Impact of avalanche type of transport on internal transport barrier formation in tokamak plasmas.

In magnetic fusion plasmas, a transport barrier is essential to improve the plasma confinement. The key physics behind the formation of a transport barrier is the suppression of the micro-scale turbulent transport. On the other hand, long-range transport events, such as avalanches, has been recognized to play significant roles for global profile formations. In this study, we observed the impact of the avalanche-type of transport on the formation of a transport barrier for the first time. The avalanches are found to inhibit the formation of the internal transport barrier (ITB) observed in JT-60U tokamak. We found that (1) ITBs do not form in the presence of avalanches but form under the disappearance of avalanches, (2) the surface integral of avalanche-driven heat fluxe is comparable to the time rate change of stored energy retained at the ITB onset, (3) the mean E × B flow shear is accelerated via the ion temperature gradient that is not sustained under the existence of avalanches, and (4) after the ITB formation, avalanches are damped inside the ITB, while they remain outside the ITB.

Energy-selective confinement of fusion-born alpha particles during internal relaxations in a tokamak plasma.

Long-pulse operation of a self-sustained fusion reactor using toroidal magnetic containment requires control over the content of alpha particles produced by D-T fusion reactions. On the one hand, MeV-class alpha particles must stay confined to heat the plasma. On the other hand, decelerated helium ash must be expelled before diluting the fusion fuel. Here, we report results of kinetic-magnetohydrodynamic hybrid simulations of a large tokamak plasma that confirm the existence of a parameter window where such energy-selective confinement can be accomplished by exploiting internal relaxation events known as sawtooth crashes. The physical picture - a synergy between magnetic geometry, optimal crash duration and rapid particle motion - is completed by clarifying the role of magnetic drifts. Besides causing asymmetry between co- and counter-going particle populations, magnetic drifts determine the size of the confinement window by dictating where and how much reconnection occurs in particle orbit topology.

Vacuum ultraviolet photoluminescence of NaMgF3:Sm and NaMgF3:Sm,Ce: energy levels of the lanthanides in NaMgF3:Ln compounds.

The luminescence properties of NaMgF3:Sm and NaMgF3:Ce,Sm were studied in the vacuum ultraviolet spectral region. Excitation bands corresponding to the charge transfer processes F- â†’ Sm3+, O2- â†’ Sm3+, and O2- â†’ Ce3+, and the energy transfer processes Ce3+ â†’ Sm3+and O2- â†’ Sm3+, were observed. The energies of the Sm3+charge transfer transitions and the crystal field split Ce3+4f05d1transitions were used to construct a complete host referred binding energy diagram for the series of lanthanide-doped NaMgF3:Ln compounds. We demonstrate that the optical and luminescence properties predicted by the binding energy diagram are in good agreement with those predicted by the binding energy diagram constructed via the alternative impurity-informed method, and all available experimental data regarding the NaMgF3:Ln compounds. We demonstrate that NaMgF3:Ln compounds are model systems for the study of charge trapping phenomena and divalent lanthanide luminescence. Ultimately, we validate that the impurity-informed method can be used to establish the energy levels of lanthanides in fluoride systems.

Conceptual design of a collimator for the neutron emission profile monitor in JT-60SA using Monte Carlo simulations.

Materials and structures of a collimator for a new neutron emission profile monitor in JT-60SA are examined through Monte Carlo simulations using the Monte Carlo N-Particle transport code. First, the shielding properties of various material combinations are compared in order to determine a combination with high shielding performances against both neutrons and gamma-rays. It is found that a collimator consisting of borated polyethylene and lead has a high shielding performance against neutrons. Moreover, a high shielding performance against gamma-rays is obtained when a lead pipe with a radial thickness of 0.01 m is inserted into a collimation tube. Second, we demonstrate that it is possible to improve the spatial resolution to a desired level by installing a thin tubular extension structure that fits into the limited space available between the main collimator block and the tokamak device. Finally, the collimator structures that meet both the targeted spatial resolutions (<10% of the plasma minor radius) and the targeted counting rate (105 cps order) are discussed.

Proposal for a new classification for perihilar cholangiocarcinoma based on tumour depth.

BACKGROUND: The T system for distal cholangiocarcinoma has been revised from a layer-based to a depth-based approach in the current American Joint Committee on Cancer (AJCC) classification. In perihilar cholangiocarcinoma, tumour depth in the staging scheme has not yet been addressed. The aim of this study was to propose a new T system using measured tumour depth in perihilar cholangiocarcinoma. METHODS: Patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2001 and 2014 were reviewed retrospectively. The vertical distance between the top of the tumour and deepest invasive cells was measured as invasive tumour thickness (ITT) by two independent pathologists. Log rank statistics were used to determine cut-off points, and the concordance (C) index was used to assess survival discrimination of each T system. RESULTS: ITT was measurable in all 440 patients, with a median value of 6·0 (range 0-45) mm. The median difference in ITT between observers was 0·6 (range 0-20) mm. Cut-off points for prognosis were 1, 5 and 8 mm. Five-year survival decreased with increasing ITT (P < 0·001): 67 per cent for ITT less than 1 mm (25 patients), 54·9 per cent for ITT 1 mm and over to less than 5 mm (138 patients), 43·4 per cent for ITT 5 mm and over to less than 8 mm (118 patients), and 32·2 per cent for ITT 8 mm and over (159 patients). The C-index of this classification was comparable to that of the current AJCC T classification (0·598 versus 0·589). CONCLUSION: ITT is a reliable approach for making a depth assessment in perihilar cholangiocarcinoma. A four-tier ITT classification with cut-off points of 1, 5 and 8 mm is an adequate alternative to the current layer-based T classification.

Quantitative analysis of mammalian chromosome by scanning transmission soft X-ray microscopy.

Soft X-ray spectromicroscopy was applied to study the quantitative distribution of DNA and protein in a mammalian chromosome at the spatial resolution of 100 nm. The quantities of DNA and protein were evaluated using 1s-π* transition in the NEXAFS spectra at the nitrogen K absorption edge. DNA was not uniformly distributed in the chromosome and DNA/protein ratio was less than 0.497. The present analysis revealed the clues to identify other molecules that contribute to the absorption spectrum of the sample. The results suggested that accumulation of the absorption spectra of relevant molecules would support the refinement of the analysis.

Initial severity of major depression and efficacy of new generation antidepressants: individual participant data meta-analysis.

OBJECTIVE: The role of baseline severity as effect modifier in various psychiatric disorders is a topic of controversy and of clinical import. This study aims to examine whether baseline severity modifies the efficacy of various antidepressants for major depression through individual participant data (IPD) meta-analysis. METHOD: We identified all placebo-controlled, double-blind randomised trials of new generation antidepressants in the acute phase treatment of major depression conducted in Japan and requested their IPD through the public-private partnerships (PPPs) between the relevant academic societies and the pharmaceutical companies. The effect modification by baseline depression severity was examined through six increasingly complex competing mixed-effects models for repeated measures. RESULTS: We identified eleven eligible trials and obtained IPD from six, which compared duloxetine, escitalopram, mirtazapine, paroxetine or bupropion against placebo (total n = 2464). The best-fitting model revealed that the interaction between baseline severity and treatment was not statistically significant (coefficient = -0.04, 95% confidence interval: -0.16 to 0.08, P = 0.49). Several sensitivity analyses confirmed the robustness of the findings. CONCLUSION: We may expect as much benefit from antidepressant treatments for mild, moderate or severe major depression. Clinical practice guidelines will need to take these findings into consideration.

Edoxaban is effective in reducing the incidence of asymptomatic phlebographic events following closed-wedge high tibial osteotomy.

INTRODUCTION: The purpose of this study was twofold: to investigate whether edoxaban significantly decreases the rate of venous thromboembolism (VTE) following closed-wedge high tibial osteotomy (CWHTO), in terms of phlebographic event, and to determine whether edoxaban is safe or increases the rate of hemorrhagic complications. We hypothesized that edoxaban would decrease the incidence of VTE and would not increase the rate of hemorrhagic complications. MATERIALS AND METHODS: We randomly enrolled 60 patients undergoing CWHTO. The patients were divided into two groups: one group receiving edoxaban (15mg in 5 patients, 30mg in 23 patients) and a non-edoxaban group. All patients underwent computed tomography venography on day 7to diagnose postoperative VTE. Blood samples were obtained on the day before CWHTO and on postoperative days 1, 3, 7 and 14. The incidence of VTE and hemorrhagic events in both groups was compared using unpaired Student t-test or chi-square test. RESULTS: The incidence of VTE was significantly greater in the non-edoxaban group (31.3% versus 7.1%; P=0.02). The incidence of deep vein thrombosis (DVT) was also significantly greater in the non-edoxaban group (28.1% versus 3.6%; P=0.01). A single patient from the edoxaban group experienced major bleeding. On days 3 and 7, D-dimer levels were significantly lower in the edoxaban group (P=0.03 and 0.003, respectively). On days 3, 7 and 14, activated partial thromboplastin time was significantly greater in the edoxaban group (P=0.02, 0.01 and 0.006, respectively). CONCLUSION: Patients undergoing CWHTO are at risk of postoperative VTE. Edoxaban helps prevent asymptomatic phlebographic VTE and DVT following CWHTO; however, the risk of major bleeding must be considered. LEVEL OF EVIDENCE: II.

Protocol registration and selective outcome reporting in recent psychiatry trials: new antidepressants and cognitive behavioural therapies.

OBJECTIVE: The selective reporting of favorable outcomes has a serious influence on our evidence base. However, this problem has not yet been systematically investigated in the field of psychiatry. Our study aimed to evaluate registration and outcome reporting in randomized controlled trials (RCTs) of standard treatments for depression: cognitive behavioural therapy (CBT) or new-generation antidepressants (ADs). METHOD: We searched for reports of RCTs examining the efficacy of CBT or AD for depression that were published between 2011 and 2013. We then compared their primary outcomes in the trial registries and those in publications. RESULTS: We identified 170 trials. Among them, 92 trials (54.1%) were registered, 43 trials (25.3%) were properly registered, and only 32 (18.8%) trials were both properly registered and reported (the primary outcomes as recorded in the registries were reported in publications). There was no statistically significant difference in the proportions of properly registered and reported trials for CBT or AD (relative risk: 0.51, 95% CI: 0.25-1.03). High impact factor journals, commercial funding, publication of protocol, and relatively large sample size were significant predictors of proper registration and reporting. CONCLUSION: The prevalence of proper registration and reporting is still very low in depression trials.

Untreated Gleason Grade Progression on Serial Biopsies during Prostate Cancer Active Surveillance: Clinical Course and Pathological Outcomes.

PURPOSE: We describe the outcomes of patients with low risk localized prostate cancer who were upgraded on a surveillance biopsy while on active surveillance and evaluated whether delayed treatment was associated with adverse outcome. MATERIALS AND METHODS: We included men in the study with lower risk disease managed initially with active surveillance and upgraded to Gleason score 3+4 or greater. Patient demographics and disease characteristics were compared. Kaplan-Meier curve was used to estimate the treatment-free probability stratified by initial upgrade (3+4 vs 4+3 or greater), Cox regression analysis was used to examine factors associated with treatment and multivariate logistic regression analysis was used to evaluate the factors associated with adverse outcome at surgery. RESULTS: The final cohort comprised 219 men, with 150 (68%) upgraded to 3+4 and 69 (32%) to 4+3 or greater. Median time to upgrade was 23 months (IQR 11-49). A total of 163 men (74%) sought treatment, the majority (69%) with radical prostatectomy. The treatment-free survival rate at 5 years was 22% for 3+4 and 10% for 4+3 or greater upgrade. Upgrade to 4+3 or greater, higher prostate specific antigen density at diagnosis and shorter time to initial upgrade were associated with treatment. At surgical pathology 34% of cancers were downgraded while 6% were upgraded. Cancer volume at initial upgrade was associated with adverse pathological outcome at surgery (OR 3.33, 95% CI 1.19-9.29, p=0.02). CONCLUSIONS: After Gleason score upgrade most patients elected treatment with radical prostatectomy. Among men who deferred definitive intervention, few experienced additional upgrading. At radical prostatectomy only 6% of cases were upgraded further and only tumor volume at initial upgrade was significantly associated with adverse pathological outcome.

Evaluation of rhBMP-2/collagen/TCP-HA bone graft with and without bone marrow cells in the canine femoral multi defect model.

Recombinant human bone morphogenetic protein-2, when applied to an absorbable type 1 bovine collagen sponge (rhBMP-2/ACS) is an effective therapy in many bone grafting settings. Bone marrow aspirate (BMA) has also been used as a source of transplantable osteogenic connective tissue progenitors. This study was designed to characterize the performance of a scaffold comprising rhBMP-2/ACS in which the sponge wraps around tri-calcium phosphate hydroxyapatite granules (rhBMP-2/ACS/TCP-HA) and to test the hypothesis that addition of BMA will improve the performance of this construct in the Canine Femoral Multi Defect Model. In each subject, two sites were grafted with rhBMP-2/ACS/TCP-HA scaffold loaded with BMA clot and two other sites with rhBMP-2/ACS/TCP-HA scaffold loaded with wound blood (WB). After correction for unresorbed TCP-HA granules, sites grafted with rhBMP-2/ACS/TCP-HA+BMA and rhBMP-2/ACS/TCP-HA+WB were similar, with mean percent bone volumes of 10.9 %±1.2 and 11.2 %±1.2, respectively. No differences were seen in quantitative histomorphometry. While bone formation using both constructs was robust, this study did not support the hypothesis that the addition of unprocessed bone marrow aspirate clot improved bone regeneration in a site engrafted with rhBMP-2/ACS/TCP-HA+BMA. In contrast to prior studies using this model, new bone formation was greater at the center of the defect where TCP-HA was distributed. This finding suggests a potential synergy between rhBMP-2 and the centrally placed ceramic and cellular components of the graft construct. Further optimization may also require more uniform distribution of TCP-HA, alternative cell delivery strategies, and a more rigorous large animal segmental defect model.

Silencing of RUNX2 enhances gemcitabine sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the stimulation of TAp63-mediated cell death.

Runt-related transcription factor 2 (RUNX2) has been considered to be one of master regulators for osteoblast differentiation and bone formation. Recently, we have described that RUNX2 attenuates p53/TAp73-dependent cell death of human osteosarcoma U2OS cells bearing wild-type p53 in response to adriamycin. In this study, we have asked whether RUNX2 silencing could enhance gemcitabine (GEM) sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells. Under our experimental conditions, GEM treatment increased the expression level of p53 family TAp63, whereas RUNX2 was reduced following GEM exposure, indicating that there exists an inverse relationship between the expression level of TAp63 and RUNX2 following GEM exposure. To assess whether TAp63 could be involved in the regulation of GEM sensitivity of AsPC-1 cells, small interfering RNA-mediated knockdown of TAp63 was performed. As expected, silencing of TAp63 significantly prohibited GEM-dependent cell death as compared with GEM-treated non-silencing cells. As TAp63 was negatively regulated by RUNX2, we sought to examine whether RUNX2 knockdown could enhance the sensitivity to GEM. Expression analysis demonstrated that depletion of RUNX2 apparently stimulates the expression of TAp63, as well as proteolytic cleavage of poly ADP ribose polymerase (PARP) after GEM exposure, and further augmented GEM-mediated induction of p53/TAp63-target genes, such as p21 (WAF1) , PUMA and NOXA, relative to GEM-treated control-transfected cells, implying that RUNX2 has a critical role in the regulation of GEM resistance through the downregulation of TAp63. Notably, ablation of TAp63 gave a decrease in number of γH2AX-positive cells in response to GEM relative to control-transfected cells following GEM exposure. Consistently, GEM-dependent phosphorylation of ataxia telangiectasia-mutated protein was remarkably impaired in TAp63 knockdown cells. Collectively, our present findings strongly suggest that RUNX2-mediated repression of TAp63 contributes at least in part to GEM resistance of AsPC-1 cells, and thus silencing of RUNX2 may be a novel strategy to enhance the efficacy of GEM in p53-deficient pancreatic cancer cells.

A study on fast digital discrimination of neutron and gamma-ray for improvement neutron emission profile measurement.

Neutron and γ-ray (n-γ) discrimination with a digital signal processing system has been used to measure the neutron emission profile in magnetic confinement fusion devices. However, a sampling rate must be set low to extend the measurement time because the memory storage is limited. Time jitter decreases a discrimination quality due to a low sampling rate. As described in this paper, a new charge comparison method was developed. Furthermore, automatic n-γ discrimination method was examined using a probabilistic approach. Analysis results were investigated using the figure of merit. Results show that the discrimination quality was improved. Automatic discrimination was applied using the EM algorithm and k-means algorithm.

Evaluation of two-stage system for neutron measurement aiming at increase in count rate at Japan Atomic Energy Agency-Fusion Neutronics Source.

In order to increase the count rate capability of a neutron detection system as a whole, we propose a multi-stage neutron detection system. Experiments to test the effectiveness of this concept were carried out on Fusion Neutronics Source. Comparing four configurations of alignment, it was found that the influence of an anterior stage on a posterior stage was negligible for the pulse height distribution. The two-stage system using 25 mm thickness scintillator was about 1.65 times the count rate capability of a single detector system for d-D neutrons and was about 1.8 times the count rate capability for d-T neutrons. The results suggested that the concept of a multi-stage detection system will work in practice.

Waiting list may be a nocebo condition in psychotherapy trials: a contribution from network meta-analysis.

OBJECTIVE: Various control conditions have been employed in psychotherapy trials, but there is growing suspicion that they may lead to different effect size estimates. The present study aims to examine the differences among control conditions including waiting list (WL), no treatment (NT) and psychological placebo (PP). METHOD: We comprehensively searched for all randomized controlled trials (RCTs) comparing cognitive-behaviour therapies (CBT) against various control conditions in the acute phase treatment of depression, and applied network meta-analysis (NMA) to combine all direct and indirect comparisons among the treatment and control arms. RESULTS: We identified 49 RCTs (2730 participants) comparing WL, NT, PP and CBT. This network of evidence was consistent, and the effect size estimates for CBT were substantively different depending on the control condition. The odds ratio of response for NT over WL was statistically significant at 2.9 (95% CI: 1.3-5.7). However, the quality of evidence, including publication bias, was less than ideal and none of the preplanned sensitivity analyses limiting to high-quality studies could be conducted, while findings of significant differences did not persist in post hoc sensitivity analyses trying to adjust for publication bias. CONCLUSION: There may be important differences in control conditions currently used in psychotherapy trials.

The role of metabolic imaging in radiation therapy of prostate cancer.

The goal of this study was to correlate prostatic metabolite concentrations from snap-frozen patient biopsies of recurrent cancer after failed radiation therapy with histopathological findings, including Ki-67 immunohistochemistry and pathologic grade, in order to identify quantitative metabolic biomarkers that predict for residual aggressive versus indolent cancer. A total of 124 snap-frozen transrectal ultrasound (TRUS)-guided biopsies were acquired from 47 men with untreated prostate cancer and from 39 men with a rising prostate-specific antigen and recurrent prostate cancer following radiation therapy. Biopsy tissues with Ki-67 labeling index ≤ 5% were classified as indolent cancer, while biopsy tissues with Ki-67 labeling index > 5% were classified as aggressive cancer. The majority (15 out of 17) of cancers classified as aggressive had a primary Gleason 4 pattern (Gleason score ≥ 4 + 3). The concentrations of choline-containing phospholipid metabolites (PC, GPC, and free Cho) and lactate were significantly elevated in recurrent cancer relative to surrounding benign tissues. There was also a significant increase in [PC] and reduction in [GPC] between untreated and irradiated prostate cancer biopsies. The concentration of the choline-containing phospholipid metabolites was significantly higher in recurrent aggressive (≈ twofold) than in recurrent indolent cancer biopsies, and the receiver operating characteristic (ROC) curve analysis of total choline to creatine ratio (tCho/Cr) demonstrated an accuracy of 95% (confidence interval = 0.88-1.00) for predicting aggressive recurrent disease. The tCho/Cr was significantly higher for identifying recurrent aggressive versus indolent cancer (tCho/Cr = 2.4 ± 0.4 versus 1.5 ± 0.2), suggesting that use of a higher threshold tCho/Cr ratio in future in vivo (1)H MRSI studies could improve the selection and therapeutic planning for patients who would benefit most from salvage focal therapy after failed radiation therapy.

Analyses of shape of eyes and structure of optic nerves in eyes with tilted disc syndrome by swept-source optical coherence tomography and three-dimensional magnetic resonance imaging.

PURPOSE: To evaluate the deeper structures of the optic nerve and to analyze the shape of eyes with tilted disc syndrome (TDS) by swept-source optical coherence tomography (OCT) and three-dimensional magnetic resonance imaging (3D MRI). METHODS: The medical records of 54 eyes of 36 patients with TDS were reviewed. The patients with TDS and high myopia were analyzed separately from those without high myopia. All the eyes were examined with a swept-source OCT, and 22 of the eyes were examined by 3D MRI. RESULTS: A total of 38 eyes of 29 patients were highly myopic and 16 eyes of 15 patients were not highly myopic. The representative OCT findings of the optic disc were: a sloping of the lamina cribrosa posteriorly from the upper part to the lower part, a protrusion of the upper edge of Bruch's membrane, and choroid. The distance and the depth of the most protruded point from the fovea were significantly greater in the eyes with non-highly myopic TDS than those with highly myopic TDS. In the 3D MRI, the lower part of the posterior segment was protruded outward, and the optic nerves attached at the upper nasal edge of the protrusion. CONCLUSIONS: The abnormalities detected by swept-source OCT and 3D MRI analyses indicate the possibility that the essential pathology of TDS is a deformity of the inferior globe below the optic nerve, and the positional relation between the fovea and the inferior protrusion determines the degree of myopia.

Estimates of genetic relatedness among males in a polygynous wasp.

Cyclical oligogyny is considered to be the mechanism that is most likely to be responsible for stabilizing cooperation in polygynous, epiponine wasps, in which single-queen colonies produce new queens and multiple-queen colonies produce males. In contrast with the number of studies on relatedness among adult females, we know little about relatedness among males in polygynous epiponine wasps. We estimated worker and male relatedness in the Brazilian epiponine wasp Polybia paulista Ihering and found that colonies of P. paulista produced males when they contained multiple queens. Although average relatedness within males did not differ significantly from 0.5, the number of alleles observed suggests that there were more than one queen to produce males in each colony. Our data would be helpful to elucidate dynamics of the male production in a colony of epiponine wasps.

The pilot study: sphingomyelin-fortified milk has a positive association with the neurobehavioural development of very low birth weight infants during infancy, randomized control trial.

AIM: This study was a randomised control trial to examine the effects of sphingomyelin (SM), on the mental, motor and behavioural development of premature infants. PATIENTS AND METHODS: Randomised, double-blind controlled trial, enroling infants born with a birth weight of less than 1500 g between January 2004 and October 2007 at Juntendo University Hospital, with follow-up to 18 months. Twenty-four preterm babies were randomly assigned; 12 were assigned to a test group and fed SM-fortified milk (SM 20% of all phospholipids in milk) and 12 were assigned to a control group (SM 13% of all phospholipids in milk). We analysed the composition of the plasma phospholipids and red-cell-membrane fatty acids, after which VEP, Fagan, BSID-II, attention and memory tests were performed. RESULTS: The percentage of SM in the total phospholipids was significantly higher in the trial group than in the control group at 4, 6 and 8 weeks. The Behaviour Rating Scale of the BSID-II, the Fagan test scores, the latency of VEP, and sustained attention test scores at 18 months were all significantly better in the trial group than in the control group. CONCLUSION: This study is the first to report that nutritional intervention via administration of SM-fortified milk has a positive association with the neurobehavioural development of low-birth-weight infants. However, detailed studies on the effects of SM on longer-term development are required.