Tunnel-Structured Phosphate Exhibiting High Proton Conductivity and Thermal Stability over a Wide Intermediate Temperature Range.

For the practical application of fuel cells in vehicles, it is a challenge to develop a proton solid electrolyte that coexhibits thermal stability and high proton conductivity at wide intermediate temperatures. Here, we report on the tunnel structured phosphate KNi1-xH2x(PO3)3·yH2O, which exhibits high proton conductivity at room temperature up to 500 °C, with the conductivity value reaching 1.7 × 10-2 S cm-1 at 275 °C for x = 0.18. This material, composed of the smallest cations that form the tunnel framework with face-shared (KO6) and (NiO6) chains and PO4 tetrahedral chains, retained the rigid framework up to 600 °C. Two oxygen sites of water molecules located adjacent to each other along the PO4 tetrahedral chains in the tunnel provided the proton conduction pathway. The sample maintained a conductivity of 5.0 × 10-3 S cm-1 for 10 h at 150 °C while changing the measurement atmosphere to a N2 gas flow, a 4% H2-96% Ar gas flow, and an O2 gas flow. The conductivity value at x = 0.18 obtained from the DC measurement was in the order of 10-6 S cm-1, close to the instrument's measurement limit. These results demonstrate that tunnel phosphate has potential as a proton solid electrolyte for next-generation fuel cells.

Monte carlo simulation study on the dose and dose-averaged linear energy transfer distributions in carbon ion radiotherapy.

Dose-averaged linear energy transfer (LETd) is conventionally evaluated from the relative biological effectiveness (RBE)-LETd fitted function used in the treatment planning system. In this study, we calculated the physical doses and their linear energy transfer (LET) distributions for patterns of typical CIRT beams using Monte Carlo (MC) simulation. The LETd was then deduced from the MC simulation and compared with that obtained from the conventional method. The two types of LETd agreed well with each other, except around the distal end of the spread-out Bragg peak. Furthermore, an MC simulation was conducted with the material composition of water and realistic materials. The profiles of physical dose and LETd were in good agreement for both techniques. These results indicate that the previous studies to analyze the minimum LETd in CIRT cases are valid for practical situations, and the material composition conversion to water little affects the dose distribution in the irradiation field.

Development of the DICOM-based Monte Carlo dose reconstruction system for a retrospective study on the secondary cancer risk in carbon ion radiotherapy.

Objective.A retrospective study on secondary cancer risk on carbon ion radiotherapy (CIRT) is ongoing at the Heavy Ion Medical Accelerator in Chiba (HIMAC). The reconstruction of the whole-body patient dose distribution is the key issue in the study because dose distribution only around the planning target volume was evaluated in the treatment planning system.Approach.We therefore developed a new dose reconstruction system based on the Particle and Heavy Ion Transport code System (PHITS) coupled with the treatment plan DICOM data set by extending the functionalities of RadioTherapy package based on PHITS (RT-PHITS). In the system, the geometry of patient-specific beam devices such as the range shifter, range compensator, and collimators as well as the individual patient's body are automatically reconstructed. Various functions useful for retrospective analysis on the CIRT are implemented in the system, such as those for separately deducing dose contributions from different secondary particles and their origins.Main results.The accuracy of the developed system was validated by comparing the dose distribution to the experimental data measured in a water tank and using a treatment plan on an anthropomorphic phantom.Significance.The extended RT-PHITS will be used in epidemiological studies based on clinical data from HIMAC.

First experimental verification of the neutron field of Nagoya University Accelerator-driven neutron source for boron neutron capture therapy.

As the commissioning phase of the Nagoya University Accelerator-driven Neutron Source for boron neutron capture therapy, in-phantom thermal neutron flux measurements were conducted using a small 6LiF/Eu:CaF2 scintillator detector and activation foils. The spatial distribution of the measured thermal neutron flux agreed with the Monte Carlo simulation results. Based on this comparison, the free-in-air neutron spectrum, calculated at the exit aperture, was verified and the epithermal neutron flux, at a 0.25 mA proton current, was evaluated as (1.49 ± 0.10) × 107 n/(cm2 s).

Noninvasive diagnosis of liver fibrosis: utility of data mining of both ultrasound elastography and serological findings to construct a decision tree.

OBJECTIVE: Although liver biopsy is the gold standard for viral liver disease management, it is invasive and the sampling error rate is problematic. Real-time tissue elastography (RTE), a recently developed method of ultrasound elastography, can be used to assess liver fibrosis noninvasively but the overlap between fibrosis stages limits its ability to assess liver fibrosis adequately when used alone. METHODS: A multicenter collaborative study involving 542 patients with chronic viral hepatitis and cirrhosis who were scheduled to undergo liver biopsy compared the image features obtained from RTE image analysis, the liver fibrosis index (LFI), and pathological diagnosis. RTE and a blood test were performed on the same day as the liver biopsy. Data mining was also performed to construct a decision tree, and its diagnostic performance for assessing liver fibrosis was evaluated. RESULTS: The LFI was higher in patients with chronic hepatitis C (CHC) than in those with chronic hepatitis B (CHB). When a decision tree was constructed by data mining of RTE and serological findings, the diagnostic accuracy was very high for all fibrosis stages, with respective rates at F1, F2, F3, and F4 of 94.4, 54.1, 38.7, and 81.3% for patients with CHC and of 97.1, 50.0, 43.8, and 80.6% for patients with CHB. CONCLUSIONS: The variation in LFI values between the different etiologies appears to reflect the difference in the development style of liver fibrosis. The decision tree for assessing liver fibrosis constructed by data mining of both RTE and serological findings had a high diagnostic performance in assessing liver fibrosis and shows promising clinical utility.

Effect of vitamin K2 on the recurrence of hepatocellular carcinoma.

UNLABELLED: Hepatocellular carcinoma (HCC) is characterized by frequent recurrence, even after curative treatment. Vitamin K2, which has been reported to reduce HCC development, may be effective in preventing HCC recurrence. Patients who underwent curative ablation or resection of HCC were randomly assigned to receive placebo, 45 mg/day, or 90 mg/day vitamin K2 in double-blind fashion. HCC recurrence was surveyed every 12 weeks with dynamic computed tomography/magnetic resonance imaging, with HCC-specific tumor markers monitored every 4 weeks. The primary aim was to confirm the superiority of active drug to placebo concerning disease-free survival (DFS), and the secondary aim was to evaluate dose-response relationship. Disease occurrence and death from any cause were treated as events. Hazard ratios (HRs) for disease occurrence and death were calculated using a Cox proportional hazards model. Enrollment was commenced in March 2004. DFS was assessed in 548 patients, including 181 in the placebo group, 182 in the 45-mg/day group, and 185 in the 90-mg/day group. Disease occurrence or death was diagnosed in 58, 52, and 76 patients in the respective groups. The second interim analysis indicated that vitamin K2 did not prevent disease occurrence or death, with an HR of 1.150 (95% confidence interval: 0.843-1.570, one-sided; P=0.811) between the placebo and combined active-drug groups, and the study was discontinued in March 2007. CONCLUSION: Efficacy of vitamin K2 in suppressing HCC recurrence was not confirmed in this double-blind, randomized, placebo-controlled study.

Measurement of serum hepcidin-25 levels as a potential test for diagnosing hemochromatosis and related disorders.

BACKGROUND: Iron overload syndromes include a wide spectrum of genetic and acquired conditions. Recent studies suggest suppressed hepcidin synthesis in the liver to be the molecular basis of hemochromatosis. However, a liver with acquired iron overload synthesizes an adequate amount of hepcidin. Thus, hepcidin could function as a biochemical marker for differential diagnosis of iron overload syndromes. METHODS: We measured serum iron parameters and hepcidin-25 levels followed by sequencing HFE, HJV, HAMP, TFR2, and SLC40A1 genes in 13 Japanese patients with iron overload syndromes. In addition, we performed direct measurement of serum hepcidin-25 levels using liquid chromatography-tandem mass spectrometry in 3 Japanese patients with aceruloplasminemia and 4 Italians with HFE hemochromatosis. RESULTS: One patient with HJV hemochromatosis, 2 with TFR2 hemochromatosis, and 3 with ferroportin disease were found among the 13 Japanese patients. The remaining 7 Japanese patients showed no evidence for genetic basis of iron overload syndrome. As far as the serum hepcidin-25 was concerned, seven patients with hemochromatosis and 3 with aceruloplasminemia showed markedly decreased serum hepcidin-25 levels. In contrast, 3 patients with ferroportin disease and 7 with secondary iron overload syndromes showed serum hepcidin levels parallel to their hyperferritinemia. Patients with iron overload syndromes were divided into 2 phenotypes presenting as low and high hepcidinemia. These were then associated with their genotypes. CONCLUSION: Determining serum hepcidin-25 levels may aid differential diagnosis of iron overload syndromes prior to genetic analysis.

A patient with isolated adrenocorticotropin deficiency presenting with repetitive oesophageal ulcer and stenosis.

Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a potentially fatal condition that is difficult to diagnose. The authors diagnosed IAD in a patient who presented with recurrent oesophageal ulceration resulting in oesophageal stenosis. The recurrent oesophageal ulcers were due to frequent nausea and vomiting that were the presenting digestive symptoms of adrenal insufficiency. Severe hypoglycaemia during this patient's course suggested the diagnosis of adrenal insufficiency. This case is educational because digestive symptoms are the most common symptoms in patients with adrenal insufficiency, but the diagnosis of adrenal insufficiency in such patients is not easy.

[Esophagogastric variceal bleeding in a case of liver cirrhosis associated with thalassemia].

A 58-year-old man was admitted to our hospital because of hematemesis. Laboratory tests indicated microcytic hypochromic anemia and iron overload. We performed urgent endoscopic examination, and diagnosed bleeding from esophagogastric varices. Abdominal CT showed liver cirrhosis and marked splenomegaly, but no evidence of gastrorenal shunt. The varices were treated by Hassab's operation and splenectomy. Pathologic examination revealed hepatocytes in the cirrhotic nodules filled with iron pigment. The cause of the liver cirrhosis was considered to be due to iron overload resulting from thalassemia. We diagnosed the cause of the microcytic anemia as thalassemia by gene analysis, which revealed heterozygosity of a deletion (deltabeta thalassemia Jpn-type II) and one point mutation (-31A-->G).

[A case of portal vein thrombosis associated with congenital protein S deficiency].

A 25-year-old man was admitted to our hospital because of abdominal pain, nausea and low-grade fever. An abdominal CT showed remarkable thickening of the wall of the small intestine and extensive thrombosis of the mesenteric, portal and splenic veins. Because neither intestinal infarction nor peritonitis was seen, anticoagulation therapy was chosen. Heparin was administered intravenously and was used alternatively with warfarin later. The patient's symptoms and clinical data improved gradually. Concerning the etiological factors of the thrombosis, only protein S activity definitely decreased. Genetic analysis indicated a variant of protein S, protein S Tokushima.

[A case of gastrointestinal stromal tumor with liver and bone metastases effectively treated with radiofrequency ablation and imatinib mesylate].

A 58-year-old man was admitted because of perforation of the small intestine by a gastrointestinal stromal tumor (GIST). First, the small intestine including a GIST was resected; and then 2 month later, a part of the liver (S5) conforming to metastatic lesion was surgically removed. Twelve months later, another liver metastases was found, and surgical treatment was recommended; but the patient requested non-surgical therapy, so a radiofrequency ablation (RFA) was successfully performed. After that, recurrence of liver metastasis was not observed, but another metastasis was observed on the fifth lumbar vertebra; so administration of imatinib mesylate was started. 28 months after the initial administration the metastatic liver lesion was still invisible, and the bone metastatic lesion had not grown. The patient is alive with good performance status. This report shows that multi-modality therapy by surgery, RFA and imatinib mesylate was effective for liver and bone metastases of GIST.

Endoscopic color Doppler ultrasonographic evaluation of recurrent esophagogastric varices following endoscopic injection sclerotherapy.

BACKGROUND: Endoscopic injection sclerotherapy (EIS) for treatment of esophagogastric varices is well established in Japan. However, varices may still recur unpredictably following EIS. We studied this problem using endoscopic color Doppler ultrasonography (ECDUS) and specifically examined esophagogastric blood flows. METHODS: Prophylactic EIS was performed by intravariceal injection of 5% ethanolamine oleate (EO) in 49 patients with esophageal varices secondary to liver cirrhosis. No patient had documented hepatocellular carcinoma (HCC) before EIS, and patients who developed HCC during follow-up were excluded. We performed ECDUS before EIS, and 2 weeks and 2 years later. The esophagogastric intra- and extramural venous blood flows, including flow in the azygos vein, were compared between these observations. Gastric intramural blood flow and changes in extramural gastric blood flow, including the azygos vein flow, were scored. Dynamic computer tomography (CT), ultrasonography (US), and color Doppler-ultrasonography (CDUS) were also performed before EIS and 1 month following the procedure. Thereafter, patients underwent CT and US examinations every 6 months for 2 years to detect any development of porto-systemic shunts or HCC. RESULTS: The average number of EIS procedure per patient was 3.1+/-0.8 (mean+/-SD), and the total amount of sclerosant injected was approximately 33.5+/-6.5 ml. The overall recurrence rate over the 2-year follow-up was 36.7%. The gastric intra- and extramural blood flows did not differ between those patients with or without major shunts before EIS. In patients with recurrent variceal formation, the gastric intramural blood flow score following EIS (2.1+/-0.5) was significantly higher than that in patients without recurrence (0.8+/-0.6) (P<0.01). In addition, gastric extramural blood flow score following EIS (0.8+/-0.6) was significantly lower in patients with recurrence than that in those without recurrence (1.7+/-0.5) (P<0.01). The same differences held after exclusion of patients with major shunts. The gastric intramural blood flow score in patients with recurrent variceal formation (2.1+/-0.4) was significantly higher than that in patients without recurrence score (P<0.01). Moreover, gastric extramural blood flow score in patients with recurrent variceal formation (1.0+/-0.7) was significantly lower than in patients without recurrence (1.6+/-0.5) (P<0.01). CONCLUSIONS: Two characteristics were observed in patients with recurrent cases of esophageal varices 2 weeks following EIS. The first was the maintenance of gastric intramural blood flow. The second was the absence of dilation of the gastric extramural blood vessels. These observations may enable us to predict the recurrence of esophagogastric varices using ECDUS within 2 weeks following EIS.