 30-beat at an amplitude of 10V from the ostium of the coronary sinus; increasing from 240 to 320 ppm in steps of 20 ppm or failure to 1:1 atrial capture. Inducibility was defined as AF/AT lasting more than 5 minutes following burst pacing. Left atrial LVA and other co-variates were analyzed with regard to burst pacing positivity. Results AF/AT was induced by burst pacing in 23 patients (39%). Univariate analysis revealed that past history of stroke, CHADS2 score and presence of left atrial LVA were significantly associated with the inducibility of AF/AT. Multivariate analysis revealed that only the presence of LVA was associated with the inducibility (OR 1.5: per 10% increase; p=0.04). We focused on the relationship between the extent of LVA and burst positivity. AF/AT inducibility increased as low voltage area increased, and it was as high as 72.7% when low voltage area was more than 20% (P Conclusions Presence of left atrial LVA is an independent predictor of atrial tachyarrhythmia inducibility after PVI in patients with persistent AF. A large amount of low voltage area is related to AT inducibility rather than AF. Extent of LVA and burst positivity Funding Acknowledgement Type of funding source: None

Background/Introduction It has been reported that heart failure (HF) readmission has not declined even with current cardiology practice in the last 10 years. It has been also reported that HF readmission tends to occur shortly after discharge. This may be due to overwork and excessive salt intake after discharge. In other words, it is conceivable that patient factors are largely attributable, which should be intervene for better clinical outcomes. Purpose We hypothesized and investigated whether an early follow-up visit at outpatient care within 2 weeks after discharge affects the re-admission rate and prognosis in patients with decompensated HF. Methods We retrospectively investigated consecutive 407 hospitalized patients due to decompensated HF. After exclusion of 99 patients with in-hospital death, transfer to another hospital and readmission within 2 weeks after discharge, consecutive 308 out of 407 patients were investigated. Two-year clinical outcomes after discharge were collected and analyzed. An early follow-up was defined as an outpatient care visit within 2 weeks after discharge with the adjustment of drugs and/or the lifestyle guidance, if necessary. A setting of early follow-up in each patient was according to a physician's discretion. Results One hundred-twenty eight patients underwent early follow-up visits and other 180 patients were without it. An univariate analysis showed that the early follow-up was significantly associated with a lower HF readmission rate during 2 years (17.1% in the early follow-up group, 34.4% in the control group, p≤0.001, OR=0.397, 95% CI=0.230–0.685, Figure) and a 2-year composite adverse outcome (all cause death and HF readmission; 18.7% vs. 40.5%, p Conclusions The present study suggests that an early follow-up approach after discharge in decompensated HF patients may improve the long-term prognosis. These results were not dependent on whether a medication adjustment was performed or not. An early follow-up may help improve patient factors of HF worsening. Main results Funding Acknowledgement Type of funding source: None

To compare the radiation dose, diagnostic accuracy, and the resultant ablation procedures using 80 and 120-kVp cardiac computed tomography angiography (CCTA) protocols with the same contrast-to-noise ratio in patients scheduled for atrial fibrillation (AF) ablation.This retrospective study was performed following institutional review board approval. We divided 140 consecutive patients who had undergone CCTA using a 64-MDCT scanner into two equal groups. Standard deviation (SD) of the CT number was set at 25 Hounsfield units (HU) for the 120-kVp protocol. To facilitate a reduction in radiation dose it was set at 40 HU for the 80 kVp protocol. We compared the two protocols with respect to the radiation dose, the diagnostic accuracy for detecting left atrial appendage (LAA) thrombi, matching for surface registration, and the resultant ablation procedures.At 120 kVp, the dose length product (DLP) was 2.2 times that at 80 kVp (1269.0 vs 559.0 mGy cm, p 0.01). The diagnostic accuracy for thrombus detection was 100% using both protocols. There was no difference between the two protocols with respect to matching for surface registration. The protocols did not differ with respect to the subsequent time required for the ablation procedures and the ablation fluoroscopy time, and the radiation dose (p = 0.54, 0.33, and 0.32, respectively).For the same CNR, the DLP at 80 kVp (559.0 mGy cm) was 56% of that delivered at 120 kVp (1269.0 mGy cm). There was no reduction in diagnostic accuracy.Maintaining CNR allows for a reduction in the radiation dose without reducing the image quality.

Patients receiving cancer chemotherapy may experience a number of potentially severe adverse drug reactions. It is crucial for all members of the health care team to monitor the effect of medicines on the patient to ensure the safety and efficacy of the chemotherapy. The present study prepared medication instruction sheets (MISs) on hematological malignancy and conducted a questionnaire survey to verify their usefulness among physicians, dentists, and nurses. MISs were prepared for 103 chemotherapy and 44 pretreatment regimens for hematopoietic stem cell transplantation in the Department of Hematology at Kyushu University Hospital. Eight questions were prepared to investigate whether MISs could help physicians, dentists, and nurses manage cancer chemotherapy more safely, effectively, and efficiently, as well as in the sharing of information. A total of 35 medical staff working in inpatient wards, including 8 physicians, 3 dentists, and 24 nurses, participated in the questionnaire survey. All of the staff responded to the questionnaire survey, which showed that the MISs were favorably accepted by the participants. There was no negative opinion on the management of chemotherapy using the MISs. The MIS was a useful tool for sharing information on cancer chemotherapy between patients and medical staff and for enabling efficient management, thereby improving the safety and efficacy of treatment.

The Cherenkov Telescope Array (CTA) is the major next-generation observatory for ground-based very-high-energy gamma-ray astronomy. It will improve the sensitivity of current ground-based instruments by a factor of five to twenty, depending on the energy, greatly improving both their angular and energy resolutions over four decades in energy (from 20 GeV to 300 TeV). This achievement will be possible by using tens of imaging Cherenkov telescopes of three successive sizes. They will be arranged into two arrays, one per hemisphere, located on the La Palma island (Spain) and in Paranal (Chile). We present here the optimised and final telescope arrays for both CTA sites, as well as their foreseen performance, resulting from the analysis of three different large-scale Monte Carlo productions.© 2019, We gratefully acknowledge financial support from the following agencies and organizations: State Committee of Science of Armenia, Armenia; The Australian Research Council, Astronomy Australia Ltd, The University of Adelaide, Australian National University, Monash University, The University of New South Wales, The University of Sydney, Western Sydney University, Australia; Federal Ministry of Science, Research and Economy, and Innsbruck University, Austria; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Ministry of Science, Technology, Innovations and Communications (MCTIC), Brasil; Ministry of Education and Science, National RI Roadmap Project D01-153/28.08.2018, Bulgaria; The Natural Sciences and Engineering Research Council of Canada and the Canadian Space Agency, Canada; CONICYT-Chile grants PFB-06, FB0821, ACT 1406, FONDECYT-Chile grants 3160153, 3150314, 1150411, 1161463, 1170171, Pontificia Universidad Catolica de Chile Vice-Rectory of Research internationalization grant under MINEDUC agreement PUC1566, Chile, Croatian Science Foundation, Rudjer Boskovic Institute, University of Osijek, University of Rijeka, University of Split, Faculty of Electrical Engineering, Mechanical Engineering and Naval Architecture, University of Zagreb, Faculty of Electrical Engineering and Computing, Croatia; Ministry of Education, Youth and Sports, MEYS LM2015046, LTT17006 and EU/MEYS CZ.02.1.01/0.0/0.0/16_013/0001403, CZ.02.1.01/0.0/0.0/17_049/0008422, Czech Republic; Ministry of Higher Education and Research, CNRS-INSU and CNRS-IN2P3, CEA-Irfu, ANR, Regional Council Ile-de France, Labex ENIGMASS, OSUG2020, P210 and OCEVU, France; Max Planck Society, BMBF, DESY, Helmholtz Association, Germany; Department of Atomic Energy, Department of Science and Technology, India; Istituto Nazionale di Astrofisica (INAF), Istituto Nazionale di Fisica Nucleare (INFN), MIUR, Istituto Nazionale di Astrofisica (INAF-OABRERA) Grant Fondazione Cariplo/Regione Lombardia ID 2014-1980/RST_ERC, Italy; ICRR, University of Tokyo, JSPS, MEXT, Japan; Netherlands Research School for Astronomy (NOVA), Netherlands Organization for Scientific Research (NWO), Netherlands; University of Oslo, Norway; Ministry of Science and Higher Education, DIR/WK/2017/12, the National Centre for Research and Development and the National Science Centre, UMO-2016/22/M/ST9/00583, Poland; Slovenian Research Agency, Slovenia, grants P1-0031, P1-0385, 10-0033, J1-9146; South African Department of Science and Technology and National Research Foundation through the South African Gamma-Ray Astronomy Programme, South Africa; MINECO National R+D+I, Severo Ochoa, Maria de Maeztu, CDTI, PAIDI, UJA, FPA2017-90566-REDC, Spain; Swedish Research Council, Royal Physiographic Society of Lund, Royal Swedish Academy of Sciences, The Swedish National Infrastructure for Computing (SNIC) at Lunarc (Lund), Sweden; Swiss National Science Foundation (SNSF), Ernest Boninchi Foundation, Switzerland; Durham University, Leverhulme Trust, Liverpool University, University of Leicester, University of Oxford, Royal Society, Science and Technology Facilities Council, UK; U.S. National Science Foundation, U.S.Department of Energy, Argonne National Laboratory, Barnard College, University of California, University of Chicago, Columbia University, Georgia Institute of Technology, Institute for Nuclear and Particle Astrophysics (INPAC-MRPI program), Iowa State University, the Smithsonian Institution, Washington University McDonnell Center for the Space Sciences, The University of Wisconsin and the Wisconsin Alumni Research Foundation, USA. The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreements no 262053 and no 317446. This project is receiving funding from the European Union's Horizon 2020 research and innovation programs under agreement no 676134.

We evaluate the feasibility of an efficient laser plasma acceleration driven by an intense mid-infrared pulse. The driving wavelength of 1.5 μm with a relativistic-laser-intensity (a 0 = 2) can improve the number of accelerated electrons as an order of magnitude, compared with that driven by the same intensity of Ti:sapphire laser.

We discuss the feasibility of an efficient laser wakefield acceleration driven by an intense mid-infrared pulse. TW-scale 1.5 μm laser pulse can improve the number of accelerated electrons as an order of magnitude, compared with that driven by a Ti:sapphire laser (0.8 μm).

The genetic diversity of native chicken populations from Myanmar, Thailand, and Laos was examined by using 102 insertion and/or deletion (indels) markers. Most of the indels loci were polymorphic (71% to 96%), and the genetic variability was similar in all populations. The average observed heterozygosities (H O ) and expected heterozygosities (H E ) ranged from 0.205 to 0.263 and 0.239 to 0.381, respectively. The coefficients of genetic differentiation (Gst) for all cumulated populations was 0.125, and the Thai native chickens showed higher Gst (0.088) than Myanmar (0.041) and Laotian (0.024) populations. The pairwise Fst distances ranged from 0.144 to 0.308 among populations. A neighbor-joining (NJ) tree, using Nei's genetic distance, revealed that Thai and Laotian native chicken populations were genetically close, while Myanmar native chickens were distant from the others. The native chickens from these three countries were thought to be descended from three different origins (K = 3) from STRUCTURE analysis. Genetic admixture was observed in Thai and Laotian native chickens, while admixture was absent in Myanmar native chickens.