Search for the Majorana Nature of Neutrinos in the Inverted Mass Ordering Region with KamLAND-Zen.

The KamLAND-Zen experiment has provided stringent constraints on the neutrinoless double-beta (0νßß) decay half-life in ^{136}Xe using a xenon-loaded liquid scintillator. We report an improved search using an upgraded detector with almost double the amount of xenon and an ultralow radioactivity container, corresponding to an exposure of 970 kg yr of ^{136}Xe. These new data provide valuable insight into backgrounds, especially from cosmic muon spallation of xenon, and have required the use of novel background rejection techniques. We obtain a lower limit for the 0νßß decay half-life of T_{1/2}^{0ν}>2.3×10^{26} yr at 90% C.L., corresponding to upper limits on the effective Majorana neutrino mass of 36-156 meV using commonly adopted nuclear matrix element calculations.

Precision Analysis of the

We present a precision analysis of the ^{136}Xe two-neutrino ßß electron spectrum above 0.8 MeV, based on high-statistics data obtained with the KamLAND-Zen experiment. An improved formalism for the two-neutrino ßß rate allows us to measure the ratio of the leading and subleading 2νßß nuclear matrix elements (NMEs), ξ_{31}^{2ν}=-0.26_{-0.25}^{+0.31}. Theoretical predictions from the nuclear shell model and the majority of the quasiparticle random-phase approximation (QRPA) calculations are consistent with the experimental limit. However, part of the ξ_{31}^{2ν} range allowed by the QRPA is excluded by the present measurement at the 90% confidence level. Our analysis reveals that predicted ξ_{31}^{2ν} values are sensitive to the quenching of NMEs and the competing contributions from low- and high-energy states in the intermediate nucleus. Because these aspects are also at play in neutrinoless ßß decay, ξ_{31}^{2ν} provides new insights toward reliable neutrinoless ßß NMEs.

Publisher's Note: Search for Majorana Neutrinos Near the Inverted Mass Hierarchy Region with KamLAND-Zen [Phys. Rev. Lett. 117, 082503 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.082503.

Search for Majorana Neutrinos Near the Inverted Mass Hierarchy Region with KamLAND-Zen.

We present an improved search for neutrinoless double-beta (0νßß) decay of ^{136}Xe in the KamLAND-Zen experiment. Owing to purification of the xenon-loaded liquid scintillator, we achieved a significant reduction of the ^{110m}Ag contaminant identified in previous searches. Combining the results from the first and second phase, we obtain a lower limit for the 0νßß decay half-life of T_{1/2}^{0ν}>1.07×10^{26} yr at 90% C.L., an almost sixfold improvement over previous limits. Using commonly adopted nuclear matrix element calculations, the corresponding upper limits on the effective Majorana neutrino mass are in the range 61-165 meV. For the most optimistic nuclear matrix elements, this limit reaches the bottom of the quasidegenerate neutrino mass region.

Search for nucleon decay via n→ν[over ¯]π0 and p→ν[over ¯]π+ in Super-Kamiokande.

We present the results of searches for nucleon decay via n→ν[over ¯]π0 and p→ν[over ¯]π+ using data from a combined 172.8 kt·yr exposure of Super-Kamiokande-I,-II, and-III. We set lower limits on the partial lifetime for each of these modes: τn→ν[over ¯]π0>1.1×10(33) years and τp→ν[over ¯]π+>3.9×10(32) years at a 90% confidence level.

Search for dinucleon decay into kaons in Super-Kamiokande.

A search for the dinucleon decay pp → K+ K+ has been performed using 91.6 kton·yr data from Super-Kamiokande-I. This decay provides a sensitive probe of the R-parity-violating parameter λ112''. A boosted decision tree analysis found no signal candidates in the data. The expected background was 0.28±0.19 atmospheric neutrino induced events and the estimated signal detection efficiency was 12.6%±3.2%. A lower limit of 1.7×10(32) years has been placed on the partial lifetime of the decay O16 → C14K+ K+ at 90% C.L. A corresponding upper limit of 7.8×10(-9) has been placed on the parameter λ112''.

Limit on neutrinoless ßß decay of 136Xe from the first phase of KamLAND-Zen and comparison with the positive claim in 76Ge.

We present results from the first phase of the KamLAND-Zen double-beta decay experiment, corresponding to an exposure of 89.5 kg yr of (136)Xe. We obtain a lower limit for the neutrinoless double-beta decay half-life of T(1/2)(0ν)>1.9×10(25) yr at 90% C.L. The combined results from KamLAND-Zen and EXO-200 give T(1/2)(0ν)>3.4×10(25) yr at 90% C.L., which corresponds to a Majorana neutrino mass limit of <(120-250) meV based on a representative range of available matrix element calculations. Using those calculations, this result excludes the Majorana neutrino mass range expected from the neutrinoless double-beta decay detection claim in (76)Ge, reported by a part of the Heidelberg-Moscow Collaboration, at more than 97.5% C.L.

Evidence for the appearance of atmospheric tau neutrinos in super-Kamiokande.

Super-Kamiokande atmospheric neutrino data were fit with an unbinned maximum likelihood method to search for the appearance of tau leptons resulting from the interactions of oscillation-generated tau neutrinos in the detector. Relative to the expectation of unity, the tau normalization is found to be 1.42 ± 0.35(stat)(-0.12)(+0.14)(syst) excluding the no-tau-appearance hypothesis, for which the normalization would be zero, at the 3.8σ level. We estimate that 180.1 ± 44.3(stat)(-15.2)(+17.8) (syst) tau leptons were produced in the 22.5 kton fiducial volume of the detector by tau neutrinos during the 2806 day running period. In future analyses, this large sample of selected tau events will allow the study of charged current tau neutrino interaction physics with oscillation produced tau neutrinos.

Activation of JNK and high expression level of CD133 predict a poor response to sorafenib in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer deaths worldwide. While sorafenib, a multikinase inhibitor targeting the Raf/extracellular signal-regulated protein kinase (ERK) pathway, has been shown recently to provide a survival advantage to patients with advanced HCC, a predictive biomarker has not been developed. We studied whether c-Jun N-terminal kinase (JNK), which promotes liver carcinogenesis in mice, affects therapeutic response to sorafenib in HCC patients. METHODS: We collected pathological specimens from 39 patients with advanced HCC before starting sorafenib treatment, and measured JNK activity in HCCs. RESULTS: In patients treated with sorafenib, the expression of phospho-c-Jun in HCC, as a read out of JNK activity, was significantly higher (P<0.001) in the non-responder group than in the responder group. c-Jun N-terminal kinase activation in HCC was associated with a decreased time to progression and a poor overall survival (P=0.0028 and P=0.0008, respectively). CONCLUSION: In addition, JNK activity was significantly correlated with CD133 expression level. Correspondingly, high expression level of CD133 was linked to a poor response to sorafenib. Furthermore, D-JNKi, a specific JNK inhibitor, reduced the growth of xenografted CD133(+) cells in athymic mice. In conclusion, JNK activation was positively correlated with CD133 expression level and inversely correlated with the therapeutic response to sorafenib, suggesting that JNK activity may be considered as a new predictive biomarker for response to sorafenib treatment.

Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis.

BACKGROUND: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. MATERIALS AND METHODS: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. RESULTS: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. CONCLUSIONS: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.

Search for differences in oscillation parameters for atmospheric neutrinos and antineutrinos at Super-Kamiokande.

We present a search for differences in the oscillations of antineutrinos and neutrinos in the Super-Kamiokande-I, -II, and -III atmospheric neutrino sample. Under a two-flavor disappearance model with separate mixing parameters between neutrinos and antineutrinos, we find no evidence for a difference in oscillation parameters. Best-fit antineutrino mixing is found to be at (Δm2,sin2 2θ)=(2.0×10(-3) eV2, 1.0) and is consistent with the overall Super-K measurement.

Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib.

BACKGROUND: Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. PATIENTS AND METHODS: We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. RESULTS: Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin-bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). CONCLUSION: NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients.

Total hip arthroplasty using proximal porous coating stem with distal sleeve: mid-term outcome.

PURPOSE: To report mid-term results of total hip arthroplasty (THA) using the Opti-Fix Plus Hip System (Opti-Fix Hip), and to assess the correlations between peri-implant bone changes and the distal medullary occupancy rate. METHODS: 11 men (13 hips) and 53 women (58 hips) aged 24 to 87 (mean, 61) years underwent THA using the Opti-Fix Hip, with a modular stem and a distal sleeve, and were followed up for a mean of 6.5 (range, 4.8-9.6) years. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) hip score. Implant stability, bone changes around the implant, and the occupancy rate of the stem in the medullary space were examined radiologically. Bone changes around the implant were assessed based on the radiological evidence of a pedestal, osteolysis, stress shielding, and radiolucent lines. RESULTS: The mean JOA score increased significantly after surgery and was maintained at the latest follow-up. Around the acetabular and femoral components respectively, 38 and 58 hips had radiolucent lines, whereas one and 54 hips developed osteolysis. A pedestal appeared in 21 hips and grade-III or higher stress shielding in 30 hips. Two hips showed loosening of the acetabular components, but none in the femoral components. Osteolysis around the stem was frequently observed in hips with poor distal medullary occupancy. CONCLUSION: Clinical and radiological outcomes of the Opti-Fix Hip were favourable. The low incidence of osteolysis in the distal stem suggests that the proximal circumferential porous coating was effective. Minor osteolysis around the proximal stem was frequently observed, indicating early excessive wear of the polyethylene liner. Its high distal medullary occupancy rate could inhibit stem micromotion and aseptic loosening.

Effects of monthly feedback of VFA measured by dual BIA method in Japanese patients with obesity: a randomized controlled study.

Objective: To investigate the effects of monthly feedback of changes in visceral fat area (VFA) as measured by dual bioelectrical impedance analysis method and the importance of VFA in individuals with obesity. Methods: Thirty-eight Japanese patients with obesity underwent VFA measurements. The feedback group was given feedback on VFA measurements each month for 4 months. The control group underwent VFA measurements at the beginning and end of the study but was not informed of the results. All the study participants completed eating behaviour and weight efficacy lifestyle questionnaires. Results: Mean age was 53.9 (14.3) years; mean body mass index was 30.6 (4.3) kg m-2. At the 4-month follow-up, there was no significant difference in VFA reduction between the control and feedback groups (-4.4% vs. -3.0%; 95% CI, -3.8 to 5.5). In post-hoc analysis using the overall group irrespective of allocation, changes of eating style were significantly associated with a reduction in VFA at 4 months (p = 0.034). Conclusions: Monthly feedback on changes in VFA does not reduce VFA. More frequent feedback may be required. In post-hoc analysis, changes of eating style were associated with a reduction in VFA.

Nomogram based on metabolic equivalents and age for assessing aerobic exercise capacity in men.

OBJECTIVES: The goal of this study was to create a nomogram, based on maximal exercise capacity (in metabolic equivalents [METs]) and age, for assessing a patient's ability to perform dynamic exercise to quantify the level of physical disability or relative capacity for physical activity. BACKGROUND: Providing an estimation of exercise capacity relative to age is clinically useful. Such an estimate can be derived from measured or estimated maximal oxygen uptake (in METs) from treadmill exercise testing and age. It is an effective means of communicating to patients their cardiopulmonary status, encouraging improvement in exercise capacity and quantifying disability. METHODS: Exercise test results of 1,388 male patients (mean age 57 years, range 21 to 89) free of apparent heart disease who were referred for exercise testing for clinical reasons were retrospectively reviewed. This referral group as well as subgroups of active (n = 346) and sedentary (n = 253) patients were analyzed to determine norms for age and for age by decades for exercise test responses, including METs, maximal heart rate and maximal systolic blood pressure. Regression equations were calculated from this information, and a nomogram for calculating degree of exercise capacity from age and MET level achieved by a patient was created. A similar analysis was performed in a separate group of 244 apparently healthy, normal male volunteers (mean age 45 +/- 14 years, range 18 to 72) who underwent exercise testing with direct measurement of expired gases. RESULTS: Equations for predicted METs for age were derived for the entire clinical referral group (METs = 18.0-0.15[Age]) and for the subgroups of active (METs = 18.7-0.15[Age]) and sedentary (METs = 16.6-0.16[Age]) patients. All results achieved statistical significance, with p values < 0.001. In the volunteer group of normal men who performed exercise testing with ventilatory gas exchange, the decline in maximal heart rate and METs with age was not as steep as in the referral group. Although the normal group confirmed nomograms published previously among similar subjects, the equations derived from the patients differed from those previously reported; in contrast to previous studies using healthy volunteers, the equations and nomograms for the referral group are more appropriate for patients typically referred for testing in a hospital or office-based internal medicine practice. CONCLUSIONS: Norms for METs based on age are presented as well as population-specific nomograms that enable physicians to assess patients' exercise capacity relative to their age group.

Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial Infarction Investigations in Japan.

OBJECTIVES: To determine the clinical features of a novel heart syndrome with transient left ventricular (LV) apical ballooning, but without coronary artery stenosis, that mimics acute myocardial infarction, we performed a multicenter retrospective enrollment study. BACKGROUND: Only several case presentations have been reported with regard to this syndrome. METHODS: We analyzed 88 patients (12 men and 76 women), aged 67 +/- 13 years, who fulfilled the following criteria: 1) transient LV apical ballooning, 2) no significant angiographic stenosis, and 3) no known cardiomyopathies. RESULTS: Thirt-eight (43%) patients had preceding aggravation of underlying disorders (cerebrovascular accident [n = 3], epilepsy [n = 3], exacerbated bronchial asthma [n = 3], acute abdomen [n = 7]) and noncardiac surgery or medical procedure (n = 11) at the onset. Twenty-four (27%) patients had emotional and physical problems (sudden accident [n = 2], death/funeral of a family member [n = 7], inexperience with exercise [n = 6], quarreling or excessive alcohol consumption [n = 5] and vigorous excitation [n = 4]). Chest symptoms (67%), electrocardiographic changes (ST elevation [90%], Q-wave formation [27%] and T-wave inversion [97%]) and elevated creatine kinase (56%) were found. After treatment of pulmonary edema (22%), cardiogenic shock (15%) and ventricular tachycardia/fibrillation (9%), 85 patients had class I New York Heart Association function on discharge. The LV ejection fraction improved from 41 +/- 11% to 64 +/- 10%. Transient intraventricular pressure gradient and provocative vasospasm were documented in 13/72 (18%) and 10/48 (21%) of the patients, respectively. During follow-up for 13 +/- 14 months, two patients showed recurrence, and one died suddenly. CONCLUSIONS: A novel cardiomyopathy with transient apical ballooning was reported. Emotional or physical stress might play a key role in this cardiomyopathy, but the precise etiologic basis still remains unclear.

Angiographic patterns and severe coronary artery disease. Exercise test correlates.

In a Veterans Affairs Medical Center, we studied 607 male patients to determine whether patterns and severity of coronary artery disease could be predicted by means of standard clinical and exercise test data. We found significant differences in clinical, hemodynamic, and electrocardiographic measurements among patients with progressively increasing disease severity determined by angiography. Left main disease produced responses significantly different from those of three-vessel disease only when accompanied by a 70% or greater narrowing of the right coronary artery. Discriminant function analysis revealed that the maximum amount of horizontal or downsloping ST depression in exercise and/or recovery was the most powerful predictor of disease severity, with 2-mm ST depression yielding a sensitivity of 55% and a specificity of 80% for prediction of severe coronary artery disease (three-vessel disease plus left main disease). Patients with increasingly severe disease also demonstrated a greater frequency of abnormal hemodynamic responses to exercise.

Magnesium and ischemic heart disease: a review of epidemiological, experimental, and clinical evidences.

Magnesium (Mg) plays an essential role in a wide range of fundamental cellular reactions in patients with ischemic heart disease. It has been well known that Mg plays a pivotal role in control of cardiac excitability, neuromuscular transmission, vasomotor tone, and blood pressure, among other functions. Especially, many epidemiological, experimental, and clinical studies support a pathological role for Mg in the etiology and development of major coronary risk factors as diabetes mellitus, hypertension, and hyperlipidemia as well as ischemic heart disease. Furthermore, the therapeutic value of Mg in the management of coronary risk factors and ischemic heart disease has been clarified. Dietary Mg supplementation should be considered as a preventive element in atherosclerosis and ischemic heart disease.

Effect of the maze procedure for atrial fibrillation on atrial and brain natriuretic peptide.

We studied plasma levels of atrial and brain natriuretic peptides at rest and after exercise before and after intracardiac surgery with and without the maze procedure in patients with chronic heart failure secondary to valvular heart disease. The present study found that an increased response of both cardiac natriuretic peptides is attenuated with resulting water retention after the maze procedure.

Predictors of disease severity and survival in patients with coronary artery disease.

BACKGROUND: The objective of this study was to determine whether coronary angiographic findings and survival could be predicted using standard clinical and exercise-test data. METHODS: Five hundred and ninety-five men who had undergone both exercise treadmill testing and cardiac catheterization were followed for up to 5 years. Left main (LM) disease (> or = 50% stenosis) was present in 42 patients, whereas 30 patients had LM equivalent disease (> or = 70% stenosis of both the proximal left anterior descending and circumflex coronary artery disease (n = 152), one-vessel disease (n = 186), two-vessel disease (n = 118), three-vessel disease (n = 67), LM or LM equivalent disease without significant (> or = 70%) right coronary artery involvement (n = 26), and LM or LM equivalent disease with right coronary artery involvement (n = 46). RESULTS: ST-segment depression was more marked, whereas ejection fraction, maximal heart rate, maximal systolic blood pressure, and exercise capacity were lower in each group as disease severity worsened. Using Kaplan-Meier analysis, the subgroup with the poorest survival was found to be those with LM or LM equivalent disease with right coronary artery disease, and the next worse was the three-vessel disease group, in which survival was poorer than in all other subgroups (P < 0.01). Stepwise regression analysis revealed that the most powerful predictor for coronary artery disease severity was exercise-induced ST depression (P < 0.001), but it predicted survival poorly. History of congestive heart failure, low ejection fraction (50% or lower), and poor exercise capacity (5 metabolic equivalents or less) emerged as strong predictors of survival using stepwise Cox regression analysis (P < 0.001). CONCLUSION: Exercise-induced ST depression predicted the severity of angiographic disease but not survival, whereas the strongest predictors of survival were history of congestive heart failure, low ejection fraction, and poor exercise capacity.