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Purpose: Oral adjuvant uracil and tegafur plus leucovorin (UFT/LV) is not inferior to standard weekly fluorouracil and folinate for stage II/III colon cancer. However, protein-bound polysaccharide K (PSK) has been evaluated as postoperative adjuvant therapy for colorectal cancer. This report is the first of MCSGO-CCTG, which compared UFT/LV to UFT/PSK as adjuvant chemotherapy for stage IIB or III colorectal cancer in patients who had undergone Japanese D2/D3 lymph node dissection. Methods: The primary endpoint was the 3-year disease-free survival (DFS). A randomized non-inferiority study compared UFT/LV to UFT/PSK. The overall survival, adverse events, compliance, and quality of life were also investigated as the secondary endpoints. Results: Between March 2006 and December 2010, 357 patients were randomized to UFT/PSK ( n = 178) or UFT/LV ( n = 179) (median age 65 years, colon/rectum 67.4/32.6%, stage IIB/IIIA/IIIB/IIIC 11.1/15.7/55.0/18.2%). The 3-year DFS rate was 82.3% in those receiving UFT/LV and 72.1% in those receiving UFT/PSK. The non-inferiority of UFT/PSK adjuvant therapy to UFT/LV therapy was not verified (−9.06%, 90% confidence interval −17.06 to −1.06%). The 3-year overall survival rate was 95.4% in those receiving UFT/LV and 90.7% in those receiving UFT/PSK. Conclusions: As adjuvant chemotherapy for stage IIB and III colorectal cancer patients, UFT/PSK adjuvant therapy was not non-inferior to UFT/LV therapy with respect to the DFS. [ABSTRACT FROM AUTHOR]

Background and Aim Inappropriate innate immune responses have been suggested to contribute to the pathogenesis of primary sclerosing cholangitis ( PSC). We evaluated the associations of expressions of toll-like receptor ( TLR) 4, TLR9, and nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family pyrin domain containing 3 ( NLRP3) in the biliary epithelial cells ( BECs) with clinical features of PSC patients. Methods We retrospectively evaluated the expressions of TLR4, TLR9, and NLRP3 in the intrahepatic BECs by immunohistochemical staining in 21 PSC patients and 10 normal controls. In PSC, 17 patients underwent liver biopsy, and, in the other four patients, liver specimens were obtained at the time of liver transplantation. Results TLR9 expressions in BECs were higher in PSC patients than in normal controls. TLR9 expressions were correlated with Ludwig fibrosis scores in PSC patients. TLR4 and NLRP3 expressions were similar between PSC patients and normal controls. Seventeen PSC patients undergoing liver biopsy were followed up during a median period of 55.7 months. Four reached to liver transplantation and four developed cholangiocarcinoma. Patients developing cholangiocarcinoma showed lower NLRP3 expressions than the others. Patients reaching to liver transplantation showed higher TLR9 expressions. Expression levels of TLR9 and NLRP3 were not correlated with liver biochemical tests and Mayo risk scores. Conclusions In PSC, excessive immune responses through TLR9 signaling may be associated with the disease progression. Insufficient immune response through NLRP3 signaling may be associated with the development of cholangiocarcinoma. Evaluation of TLR9 and NLRP3 expressions in BECs may be useful for predicting the prognosis as an auxiliary marker. [ABSTRACT FROM AUTHOR]

Background/Aims: Recently, we found the presence of anti-60S ribosomal protein L29 antibody (anti-RPL29) in human sera, inhibiting the proliferation of pancreatic cancer cells in vitro. We aimed to estimate the association of serum anti-RPL29 levels with clinical features in patients affected with unresectable pancreatic cancer. Methods: We retrospectively reviewed 105 patients with unresectable pancreatic cancer. Serum anti-RPL29 levels were measured by the indirect enzyme-linked immunosorbent assay. The cut-off was represented by the 95th percentile in 62 healthy volunteers. Results: Median survival time (MST) was 11.1 months in 49 patients showing serum anti-RPL29 level >cut-off and 7.4 months in 56 patients showing serum anti-RPL29 level ≤cut-off. In locally advanced disease, MST was 17.9 months in 22 patients showing serum anti-RPL29 level >cut-off and 10.0 months in 19 patients showing serum anti-RPL29 level ≤cut-off. In metastatic disease, MST was 8.7 months in 27 patients showing serum anti-RPL29 level >cut-off and 5.9 months in 37 patients showing serum anti-RPL29 level ≤cut-off. In the multivariate Cox proportional hazard model, serum anti-RPL29 level >cut-off, abdominal or back pain, performance status, and metastatic disease were identified as independent prognostic factors. Conclusion: Serum anti-RPL29 levels may be a novel candidate for a prognostic marker for unresectable pancreatic cancer. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim Recently, serum levels of anti-programmed cell death-1 (anti- PD-1) antibodies have been reported to be useful for the discrimination of type 1 autoimmune hepatitis ( AIH) from drug-induced liver injury ( DILI) and to be associated with clinical features of type 1 AIH. This multicenter study aimed to validate the usefulness of serum anti- PD-1 antibody as a serological marker for type 1 AIH. Methods Serum samples before the initiation of corticosteroid treatment were obtained from 71 type 1 AIH patients and 37 DILI patients. Serum levels of anti- PD-1 antibodies were measured by indirect enzyme-linked immunosorbent assay. Results Serum levels of anti- PD-1 antibodies were higher in type 1 AIH patients than in DILI patients ( P < 0.001). The receiver-operator curve analysis showed that serum levels of anti- PD-1 antibodies were useful for the discrimination of type 1 AIH from DILI (area under the curve, 0.80). On the other hand, the multivariate Cox proportional hazard model showed that positivity for serum anti- PD-1 antibody, probable diagnosis based on the revised scoring system proposed by the International Autoimmune Hepatitis Group, and prothrombin activity of less than 60% were associated with the later normalization of serum transaminase levels. During the clinical course, the disease relapsed more frequently in patients positive for serum anti- PD-1 antibody (36% vs 11%). Conclusion This study suggests that serum anti- PD-1 antibody is useful for the diagnosis of type 1 AIH as an auxiliary diagnostic marker, and that serum levels of anti- PD-1 antibodies reflect clinical features of type 1 AIH. [ABSTRACT FROM AUTHOR]

Background and Aim Recently, the association of the dysfunction of programmed cell death ( PD)-1 expressed on activated lymphocytes with the pathogenesis of autoimmune hepatitis ( AIH) has been speculated. This study aimed to investigate the association of serum anti- PD-1 antibodies with clinical characteristics of type 1 AIH. Methods Serum samples before the initiation of prednisolone treatment were obtained from 52 type 1 AIH patients, 24 patients with drug-induced liver injury ( DILI), 30 patients with acute viral hepatitis ( AVH), 11 patients with primary sclerosing cholangitis ( PSC), and 62 healthy volunteers. Titers of serum anti- PD-1 antibodies were measured by indirect enzyme-linked immunosorbent assay. The cutoff level was represented by a mean absorbance + 2 standard deviations in healthy volunteers. Results Prevalence of serum anti- PD-1 antibodies was 63% in type 1 AIH patients, 8% in DILI patients, 13% in AVH patients, 18% in PSC patients, and 3% in healthy volunteers. In type 1 AIH patients, titers of serum anti- PD-1 antibodies were correlated with serum levels of bilirubin (r = 0.31, P = 0.030) and alanine aminotransferase (r = 0.31, P = 0.027) but not serum immunoglobulin G levels. Positivity for serum anti- PD-1 antibodies was associated with the later normalization of serum alanine aminotransferase levels after the initiation of prednisolone and the disease relapse. Conclusions Serum anti- PD-1 antibodies would be useful for the discrimination of type 1 AIH from DILI, AVH, and PSC as an auxiliary diagnostic marker. Furthermore, anti- PD-1 antibodies may be associated with clinical characteristics of type 1 AIH. [ABSTRACT FROM AUTHOR]

A fast and accurate capacitance measurement technique, direct charge measurement (DCM), is introduced to improve productivity of semiconductor parametric testing. The approach is simpler and much faster compared with conventional method using charge-based capacitance measurement (CBCM) or LCR meter. On-chip active device is not an essential necessity for DCM test structure and it is easy to implement parallel measurements. The basic theory, parallel measurement method and mathematical analysis on non-linear MOS capacitance measurement are explained. For interconnect capacitance measurement, an extension of DCM, degenerated exhaustive direct charge measurement (DEDCM) is presented as a faster, more accurate and thorough characterization technique. Experimental results show good data matching and significant throughput improvement over conventional LCR meter measurements. [ABSTRACT FROM AUTHOR]

Aim The number of patients with autoimmune hepatitis ( AIH) showing acute presentation has increased. This study aimed to assess their prognosis. Methods A survey of AIH patients by sending questionnaires was performed, and 96 patients showing acute presentation were investigated. Results The median age was 58 years and 78 patients (81%) were female. Eighty-four patients (88%) were positive for antinuclear antibody and/or anti-smooth muscle antibody. The median serum immunoglobulin G level was 2252 mg/ dL. Twenty-five patients (26%) showed histological acute hepatitis. As initial treatment, 88 patients (92%) were treated with corticosteroid, and 28 of them received pulse steroid treatment. Overall, 11 patients (11%) reached fatal outcomes (nine death and two liver transplantation). Patients with histological acute hepatitis showed higher serum bilirubin levels, lower prothrombin activities and higher prothrombin time-international normalized ratios ( PT-INR) and reached fatal outcomes more frequently. With a multivariate logistic regression analysis, prothrombin activity and PT-INR at presentation was associated with fatal outcomes. Nine of 13 patients (69%) showing prothrombin activity of 40% or lower at presentation and nine of 19 patients (47%) showing PT-INR of 1.5 or higher reached fatal outcomes. Furthermore, of 13 patients showing prothrombin activity of 40% or lower and/or PT-INR of 1.5 or higher at presentation who were treated with pulse steroid treatment, four (31%) died from infectious disease. Conclusion Prothrombin activity and PT-INR are prognostic factors for AIH showing acute presentation. Physicians should pay attention to the development of infectious disease when pulse steroid treatment is performed. [ABSTRACT FROM AUTHOR]

The liver constantly encounters food-derived antigens and bacterial components such as lipopolysaccharide translocated from the gut into the portal vein. Bacterial components stimulate Toll-like receptors ( TLR), which are expressed on Kupffer cells, biliary epithelial cells, hepatocytes, hepatic stellate cells, endothelial cells and dendritic cells and recognize specific pathogen-associated molecular patterns. The signaling of TLR to its main ligand triggers inflammation. Usually, in order to protect against hyperactivation of the immune system and to prevent organ failure by persistent inflammation, TLR tolerance to repeated stimuli is induced. In chronic liver diseases, a breakdown in TLR tolerance occurs. Furthermore, Kupffer cells, hepatic stellate cells and natural killer T cells are key components of innate immunity. Decreased numbers and impaired ability of these cells lead to failures in immune tolerance, resulting in persistent inflammation. Recently, the activation of inflammasome was revealed to control the secretion of pro-inflammatory cytokines such as interleukin-1β in response to bacterial pathogens. Innate immunity seems to be an important contributor to the pathogenesis of fatty liver disease and autoimmune liver disease. Recently, probiotics were reported to affect various liver diseases via shifts in gut microbiota and the stability of intestinal permeability. However, many unresolved questions remain. Further analysis will be needed to gain a more comprehensive understanding of the association of innate immunity with the pathogenesis of various liver diseases. [ABSTRACT FROM AUTHOR]

Background/Aims: In patients with septic shock, the degree of liver dysfunction is correlated with serum levels of soluble intercellular adhesion molecule (sICAM)-1. We aimed to assess the usefulness of serum levels of soluble adhesion molecules as prognostic factors for acute liver failure (ALF). Methods: Serum levels of soluble platelet endothelial cell adhesion molecule (sPECAM)-1, sICAM-3, soluble endothelial (sE) selectin, sICAM-1, soluble platelet selectin, and soluble vascular cell adhesion molecule-1 on admission were measured in 37 ALF patients and 34 healthy controls. Results: Twenty-two ALF patients (59%) reached to fatal outcomes. Serum levels of sPECAM-1, sICAM-3, sE-selectin and sICAM-1 were higher in ALF patients than healthy controls. In 37 ALF patients, by the multivariate logistic regression analysis, ratio of direct to total bilirubin (per 0.1 increase; OR 0.11, 95% CI 0.01-0.99), serum sPECAM-1 level (per 100 ng/ml increase; OR 4.37, 95% CI 1.23-15.5) and serum sICAM-1 level (per 100 ng/ml increase; OR 0.49, 95% CI 0.27-0.89) were associated with fatal outcomes. Using receiver operating characteristics curve, each area under the curve of serum sPECAM-1 and sICMA-1 levels as prognostic factors was 0.71 and 0.74, respectively. Conclusion: Serum sPECAM-1 and sICAM-1 levels may be useful for predicting the prognosis of ALF. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The Muon Science Establishment (MUSE) is one of the major experimental facilities, along with those for neutron, hadron and neutrino experiments, in J-PARC. It makes up a part of the Materials and Life Science Experiment Facility (MLF) that hosts a tandem neutron facility (JSNS) driven by a single proton beam. The facility consists of a superconducting solenoid (for pion confinement) with a modest-acceptance (about 45 mSr) injector of pions and muons obtained from a 20mm thick edge-cooled stationary graphite target, delivering a 'surface muon' beam (&MGR;+) and a 'decay muon' beam (&MGR;+/&MGR; -) for a wide variety of applications. It has recently been confirmed that the beamline has the world's highest muon intensity (&SIM;106 &MGR;+/s) at a proton beam power of 120kW. The beamline is furnished with two experimental areas (D1 and D2) at the exit branches, where an apparatus for muon spin rotation/relaxation experiments (&MGR;SR) is currently installed at the D1 area while test experiments are conducted at the D2 area. In this paper, the current performance of the MUSE facility as a whole is reviewed. The facility is still in the early stage of development, including both beamlines and infrastructure for experiments, and plans for upgrading it are discussed together with perspectives for research works envisaged with unprecedented high-intensity muons. [ABSTRACT FROM AUTHOR]

Aim: In order to rescue more patients with fulminant hepatitis (FH) in a setting of the shortage of liver grafts, it is important not only to determine the suitable timing for liver transplantation (LT) but also to reduce avoidable operations for patients surviving without LT. This study aimed to identify prognostic parameters for survival without LT in FH patients. Methods: In 96 FH patients who did not receive LT, we examined prognostic parameters at the time of the diagnosis of FH, which were associated with patient's survival. Results: Fifty-three patients (55%) were female. The median age was 48 years. At the time of the diagnosis of FH, hepatic coma grade was II in 63 patients (66%), III in 22 (23%) and IV in 11 (11%). Forty-six patients (48%) were in a state of systemic inflammatory response syndrome (SIRS). Four parameters of age (<45 years), SIRS (no), direct bilirubin/total bilirubin ratio (>0.65), and total bilirubin (<12.0 mg/dL) were associated with patient's survival. Overall survival rate of eight patients ulfilling all four parameters were 88%. In 17 patients fulfilling any three parameters, 2-week, 4-week and overall survival rates were 82%, 77% and 71%, respectively. On the other hand, overall survival rate of 38 patients fulfilling any one parameter or none was less than 10%. Conclusions: Patients fulfilling all four parameters will be successfully treated without LT. In patients fulfilling any three parameters, intensive care including artificial liver support in expectation of hepatic regeneration during a few weeks may be possible. [ABSTRACT FROM AUTHOR]

Background/Aims: The efficacy of gemcitabine (GEM) on unresectable pancreatic cancer has been reported. However, in elderly patients, severe toxicities are frequently observed. In this study we aimed to assess the efficacy of low-dose GEM on unresectable pancreatic cancer in elderly patients. Methods: We reviewed 68 elderly patients (≥65 years) with unresectable pancreatic cancer. Thirty-six patients were treated with low-dose GEM (600-800 mg/m2; GEM group), and the other 32 received best supportive care (BSC group). Results: Median survival was 7.6 and 2.3 months in the GEM and BSC groups, respectively. In the GEM group, the median survival period was longer in 24 patients showing partial response or stable disease than in 12 patients showing progressive disease (11.4 vs. 5.3 months). Furthermore, the patients showing progressive disease had better 6-month survival than patients in the BSC group. Thirteen patients (36%) developed severe toxicities (grade 3 or 4). Low-dose GEM, stage of disease and performance status were associated with the prognosis. Conclusions: Low-dose GEM may improve the prognosis of elderly patients with unresectable pancreatic cancer. Furthermore, frequencies of severe toxicity seem lower in patients treated with low-dose GEM compared with previous reports. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We conducted this prospective study to elucidate the long-term outcome and incidence of hepatocellular carcinoma (HCC) development after nucleos(t)ide analog (NA) treatment in patients with chronic hepatitis B (CHB) or cirrhosis. CHB or cirrhosis patients without past NA treatment or HCC were started on entecavir (ETV) or lamivudine (LVD), and prospectively followed up with monthly blood tests, and with abdominal imaging every 6 months in CHB and every 3 months in cirrhosis patients. A total of 256 subjects with CHB ( n = 194) or cirrhosis ( n = 62) received ETV ( n = 129) or LVD ( n = 127) for 4.25 years (range: 0.41-10.0). After NA treatment, serum HBV DNA, alanine aminotransferase and α-fetoprotein (AFP) dropped significantly, along with significant increases in serum albumin and prothrombin time. Drug-resistance developed in 60 cases in the LVD group and in only one case in the ETV group. HCC developed in 35 patients, and the incidence at years 1, 3, 5, 7 and 10 was significantly higher in patients with cirrhosis (8.1%, 17.5%, 43.2%, 46.7% and 53.4%, respectively) than chronic hepatitis (1.6%, 3.5%, 3.5%, 7.1% and 29.6%, respectively), with no difference between ETV and LVD. After NA treatment, the sensitivity/specificity for HCC of AFP and des-γ-carboxy prothrombin (DCP) was 45.7%/97.3% and 33.3%/96.2%, respectively, with the specificity of AFP being higher than at baseline (64.4%), at the cut-off of 10 ng/mL. NA exerted a long-term efficacy and improved hepatic reservation in CHB and cirrhosis. After NA treatment, AFP dropped to lower than 10 ng/mL with marked elevation of specificity, leading to an earlier detection of HCC. [ABSTRACT FROM AUTHOR]

Recently, the associations of +49A/G polymorphisms of cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene with the susceptibility to type 1 autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) have been reported; however these associations are yet to be fully elucidated. This study aimed to identify the associations of CTLA-4 gene +49A/G polymorphisms with the susceptibility to type 1 AIH and PBC by using a meta-analysis. PubMed was searched by using the following keywords: ' autoimmune hepatitis AND ( polymorphism OR polymorphisms)' or ' primary biliary cirrhosis AND ( polymorphism OR polymorphisms)'. Meta-analyses of five studies including 526 patients with type 1 AIH and 631 controls and seven studies including 1500 patients with PBC and 2345 controls were performed. For type 1 AIH, the odds ratio (OR) of G allele was 1.26 [95% confidence interval (CI) 1.06-1.51] although G/G homozygosity was not associated with the susceptibility to type 1 AIH. On the other hand, the OR of A/A homozygosity for type 1 AIH was 0.66 (95% CI 0.50-0.86). For PBC, the OR of G allele was 1.20 (95% CI 1.06-1.34). Furthermore, G/G homozygosity was significantly associated with the susceptibility to PBC (OR 1.29, 95% CI 1.01-1.66). The OR of A/A homozygosity for PBC was 0.81 (95% CI 0.70-0.94). This study suggests that CTLA-4 gene +49A/G polymorphisms may be associated with the susceptibility to type 1 AIH and PBC. Especially, while G/G genotype may be associated with the susceptibility to PBC, A/A genotype may be protective against type 1 AIH and PBC. [ABSTRACT FROM AUTHOR]

In animal models for acute liver injury, the administration of some angiogenic factors such as vascular endothelial growth factor (VEGF) and granulocyte-colony stimulating factor (G-CSF) are shown to reduce liver injury and improve liver proliferative capacity. The aim of the present study was to assess the role of angiogenic factors in fulminant hepatic failure (FHF). Serum levels of nine angiogenic factors (angiopoietin-2, follistatin, G-CSF, hepatocyte growth factor [HGF], interleukin-8, leptin, platelet-derived growth factor [PDGF]-BB, platelet endothelial cell adhesion molecule-1 and VEGF) were measured using the Bio-Plex Protein Array System in 30 patients, 17 of whom were diagnosed with FHF, 13 with acute hepatitis (AH), and 20 controls. Serum levels of PDGF-BB and VEGF were lower in FHF patients than AH patients and controls (PDGF-BB; 2050 ± 1572 pg/mL vs 4521 ± 2419 pg/mL vs 8506 ± 5500 pg/mL, VEGF; 39 ± 38 pg/mL vs 144 ± 122 pg/mL vs 205 ± 121 pg/mL). By using univariate logistic regression models, serum levels of PDGF-BB and VEGF were associated with poor outcomes. Serum PDGF-BB levels were strongly correlated with serum VEGF levels (r = 0.70). Furthermore, serum PDGF-BB levels were significantly correlated with platelet counts (r = 0.79), PT activity (r = 0.37) and D.Bil/T.Bil ratio (r = 0.50), while serum VEGF levels were significantly correlated with platelet counts (r = 0.68) and PT activity (r = 0.38). We consider that serum levels of PDGF-BB and VEGF are worth investigating as biomarkers for predicting outcomes of FHF patients. [ABSTRACT FROM AUTHOR]

The muon science facility (MUSE, abbreviation of MUon Science Establishment), along with the neutron, hadron, and neutrino facilities, is under construction at the Japan Proton Accelerator Research Complex (J-PARC) in Tokai. The MUSE facility is located in the Materials and Life Science Experimental Facility (MLF), which is a building integrating both neutron and muon science programs. About 85% of the 3 GeV, 333 μA (1 MW) beam from the Rapid Cycle Synchrotron (RCS) is sent to the MLF for the production of intense pulsed neutron and muon beams, while the remaining 15% is sent to the 50 GeV ring for further acceleration for the kaon and neutrino physics programs. [ABSTRACT FROM AUTHOR]

Background/Aims: The prevalence of reflux esophagitis, which might lead to development of Barrett’s esophagus and esophageal adenocarcinoma, has been increasing. The aim of this study was to assess risk factors for reflux esophagitis. Methods: We conducted a cross-sectional study of 1,495 Japanese subjects undergoing health checkups (822 males and 673 females; median age 50 years) at a tertiary care center. Results: One hundred and twenty-seven subjects (8%) had reflux esophagitis and hiatal hernia was observed in 292 subjects (20%). Reflux esophagitis (13 vs. 3%) and hiatal hernia (28 vs. 9%) were more frequent in males than females. Significant differences in clinical backgrounds were observed between females and males. Multivariate logistic regression analyses revealed that hiatal hernia (OR 6.63, 95% CI 2.47–17.8; p = 0.0002) was associated with reflux esophagitis in females. In males, age (per 1-year increment: OR 0.96, 95% CI 0.94–0.99; p = 0.007), hiatal hernia (OR 3.16, 95% CI 2.05–4.87; p < 0.0001) and waist circumference (per 1-cm increase: OR 1.09, 95% CI 1.02–1.15; p = 0.006) were associated with reflux esophagitis. Conclusions: Abdominal obesity may be an important risk factor for reflux esophagitis in males compared with females. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: The peak age of the presentation of autoimmune hepatitis (AIH) is between 40 years and 50 years. Elderly patients have been reported to have higher frequencies of concurrent thyroid or rheumatic diseases and histological cirrhosis and a lower occurrence of treatment failure. In this study, we assessed the clinical features of Japanese type 1 AIH in adolescence and early adulthood. Methods: Fifteen patients aged ≤ 30 years (group 1) were compared with 79 patients aged between 40 years and 50 years (group 2). Results: At presentation, patients aged ≤ 30 years accounted for 9% of the study population. Although frequencies of extrahepatic concurrent autoimmune diseases were similar between groups 1 and 2, a tendency toward a lower frequency of concurrent autoimmune thyroiditis was shown in group 1 (0 vs. 18%, P = 0.08). Group 1 had a lower frequency of human leukocyte antigen DR4 (27 vs. 78%, P = 0.002), and histological acute hepatitis was shown more frequently in group 1 (27 vs. 4%, P = 0.002). However, there were no differences in frequencies of the normalization of serum transaminase levels after the introduction of corticosteroid treatment or relapse after the normalization of serum transaminase levels between the two groups. Conclusions: Japanese type 1 AIH patients in adolescence and early adulthood respond well to corticosteroid treatment. However, they may frequently show atypical features, and the diagnosis of type 1 AIH in adolescence and early adulthood may be difficult and should be made carefully. [ABSTRACT FROM AUTHOR]

In patients chronically infected with hepatitis B virus, interferon has been used for the purpose of viral suppression by loss of hepatitis B e antigen (HBeAg) with or without seroconversion to antibody to HBeAg (anti-HBe). However, discussion about the effect of interferon on the development of hepatocellular carcinoma (HCC) has been controversial. We conducted a meta-analysis of published studies. Eight studies were retrieved (1,303 patients), including two randomized controlled trials (RCTs) and six non-RCTs (553 patients received interferon treatment). The pooled estimate of the preventive effect of treatment was significantly in favor of interferon (risk difference −5.0%; 95% CI −9.4 to −0.5, P = 0.028). By subgroup analyses, the preventive effect of interferon treatment was shown in the Asian population (risk difference −8.5%; 95%CI −13.6 to −3.6, P = 0.0012), the population with the incidental rate of HCC ≥10% if untreted with interferon (risk difference −9.4%; 95%CI −14.2 to −4.6, P = 0.0001), and the population with the proportion of HBeAg-positive patients to the study population ≥70% (RD −6.0%; 95%CI −11.8 to −0.2, P = 0.043). However, the preventive effect of interferon was not shown in the European population, the population with a lower incidental rate of HCC if untreated with interferon, and the population with the lower proportion of HBeAg-positive patients to the study population. An evaluation using the Begg method indicated no evidence of publication bias. Interferon treatment is considered to restrain HCC development in patients with chronic hepatitis B virus infection, especially in HBeAg-positive Asians. [ABSTRACT FROM AUTHOR]

Abstract: The muon science facility (MUSE), along with neutron, hadron, and neutrino facilities, is one of the experimental areas of the J-PARC (Japan Proton Accelerator Research Complex) project, which was approved for construction between 2001 and 2008. The MUSE facility is located in the Materials and Life Science Facility (MLF), which is a building integrated to include both neutron and muon science programs. Construction of the MLF building was started at the beginning of 2004, and was recently completed at the end of the 2006 fiscal year. We have been working on the installation of the beamline components, expecting the first muon beam in the autumn of 2008. For Phase 1, we are planning to install one superconducting decay/surface channel with a modest-acceptance (about 40mSr) pion injector, with an estimated surface muon rate of and a beam size of 25mm diameter, and a corresponding decay muon rate of for 60MeV/c (up to for 120MeV/c) with a beam size of 50mm diameter. These intensities correspond to more than 10-times what is available at the RIKEN/RAL muon facility, which currently possess the most intense pulsed muon beams in the world. In addition to Phase 1, we are planning to install, a surface muon channel with a modest-acceptance (about 50mSr), mainly for experiments related to material sciences, and a super-omega muon channel with a large acceptance of 400mSr. In the case of the super-omega muon channel, the goal is to extract surface muons/s for the generation of ultra-slow muons and negative cloud muons/s with a momentum of 30–60MeV/c. One of the important goals for this beamline is to generate intense ultra-slow muons at MUSE, utilizing an intense pulsed VUV laser system. ultra-slow muons/s are expected, which will allow for an extension of into the area of thin film and surface science. At this symposium, the current status of J-PARC MUSE will be reported. [Copyright &y& Elsevier]

Aim: Antinuclear antibodies (ANA) are the main serologic markers of type 1 autoimmune hepatitis (AIH); however 20–30% of patients are negative for ANA. We assessed the clinical features of ANA-negative patients. Methods: A retrospective analysis was performed of 176 patients with type 1 AIH (153 females, median age 55 years). A diagnosis of AIH was made based on the revised scoring system proposed by the International Autoimmune Hepatitis Group. ANA titers were measured using a standard indirect immunofluorescence technique. Results: Thirty-eight patients (22%) had low titers of ANA (1:40 or 1:80), and 114 (65%) had high titers (≥ 1:160). Of 24 ANA-negative patients, 15 were positive for smooth muscle antibodies (SMA). Three of nine both ANA- and SMA-negative patients developed ANA during follow-up. The other six were diagnosed based on histological characteristics. Thirteen ANA-negative patients relapsed after the normalization of serum alanine aminotransferase (ALT) levels. ANA-negative patients more frequently showed acute presentation and, at presentation, had lower serum immunoglobulin G levels, higher serum levels of bilirubin and transaminase, and higher frequencies of histological acute hepatitis and zone 3 necrosis than those with high titers. However, the frequency of advanced stage of fibrosis was similar. The response to corticosteroids was not different among the three groups. Conclusions: ANA-negative type 1 AIH shows acute-onset more frequently but may include not only acute autoimmune hepatitis, but also acute exacerbation of inactive chronic disease. Regarding the diagnosis of ANA-negative AIH, the determination of ANA during follow-up and the response to immunosuppressive treatment may be helpful. [ABSTRACT FROM AUTHOR]

Aim: A low platelet count leads to dose reduction of interferon (IFN) and is associated with failure to achieve a sustained virological response (SVR) in chronic hepatitis C patients. However, partial splenic embolization (PSE) is effective for treating thrombocytopenia resulting from hypersplenism. Methods: We compared the clinical features of 10 patients receiving PSE prior to the combination therapy of IFN and ribavirin (RBV) (PSE group) with those of 10 non-receiving PSE patients (non-PSE group). Results: In all 10 patients, PSE was successfully performed without serious adverse events. After PSE, leukocyte, neutrophil, and platelet counts significantly increased. The period from PSE to the initiation of the combination therapy was 15 (7–21) days. In the PSE group, two of six patients (33%) infected with genotype 1, and all four patients infected with genotype 2, achieved SVR. In the non-PSE group, only three patients infected with genotype 2 achieved SVR. Two patients in the PSE group and one in the non-PSE group discontinued the combination therapy. Three patients of the PSE group and five of the non-PSE group reduced the dose of pegylated IFN-α-2b because of thrombocytopenia. In the PSE group, platelet counts during the combination therapy fell to baseline levels; however, they did not fall to lower levels than baseline levels. In the non-PSE group, platelet counts 1 month after the initiation of the therapy were lower than baseline levels. Conclusion: The increase of platelet counts after PSE may allow the safe use of IFN and RBV and improve the SVR rate in chronic hepatitis C patients with thrombocytopenia. [ABSTRACT FROM AUTHOR]

Aim: Longstanding cirrhosis has been recognized as a risk factor for the development of hepatocellular carcinoma in patients with autoimmune hepatitis (AIH). Thus, the accurate determination of cirrhosis is important for prognostication, decisions regarding treatment and monitoring of disease progression. The aim of this study was to identify independent predictors of cirrhosis and to develop a model for estimating cirrhosis in patients with type 1 AIH. Methods: Using the training sample, consisting of 121 patients with type 1 AIH, we retrospectively examined independent predictors of cirrhosis and constructed a model for estimating cirrhosis. Validation was prospectively performed in the validation sample, consisting of 35 patients. Results: Using a stepwise multiple linear regression analysis, three predictors of serum immunoglobulin A level, ratio of aspartate aminotransferase to alanine aminotransferase, and platelet count were elicited, and a model for estimating cirrhosis was determined as follows: risk score = −0.113 + 0.0006056 × immunoglobulin A (mg/dL) + 0.155 × ratio of aspartate aminotransferase to alanine aminotransferase − 0.007079 × platelet (×104/mm3). In the training sample, the sensitivity and specificity were 90% and 83%, respectively, when patients presenting a risk score ≥0.20 were estimated to be cirrhotic. When this model was applied to the validation sample, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 83%, 97%, 83%, 97% and 94%, respectively. Conclusion: It is suggested that this model could be useful for the estimation of cirrhosis in patients with type 1 autoimmune hepatitis. [ABSTRACT FROM AUTHOR]

Aim: Human leukocyte antigen (HLA) DR status affects the clinical features of autoimmune hepatitis. In Caucasians, patients with DR3 have poorer outcomes. In Japan, the relationship between HLA DR status and clinical features has yet to be fully examined. Methods: We investigated 79 patients with type 1 autoimmune hepatitis who underwent liver biopsy and were screened for HLA DR status by the polymerase chain reaction sequence specific oligonucleotide hybridization method. Results: Fifty-five patients had DR4 and 23 had DR2. Thirteen patients had both DR2 and DR4. None had DR3. Of patients aged <30 years, 70% did not have DR4. A tendency toward higher serum levels of immunoglobulin G was seen in patients with DR4 compared to those without, while patients with neither DR2 nor DR4 had lower serum levels of immunoglobulin G than those with only DR2 and those with only DR4. Patients with DR2 had a lower frequency of concurrentautoimmune disease. Concurrence of thyroid disease was seen only in patients with DR4. The cumulative incidental rate of the normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was not associated with HLA DR status. Conclusion: HLA DR status is considered to affect the clinical features of Japanese patients with type 1 autoimmune hepatitis. Japanese patients with DR2 may have different clinical features from others. In addition, diagnoses of type 1 autoimmune hepatitis should be made carefully in Japanese patients with neither DR2 nor DR4 and in those aged <30 years. [ABSTRACT FROM AUTHOR]

Aim: In Caucasians in northern Europe and North America, type 1 autoimmune hepatitis is characterized by susceptibility to human leukocyte antigens DR3 and DR4, and patients with zone III necrosis more frequently have an acute onset of the disease and a lower frequency of cirrhosis than those without. In Japanese patients, however, type 1 autoimmune hepatitis is primarily associated with DR4, and there are almost no DR3-positive patients. Thus, the clinical features of Japanese patients with type 1 autoimmune hepatitis and zone III necrosis may be different from those reported previously for Caucasians. Methods: We investigated 160 consecutive patients with type 1 autoimmune hepatitis (20 males and 140 females; median age, 55 years; range, 16–79 years). Results: Forty-seven patients (29%) had zone III necrosis, and these patients had lower serum levels of albumin and higher serum levels of total bilirubin, aspartate aminotransferaseand alanine aminotransferase. Histologically, zone III necrosis was found more frequently in patients with acute hepatitis than in those with chronic hepatitis. However, there was no difference in the frequency of cirrhosis between patients with and without zone III necrosis. In addition, normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was slightly more frequent in patients with zone III necrosis (95% vs. 88%). Conclusion: In Japanese patients, zone III necrosis may reflect not only acute autoimmune hepatitis, but also acute exacerbation of pre-existing chronic disease. Furthermore, patients with zone III necrosis may respond better to corticosteroid treatment than those without. [ABSTRACT FROM AUTHOR]

Background and Aim: Many patients continue to die due to the rapid development of cerebral edema and/or multiple organ failure prior to receiving a liver transplantation. Methods: We investigated the prognostic factors associated with 1-week fatal outcomes after the diagnosis of fulminant hepatic failure, which were associated with fatal outcomes prior to receiving liver transplantation, in 104 patients with non-acetaminophen-related fulminant hepatic failure. Results: With a multivariate logistic regression analysis, age (>40 years), systemic inflammatory response syndrome (SIRS) and plasma prothrombin activities (≤10%) were significantly associated with fatal outcomes at 1 week after diagnosis in 104 patients. At the time of diagnosis, 50 patients (48%) were in a state of SIRS. Significant differences were observed between patients with and without SIRS regarding the period from the initial symptoms to the diagnosis of fulminant hepatic failure, hepatic coma grade, serum alanine aminotransferase level, serum creatinine level and plasma prothrombin activity. With a multivariate logistic regression analysis, age (>40 years), cause of fulminant hepatic failure (viral hepatitis), plasma prothrombin activity (≤10%) and no administration of protease inhibitor were significantly associated with the 1-week fatal outcomes of 50 patients with SIRS. Conclusions: Patients with SIRS exhibited hepatic failure of increased severity and SIRS may reduce the probability of receiving a liver transplantation. In order to estimate the efficacy of protease inhibitor for patients with SIRS, a prospective randomized trial is required. [ABSTRACT FROM AUTHOR]

Hepatitis B virus infection is the most frequent cause of fulminant hepatic failure. Recently, systemic inflammatory response syndrome has been reported to be important in patients with fulminant hepatic failure. However, prognostic factors for fulminant hepatitis B have not been fully examined. In this study, we analyzed prognostic factors for fulminant hepatitis B in order to accurately identify patients with fatal outcomes. Of 110 consecutive patients with fulminant hepatic failure, 36 (33%) were diagnosed with fulminant hepatitis B. Five of the 36 patients received liver transplants, and we analyzed prognostic factors associated with fatal outcomes in the other 31 patients, who consisted of 15 men and 16 women with a median age of 45 (range, 20–74) years. Eleven patients (35%) survived without liver transplantation, and the remaining 20 (65%) died. Nonsurvivors were older and had a higher prevalence ratio of systemic inflammatory response syndrome than survivors. Treatments were similar between survivors and nonsurvivors. Using a multivariate Cox proportional hazard model, age (>45 years), systemic inflammatory response syndrome, and ratio of total to direct bilirubin (>2.0) were associated with fatal outcomes. In particular, 1-week and overall survival rates of patients with systemic inflammatory response syndrome at the time of diagnosis were 39% and 8%, respectively, while those of patients without systemic inflammatory response syndrome were 94% and 56%, respectively. Systemic inflammatory response syndrome strongly affects the short-term prognosis of patients with fulminant hepatitis B, and patients with systemic inflammatory response syndrome might need urgent liver transplantation. [ABSTRACT FROM AUTHOR]

Background/Aims: Autoimmune hepatitis shows a good response to immunosuppressive treatment, and the prognosis may be determined by the clinical course. The present study was conducted in order to analyze the factors contributing to the outcomes of patients with type 1 autoimmune hepatitis. Methods: Eighty-four consecutive patients with type 1 autoimmune hepatitis were followed up regularly for a median follow-up period of 70.5 months (16.2–163 months). We analyzed the prognostic factors using time-fixed and time-dependent Cox proportional hazard models. The end point was progression of the disease to decompensated liver cirrhosis. Results: Seventy-seven patients (92%) were treated with prednisolone during the follow-up period, and 11 patients (13%) developed decompensated liver cirrhosis. Using a time-dependent multivariate model, the starting dose of corticosteroid (dose of prednisolone <20mg/day), relapse within 3 months after the normalization of serum alanine aminotransferase levels with initial treatment, and elevated serum alanine aminotransferase levels during the follow-up period (>40IU/L), all showed a significant association with progression of the disease. Conclusions: The prognosis of type 1 autoimmune hepatitis on adequate immunosuppressive treatment improves when the serum alanine aminotransferase level persists at ≤40IU/L. Factors existing prior to medical treatment may not affect the prognosis. [Copyright &y& Elsevier]

The muon science facility (MUSE), along with the neutron, hadron, and neutrino facilities, is one of the experimental areas of the J-PARC project, which was approved for construction in a period from 2001 to 2008. The MUSE facility is located in the Materials and Life Science Facility (MLF), which is a building integrated to include both neutron and muon science programs. Construction of the MLF building was started in the beginning of 2004, and was completed at the end of the 2006 fiscal year. Then, we completed the installation of the primary 3 GeV proton beam-line (the so-called M2 tunnel) components in the beginning of 2007. [ABSTRACT FROM AUTHOR]

Samples from asteroid Ryugu, brought back by asteroid explorer Hayabusa2, are important for investigating the origin and evolution of the solar system. Here, we report the elemental compositions of a 123‐mg Ryugu sample determined with a nondestructive muon elemental analysis method. This method is a powerful tool for determining bulk chemical composition, including light elements such as C, N, and O. From the muonic x‐ray spectra with three carbonaceous chondrites, the relationship between the elemental composition and muonic x‐ray intensity was determined for each element. Calibration curves showed linearity, and the elemental composition of Ryugu was quantitatively determined. The results reflect the average bulk elemental composition of asteroid Ryugu owing to the large amount of samples. Ryugu has an elemental composition similar to that of Orgueil (CI1) and should be classified as CI1. However, the O/Si ratio of Ryugu is 25% lower than that of Orgueil, indicating that Orgueil may have been seriously contaminated by terrestrial materials after its fall to Earth. These results indicate that the Ryugu sample is more representative than the CI chondrites as a solid material of the solar system. [ABSTRACT FROM AUTHOR]

The amount of C in steel, which is critical in determining its properties, is strongly influenced by steel production technology. We propose a novel method of quantifying the bulk C content in steel non-destructively using muons. This revolutionary method may be used not only in the quality control of steel in production, but also in analyzing precious steel archaeological artifacts. A negatively charged muon forms an atomic system owing to its negative charge, and is finally absorbed into the nucleus or decays to an electron. The lifetimes of muons differ significantly, depending on whether they are trapped by Fe or C atoms, and identifying the elemental content at the muon stoppage position is possible via muon lifetime measurements. The relationship between the muon capture probabilities of C/Fe and the elemental content of C exhibits a good linearity, and the C content in the steel may be quantitatively determined via muon lifetime measurements. Furthermore, by controlling the incident energies of the muons, they may be stopped in each layer of a stacked sample consisting of three types of steel plates with thicknesses of 0.5 mm, and we successfully determined the C contents in the range 0.20–1.03 wt% depth-selectively, without sample destruction. [ABSTRACT FROM AUTHOR]

We report the result of a non‐destructive elemental analysis of lunar meteorites using a negative muon beam at J‐PARC. An experimental system of six Ge semiconductor detectors and a newly designed He analysis chamber (to enable quantitative analysis of Al) was used to provide a high signal‐to‐noise ratio for the detection of major elements from lunar rocks (Mg, Si, Fe, O, Ca, and Al). We performed a Monte Carlo simulation to determine the chemical compositions at two sides and the center of a sample (at depths of 0.33 and 0.96 mm below the sample surface, respectively) of the lunar meteorite DEW 12007. These results indicate that the three interior regions of DEW 12007 are likely to be 55.8:44.2, 51.4:48.6, and 54.4:45.6 wt% mixtures of anorthositic and basaltic clasts, respectively. This study is the first quantitative analysis of a heterogeneous meteorite interior using a negative muon beam. As elemental analysis using a muon beam is non‐destructive and highly sensitive to light elements, including C, N, and O, the protocols established in this study are applicable to initial characterization of returned samples from the South Pole of the Moon. [ABSTRACT FROM AUTHOR]

Objective: No salvage treatment had been established for metastatic colorectal cancer (mCRC) with mutated KRAS before the emergence of the new drugs regorafenib and TAS-102. We performed a phase II study of third-line chemotherapy with combined bevacizumab and S-1 for mCRC. Methods: Subjects were mCRC patients with mutated KRAS who showed disease aggravation even after two regimens with oxaliplatin and irinotecan. Bevacizumab was given intravenously every 2 weeks, and S-1 was administered orally on days 1-28 of a 42-day cycle. The primary endpoint was disease control rate (DCR). Results: In total, 31 subjects were enrolled between August 2009 and June 2011. Three subjects in whom antitumor effects could not be evaluated were excluded. The median follow-up period was 8.6 months. The DCR was 67.9%, the response rate 0%, median progressionfree survival 3.7 months, and overall survival 8.6 months. In 30 subjects evaluated for safety, there was no treatment-related death. The most common adverse events were anorexia (grade ≥ 3, 20%), diarrhea (grade 3, 10%), and decreased hemoglobin (grade ≥ 3, 17%). Conclusions: The results suggest that third-line chemotherapy with combined bevacizumab and S-1 is safe and may delay the progression of mCRC resistant to oxaliplatin and irinotecan with mutated KRAS. [ABSTRACT FROM AUTHOR]

Purpose: Although early tumor shrinkage (ETS) is a predictor of improved overall survival (OS), the association between ETS and health-related quality of life (HRQOL) remains unclear for patients with metastatic colorectal cancer (mCRC) treated with first-line cetuximab plus chemotherapy.Methods: The data were collected from a prospective trial that assessed HRQOL using the EORTC QLQ-C30. The impact of ETS on HRQOL was estimated using a linear mixed-effects model for repeated measures.Results: ETS was achieved in 82 (64.1%) of 128 mCRC patients treated with first-line cetuximab plus chemotherapy, and these patients had a significantly longer OS than those without ETS (HR, 0.38; 95% CI, 0.20-0.72; P = .002). Asymptomatic patients with ETS had a favorable OS, while symptomatic patients without ETS had a worse OS (2-year OS rates, 77.8% vs. 42.5%). Symptomatic patients with ETS had similar outcomes as asymptomatic patients without ETS (2-year OS rates, 64.1% vs. 67.0%). For symptomatic patients, ETS was associated with improved HRQOL scores between baseline and 8 weeks: the mean changes for patients with and without ETS were 5.86 and -4.94 for global health status (GHS)/QOL, 26.73 and 3.79 for physical functioning, and 13.58 and -3.10 for social functioning, respectively. The improved HRQOL was comparable to that of asymptomatic patients without ETS. For asymptomatic patients, ETS showed a decreased deterioration in HRQOL.Conclusion: Our findings highlight the importance of ETS for HRQOL and prognostic estimates, and assessing ETS may provide clinically useful information for physicians and patients to make more informed decisions. [ABSTRACT FROM AUTHOR]

Purpose: Postoperative venous thromboembolism (VTE) is a major and potentially fatal postoperative complication of colorectal cancer surgery. However, there is uncertainty about the necessity for anticoagulant prophylaxis to prevent VTE after laparoscopic colorectal cancer surgery because of its associated relatively lower incidence. Currently, anticoagulant therapy is considered mainly for patients at high risk of the development of VTE. Focusing on proximal deep vein thrombosis (DVT)/ pulmonary embolism (PE), we aimed to identify those cases at high risk of the development of fatal VTE. Methods: We performed an exploratory retrospective analysis to identify the risk factors for postoperative proximal DVT and PE after laparoscopic colorectal cancer surgery in patients included in our prospective trial. Results: A logistic regression analysis revealed factors that could predict the onset of proximal DVT/PE in patients with colorectal cancer. Blood loss and tumor location were identified as the predictors of proximal DVT/PE. Conclusions: Patients with rectal cancer and those with excessive blood loss during colon cancer surgery must be monitored carefully for signs of VTE and especially proximal DVT/PE, after laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Elemental analysis based on muonic X-rays resulting from muon irradiation provides information about bulk material composition without causing damage, which is essential in the case of precious or otherwise unreachable samples, such as in archeology and planetary science. We developed a three-dimensional (3D) elemental analysis technique by combining the elemental analysis method based on negative muons with an imaging cadmium telluride double-sided strip detector (CdTe-DSD) designed for the hard X-ray and soft γ -ray observation. A muon irradiation experiment using spherical plastic samples was conducted at the Japan Proton Accelerator Research Complex (J-PARC); a set of projection images was taken by the CdTe-DSD, equipped with a pinhole collimator, for different sample rotation angles. The projection images measured by the CdTe-DSD were utilized to obtain a 3D volumetric phantom by using the maximum likelihood expectation maximization algorithm. The reconstructed phantom successfully revealed the 3D distribution of carbon in the bulk samples and the stopping depth of the muons. This result demonstrated the feasibility of the proposed non-destructive 3D elemental analysis method for bulk material analysis based on muonic X-rays. [ABSTRACT FROM AUTHOR]

A novel nondestructive light element analysis method for bulk materials using muon beams was demonstrated. This method is based on the lifetime measurement of muons in a material and performed by measuring muon-decay electrons and identifying elements using the atomic number based on muon lifetimes. Muon irradiation on pure iron and two steel samples with known carbon contents was conducted to prepare a calibration curve for the quantitative analysis. We also performed a muon lifetime measurement for a Japanese sword and successfully determined its carbon content as 0.51 wt% using the calibration curve, without sample destruction. [ABSTRACT FROM AUTHOR]

Background and Aims: It still remains controversial whether gastric mucosal atrophy and intestinal metaplasia are reversible after eradication of Helicobacter pylori infection. The aims of this study were to evaluate the histological changes in gastric mucosa after H. pylori eradication during long-term follow-up periods, and to verify the propriety of H. pylori eradication for the elderly population. Methods: Two hundred and forty-one patients with H. pylori infection and 84 cases more than 60 years old were classified as the elderly group. The mean follow-up period was 101 months. A series of endoscopic examinations with five-point biopsies were performed before and every year after H. pylori eradication. We evaluated the histological grades according to the Updated Sydney System. Statistical analysis was performed using the Wilcoxon signed rank test and the Mann–Whitney U-test, and P < 0.05 was considered to be statistically significant. Results: The atrophic grades improved only at the angle in the 5th year and at all points, except for the antrum, in the 10th year after H. pylori eradication. In the elderly group, the atrophic score improved in both the 5th and 10th year. However, improvement in the younger group was achieved only in the 10th year. The metaplastic score did not change in either the 5th or 10th year after H. pylori eradication in all patients. Conclusion: Eradication of H. pylori infection improved gastric atrophy and prevented the progression of intestinal metaplasia in the elderly population during the long-term follow-up periods. H. pylori eradication for the elderly population is effective. [ABSTRACT FROM AUTHOR]

Abstract: We have produced a pulsed beam of low energy (ultra slow) polarized positive muons (LE-μ+) and performed several demonstration muon spin rotation/relaxation (μSR) experiments at ISIS RIKEN-RAL muon facility in UK. The energy of the muons implanted into a sample is tuneable between 0.1keV and 18keV. This allows us to use muons as local magnetic microprobes on a nanometre scale. The control over the implantation depth is from several nanometres to hundreds of nanometres depending on the sample density and muon energy. The LE-μ+ are produced by two-photon resonant laser ionization of thermal muonium atoms. Currently ∼15 LE-μ+/s with 50% spin polarization are transported to the μSR sample position, where they are focused to a small spot with a diameter of only 4mm. The overall LE-μ+ generation efficiency of 3×10−5 is comparable to that obtained when moderating the muon beam to epithermal energies in simple van der Waals bound solids. In contrast to other methods of LE-μ+ generation, the implantation of the muons into the sample can be externally triggered with the duration of the LE-μ+ pulse being only 7.5ns. This allows us to measure spin rotation frequencies of up to 40MHz. [Copyright &y& Elsevier]

Abstract: To make use of cadmium (Cd) as a poison structure in the liquid hydrogen moderator, various cladding methods such as explosion, heating up a solder of 70%Cd–30%Zn in Al case, cold spraying and cold rolling as well as HIP method were tested to seek the best fabrication method. Cd could be partially bonded to aluminum (Al) in all cases. The explosion method made a rather rigid bond between Al and Cd but generated a crack on Al plates behind Cd plate. Solder also bonded well with the Al case, although a part of the Al case was dissolved due to a mixture of Zn and Al. A porous Al layer on Cd plate was formed in the cold spray treatment. The applicability of the ultrasonic test is also discussed for the non-destructive defect inspection of the bonded materials. [Copyright &y& Elsevier]

Negative and positive muon-induced single-event upsets (SEUs) are studied in 20-nm bulk planar SRAMs. Muon irradiation is performed using a mono-energetic source with varying the muon energy. The energy dependence of the cross sections (CSs) of SEUs and multiple-cell upsets (MCUs) shows the significant contribution of muon capture reactions for the negative muon, as reported in previous studies. Interestingly, MCU events are found for the positive muon, in contrast to the previous studies. The CSs for the negative and positive muons are compared with that for the other terrestrial radiations: high-energy neutrons, thermal neutrons, and alpha particles. The voltage dependence of the SEU CS, together with the empirical model for charge collection, demonstrates the difference in the contributing secondary ions among the negative muon, the high-energy neutron, and the thermal neutron. The MCU events are thoroughly analyzed in terms of their ratio to the total events and their fail bit patterns. The results reveal that the MCU characteristics for the negative muon are different from that for the other terrestrial radiations due to the muon capture reactions, where parasitic bipolar effects and the isotropic emission of secondary ions are important factors. [ABSTRACT FROM AUTHOR]

In view of the fact that little analysis of the mechanism for the achievement of high resolution or a high aspect ratio in the thick-film resist process has been performed, we have studied development properties with respect to differences between the development methods employed for pattern formation using thick-film resists. This study identifies the most effective development method for thick-film resists and reports the mechanism of development. For this investigation, we use a development rate measurement system, a mask aligner, and lithography simulator to examine the dipping development method, the step puddle development method, the vibration development method, and the reverse development method. We employ a thick-film positive resist composed of diazo-naphthoquinone (DNQ) and Novolak resin, which is coated on a silicon substrate to a thickness of 24 µm. After prebaking, the coated substrate is placed in a vacuum desiccator to remove water, followed by immersion in deionized water for a fixed period. A mask pattern is transferred to the resist-coated substrate with a Mask Aligner Q4000 made by Quintel Corporation, and then the rate of development is measured. A laser microscope analysis of the result indicates that the step puddle development method gives the highest pattern resolution and sharpness, followed by the vibration development method, the dipping development method, and lastly the reverse development method. The mechanisms of the development are studied by comparing the development contrast and the energy of activation involved in each development method, and by conducting resist pattern simulations. The results indicate that the factors responsible for retarding the progression of the development process and causing a degradation of pattern profile and resolution are development inhibition due to N2 released from inside the resist during the development process, and due to products that are dissolved in the development solution. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(7): 1–13, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10141 [ABSTRACT FROM AUTHOR]

The status and prognostic value of the disagreement between physician and patient assessments of symptomatic adverse events (AEs) remain unclear for patients with metastatic colorectal cancer treated with first‐line cetuximab plus chemotherapy. Paired data on patient‐reported outcomes using the EORTC QLQ‐C30 and physician‐reported outcomes using the NCI‐CTCAE for eight symptomatic AEs (fatigue, pain, insomnia, dyspnea, constipation, appetite loss, nausea/vomiting, and diarrhea) were collected from a prospective trial assessing the relationships between treatment efficacy, AEs, and quality of life. The overall agreement rates between patient and physician reporting at 4 weeks ranged from 40.2% to 76.5% for 129 patients. The level of agreement based on Cohen's κ statistics was slight to poor for dyspnea, pain, fatigue, and insomnia, while it was moderate to fair for the remaining AEs. No clinicopathological characteristics of disagreement were found. The underreporting by physicians ranged from 12.5% (nausea/vomiting) to 56.7% (fatigue). The 2‐year overall survival (OS) rate was more favorable for patients with high agreement than for those with low agreement (71.2% vs. 46.5%, p =.016), and the agreement status was an independent factor of OS (HR, 2.31; 95% CI, 1.13–4.71; p =.022). For patients who were reported as asymptomatic by the physician, the presence of patient‐reported symptoms resulted in a trend toward poor prognostic outcomes for appetite loss, dyspnea, diarrhea, and constipation. These findings provide the clinical importance of the monitoring of patient‐reported symptoms that can be complementary to physician‐reported data to ensure more accurate clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Oxaliplatin‐induced peripheral neuropathy (OIPN) is a common adverse events that can limit a patient's quality of life during/after chemotherapy. However, no appropriate methods have been established yet for monitoring the risk of progression of OIPN. Methods: A simple assessment tool using gem clips, the CLIP test, was established and its performance in predicting the risk of progression to ≥grade 2 peripheral sensory neuropathy (CTCAE ver. 4.0) was investigated in patients receiving chemotherapy with oxaliplatin. Results: Among 101 patients included in this study, 71 patients developed CTCAE ≥grade 1 peripheral neuropathy (grade 1, n = 67; grade 2, n = 4) at a median of 63 (range, 14–259) days after the start of treatment. Of the 67 patients with grade 1 peripheral neuropathy, 17 showed progression to ≥grade 2 neuropathy after a median interval of 84 (range, 21–246) days. Of these patients, 27 showed a positive result of the CLIP test at a median of 91 (range, 14–224) days, excluding one patient who already showed a positive result of the test at the baseline. Therefore, the risk ratio for the development of CTCAE ≥grade 2 peripheral neuropathy was 8.3 in the patients who showed a positive result on the CLIP test. Multivariate analysis confirmed that a positive results on the CLIP test was significantly correlated with the risk of future development of CTCAE ≥grade 2 peripheral neuropathy (odds ratio, 9.37; P = 0.002). Conclusion: A positive result on the CLIP test predict is predictive of the risk of progression of OIPN during chemotherapy with oxaliplatin. [ABSTRACT FROM AUTHOR]

Background: Older or frail patients are often underrepresented in clinical trials for metastatic colorectal cancer (mCRC). We here assessed the efficacy and safety of 5-fluorouracil (5-FU)–leucovorin plus bevacizumab in such patients. Methods: The study (OGSG 0802) was designed as a single-arm, open-label, multicenter phase II trial. Eligible patients had mCRC and at least one of the following: an age of ≥ 65 years, an Eastern Cooperative Oncology Group performance status of 1 or 2, a serum albumin level of ≤ 3.5 g/dL, incompatibility with oxaliplatin or irinotecan, and a history of abdominal or pelvic radiotherapy. Patients received 5-FU (600 mg/m2) and l-leucovorin (200 mg/m2) on days 1, 8, and 15 together with bevacizumab (5 mg/kg) on days 1 and 15 every 4 weeks. The primary end point was objective response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival (OS), and safety. Results: Forty-one patients were enrolled and eligible. Median age was 76 years (range 56–90 years), and 51% of patients had a performance status of 0. The ORR was 36.6% [95% confidence interval (CI) 22.1–53.1%], median PFS was 9.4 months (95% CI 7.4–17.7 months), and median OS was 24.0 months (95% CI 19.9 months—not reached). The most common treatment-related adverse events of grade ≥ 3 were neutropenia (24%), anorexia (10%), leukopenia (7%), and mucositis/stomatitis (7%). There were no treatment-related deaths. Conclusion: Weekly 5-FU–leucovorin with biweekly bevacizumab may be a tolerable and effective treatment option for older or frail patients with mCRC. [ABSTRACT FROM AUTHOR]

A neutron irradiation test of static random access memories (SRAMs) was performed using a spallation neutron source at Materials and Life Science Experimental Facility (MLF) in the Japan Proton Accelerator Research Complex (J-PARC). The probability of neutron-induced single-event upsets (SEUs) was measured for 65-nm bulk and silicon on thin buried oxide (SOTB) SRAMs under neutron irradiation at the BL10 experimental facility. The measured SEU data were compared with the previous data of the same SRAMs which were measured at other irradiation facilities having different neutron spectra. The differences in the operating voltage dependence of the measured SEU probabilities are discussed with particular attention to the impact of irradiation side on SEUs. The particle and heavy ion transport code system (PHITS) simulation based on the simple sensitive volume model qualitatively reproduced the operating voltage dependence seen in the measured ratio of SEUs for the Bulk SRAM between the resin side and board side irradiations under different neutron fields. [ABSTRACT FROM AUTHOR]