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To establish systematic guidelines for accelerator decommissioning, a large-scale activation survey was conducted at representative synchrotron radiation facilities in Japan. The neutron flux during accelerator operation was measured with various dosimeters. A Monte Carlo simulation was conducted for some facilities to verify the special neutron distribution and their spectra. Beam loss points, reflected as high-dose-rate areas, were identified by a whole-beamline survey with a survey meter, and the generated radionuclides and their activity were determined with a lanthanum bromide (LaBr3) scintillation spectrometer. In all facilities, the activation level was quite low. Whole-beamline tunnels made of concrete were not activated, and no radionuclides were detected except for natural nuclides. In addition, almost all beamline components were either not or minimally activated. Although the acceleration energy is very high for radiation synchrotron facilities, the generation of radioactive waste would be very low.

Typically, the concentrations of cobalt and europium, which are trace elements in concrete, are difficult to determine by chemical analysis. While data sheets do not usually contain this information, it is important for the decommissioning of accelerators, especially for the decontamination of activated concrete. To understand the variations in trace element concentrations in concrete, we analyzed cobalt and europium concentrations in concrete samples from accelerator facilities in Japan by neutron activation analysis, which is suitable for trace element analysis on the order of parts per million (ppm).

The third G20 Health Ministers' Meeting was held in Okayama, Japan on October 19-20, 2019. The authors were involved in the decision making of the substantial issues of this meeting including theme setting, schedule management, facilitating the discussion, and preparation for the ministers' meeting. Here, we summarize our lessons of experience from hosting G20 Okayama Health Ministers' Meeting as: i) Utilizing the occasion of existing major health related meeting to gain efficiency; ii) Collaboration with other G20 tracks such as finance can function as a tool to facilitate inter-sectoral collaboration within other G20 members; iii) Two-day Health Working Group before the ministerial meeting provides sufficient time for negotiation of the declaration text; and iv) Inclusion of residents and representatives of the host city provides great opportunity to create G20 legacy. Such an experience of Japanese policymaking is rarely shared in English and the lessons learned from our experience shall provide meaningful advice for Saudi Arabia colleagues who are to hold the next G20 Health Ministers' Meeting as well as for the preparation of other G20 ministerial meetings.

Autism spectrum disorder (ASD) and schizophrenia share many phenotypic characteristics, but their association with prefrontal function have not been directly compared. The aim of this study is to compare cognitive profiles and their association with the prefrontal function between the two groups. We explored prefrontal dysfunction among adult individuals with ASD (n = 32), schizophrenia (n = 87), and healthy controls (HCs; n = 50). We assessed cognitive function in all participants using the Brief Assessment of Cognition in Schizophrenia (BACS). The BACS data of patients with schizophrenia were entered into hierarchical cluster analyses to assign subjects to a specific subgroup based on individual profiles. Using near-infrared spectroscopy, we measured hemodynamic responses in the fronto-temporal regions during a working memory task. Among the patients with schizophrenia, we defined 4 neurocognitive subgroups, including a global impairment, a mild impairment, and 2 selective impairment groups. Compared to the HCs, the ASD and schizophrenia groups had much weaker hemodynamic responses in the left DLPFC, left frontopolar cortex (FPC), and left inferior frontal gyrus. The ASD group showed a similar level of cognitive impairment with the mild level subgroup of schizophrenia. Additionally, the two groups shared reduced activity in the left DLPFC and left FPC during the task compared to HCs. Moreover, the BACS composite scores correlated positively with hemodynamic responses in a broad area involving fronto-temporal regions in the total patient sample. This research indicates considerable similarity in the left PFC dysfunction and its association with cognitive deficits between the disorders. These findings may guide future studies that investigate pathophysiological similarities between ASD and schizophrenia.

Aim Hepatocellular adenoma (HCA) has a lower prevalence in Japan than in Western countries and HCA subtypes have been reported for only a few Japanese patients. We analyzed HCA subtype data 38 patients from 23 hospitals in Japan in order to examine character and difference between Western countries. Methods To confirm HCA and to analyze subtypes, we performed immunohistochemical examinations. Results Thirty-eight cases were found to have HCA without cirrhosis. The male/female ratio was 18/20. Ages ranged from 15 to 79 (average, 43.2) years. Male and elder patients are not rare, furthermore, most of elder patients are male. Glycogen storage disease, past history of medicament use, hepatitis B virus surface antigen-positivity, antihepatitis C virus -positivity, diabetes mellitus, obesity, lipid metabolism disorder and alcoholism were present in of 6, 8, 1, 1, 6, 6, 4, and 6 cases, respectively. As to HCA subtypes, HNF1alpha-inactivated HCA, beta-catenin activated HCA (b-HCA), inflammatory HCA (IHCA) and unclassified HCA (U-HCA) accounted for nine (23.7%), four (10.5%), 17 (44.7%) and eight (21.1%) cases, respectively. Two cases showed coexistence of HCA and hepatocellular carcinoma (HCC) at surgery, and another had HCC which had been detected 23 years after HCA diagnosis. The HCA subtype of one of the former cases was U-HCA, while the remaining two had b-HCA and U-HCA. Conclusions In Japanese HCA cases, the proportions of U-HCA, male and elder cases were slightly higher than in Western countries, and most of elder patients were male. IHCA was however common regardless of race, and was assumed to be the predominant subtype of HCA.

This data article features four figures showing the correlations between the biomass of fish and scallop landed in Okhotsk subprefecture (Hokkaido, Japan) and airfreights from Memanbetsu Airport, a dominant airport in the subprefecture. Total landings of fish and scallop were collected from Hokkaido government office website while the airfreight data were acquired from the Memanbetsu Airport management office. The second and third figures in this data article are in a matrix heatmap format and a line graph, representing the statistical monthly data of airfreights from the airport and fish and scallop landings in the subprefecture; data were gathered from 2009 to 2018. Data were gathered from 2009 to 2018. The airfreight data reflect the increase and decrease in the total fish or scallop landings in the subprefecture. A Pearson's correlation coefficient and cross-correlation statistics between monthly airfreight and monthly fish landings were performed to assess their correlation and annual periodic relationship. This article also provides a data figure that shows an increasing active opening ratio to secure human resources in the motor truck transportation industry in Japan. This may be due to a workforce shortage in this trade. Annual data on the active opening ratio for jobs in Japan from 2001 to 2018 were collected from the open data available on the website of the Japanese Ministry of Health, Labour and Welfare.

// Teruhisa Higuchi 1 , Mitsuhiko Moriyama 1 , Akiko Fukushima 1 , Hiroshi Matsumura 1 , Shunichi Matsuoka 1 , Tatsuo Kanda 1 , Masahiko Sugitani 2 , Akiko Tsunemi 3 , Takahiro Ueno 3 and Noboru Fukuda 3 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Itabashi-Ku, Tokyo 173-8610, Japan 2 Department of Pathology, Nihon University School of Medicine, Itabashi-Ku, Tokyo 173-8610, Japan 3 Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Itabashi-Ku, Tokyo 173-8610, Japan Correspondence to: Tatsuo Kanda, email: kandat-cib@umin.ac.jp , kanda.tatsuo@nihon-u.ac.jp Mitsuhiko Moriyama, email: moriyama.mitsuhiko@nihon-u.ac.jp Keywords: iron; NASH; SHRSP5 rat; intestine; HAMP Received: May 18, 2017 Accepted: May 09, 2018 Published: May 25, 2018 ABSTRACT Background: Excess iron is associated with non-alcoholic steatohepatitis (NASH). Results: mRNA expression of duodenal cytochrome b, divalent metal transporter 1, ferroportin 1, hepcidin, hephaestin and transferrin receptor 1 in liver were higher in high fat, high cholesterol-containing diet (HFCD) group than in normal diet (ND) group. mRNA levels of divalent metal transporter 1 and transferrin receptor 1, which stimulate iron absorption and excretion, were enhanced in small intestine. Epithelial mucosa of small intestine in HFCD group was characterized by plasma cell and eosinophil infiltration and increased vacuoles. Iron absorption was enhanced in this NASH model in the context of chronic inflammation of small intestinal epithelial cells, consequences of intestinal epithelial cell impairment caused by HFCD. Iron is transported to hepatocytes via portal blood, and abnormalities in iron absorption and excretion occur in small intestine from changes in iron transporter expression, which also occurs in NASH liver. Knockdown of hepcidin antimicrobial peptide led to enhanced heavy chain of ferritin expression in human hepatocytes, indicating association between hepcidin production and iron storage in hepatocytes. Conclusions: Iron-related transporters in liver and lower/upper portions of small intestine play critical roles in NASH development. Methods: Expression of iron metabolism-related genes in liver and small intestine was analyzed in stroke-prone spontaneously hypertensive rats (SHR-SP), which develop NASH. Five-week-old SHR-SP fed ND or HFCD were examined. mRNA and protein levels of iron metabolism-related genes in liver and small intestine from 12- and 19-week-old rats were evaluated by real-time RT-PCR and immunohistochemistry or Western blot.

Energy-recovery linacs (ERLs) are promising for advanced synchrotron light sources, high-power free electron lasers (FELs), high-brightness gamma-ray sources , and electron–ion colliders. To demonstrate the critical technology of ERL-based light sources, we have designed and constructed a test accelerator, the compact ERL (cERL). Using advanced technology that includes a photocathode direct current (DC) electron gun and two types of 1.3-GHz-frequency superconducting cavities, the cERL was designed to be capable of recirculating low emittance ( ≤ 1 mm ⋅ mrad) and high average-current ( ≥ 10 mA) electron beams while recovering the beam energy. During initial commissioning, the cERL demonstrated successful recirculation of high-quality beams with normalized transverse emittance of ∼ 0.14 mm ⋅ mrad and momentum spread of ∼ 1.2 × 10−4 (rms) at a beam energy of 20 MeV and bunch charge below 100 fC. Energy recovery in the superconducting main linac was also demonstrated for high-average-current continuous-wave beams. These results constitute an important milestone toward realizing ERL-based light sources.

Background: The concrete walls inside the vaults of cyclotron facilities are activated by neutrons emitted by the targets during radioisotope production. Reducing the amount of radioactive waste created in such facilities is very important in case they are decommissioned. Thus, we proposed a strategy of reducing the neutron activation of the concrete walls in cyclotrons during operation. Materials and Methods: A polyethylene plate and B-doped Al sheet (30 wt% of B and 2.5 mm in thickness) were placed in front of the wall in the cyclotron room of a radioisotope production facility for pharmaceutical use. The target was Xe gas, and a Cu block was utilized for proton dumping. The irradiation time, proton energy, and beam current were 8 hours, 30 MeV, and 125 μA, respectively. To determine a suitable thickness for the polyethylene plate set in front of the B-doped Al sheet, the neutron-reducing effects achieved by inserting such sheets at several depths within polyethylene plate stacks were evaluated. The neutron fluence was monitored using an activation detector and 20-g on de Au foil samples with and without 0.5-mm-thick Cd foil. Each Au foil sample was pasted onto the center of a polyethylene plate and B-doped Al sheet, and the absolute activity of one Au foil sample was measured as a standard using a Ge detector. The resulting relative activities were obtained by calculating the ratio of the photostimulated luminescence of each foil sample to that of the standard Au foil. Results and Discussion: When the combination of a 4-cm-thick polyethylene plate and Bdoped Al sheet was employed, the thermal neutron rate was reduced by 78%. Conclusion: The combination of a 4-cm-thick polyethylene plate and B-doped Al sheet effectively reduced the neutron activation of the investigated concrete wall.

A series of nuclides (14C, 26Al, and 36Cl) was measured using the 12UD Pelletron tandem accelerator before replacement by the horizontal 6 MV tandem accelerator at the University of Tsukuba Tandem Accelerator Complex (UTTAC). This paper considers the modification of the accelerator mass spectrometry (AMS) measurement parameters to suit the current 6 MV tandem accelerator setup (e.g., terminal voltage, detected ion charge state, gas pressure, and entrance window material in detector). The Particle and Heavy Ion Transport code System (PHITS) was also used to simulate AMS measurement to determine the best conditions to suppress isobaric interference. The spectra of 41Ca and 41K were then successfully separated and their nuclear spectra were identified; the system achieved a background level of 41Ca/40Ca ∼ 6 × 10 - 14 .

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) are associated with cognitive dysfunction both in adulthood and in later life. In this study, we directly compared neurocognitive function between these three conditions in later life, employing stringent definitions of euthymia and symptomatic remission. Cognitive function in 60 elderly outpatients with MDD, BD, or SZ (20 patients per group) was assessed using the Japanese version of the Brief Assessment of Cognition in Schizophrenia. Patients with MDD had significantly higher z scores than both the other groups with large or moderately large effect sizes, for verbal fluency, attention and speed of information processing, and composite scores. In contrast, there were no significant differences in the degree of neurocognitive impairment between patients with BD and SZ. In later life, patients with BD and SZ showed a similar degree of neurocognitive impairment, while patients with MDD showed smaller impairments in several neurocognitive domains compared to patients with either of the other two disorders.

Aim Impaired social functioning is a common characteristic of patients with schizophrenia. Social functioning requires the complex operation of various executive functions. Deficits in the prefrontal cortex (PFC) have been implicated in executive dysfunction. Here we aimed to clarify the relationship between subjectively and objectively assessed social functioning, and their associations with PFC function in patients with schizophrenia. Methods Twenty-three patients and twenty-two age- and sex-matched healthy controls (HCs) were assessed. In the schizophrenia group, self- and caregiver-rated social functioning was measured using the Specific Level of Functioning Assessment (SLOF). The hemodynamic responses elicited by a verbal fluency task (VFT) in three regions of interest in the fronto-temporal area were measured using multi-channel near-infrared spectroscopy (NIRS). We also investigated psychiatric symptoms, neurocognition, and cognitive insight to assess possible confounding factors. Results Significant positive correlations were found between self- and caregiver-rated SLOF composite scores and three subdomain scores. Self- and caregiver-rated SLOF composite scores were significantly associated with dorsolateral PFC and frontopolar cortex (DLPFC/FPC) activation during the VFT. Psychiatric symptoms, global functioning, neurocognition, and cognitive insight were not associated with NIRS signals. General psychopathology was associated with NIRS signals in the ventro-lateral PFC and the anterior temporal cortex. DLPFC and FPC activity may be associated with social functioning in patients with schizophrenia. Conclusion Our results suggest that the two distinct assessments of social functioning were significantly correlated. Moreover, DLPFC and FPC function was strongly associated with social functioning and the ability to carry out daily life in patients with schizophrenia.

Background: The involvement of serum ornithine carbamoyltransferase (OCT) in the progression of chronic hepatitis and liver cirrhosis is unclear. Methods: A total 256 patients with chronic hepatitis C and 5 healthy controls were examined. Serum OCT concentrations were measured by enzyme-linked immunosorbent assay. Serum OCT concentrations were compared with serum cytokine and chemokine levels, and with disease severity and development of hepatocellular carcinoma (HCC). Results: The median OCT concentrations were 21.8 ng/ml for healthy controls, 36.7 ng/ml for F0 stage disease, 48.7 ng/ml for F1 stage, 77.9 ng/ml for F2 stage, 104.8 ng/ml for F3 stage, and 121.4 ng/ml for F4 stage. OCT concentrations were correlated with aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, platelet counts, indocyanine green retention rate at 15 min, prothrombin times, the molar ratio of branched chain amino acids to tyrosine, and tyrosine. Furthermore, there were significant correlations among OCT concentrations and IP10 and IL18 levels. There were weak correlations between serum OCT concentrations and liver histology. The cumulative incidence of HCC in the high-OCT concentration group (≥75.3 ng/ml) was higher than that in the low-OCT concentration group. Conclusion: The measurement of serum OCT concentration may provide a useful marker of disease severity, and thus could be a useful marker for a high risk of HCC occurrence.

Objective: This study aimed to assess the relationship between steatosis and long-term outcomes of patients with chronic hepatitis C (CH) and liver cirrhosis (LC). Patients and methods: The study population included 282 subjects with CH or LC who underwent liver biopsy at our institute. All patients achieved a sustained virological response (SVR) to interferon (IFN). Clinical characteristics, including age, gender and body mass index (BMI), were compared. The liver biopsy specimens of all patients were examined and scores were assigned to indicate the severity of each of the following features: inflammatory cell infiltration in the periportal, parenchymal and portal areas; F (fibrosis) stage; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; bile duct damage; hepatic steatosis. Results: Of the 282 patients, 112 (39.7%) were free of steatosis. The other 170 patients (60.3%) had steatosis. The blood biochemical parameters of the patients with hepatic steatosis were significantly poorer than those of patients free of steatosis. Inflammatory cell infiltration and F stage were both significantly more severe in patients with than in those without steatosis. The incidences of hepatocellular carcinoma differed significantly between the two groups. However, the incidences of hepatocellular carcinoma did not differ significantly between the groups with BMI above and below 25. Conclusion: We consider hepatic steatosis to potentially affect the blood biochemical parameters and clinical profiles of Japanese patients with CH due to hepatitis virus type C. Patients with this form of CH showed favorable clinical responses to IFN. Furthermore, fibrosis and steatosis appear to affect the long-term outcomes of these patients. However, BMI alone cannot be used to predict HCC development.

Three methods to detect neutrons emitted from an electrostatic accelerator were examined. These were gold foil activation, thermoluminescent dosimeters (TLDs), and CR-39. The gold-foil activation method has previously been proven effective in the measurement of neutrons emitted from cyclotron sources. In the case of electrostatic accelerators, a greater amount of fast neutrons and a smaller amount of thermal neutrons are observed compared to a cyclotron accelerator. Therefore, the error in calculating the thermal neutron flux became unacceptably large. By comparison the CR-39 detectors were apparently unable to measure thermal neutrons well, because some tracks were also generated by fast neutrons causing a signal interference. In the case of TLDs, as the material was not sensitive to fast neutrons, it was not affected by them, and hence could adequately measure the thermal neutron flux. However, it was found that in some cases its measurements could be offset by the influence of high dose rate of gamma rays.

Accelerator operations often generate neutrons that may activate concrete in the accelerator room. When accelerators are decommissioned, the concrete will remain as radioactive waste. Not all of concrete in the room will be radioactive wastes, but at place with large amount of neutrons will be radioactive wastes. Therefore, it is very important to determine where and how many neutrons are generated during accelerator operation. We used gold foils to obtain this information in positron emission tomography (PET) cyclotron facilities. We obtained concrete core samples from a PET cyclotron to determine the amount of radioactivity contained in concrete. We obtained the operational parameters (particle, radioactive product, current, and operation time) of the PET cyclotron facility and estimated the radioactivity generated in concrete using the operational parameters and gold foil results. A comparison of the estimated and core sampling measurement results showed good agreement.

Activated accelerator magnets were measured with three different types of commercially available gamma-ray imaging devices (pinhole, Compton scattering, and masked type) and the results were compared to simplify a distinction between activated/non-activated areas in the magnet during the decommissioning of an accelerator facility. In general, an activated magnet includes 60Co and emits gamma rays over 1 MeV; however, current devices are not designed to detect such high-energy photons. Our results showed that two devices could identify the location of highly activated areas, although they could not detect the total absorption peaks of the 1173 and 1333 keV photons from 60Co.

An in situ method to determine the specific activity in concrete structures using a survey meter was established in this study for decommissioning accelerator rooms. This method is much simpler than the conventional sampling method that requires core boring. A survey meter (T-SP2, TAC Inc., Japan) was customised and equipped with a small detector probe, whose size allowed the design of a light-weight Pb shield. For dose rate measurement, a Pb shield thickness of 4.5 cm was enough to shield ambient γ-rays, and its weight (16 kg) was low enough for the device to be carried by a human. A calibration curve was obtained to quickly and easily convert the net contact dose rate on concrete into the specific activity in a PET cyclotron room. The specific activity detection limit for this device was lower than the clearance limit of 152Eu and 60Co in activated materials. Therefore, this method can be used for separating nonactivated concrete from activated concrete during decommissioning. A general correction factor for the slope of the calibration curve was also obtained for use at other accelerator facilities.

Network management tasks are increasing its complexity because of the development of the IoT environment, virtualization technologies. To keep the safety and security of the network systems, the advances of analysis method for various network data is required for the practical problem-solving. Although many IT tools to support the data analysis works in network management, it is not enough for adaptation to developing environment. Also, the solutions do not consider the knowledge variety of users. In this paper, we propose an agent-based approach for data presentation to support the analysis from multiple aspects in network management works. Concretely, we design the self-organized analysis procedure based on the cooperation among agents and the interactive requirement estimation mechanism to improve the support functions for the diverse of the users’ knowledge. The evaluation experiments show the effectiveness of the prototypical system designed according to the proposed approach.

This data article features a figure and tables that show the correlations among brand value by Brand Valuation (Interbrand Japan, Inc. Tokyo, Japan), market capitalization, and the consolidated overseas sales ratios of Japanese companies. The figure shows the scatter plot for market capitalization vs. brand value for Japanese companies. The lines in the plot show the regression fits for two groups of companies (domestic and global) with consolidated overseas sales ratios below or above 30%, respectively. The Pearson's correlation coefficients between brand value and market capitalization are calculated for global and domestic companies separately. Additionally, cross-tabulation statistics and Chi-square test of independence for brand values and consolidated overseas sales ratios were performed to assess their correlation.

This paper presents a novel impulse radio transceiver based on a 2-bit pulse-position modulation (PPM) system for E-band wireless communication systems. We propose a time-based modulation architecture for a wireless transceiver. This is a promising architecture for deep-submicron and nanoscale CMOS technology. The performance of the wireless transceiver can be enhanced as the speed of the CMOS circuit increases. The transmitter is composed of four circuit blocks: a pulse-position modulator, impulse generator, millimeter-wave bandpass filter, and power amplifier. The receiver is comprised of a conventional quadrature demodulator. The transmitter and receiver chipset is fabricated in 55-nm standard CMOS technology. In transceiver loop-back tests, a data rate of 7.0 Gb/s with repetition data and 4.6 Gb/s with pseudo-random bit sequence (PRBS) data are demonstrated.

A new time projection chamber (TPC) was developed for neutron lifetime measurement using a pulsed cold neutron spallation source at the Japan Proton Accelerator Research Complex (J-PARC). Managing considerable background events from natural sources and the beam radioactivity is a challenging aspect of this measurement. To overcome this problem, the developed TPC has unprecedented features such as the use of polyether-ether-ketone plates in the support structure and internal surfaces covered with $^6$Li-enriched tiles to absorb outlier neutrons. In this paper, the design and performance of the new TPC are reported in detail., 33 pages, 10 figures

The production cross sections of 10Be and 26Al were measured by accelerator mass spectrometry using 89Y, 159Tb, and natCu targets bombarded by protons with energies Ep of 120 GeV and 392 MeV. The production cross sections obtained for 10Be and 26Al were compared with those previously reported using Ep = 50 MeV–24 GeV and various targets. It was found that the production cross sections of 10Be monotonically increased with increasing target mass number when the proton energy was greater than a few GeV. On the other hand, it was also found that the production cross sections of 10Be decreased as the target mass number increased from that of carbon to those near the mass numbers of nickel and zinc when the proton energy was below approximately 1 GeV. They also increased as the target mass number increased from near those of nickel and zinc to that of bismuth, in the same proton energy range. Similar results were observed in the production cross sections of 26Al, though the absolute values were quite different between 10Be and 26Al. The difference between these production cross sections may depend on the impact parameter (nuclear radius) and/or the target nucleus stiffness.

Cortisol dysregulation has been proposed to be involved in depression. Hypothalamic–pituitary–adrenal (HPA) axis dysregulation associated with major depressive disorder (MDD) was previously reported to be higher in the elderly. Furthermore, insulin resistance and the prevalence of type 2 diabetes are known to increase with aging. The aim of the present study was to determine whether a relationship existed between plasma cortisol levels following the dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test and insulin resistance evaluated by the homeostasis model assessment of insulin resistance (HOMA-R) in elderly MDD subjects. Fifteen unmedicated MDD inpatients and 17 age- and sex-matched healthy controls participated in this study. After overnight fasting, blood samples were collected to measure plasma glucose and insulin concentrations, estimate HOMA-R, and perform the DEX/CRH test to evaluate HPA axis function. The value of the area under the time curve of plasma cortisol concentrations (CortAUC) and peak cortisol values (Cortpeak) following the administration of DEX/CRH both correlated with HOMA-R in MDD group. In contrast, neither CortAUC nor Cortpeak correlated with HOMA-R in controls. This is the first study to directly demonstrate the relationship between HPA axis dysregulation assessed with the DEX/CRH test and the index of insulin resistance estimated as HOMA-R in elderly MDD patients.

Recent advances in interferon-free treatment could lead to the eradication of hepatitis C virus (HCV) from patients infected with HCV. One of the direct-acting anti-viral agents, HCV NS5A inhibitor, is available for these combination therapies. However, naturally occurring resistance-associated variants (RAVs) to HCV NS5A inhibitors in treatment-naïve patients chronically infected with HCV genotype 1b are still unknown.We performed ultra-deep sequencing and analysed previously reported RAVs in a total 132 HCV genotype 1b-infected Japanese patients who had never used HCV NS5A inhibitors. We also performed direct-sequencing by Sanger method in consecutively selected 50 of the total 132 samples, and the differences between the results of the two methods were compared.In the comparison of the variant frequencies of ultra-deep sequencing with RAVs of direct-sequencing by Sanger method in 50 patients, we identified 32 RAVs by direct-sequencing with the Sanger method; minimum variant frequency was shown by ultra-deep sequencing to be 9%. A total of 110 RAVs were identified only by ultra-deep sequencing. In the samples from all 132 patients, L31W (2.3%), L31V (49.2%), L31F (41.7%), L31M (1.5%), L31I (5.3%), L31S (2.0%), L31P (3.0%) and L31R (0.8%), and Y93N (2.3%), Y93H (25%), Y93C (0.8%), Y93P (2.3%) and Y93D (0.8%) were identified.We demonstrated naturally-occurring RAVs of HCV NS5A inhibitors by ultra-deep sequencing and that several mutations including Y93H are common in HCV NS5A inhibitor-treatment-naïve patients with chronic HCV genotype 1b. Careful attention should be paid to these RAVs, and further improvement of treatment options might be needed.