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A group of iron artefacts were excavated from the stratigraphic layers at Kaman-Kalehöyük in Central Anatolia, which were dated to the Middle and Early Bronze Ages. Some of them were re-analysed to discuss the state of iron production during such early periods, in terms of intentional carburization. The artefacts were re-examined via a minimally invasive approach by using optical microscope, scanning electron microscopy and energy dispersive spectroscopy to determine their chemical composition and microstructure. It was observed that the artefacts are composed of iron and/or steel. However, it is difficult to assert that they were produced as steel intentionally, because of their varying C contents and the lack of correlation between C content and artefact type. Such a finding could highlight the range in early efforts to smelt iron, while ancient metal workers were trying to figure out how to control furnace conditions during the Bronze Age in Central Anatolia.

This conceptual design report provides a detailed account of the European Spallation Source neutrino Super Beam (ESS$\nu$SB) feasibility study. This facility has been proposed after the measurements reported in 2012 of a relatively large value of the neutrino mixing angle $\theta_{13}$, which raised the possibility of observing potential CP violation in the leptonic sector with conventional neutrino beams. The measured value of $\theta_{13}$ also privileges the $2^{nd}$ oscillation maximum for the discovery of CP violation instead of the more typically studied $1^{st}$ maximum. The sensitivity at this $2^{nd}$ oscillation maximum is about three times higher than at the $1^{st}$ one, which implies a reduced influence of systematic errors. Working at the $2^{nd}$ oscillation maximum requires a very intense neutrino beam with an appropriate energy. The world's most intense pulsed spallation neutron source, the European Spallation Source (ESS), will have a proton linac operating at 5\,MW power, 2\,GeV kinetic energy and 14~Hz repetition rate (3~ms pulse duration, 4\% duty cycle) for neutron production. In this design study it is proposed to double the repetition rate and compress the beam pulses to the level of microseconds in order to provide an additional 5~MW proton beam for neutrino production. The physics performance has been evaluated for such a neutrino super beam, in conjunction with a megaton-scale underground water Cherenkov neutrino detector installed at a distance of 360--550\,km from ESS. The ESS proton linac upgrades, the accumulator ring required for proton-pulse compression, the target station design and optimisation, the near and far detector complexes, and the physics potential of the facility are all described in this report. The ESS linac will be operational by 2025, at which point the implementation of upgrades for the neutrino facility could begin., Comment: 216 pages

Objectives The aim of this AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial subgroup analysis was to examine rivaroxaban monotherapy benefits and their relation to the time between stenting and enrollment among patients after coronary stenting. Background Of 2,215 patients with atrial fibrillation and stable coronary artery disease in the AFIRE trial, rivaroxaban monotherapy was noninferior to rivaroxaban plus antiplatelet therapy (combination therapy) in terms of efficacy and superior for safety endpoints. However, thrombotic risk after antiplatelet therapy cessation remained a concern among 1,444 patients who had undergone coronary stenting >1 year before enrollment. Methods The benefits of rivaroxaban monotherapy in coronary stenting subgroups were assessed for efficacy (a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death of any cause), safety (major bleeding defined according to International Society on Thrombosis and Haemostasis criteria), ischemic endpoints, net adverse clinical event, and time between stenting and enrollment. Results Efficacy and safety endpoints for monotherapy were superior to combination therapy, with HRs of 0.70 for efficacy (95% CI: 0.50-0.98; P = 0.036) and 0.55 for safety (95% CI: 0.33-0.92; P = 0.019). For ischemic endpoints, the HR was 0.82 (95% CI: 0.58-1.15; P = 0.240). The HR became smaller with longer time between stenting and enrollment (efficacy, P for interaction = 0.158; safety, P = 0.097). Conclusions In patients with atrial fibrillation after coronary stenting, the benefits of rivaroxaban monotherapy for efficacy and safety endpoints were consistent with those in the whole AFIRE trial population. The benefits became apparent with longer time between stenting and enrollment. (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study [AFIRE]; UMIN000016612 , NCT02642419 )

Background It remains unknown if concomitant left atrial appendage closure (LAAC) at the time of left ventricular assist device (LVAD) surgery can reduce ischemic cerebrovascular accidents. Purpose The purpose of this study is to assess the impact of LAAC at LVAD surgery on the incidence of ischemic cerebrovascular accidents. Methods Between January 2012 and November 2021, 310 patients underwent LVAD surgery with HeartMate II or III. Out of 310 patients, 98 patients (31.6%) underwent concomitant LAAC. The cohort was divided into two groups: patients with LAAC (Group A, n=98) and without LAAC (Group B, n=212). To minimize device bias, LVAD surgery with HeartWare HVAD device was excluded. The ischemic cerebrovascular accident was defined as ischemic stroke, hemorrhagic stroke or transient ischemic attack. We reviewed early and long-term clinical outcomes. The incidence of ischemic cerebrovascular accidents was compared between two groups using the Kaplan-Meier method. We also investigated if LAAC was associated with ischemic cerebrovascular accidents by Cox proportional hazards analysis. Results There were no significant differences in baseline characteristics between two groups including age (Group A: 55.0±12.3 years old, Group B: 56.9±14.1 years old, p=0.26), preoperative CHADS2 score (Group A: 2.40±1.1, Group B: 2.58±1.1, p=0.19) and history of atrial fibrillation (Group A: 42.9%, Group B: 42.5%, p=0.95). In-hospital mortality was not significantly different between the two groups (Group A: 7.1%, Group B: 12.3%, p=0.16). In terms of postoperative complications, there were no significant differences between two groups in requiring extracorporeal membrane oxygenation, re-exploration for bleeding and newly required hemodialysis. Median follow up period was 474 days. Thirty-five patients (11.2%) developed ischemic cerebrovascular accidents (5 patients in Group A and 30 patients in Group B). The rate of freedom from ischemic cerebrovascular accidents in Group A (94.1% at 500 days and 94.1% at 1500 days) was significantly higher than that in Group B (88.2% at 500 days and 77.4% at 1500 days; log rank=0.024). In a Cox proportional hazards regression analysis including LAAC, age, history of atrial fibrillation, diabetes mellitus and Heartmate 3 device implantation, LAAC was associated with reducing the incidence of ischemic cerebrovascular accidents (hazard ratio 0.37, 95% CI 0.13–0.89, p=0.02). Conclusion Concomitant LAAC at the time of LVAD surgery can reduce ischemic cerebrovascular accidents without increasing perioperative mortality and complications. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: None. Background New or worsening tricuspid regurgitation (TR) is associated with right-sided heart failure and worsened outcomes. Cardiac Implantable Electronic Devices (CIEDs), which are being implanted at growing rates worldwide, are increasingly being recognized as associated with TR occurrence related to interference with the tricuspid valve (TV) apparatus. Purpose: We sought to identify echocardiographic features in the right ventricle and TV that differentiate patients who have anatomically demonstrated interference with the TV on direct pathology inspection. Methods Explanted hearts from 44 consecutive patients undergoing orthotopic heart transplant (55 ±13 yrs, 68% men) with known implanted CIEDs were dissected to assess the presence (n = 18) or absence (n = 26) of CIED interference with the TV (Figure). Echocardiographic measurements performed prior to transplantation, including left and right ventricular (LV, RV) size and performance metrics as well as TR severity, were compared between both groups using non-parametric testing. Results Echocardiographic features of patients with and without anatomically demonstrated TV interference are shown in the Table. Although overall LV dimensions and volumes were not different between the two groups and LV ejection fraction was severely reduced in both groups, patients demonstrating CIED interference trended towards larger right atrial volumes (Table) and also larger RV and tricuspid annular sizes. Importantly, however, they were more than 4 times likely to have abnormal right ventricular function. Lastly, patients with tricuspid apparatus interference tended to have more significant TR, although these differences have not reached statistical significance (Table). Conclusion CIED interreference with tricuspid valve apparatus occurs frequently (41%) among patients with CIEDs, who undergo orthotopic heart transplantation. This may be associated with worsening TV function with subsequent changes in right atrial and ventricular geometry and function. In light of prior data showing poor outcomes with CIED associated TR, this study emphasizes the importance of non-invasive assessment of CIED interference with the tricuspid valve, in order to improve device placement and patient outcomes. Abstract Figure Abstract Table

Context: To identify VA and non-VA Emergency Department (ED) and hospital utilization by veterans with spinal cord injury and disorders (SCI/D) in California. Design: Retrospective cohort study. Setting: VA and Office of Statewide Health Planning and Development (OSHPD) in California. Participants: Total 300 veterans admitted to the study VA SCI/D Center for initial rehabilitations from 01/01/1999 through 08/17/2014. Interventions: N/A. Outcome Measures: Individual-level ED visits and hospitalizations during the first-year post-rehabilitation. Results: Among 145 veterans for whom ED visit data available, 168 ED visits were identified: 94 (55.2%) at non-VA EDs and 74 (44.8%) at the VA ED, with a mean of 1.16 (±2.21) ED visit/person. Seventy-seven (53.1%) veterans did not visit any ED. Of 68 (46.9%) veterans with ≥ one ED visit, 20 (29.4%) visited the VA ED only, 34 (50.0%) visited non-VA EDs only, and 14 (20.6%) visited both VA and non-VA EDs. Among 212 Veterans for whom hospitalization data were available, 247 hospitalizations were identified: 82 (33.2%) non-VA hospitalizations and 165 (66.8%) VA hospitalization with a mean of 1.17 (±1.62) hospitalizations/person. One hundred-seven (50.5%) veterans had no hospitalizations. Of 105 veterans with ≥ one hospitalization, 58 (55.2%) were hospitalized at the study VA hospital, 15 (14.3%) at a non-VA hospital, and 32 (30.5%) at both VA and non-VA hospitals. Conclusion: Non-VA ED and hospital usage among veterans with SCI/D occurred frequently. The acquisition of non-VA healthcare data managed by state agencies is vital to accurately and comprehensively evaluate needs and utilization rates among veteran populations.

In order to improve the quality of life of dialysis patients, our group have been developing an implantable hemofiltration device (IHFD) composed of multiple layers of dialysis membranes and microfluidic channels. To improve the hemodialysis performance of IHFD, preventing the negative filtration, which is caused by the oncotic pressure of blood, is mandatory. In this study, we fabricated IHFDs with five different microchannel designs and experimentally investigated the performance of each device in in vitro experiment. In addition, the successful IHFD was further evaluated by ex vivo experiments with a beagle dog. The experiments verified the effectiveness of the microchannel design, which will be used for the IHFD for in vivo experiments with pigs in the future.

Objectives The Erection Hardness Score (EHS) can assess erectile hardness with a single question and is readily used in routine clinical practice. We investigated the correlation between EHS and both erectile function and metabolic risk, lifestyle, and other factors. Methods This study included 548 men who underwent a complete standard medical checkup at our hospital between July 1, 2016, and August 31, 2018, and answered the question about erectile hardness. The following variables were evaluated: age, erectile hardness on the EHS, erectile function on the Sexual Health Inventory for Men (SHIM), current medical history (diabetes, hypertension, dyslipidemia, heart disease, stroke), metabolic risk factors (abdominal circumference, hyperglycemia, high blood pressure, lipid abnormality), and lifestyle factors. First, to examine the correlation between erectile hardness and erectile function, the mean SHIM score by EHS grade was determined for each age group. Then, an analyses was performed to examine the association between erectile hardness and age, current medical history, metabolic risk factors, and lifestyle factors. Results In each age group, a lower EHS grade was associated with a lower mean SHIM score. Lipid abnormality, diabetes, and age were independent risk factors for decreased erectile hardness. Conclusion The EHS as a measure of erectile hardness was correlated with erectile functional as assessed using the SHIM, and current diabetes and lipid abnormality were independent risk factors for decreased erectile hardness. However, neither dyslipidemia nor lipid abnormality is listed as a risk factor in the ED guidelines. Traditionally, lipid abnormality was assessed based mainly on the presence or absence of current hyper-lipidemia and serum total cholesterol level. Today, the diagnostic criteria for metabolic syndrome proposed by the World Health Organization, International Diabetes Federation, and Japanese Society of Internal Medicine also recommend the use of serum triglyceride and HDL cholesterol levels, instead of total cholesterol level, for evaluating lipid abnormality. I think the assessment of lipid abnormality should be used triglyceride and HDL cholesterol levels, instead of total cholesterol level. Disclosure Work supported by industry: no.

BACKGROUND Dupilumab is an antibody against interleukin-4 receptor α, used in the treatment of atopic dermatitis (AD). OBJECTIVES To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate-to-severe AD. METHODS In this randomized, double-blind, placebo-controlled, parallel-group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0-1 and a reduction from baseline of ≥ 2 points at week 16. RESULTS Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37-32·65; P

VIAGRA was first placed on the Japanese market in 1999. Since then, PDE5 inhibitors, such as VIAGRA, have been widely used as the first alternative therapeutic medication to treat erectile dysfunction (ED). A new form of VIAGRA called VIAGRA OD Film was launched in the Japanese market on October 21st, 2016. OD film is taken orally without water and is fast dissolving. It is therefore expected to be easier to consume. Moreover, this medication is packaged in thin aluminum sheets to improve portability compared to the original tablets. For this study, we surveyed 25 patients to analyze the OD film formulation. These patients desired ED treatment and used the VIAGRA OD Film. All the participants answered our survey. They were aged between 21 and 79. Thirteen patients switched from the tablets to the OD film and 12 patients only used the OD film. The survey items included: 1) portability, 2) storage, 3) ease of consumption, 4) comfortableness, 5) level of self-consciousness with their partner, 6) thoughts on taking the film formulation, 7) comparison with the tablets, and 8) efficacy and adverse reaction. We observed that 61.5% of the patients who switched from tablets to film found that storage and portability were improved. Additionally, 61.5% of the patients who switched from tablets to film and 75.0% of the patients who were prescribed film only were able to comfortably swallow them. We also found that 69.2% who switched from tablets to film and 75.0% who were prescribed film only felt more at ease using it and 61.5% who switched from tablets to film and 66.7% who were prescribed film only felt more comfortable with the film. Finally, 28.0% of the individuals stated a negative opinion on the ease of consuming the OD film. The efficacy of the film was the same as the tablets. We identified two cases of adverse reactions with mild hot flashes and headache but no severe adverse reaction. This survey indicates that the ease of intake and portability was improved with OD film. Disclosure Work supported by industry: no.

In recent years, awareness of erectile dysfunction and the demand for treatment have been increasing even among young men. We investigated the status of young patients 40 years of age or younger with erectile dysfunction. The subjects were 208 patients who visited the urology departments of Showa University Fujigaoka Hospital and affiliated hospitals with a chief complaint of erectile dysfunction. The erectile function was assessed with the Sexual Health Inventory for Men (SHIM), diary questions on sexual intercourse from the Sexual Encounter Profile, and the Erection Hardness Score, which measures the hardness of erection. The treatment was monotherapy with sildenafil (25 or 50 mg), vardenafil (10 or 20 mg), or tadalafil (10 or 20 mg) or a combination of multiple phosphodiesterase 5 (PDE5) inhibitors. To investigate the cause, blood tests including free testosterone and the Self-rating Depression Scale questionnaire were conducted, and Pulse Wave Velocity (PWV) was measured. The median age of the patients was 36 years. As for the cause of erectile dysfunction, psychogenic erectile dysfunction was observed in 141 patients, accounting for 67.7% of the patients. However, 82.1% of patients who underwent PWV measurement showed measurements suggestive of organic changes. The efficacy rates of PDE5 inhibitors were 77% for sildenafil, 73% for vardenafil, and 85% for tadalafil. This study showed that psychogenic erectile dysfunction was common in young patients, and that PDE5 inhibitors were effective for them. In addition, the study suggested the presence of organic changes as a risk factor for erectile dysfunction even in young patients. Disclosure Work supported by industry: no.

The Technical Design for the COMET Phase-I experiment is presented in this paper. COMET is an experiment at J-PARC, Japan, which will search for neutrinoless conversion of muons into electrons in the field of an aluminium nucleus ($\mu-e$ conversion, $\mu^- N \to e^- N$); a lepton flavor violating process. The experimental sensitivity goal for this process in the Phase-I experiment is $3.1\times10^{-15}$, or 90 % upper limit of branching ratio of $7\times 10^{-15}$, which is a factor of 100 improvement over the existing limit. The expected number of background events is 0.032. To achieve the target sensitivity and background level, the 3.2 kW 8 GeV proton beam from J-PARC will be used. Two types of detectors, CyDet and StrECAL, will be used for detecting the \mue conversion events, and for measuring the beam-related background events in view of the Phase-II experiment, respectively. Results from simulation on signal and background estimations are also described., Comment: A minor correction applied in Eq. 3

Introduction: Isolated cleft of the anterior mitral valve leaflet is a very rare congenital disease and a cause of mitral regurgitation not associated with atrioventricular septal defect. In this case, we report our experience in valvuloplasty treatment for mitral regurgitation with this rare aetiology. Case description 23-year-old Russian women. Although cardiac murmur was pointed out in her childhood and she was diagnosed as mitral regurgitation, she refused treatment. After getting married with a Japanese man and moving to Japan, her symptoms had worsened and she visited our hospital for treatment. Preoperative transthoracic echocardiography (TTE) had indicated the regurgitation from the central part of the mitral valve. Preoperative transoesophageal echocardiography (TOE) had pointed out the isolated cleft of the anterior mitral valve. Surgical mitral valvuloplasty was scheduled, and the TOE after anaesthetic induction showed the isolated cleft of the anterior mitral valve the same as in the preoperative period and pointed out the posterior leaflet billowing. The operative finding was also similar to TOE: the largely bisected central anterior mitral valve and billowing, P2 billowing, shortening of P1 and P3, P2-3 cleft. There were no chords at the anterior cleft. The valvuloplasty was performed including five-time pump runs in total: 1) Continuous suture for the anterior cleft and ring annuloplasty were performed, and the regurgitation was seemed to be almost controlled at the water-leak test and the ink test; 2) Artificial chordae and leaflet plications were added to residual regurgitation from the posterior region; 3)The residual regurgitation was controlled to Mild but it became a lateral jet toward the ring; 4)Mild remnant flow was pointed out: the regurgitation seemed to be from the posterior cleft, where immediately below the ring suture; 5) Pericardium patch was added and the remnant flow was almost eliminated. The pump was weaned and the operation was finished without any problems. Discussion The cause of difficulty in this valvuloplasty was thought to be caused by the difficulty in evaluating the mitral valve morphology. It was evident that the anterior leaflet of the mitral valve was largely bisected. However, it was difficult to evaluate the coaptation line and area due to the absence of chordal cords in the anterior cleft and the billowing or shortening of the posterior leaflet. Although preoperative three-dimensional analysis helped evaluating the isolated cleft and the regurgitation was almost controlled in the evaluation in the operation field, nevertheless, a residual regurgitation occurred and indicated in the TOE after re-beating. Conclusion It is important and necessary to use fine evaluation of coaptation is needed in valvuloplasty for isolated cleft of the anterior mitral valve leaflet; not only apply three-dimensional analysis but also apply two-dimensional echocardiogram. Abstract P224 Figure.

Funding Acknowledgements Young Investigator Grant of Japanese Society of Cardiovascular Anesthesia Background / Introduction Evidences have shown that cardiac function decline and systolic phase change are caused by massive afterload of the stenosed aortic valve in patients with severe aortic valve stenosis. As a result of the reduction of the left ventricular afterload by valve replacement, the cardiac function recovers. However, it has not been clarified yet how the changes in cardiac function affect the relationship between the right and left heart systems, as well as the systole phase. TAPSE and MAPSE are known as indices of simple cardiac function evaluation by measuring the movement distance of the atrioventricular annulus. We obtained these indices (i.e. TAPSE, MAPSE) within the same heartbeat using speckle tracking analysis of the atrioventricular annulus and evaluated the changes in cardiac function and phase between the right and left heart systems. Purpose To reveal the relationship of cardiac function and time phase between the right and left heart systems by evaluating the maximum movement distance and time of the atrioventricular annulus within the same heartbeat and the same view in patients with severe aortic valve stenosis before and after TAVI. Methods A prospective cohort study was conducted. We recruited and analyzed 44 patients with severe aortic valve stenosis who received TAVI treatment, able to record baseline before treatment and follow-up 6 months and 12 months after treatment at our hospital from March 2017 to May 2019. Patients were excluded if more than 2 degree of atrioventricular valve regurgitation or incomplete data. The apical four-chamber view was used for speckle tracking analysis with the origin of the apical extension and region of interest (ROI) of the mitral annulus and tricuspid annulus. For each patient before treatment, at 6 months and 12 months after treatment, the maximum contraction distance (DM), maximum contraction time (TM) of the mitral valve annulus, maximum contraction distance (DT) and maximum contraction time (TT) of the tricuspid annulus were measured. Maximum contraction distance ratio (DM/ DT) and maximum contraction time ratio (TM/ TT) were calculated. For statistical analysis, t-test and ANOVA were used, and a significance threshold of p Results TM/ TT decreased at 12 months after TAVI, and DM/ DT increased significantly at 6 months and 12 months after TAVI when compared to baseline before treatment. Conclusions In patients with severe aortic valve stenosis, the correction of cardiac function difference between the right and left heart systems occurs from 6 months after TAVI. Moreover, the correction of contraction phase difference between the right and left heart systems at 12 months after TAVI. Thus, the synchrony between the right and left heart system is recovered 12 months after TAVI. Abstract P662 Figure.

Purpose This is a single center prospective research study using an Apple iPhone 7 stock voice recorder application to assess the relationship between LVAD frequency and invasive hemodynamics. Methods Patients were enrolled prior to their standard of care invasive speed adjustment/optimization study or routine RHC. A 35 second recorded auscultation using an iPhone 7 placed at the location of apex overlying the LVAD. Chest x-ray was utilized for estimation of ideal iPhone placement. Invasive hemodynamic data was recorded and baseline characteristics collected at time of acoustic acquisition. Acoustic data was analyzed post hoc using Audacity sound analysis software to produce frequency and decibel values for each audio file. Variation in frequency and decibels were observed between HVAD and HM3 despite differences in speed and rotational flow. Results 8 consecutive patients were studied, median age 59 years, male (63%) with 75% African American and 25% Caucasian. Mean height 173cm and weight 98kg. HVAD (3), Heartmate II (1) and Heartmate 3 (4) were included. Median CVP was 12mmHg, PCWP 17 mmHg, CO(F) 4.7, CI(F) 2.2, LVEDD 6.45cm and PASAT 62.9%. CVP was evaluated over a range of 7-15 mmHg and PCWP ranged from 10-23 mmHg. Mean frequency of HM3 was 53.5 Hz, HM2 68Hz and HVAD 49.7Hz. LVAD frequencies ranged from 48-63Hz in HM3, 68Hz HM2 and 47Hz-53Hz in HVAD. Pearson Correlation Coefficient R = -0.6616 (R² = 0.4377) for dB and PCWP (P=.07). This moderate negative correlation described a tendency for high dB variable scores to coincide with low PCWP scores. Conclusion This interim analysis demonstrates a relationship between cardiac filling pressures and acoustics. Using a universal audio recording application may aid in the medical management of LVAD patients in the inpatient and outpatient setting. This cross platform technology should be further investigated as a potential diagnostic tool.

Purpose: This study aimed to evaluate response to neoadjuvant chemotherapy (NAC) for patients with hormone receptor-negative (HR-negative) breast cancer (BC) to identify subtypes that require anthracycline treatment. Methods: In total, 103 patients with operable HR-negative BC were registered. They were randomely assigned to administration of 6 cycles of docetaxel (75mg/m2) and cyclophosphamide (600 mg/m2) (TC6) or 3 cycles of 5-fluorouracil (500 mg/m2), epirubicin (100mg/m2), and cyclophosphamide (500mg/m2) followed by 3 cycles of docetaxel (100mg/m2) (FEC-D). Cytokeratin (CK) 5/6 and EGFR expression were used to identify basal and non-basal triple-negative (TN) BC. The primary endpoint was pathological complete response (pCR); secondary endpoints were safety, breast-conserving surgery, disease-free survival, and overall survival. Predictive factors of pCR for each regimen were also evaluated. Results: The pCR rate was 36% for FEC-D and 25.5% for TC6, which did not differ significantly (P=0.265). When TN BC was subdivided into basal and non-basal subtypes, the pCR rate in the basal subtype was significantly lower for TC6 (13.6%) than for FEC-D (42.9%) (P=0.033), but did not significantly differ in the non-basal (TC6, 36.4%; FEC-D, 25.0%) and HER2-positive (TC6, 41.7%; FEC-D, 35.7%) cases. The relative dose intensities of epirubicin and docetaxel in FEC-D and docetaxel in TC6 were 96.3±13.0%, 93.5±14.6%, and 93.9±16.3% (mean±SD), respectively. Occurrence of grade ≥2 adverse events was significant in FEC-D-treated patients. Poor appetite (P The rates of breast-conserving surgery were 68.0 and 72.3% for FEC-D and TC6, respectively (P=0.641). Patients achieved pCR had better DFS (log rank test, P = 0.287) and OS (log rank test, P = 0.069), though not significant. Patients treated with FEC-D had better DFS (log rank test, P = 0.107) and OS (log rank test, P = 0.159), though not significant. Among patients with TN BC, those treated with FEC-D had significantly better DFS (log rank test, P = 0.016) and OS (log rank test, P = 0.034) than treated with TC6. Low ALDH1 expression and high topo IIα protein expression were strongly correlated with pCR in FEC-D, with odds ratios (ORs) of 4.33 [95% CI, 1.02–18.38] and 4.08 [0.97–17.2], respectively. ALDH1 was also associated with pCR in TC, OR=3.50 [0.84–14.6]. Other factors, including age, tumor size, nodal status, tumor grade, Ki67, p53, and TOP 2A status were not associated with pCR in either regimen. Conclusions:We found that TC6 was less effective than FEC-D for treating HR-negative BC because it was insufficient for TNBC, particularly for basal BC. This suggests that anthracycline is more important than taxane for basal BC. Additionally, ALDH1 could be a marker for resistance to conventional chemotherapy. Citation Format: Narui K, Ishikawa T, Shimizu D, Tanabe M, Sasaki T, Oba MS, Morita S, Nawata S, Kida K, Mogaki M, Doi T, Tsugawa K, Ogata H, Ota T, Kosaka Y, Sengoku N, Kuranami M, Saito Y, Suzuki Y, Suto A, Arioka H, Chishima T, Ichikawa Y, Endo I, Tokuda Y. A randomized phase II neoadjuvant study comparing docetaxel and cyclophosphamide (TC) with 5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel (FEC-D) for hormone receptor-negative breast cancer: The Kanagawa breast oncology group (KBOG) 1101 study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-04.

An electromagnetic calorimeter made of undoped CsI crystals is used in the J-PARC KOTO experiment to search for new physics beyond the standard model with the K L → π 0 ν ν decay. The calorimeter is designed to operate in vacuum of 0.1 Pa and in a high-rate environment where the counting rate due to K L decays is O ( 100 ) kHz. A special method to calibrate the calorimeter during the data taking without using a tracking system for charged particles is reported. The energy, position, and timing resolutions of the calorimeter were evaluated in several beam tests, and the resolutions satisfy the required performance. The energy resolution with the total energy E is 0 . 66 ⊕ 1 . 81 ∕ E [ GeV ] % in the inner region of the calorimeter.

Background The mechanisms underlying stress-induced inflammation that contribute to major depressive disorder are unknown. We examine the role of the adenosine triphosphate (ATP)/purinergic type 2X7 receptor (P2X7R) pathway and the NLRP3 (nucleotide-binding, leucine-rich repeat, pyrin domain containing 3) inflammasome in interleukin (IL)-1β and depressive behavioral responses to stress. Methods The influence of acute restraint stress on extracellular ATP, glutamate, IL-1β, and tumor necrosis factor alpha in hippocampus was determined by microdialysis, and the influence of acute restraint stress on the NLRP3 inflammasome was determined by western blot analysis. The influence of P2X7R antagonist administration on IL-1β and tumor necrosis factor alpha and on anxiety and depressive behaviors was determined in the chronic unpredictable stress rodent model. The role of the NLRP3 inflammasome was determined by analysis of Nlrp3 null mice. Results Acute restraint stress rapidly increased extracellular ATP, an endogenous agonist of P2X7R; the inflammatory cytokine IL-1β; and the active form of the NLRP3 inflammasome in the hippocampus. Administration of a P2X7R antagonist completely blocked the release of IL-1β and tumor necrosis factor alpha, another stress-induced cytokine, and activated NLRP3. Moreover, P2X7R antagonist administration reversed the anhedonic and anxiety behaviors caused by chronic unpredictable stress exposure, and deletion of the Nlrp3 gene rendered mice resistant to development of depressive behaviors caused by chronic unpredictable stress. Conclusions These findings demonstrate that psychological "stress" is sensed by the innate immune system in the brain via the ATP/P2X7R–NLRP3 inflammasome cascade, and they identify novel therapeutic targets for the treatment of stress-related mood disorders and comorbid illnesses.

Purpose Tricuspid regurgitation (TR) is a significant complication after heart transplantation (HTx). Tricuspid valve annuloplasty (TVA) may be performed empirically at the time of transplant to prevent the development of TR and right ventricular failure. This study aims to investigate the long-term impact of TVA on incidence of TR and survival. Methods All patients transplanted between 1/2010 - 8/2018 were enrolled. At our institution, we routinely perform DeVega TVA during HTx. All echocardiograms post-HTx were evaluated. TR was classified into 5 groups: none, trace, mild, moderate and severe. The incidence of significant TR (moderate or severe) over time and the effect of TR on survival were evaluated. Echocardiograms were evaluated starting 3 months post-HTx. Results 248 patients underwent HTx in this period, and 243 who underwent concomitant TVA were included in this analysis (mean age 54 years, 76% male). During 3.0 ± 2.1 years follow-up, 22 (9.1%) of patients developed significant TR. In the TVA group, survival free of significant TR was 96.9% at 6-months, 94.3% at 1 year, 91.6% at 2 years, 90.8% at 3 years, 90.8% at 4 years, and 88.8% at 5 years (Figure 1A). 5-year survival among those who experienced significant TR was numerically lower, but not significantly different (70.7% vs 81.5%, p=0.24) (Figure 1B). Only 8 (3.3%) patients required permanent pacemaker implantation over a median of 51 days (IQR 14-522) following HTx. Conclusion Significant TR after HTx is common and progressively worsens despite concomitant TVA. The association of significant TR with long-term survival and the benefit of TVA require further evaluation.

Purpose Omega-3, an unsaturated fatty acid, reduces the risk of gastrointestinal bleeding (GIB) in patients with left ventricular assist devices (LVADs). However, its biological mechanism remains uncertain. This study aims to evaluate the impact of omega-3 on angiogenesis. Methods We measured inflammatory and angiogenesis biomarkers in plasma from LVAD patients by using Bio-plex ProTM Biomarker Assay kit and compared their levels between those with and without omega-3 therapy. GIB rates were also compared between the two groups by using binomial negative regression analysis. Results Among 38 patients (mean age 56.4 years, 66% male), 16 (42%) received 4 g/day omega-3 therapy. There was no significant difference in baseline characteristics between the two groups (p >0.05 for all). The GIB rate was significantly lower in the omega-3 group (0.100 event/year vs. 0.381 event/year, p Conclusion LVAD patients treated with omega-3 have significantly lower GIB rates and significantly lower angiopoietin-2 levels. The reduction in GIB rate with omega-3 may be due to the suppression of abnormal angiogenesis.