The Long-Term Effects of Japan’s Traumatic Experience in the Second World War and Its Implications for Peace in Northeast Asia

This article is an introductory report on the work of a Japanese study group whose primary aim is peacemaking, which it seeks by promoting a greater understanding of the long-term effects of their country’s traumatic experience of the Second World War. The group does not adopt a position of victimhood but seeks to understand the full picture of Japan’s role in the war, including its role as perpetrator. We came together with the shared assumption that the country’s inability to take responsibility for its role of the war is inextricably tied to its own traumatization. If this assumption is true, then the healing of Japan’s collective wounds will be the first step toward its taking responsibility for its role in the war. We have sought to understand how the impact of the collective and cultural trauma from the war has affected the Japanese psyche, especially the devastating experience of defeat. Numerous historical and sociological studies of Japan’s role in the Second World War have been published. But we believe that this multidisciplinary group’s work to understand, through a psychological lens, Japan’s traumatic experience of the war offers a unique approach to encouraging the country to reconsider its role in a series of devastating events in the region, and the continuing effects of those event on regional political stability

Recent global movement on mental health

The Mental Health Gap Action Programme (mhGAP) proposed by the World Health Organization (WHO) is a planned action that aims at providing uniform medical care, especially mental health care and services, to all people worldwide, regardless of economic status. Because not only the levels of medical care, but also the political and economic situations vary among countries, it is extremely difficult for a plan to be successfully implemented in every country with standardized methodology, even if the directionality is ethically correct and ideal. Against this background, authorized personnel provide mental health care activities across the globe, and they report on activities and promote mutual understanding at the WHO mhGAP Forum, an informal meeting convened yearly in Geneva. The 5th mhGAP meeting was attended by 48 member states and 58 partner organizations. From Japan, 5 professionals attended the meeting and presented different viewpoints. Among various policies proposed at the Forum, one in particular about training and recruiting health professionals for low-income countries has gained a special consensus. In addition, the importance of training medical professionals who are not specialized in psychiatry and the importance of developing educational programs for educators were emphasized. It is important for Japan to proactively participate in mhGAP to contribute to global mental health initiative

A THREE-PHASE INDUCTIVE SENSOR FOR IN VIVO MEASUREMENT OF ELECTRICAL ANISOTROPY OF BIOLOGICAL TISSUES

Biological tissue will have anisotropy in electrical conductivity, due to the orientation of muscular fibers or neural axons as well as the distribution of large size blood vessels. Thus, the in vivo measurement of electrical conductivity anisotropy can be used to detect deep-seated vessels in large organs such as the liver during surgeries. For diagnostic applications, decrease of anisotropy may indicate the existence of cancer in anisotropic tissues such as the white matter of the brain or the mammary gland in the breast.In this paper, we will introduce a new tri-phase induction method to drive rotating high-frequency electrical current in the tissue for the measurement of electrical conductivity anisotropy. In the measurement, three electromagnets are symmetrically placed on the tissue surface and driven by high-frequency alternative currents of  0 kHz, modulated  with 1 kHz 3-phase signals. In the center area of three magnets, magnetic fields are superimposed to produce a rotating induction current. This current produces electrical potentials among circularly arranged electrodes to be used to find the conductivity in each direction determined by the electrode pairs. To find the horizontal and vertical signal components, the measured potentials are amplified by a 2ch lock-in amplifier phase-locked with the 1 kHz reference signal. The superimposed current in the tissue was typically 45 micro Amperes when we applied 150 micro Tesla of magnetic field. We showed the validity of our method by conducting in vitro measurements with respect to artificially formed anisotropic materials and preliminary in vivo measurements on the pig’s liver.Compared to diffusion tensor MRI method, our anisotropy sensor is compact and advantageous for use during surgical operations because our method does not require strong magnetic field that may disturb ongoing surgical operations.Biological tissue will have anisotropy in electrical conductivity, due to the orientation of muscular fibers or neural axons as well as the distribution of large size blood vessels. Thus, the in vivo measurement of electrical conductivity anisotropy can be used to detect deep-seated vessels in large organs such as the liver during surgeries. For diagnostic applications, decrease of anisotropy may indicate the existence of cancer in anisotropic tissues such as the white matter of the brain or the mammary gland in the breast.In this paper, we will introduce a new tri-phase induction method to drive rotating high-frequency electrical current in the tissue for the measurement of electrical conductivity anisotropy. In the measurement, three electromagnets are symmetrically placed on the tissue surface and driven by high-frequency alternative currents of  0 kHz, modulated  with 1 kHz 3-phase signals. In the center area of three magnets, magnetic fields are superimposed to produce a rotating induction current. This current produces electrical potentials among circularly arranged electrodes to be used to find the conductivity in each direction determined by the electrode pairs. To find the horizontal and vertical signal components, the measured potentials are amplified by a 2ch lock-in amplifier phase-locked with the 1 kHz reference signal. The superimposed current in the tissue was typically 45 micro Amperes when we applied 150 micro Tesla of magnetic field. We showed the validity of our method by conducting in vitro measurements with respect to artificially formed anisotropic materials and preliminary in vivo measurements on the pig’s liver.Compared to diffusion tensor MRI method, our anisotropy sensor is compact and advantageous for use during surgical operations because our method does not require strong magnetic field that may disturb ongoing surgical operations

Heart Disease, Other Circulatory Diseases, and Onset of Major Depression among Community Residents in Japan: Results of the World Mental Health Survey Japan 2002-2004

We examined whether selected circulatory diseases (heart disease, stroke, diabetes and hypertension) were associated with an increased risk of major depression in the Japanese community population. Face-to-face household surveys were carried out in 7 areas, and a total of 2,436 persons participated (overall response rate: 58.4%) from 2002 to 2004. The WHO Composite International Diagnostic Interview 3.0 was used to diagnose major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and additional interviews assessed the presence of circulatory diseases. Using data from a random subsample of the respondents (n=832), we conducted Cox proportional hazards models to calculate hazard ratios for the onset of major depression with comorbid circulatory diseases as a time-dependent covariate. Heart attack was significantly associated with the onset of major depression (hazard ratio [HR], 7.51 [95%Confidential Interval (CI), 1.36-41.45]) after adjusting for sex, birth cohort, smoking, alcohol intake, and education. Heart disease (HR, 2.12 [95% CI, 0.79-5.70]), diabetes (HR, 2.36 [95% CI, 0.42-13.34]) and hypertension (HR, 0.97 [95% CI, 0.37, 2.50]) were not significantly associated. There were no subjects who developed major depression after stroke. These results suggest that heart attack, and maybe also heart disease and diabetes, affect the onset of major depression.</p

Strategic use of new generation antidepressants for depression: SUN(^_^) D protocol update and statistical analysis plan

Background: SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multicenter pragmatic mega-trial to examine the optimum treatment strategy for the first- and second-line treatments for unipolar major depressive episodes. The trial has three steps and two randomizations. Step I randomization compares the minimum and the maximum dosing strategy for the first-line antidepressant. Step II randomization compares the continuation, augmentation or switching strategy for the second-line antidepressant treatment. Step III is a naturalistic continuation phase. The original protocol was published in 2011, and we hereby report its updated protocol including the statistical analysis plan. Results: We implemented two important changes to the original protocol. One is about the required sample size, reflecting the smaller number of dropouts than had been expected. Another is in the organization of the primary and secondary outcomes in order to make the report of the main trial results as pertinent and interpretable as possible for clinical practices. Due to the complexity of the trial, we plan to report the main results in two separate reports, and this updated protocol and the statistical analysis plan have laid out respective primary and secondary outcomes and their analyses. We will convene the blind interpretation committee before the randomization code is broken. Conclusion: This paper presents the updated protocol and the detailed statistical analysis plan for the SUN(^_^)D trial in order to avoid reporting bias and data-driven results. Trial registration: ClinicalTrials.gov: NCT01109693(registered on 21 April 2010)

ヒト細胞傷害性γδT細胞は膠芽腫細胞株を殺傷する：膠芽腫患者に対する免疫細胞治療の意義

Glioblastoma (GBM) is a highly aggressive brain tumor for which novel therapeutic approaches, such as immunotherapy, are urgently needed. Zoledronate (ZOL), an inhibitor of osteoclastic activity, is known to stimulate peripheral blood-derived γδT cells and sensitize tumors to γδT cell-mediated killing. To investigate the feasibility of γδT cell-based immunotherapy for patients with GBM, we focused on the killing of GBM cell lines by γδT cells and the molecular mechanisms involved in these cell–cell interactions. Peripheral blood mononuclear cells were expanded in ZOL and interleukin (IL)-2 for 14 days, and γδT cells were enriched in the expanded cells by the immunomagnetic depletion of αβT cells. Gliomas are resistant to NK cells but susceptible to lymphokine-activated killer cells and some cytotoxic T lymphocytes. When the γδT cell-mediated killing of three GBM cell lines (U87MG, U138MG and A172 cells) and an NK-sensitive leukemia cell line (K562 cells) were tested, 32 % U87MG, 15 % U138MG, 1 % A172, and 50 % K562 cells were killed at an effector:target ratio of 5:1. The γδT cell-mediated killing of all three GBM cell lines was significantly enhanced by ZOL and this ZOL-enhanced killing was blocked by an anti-T cell receptor (TcR) antibody. These results indicated that TcR γδ is crucial for the recognition of ZOL-treated GBM cells by γδT cells. Since the low level killing of GBM cells by the γδT cells was enhanced by ZOL, γδT cell-targeting therapy in combination with ZOL treatment could be effective for patients with GBM.博士（医学）・甲第635号・平成27年5月28日© Springer Verlag. The definitive version is available at " http://dx.doi.org/10.1007/s11060-013-1258-4

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer

Toward a Global View of Alcohol, Tobacco, Cannabis, and Cocaine Use: Findings from the WHO World Mental Health Surveys

Louisa Degenhardt and colleagues report an international survey of 17 countries that finds clear differences in drug use across different regions of the world