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AIM Type IV collagen 7S (T4C7S) is a valuable biomarker for detecting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). The conventional T4C7S measurement via radioimmunoassay (T4C7S RIA) has shortcomings of radioisotope usage and longer assay periods. We compared T4C7S RIA with a newly developed, fast T4C7S chemiluminescent enzyme immunoassay (T4C7S CLEIA) and examined the diagnostic accuracies of and correlation between the two techniques. METHODS We evaluated 170 biopsy-confirmed patients with NAFLD. T4C7S was measured via both T4C7S RIA and T4C7S CLEIA. The correlation between T4C7S RIA and T4C7S CLEIA was analyzed in 305 total serum samples via exploratory research and 47 validation samples. The diagnostic accuracies of T4C7S CLEIA and T4C7S RIA were compared in the sera of patients with NAFLD and test samples. RESULTS Sera T4C7S levels of T4C7S CLEIA and T4C7S RIA significantly correlated in patients' samples via exploratory (r = 0.914, P = 0.000) and validation (r = 0.929, P = 0.000) research. At a 10% coefficient, T4C7S CLEIA concentration was 0.26 ng/ml in the serum samples, indicating high accuracy at even low concentrations. T4C7S CLEIA revealed distinct changes between each stage and high sensitivity in detecting the F2 stage, indicating a higher sensitivity in detecting low fibrosis stages than T4C7S RIA in patients with NAFLD. CONCLUSIONS The T4C7S CLEIA correlated well with the T4C7S RIA. Favorably, the T4C7S CLEIA has a higher sensitivity and rapid measurement time and requires a small sample volume; thus, it is a promising and popular biomarker for fibrosis stage diagnosis in NAFLD.

The detailed mechanism underlying diabetic chorea remains uncertain. We present a male patient with recurrent diabetic hemichorea with late-onset reduced arm swing. We explored the association between hyperglycemia, changes in neurological manifestations, and brain magnetic resonance imaging findings. Hyperglycemic control did not prevent the following progressive structural changes in the putamen. Slow progressive structural changes in the putamen may lead to the recurrence of chorea and the appearance of late-onset reduced arm swing. We speculated that hyperglycemia-related vasculopathy and subsequent structural changes in the putamen may play a crucial role in diabetic chorea.

To prevent heatstroke among firefighters, an activity support system that visualizes the biometric data of firefighters has been proposed. The antenna must be capable of transmitting and receiving irrespective of the situation on the back of the antenna because the repeater may be used near a bulkhead or an obstacle in the building during system operation. In this study, a prototype antenna with an artificial magnetic conductor (AMC) was fabricated and investigated to reduce the influence of the back of the antenna. The results demonstrated that the antenna with AMC had a good maximal realized gain and impedance matching in 1.9 GHz band. In addition, it was possible to prevent the degradation of the maximal realized gain, even when the antenna was placed on a metal plate.

Heterogeneous packaging is one of the advanced technologies. Especially for high-end applications such as data center server, HPC and Artificial-Intelligence (AI), High-Bandwidth Memory (HBM) integration is a key and strongly required. As we know, the 2.5D silicon interposer packaging is an expanded solution for HBM interconnections. However, we developed 2.1D high density organic package called i-THOP® (integrated-Thin film High density Organic Package) to take advantages of an organic solution. Furthermore, we are now focusing on 2.3D i-THOP® to have more benefits in the manufacturing. The 2.3D structure consists of two substrates. One is a thin i-THOP® interposer, the other one is a conventional build-up (BU) substrate. These two substrates are combined as the interposer placed onto the build-up substrate. In this paper, the electrical properties of 2.3D i-THOP® are studied to confirm the possibility of the 2.3D structure organic packages from the perspective of signal and power integrity. Firstly, the signal integrity between two devices is simulated, comparing the differences between i-THOP® and the 2.5D silicon interposer. Secondly, the signal integrity in die-to-substrate vertical interconnection is simulated, comparing between 2.1D, 2.3D i-THOP® and the 2.5D silicon interposer. Finally, as for the power delivery point of view, power distribution network (PDN) impedance is compared between 2.1D and 2.3D i-THOP®.

Numerous biomarkers have been developed for assessing the presence and severity of liver fibrosis associated with non-alcoholic fatty liver disease (NAFLD). Fibrosis can be assessed by liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE). Here we examined whether diagnostic accuracy and applicability can be further improved by combining various biomarker measurements with LSM. A total of 278 patients with biopsy-confirmed Japanese NAFLD patients were enrolled. Area under the receiver operator characteristic curve (AUROC) was evaluated for obtaining the optimum interpretation criteria for LSM by VCTE and comparing various biomarkers alone and in combination with LSM. Liver stiffness measurements including cases with interquartile range (IQR)/median (M)

Although several studies have demonstrated correlation between white matter hyperintensities (WMH) and impairment of executive functions, the underlying anatomical-functional relationships are not fully understood. The present study sought to investigate the correlations between the volume of WMH and medial temporal lobe atrophy (MTA) using quantitative magnetic resonance image (MRI) and a variety of executive function assessments. A total of 91 patients ranging in age from 58 to 90 years with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or early phase AD were recruited from the outpatient clinic at the Department of Neurology of Nagoya City University Hospital. We administered neuropsychological batteries evaluating verbal memory, orientation, spatial ability, sustained attention, and a variety of executive functions, including verbal fluency, flexibility, inhibition, and working memory. Quantitative MRI analyses were performed using Dr. View/Linux software and a voxel-based specific regional analysis system. Significant correlations were observed between WMH, as well as MTA, and some executive function scores. Regression analysis revealed that MTA was the strongest predictor of flexibility and verbal fluency. These findings provide new insight into the relationship between quantitative MRI analyses and various types of executive dysfunction in elderly people with MCI due to AD and/or early phase AD. When cognitive function is examined in elderly patients with MCI due to AD or early phase AD, it is important to consider the involvement of WMH and MTA, which is indicative of AD pathology in cognitive dysfunction, particularly executive function.

A 29-year-old man presented with a high-grade fever, headache, and urinary retention, in addition to meningeal irritation and myoclonus in his upper extremities. A cerebrospinal fluid (CSF) examination showed pleocytosis and high adenosine deaminase (ADA) levels with no evidence of bacterial infection, including Mycobacterium tuberculosis. T2-weighted brain magnetic resonance imaging showed transient hyper-intensity lesions at the splenium of the corpus callosum (SCC), bilateral putamen, and pons during the course of the disease. The CSF was positive for anti-glial fibrillary acidic protein (GFAP) antibodies. He was diagnosed with autoimmune GFAP astrocytopathy. The present case shows that the combination of an elevated ADA level in the CSF and reversible T2-weighted hyper-intensity on the SCC supports the diagnosis of autoimmune GFAP encephalopathy.

A 58-year-old woman presented to our hospital with complaints of dysphagia. Esophagogastroduodenoscopy showed an esophagogastric junction tumor with multiple duodenal intramural metastases, and computed tomography showed peritoneal metastasis. In the middle of her fourth cycle of chemotherapy, she displayed symptoms of a left-sided multi-cranial nerve palsy. She was diagnosed with Garcin syndrome caused by meningeal carcinomatosis from gastric cancer based on the results of gadolinium-enhanced brain magnetic resonance imaging and cytology of the cerebrospinal fluid. It is important not to overlook meningeal irritation symptoms or paralysis of cranial nerves and to consider the possibility of Garcin syndrome caused by meningeal carcinomatosis.

Background Cross-sensitivity of rash has been reported between various antiepileptic drugs (AEDs). However, few studies have determined the frequency and management of cross-sensitivity in patients with super-refractory status epilepticus (SRSE). Aims of the study To examine the optimal AED for treating SRSE with cross-sensitivity. Methods We performed a retrospective review of adult patients with SRSE treated at Nagoya City University Hospital, in which we investigated the frequency of cross-sensitivity among patients with SRSE and their clinical and medical profiles. Results We identified 10 adult patients with SRSE, 5 of whom had cross-sensitivity. Stiripentol (STP) was administered when previously used AEDs had demonstrated cross-sensitivity and failed to control seizures. After initiation of STP, the dose of general anaesthetics was reduced, and status epilepticus (SE) eventually ceased with co-administered AEDs without additional adverse effects. The mean time to SE cessation after initiation of STP was 30.8 days (range, 18-46 days), mean duration of general anaesthesia was 101.2 days (range, 74-128 days), and mean number of AEDs was 9.0 (range, 6-11). Conclusions This study suggests that cross-sensitivity between AEDs is common in adults with SRSE and that STP may be useful for treating SRSE with cross-sensitivity.

An 85-year-old woman underwent endoscopic retrograde cholangiopancreatography (ERCP) for obstructive jaundice. Selective bile duct cannulation was unsuccessful because of periampullary diverticula (PAD). A pancreatic spontaneous dislodgement stent (PSDS) (5F diameter, 3 cm, straight type) was inserted to prevent post-ERCP pancreatitis. Three days after ERCP, she complained of abdominal pain, and computed tomography revealed retroperitoneal perforation because of PSDS migration to the PAD. If the papillary orifice is observed at the diverticular rim or in the diverticula, a pigtailed PSDS on the duodenal side or flanged stent on the pancreatic ductal side should be inserted in order to prevent this rare adverse event.

The aim of this study was to evaluate the association of functional mitral regurgitation (FMR), preserved or reduced ejection fraction (EF), and ischemic or nonischemic origin with outcomes in patients discharged alive after hospitalization for acute decompensated heart failure (HF). Of the 4,842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 3,357 patients were evaluated to assess the association of FMR, preserved or reduced EF, and ischemic or nonischemic origin with the primary end point (all-cause death and readmission for HF after discharge). At the time of discharge, FMR was assessed semiquantitatively (classified as none, mild, or moderate to severe) by color Doppler analysis of the regurgitant jet area. According to multivariable analysis, in the ischemic group, either mild or moderate to severe FMR in patients with a preserved EF had a significantly higher risk of the primary end point than patients without FMR (hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.12 to 2.29; p = 0.010 and HR 1.98; 95% CI 1.30 to 3.01; p = 0.001, respectively). In patients with reduced EF with an ischemic origin, only moderate to severe FMR was associated with a significantly higher risk of the primary end point (HR 1.67; 95% CI 1.11 to 2.50; p = 0.014). In the nonischemic group, there was no significant association between FMR and the primary end point in patients with either a preserved or reduced EF. In conclusion, among patients with acute decompensated HF with a preserved or reduced EF, the association of FMR with adverse outcomes may differ between patients who had an ischemic or nonischemic origin of HF.

Summary All residential homes in Japan have been required to install residential fire alarms since 2006. According to a survey by Tokyo Fire Department in 2011, the installation rate of residential fire alarms per household within the jurisdiction of the Tokyo Fire Department is 80.6%. The authors carried out an analysis of reports of cases, where residential fire alarms successfully worked. The information in these real fire incident reports is very useful for us to understand the actual circumstances as well as the behavior of the people involved in and nearby a fire incident. In many cases of successful activation of fire alarms for fires originating in a living room and bedroom, the occupants were likely to be in sleeping in the room of fire origin and did not become aware of the fire alarm, even if it sounded. By contrast, other family members and/or neighbors outside the room of fire origin were more likely to hear the sound and initiated the response activity to the fire incident. This indicates the potential for persons in the room of fire origin at the time of fire to be saved by others nearby because of the activation of residential fire alarms, even if they are sleeping and do not respond by themselves to the alarm sound. Copyright © 2017 John Wiley & Sons, Ltd.

Anti-N-methyl-d-aspartate receptor (NMDAR) limbic encephalitis is the most common form of paraneoplastic encephalitis that is associated with teratomas. Because tumor removal leads to better clinical outcomes, it is essential to reveal the location of the teratomas. This is the first reported case of anti-NMDAR encephalitis associated with teratoma of the fallopian tube. Salpingo-oophorectomy improved neurological symptoms and immunohistochemical examinations indicated the expression of NMDAR on neuroglial cells within the fallopian tube teratoma. Teratomas of the fallopian tube cause anti-NMDAR encephalitis; the imaging analysis and exploratory laparoscopies of the fallopian tube as well as of the ovary should be considered. Surgical removal of both fallopian tubes and ovaries with a normal appearance should be considered for patients in whom immunotherapy is not effective.

Aim Transient elastography (TE) is a noninvasive method for predicting liver fibrosis. However, there is limited data regarding the performance of TE in Japanese patients with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the association between liver stiffness measurement (LSM) by TE and liver fibrosis stage, and define a cut-off value for predicting liver fibrosis. Methods A total of 171 Japanese patients with biopsy-proven NAFLD underwent LSM using TE with FibroScan®. Area under receiver-operating characteristic curve (AUROC) of LSM and other noninvasive markers of liver fibrosis were compared to determine the most accurate method of predicting liver fibrosis. Results LSM significantly correlated with fibrosis stage (p

Aim Non-alcoholic fatty liver disease (NAFLD) can progress to non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH). We investigated the association among serum type IV collagen level, liver histology, and other fibrosis markers in NAFLD progression. Methods We evaluated 184 patients diagnosed with NAFLD following biopsy, including 89 males and 95 females with an average age of 52.6 and 62.6 years, respectively. Non-alcoholic fatty liver disease was classified as NAFL or NASH using Matteoni's classification, and the grade and stage of NASH were assessed using Brunt's classification. Serum type IV collagen was measured by a rapid and sensitive latex particle-enhanced turbidimetric immunoassay. Results Forty-two patients with NAFL and 142 patients with NASH were included in this study. Compared with patients with NAFL, patients with NASH showed more significant liver function disorder and increased expression of fibrosis markers including type IV collagen, collagen 7S, Mac2-binding protein (M2BP), and hyaluronic acid (HA). Expression of type IV collagen and collagen 7S, but not M2BP and HA, was more significantly elevated in patients with stage 1 NASH than in patients with NAFL, indicating that type IV collagen and collagen 7S may be better discriminators of NASH and NAFL than M2BP and HA at an early stage of fibrosis. When patients were stratified by NAFLD activity score, type IV collagen and collagen 7S were significantly elevated as NAFLD activity score progressed, whereas M2BP and HA expression were not significantly elevated. Conclusion Type IV collagen may be a useful measure of NASH severity as latex particle-enhanced turbidimetric immunoassay-based rapid type IV collagen assay can be carried out routinely.

A 46-year-old woman presenting to the Department of Hematology with swelling of the mandibular lymph nodes was diagnosed with angioimmunoblastic T-cell lymphoma (AITL) in June 2013. The patient went into complete remission in December 2013 with chemotherapy; however, she was re-evaluated because of mental confusion during May 2014. In addition to the memory disturbances, elevated cerebrospinal fluid cell count and protein were noted. Fluid attenuated inversion recovery cranial magnetic resonance imaging revealed multiple hyperintense areas in both the mammillary bodies and thalamus accompanied by contrast-enhancing in some areas. The diagnosis of recurrent AITL was made based on the brain biopsy. AITL recurrence in the cranium should be considered in patients exhibiting central nervous system symptoms although such recurrences have not been reported previously.

Background Acute decompensated heart failure (ADHF) is a leading cause of hospitalization among the elderly. Discussion of optimal management of ADHF in older patients is a growing health care priority. The aim of this study was to examine the clinical profile, management, and mortality in patients admitted with ADHF according to age. Methods We analyzed 4824 patients enrolled in the Acute Decompensated Heart Failure Syndromes registry from April 2007 to December 2011. Patient characteristics, management, and in-hospital outcomes were compared among four age groups ( Results The mean age of the overall population was 73years; approximately 20% were aged ≥85years. Older patients were more likely to be women and have preserved left ventricular ejection fraction (LVEF) and decreased renal function. Intravenous treatments were well administered in both young and elderly patients irrespective of LVEF. Invasive procedures were less frequently performed in the eldest group. The median length of hospital stay was 21days, and in-hospital cardiac death in the eldest group was four-fold higher than that in the youngest group (2.2% vs. 8.9%, P Conclusions Clinical characteristics of ADHF differ considerably with age, and cardiac death increases linearly with age. Despite a higher rate of preserved systolic function in very-elderly individuals aged ≥85years, in-hospital mortality was higher, suggesting that more suitable treatments for the elderly might be needed.

It is important that patients with nonalcoholic steatohepatitis (NASH) are diagnosed and treated early to prevent serious complications, such as liver cirrhosis or hepatocellular carcinoma. However, current methods for NASH diagnosis are invasive given that they rely on liver biopsy, making early diagnosis difficult. In this study, we developed novel noninvasive markers for the diagnosis of NASH and NASH-related fibrosis. A total of 132 Japanese patients with nonalcoholic fatty liver disease were included in this study. Blood samples were collected, and 261 biomolecules were quantified in serum. Using cluster and pathway analyses, we identified biomolecule modules connected to biological events that occur with disease progression to NASH. The modules were used as variables for diagnosis, leading to a NASH diagnostic marker associated with two biological events, that is, protective response to hepatic steatosis and hepatitis-causing innate immune response. Regarding the NASH-related fibrosis marker, immunological responses to hepatocyte injury were identified as a biological event. To develop diagnostic markers for NASH and NASH-related fibrosis, specific biomolecules were selected from each biomolecule module. The former marker was obtained by averaging the levels of four biomolecules, whereas the latter was obtained by averaging the levels of two biomolecules. Both markers achieved a diagnostic accuracy of almost 0.9 of the area under the receiver operating characteristic curve, and the latter exhibited equivalent performance in an independent group of 62 prospectively recruited patients. Conclusion: We developed highly accurate markers for the diagnosis of both NASH and NASH-related fibrosis (i.e., FM-NASH index and FM-fibro index, respectively). These markers may be used as an alternative diagnostic tool to liver biopsy. (Hepatology 2016;63:462–473)

The genetic factors affecting the natural history of nonalcoholic fatty liver disease (NAFLD), including the development of nonalcoholic steatohepatitis (NASH) and NASH-derived hepatocellular carcinoma (NASH-HCC), are still unknown. In the current study, we sought to identify genetic factors related to the development of NAFLD, NASH, and NASH-HCC, and to establish risk-estimation models for them. For these purposes, 936 histologically proven NAFLD patients were recruited, and genome-wide association (GWA) studies were conducted for 902, including 476 NASH and 58 NASH-HCC patients, against 7, 672 general-population controls. Risk estimations for NAFLD and NASH were then performed using the SNPs identified as having significant associations in the GWA studies. We found that rs2896019 in PNPLA3 [p = 2.3x10-31, OR (95%CI) = 1.85 (1.67–2.05)], rs1260326 in GCKR [p = 9.6x10-10, OR (95%CI) = 1.38(1.25–1.53)], and rs4808199 in GATAD2A [p = 2.3x10-8, OR (95%CI) = 1.37 (1.23–1.53)] were significantly associated with NAFLD. Notably, the number of risk alleles in PNPLA3 and GATAD2A was much higher in Matteoni type 4 (NASH) patients than in type 1, type 2, and type 3 NAFLD patients. In addition, we newly identified rs17007417 in DYSF [p = 5.2x10-7, OR (95%CI) = 2.74 (1.84–4.06)] as a SNP associated with NASH-HCC. Rs641738 in TMC4, which showed association with NAFLD in patients of European descent, was not replicated in our study (p = 0.73), although the complicated LD pattern in the region suggests the necessity for further investigation. The genetic variants of PNPLA3, GCKR, and GATAD2A were then used to estimate the risk for NAFLD. The obtained Polygenic Risk Scores showed that the risk for NAFLD increased with the accumulation of risk alleles [AUC (95%CI) = 0.65 (0.63–0.67)]. Conclusions: We demonstrated that NASH is genetically and clinically different from the other NAFLD subgroups. We also established risk-estimation models for NAFLD and NASH using multiple genetic markers. These models can be used to improve the accuracy of NAFLD diagnosis and to guide treatment decisions for patients., 非アルコール性脂肪性肝疾患（NAFLD）関連疾患の疾患感受性遺伝子を用いたリスク予測 --全ゲノム関連解析によって4つの疾患感受性遺伝子を同定--. 京都大学プレスリリース. 2018-02-15.

Sandwich panels were tested according to the ISO 13784-1 standard by the Fire Insurers Laboratories of Korea and the Korea Institute of Construction Technology in Korea, the Royal Institute of Tech...

This paper aims to explain and analyze the test results of the fire behavior of real-size bed mattress products when subjected to an open flame burner system with a total heat supply of 27 kW accor...

Host genetic factors have been suspected to influence histological liver damage in chronic liver disease. The nonsynonymous single-nucleotide polymorphism rs738409 CG in the patatin-like phospholipase domain-containing 3 gene (PNPLA3, also known as adiponutrin), encoding the I148 M protein variant, has been identified as a novel genetic marker for hepatic steatosis and fibrosis in nonalcoholic fatty liver disease and alcoholic liver disease. We aimed to determine whether the PNPLA3 rs738409 variant was associated with hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C.In a cross-sectional study in Japan, we analyzed 276 patients with chronic hepatitis C who underwent liver biopsy. Genotyping for rs738409 was performed using the TaqMan genotyping assay.The frequencies of the rs738409 CC, CG, and GG genotypes were 32.6, 46.4, and 21.0 %, respectively. Multivariate analysis revealed that the GG genotype was independently associated with the presence of steatosis [odds ratio (OR) 2.58, 95 % confidence interval (CI) 1.37-4.84, p = 0.003], severe necroinflammatory activity (OR 2.16, 95 % CI 1.12-4.16, p = 0.02), and advanced fibrosis (OR 2.10, 95 % CI 1.07-4.11, p = 0.03), after adjustment for age, sex, body mass index, and diabetes.The PNPLA3 rs738409 variant influences histological liver damage in Japanese patients with chronic hepatitis C. The G allele homozygotes are at higher risk for hepatic steatosis, severe necroinflammation, and advanced fibrosis.

A diagnostic marker is needed enabling early and specific diagnosis of hepatocellular carcinoma (HCC) associated with non-alcoholic steatohepatitis (NASH). Our recent findings have indicated that circulating apoptosis inhibitor of macrophage (AIM), which usually associates with IgM pentamer in the blood, is activated by its dissociation from IgM. We investigated the serum levels of IgM-free AIM for AIM activation and its possible relationship with development of HCC in NASH. Serum levels of IgM-associated and IgM-free AIM were evaluated in patients with non-alcoholic fatty liver, NASH, and NASH-HCC using enzyme-linked immunosorbent assays and immunoblots. Liver biopsy specimens were graded and staged using Brunt’s classification. Forty-two patients with fatty liver, 141 with NASH, and 26 with NASH-HCC were evaluated. Patients with stage 4 or grade 3 NASH (with or without HCC) exhibited significantly higher levels of both IgM-free and total AIM than those with fatty liver, whereas the ratio of IgM-free-to-total AIM was equivalent in these groups. Among patients with the same fibrosis stage of NASH, those with HCC had significantly higher IgM-free but not total AIM levels, resulting in a proportional increase in the IgM-free/total AIM ratio. Analysis of the areas under the receiver operating characteristic curves indicated the high sensitivity of the IgM-free AIM for NASH-HCC. Our observations suggest the activation of AIM in blood in the presence of NASH-HCC, with a significant increase in IgM-free AIM levels. IgM-free AIM serum levels appear to be a sensitive diagnostic marker for NASH-HCC.

Aim Although non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, the clinical association between non-alcoholic steatohepatitis (NASH) and lifestyle-related diseases such as obesity, type 2 diabetes mellitus (DM), hypertension (HT) and dyslipidemia (DL) has not been clarified. We studied the influence of lifestyle-related diseases and age on the development and progression of NAFLD. Methods We enrolled 550 patients with biopsy-proven NAFLD (284 men, 266 women; average age, 52 and 62 years, respectively). The effect of lifestyle-related diseases and age (≤49 vs ≥50 years) on the frequency of NASH and advanced fibrosis (≥stage 3) was studied. Results Prevalence of obesity, DM, HT and DL in male and female NASH patients was 75%/67%, 53%/54%, 66%/77% and 85/79%, respectively. DM patients had a higher frequency of NASH in the older male NAFLD group and a higher frequency of advanced fibrosis in the older female NASH group. With the increasing number of complicating lifestyle-related diseases, the rate of NASH increased in male NAFLD patients. In both sexes, aging resulted in the development of NASH and progression of liver fibrosis. Multivariate logistic regression analysis revealed that age and DM were significantly associated with the development of NASH in male NAFLD patients and progression of fibrosis in female NASH patients. Conclusion Age is strongly associated with the development and progression of NASH. Type 2 DM may play the most crucial role among lifestyle-related diseases in the development and progression of NASH.

Aim Sorafenib is the standard systemic therapy for patients with advanced hepatocellular carcinoma (HCC). We aimed to assess the efficacy and safety of sorafenib therapy in very elderly patients aged 80 years and older with advanced HCC. Methods In a retrospective multicenter study in Japan, we reviewed 185 patients (median age, 71 years; 82% male; 95% Child–Pugh class A) with advanced HCC who received sorafenib therapy. Data were compared between 24 (13%) patients aged 80 years and older and 161 (87%) patients aged less than 80 years. We used propensity score matching to adjust for differences between the two groups. Results Median overall survival was 10.6 months in all patients: 11.7 months in patients aged 80 years and older and 10.5 months in those aged less than 80 years. There were no significant differences in overall survival, tumor response, and frequency and severity of drug-related adverse events between patients aged 80 years and older and those aged less than 80 years in both the entire study cohort and the propensity-matched cohort. Conclusion Sorafenib may be effective and well tolerated, even in patients with advanced HCC who are aged 80 years and older, as well as those aged less than 80 years.

Background Randomized controlled trials concerning pulmonary artery catheters (PACs) use have yielded little evidence of their beneficial effects on survival. This study aimed to evaluate the association between PACs and in-hospital mortality in patients with acute heart failure syndromes (AHFS). Methods The Acute Decompensated Heart Failure Syndromes (ATTEND) Registry is a prospective, observational, multicenter cohort study performed in Japan, since April 2007. We analyzed data from the ATTEND Registry and evaluated the effectiveness of PAC in AHFS treatment using propensity score-matching and the Cox proportional hazards model. Results Final follow-up examinations of the 4842 patients were conducted in December 2012. During the study period, 813 patients (16.8%) were managed with PACs, of which 502 patients (PAC group) were propensity score-matched with 502 controls (Control group). Of the 1004 score-matched patients, 22 (4.4%) patients from the Control group and 7 (1.4%) from the PAC group died. The risk of all-cause death was lower in the PAC group than that in the Control group [hazard ratio (HR), 0.3; 95% confidence interval (CI), 0.13–0.70; p=0.006]. PAC-guided therapy decreased all-cause mortality in patients with lower systolic blood pressure (SBP≤100mmHg; HR, 0.09; 95% CI, 0.01–0.70; p=0.021) or inotropic therapy (HR, 0.22; 95% CI, 0.08–0.57; p=0.002). Conclusions This study revealed that appropriate PAC use effectively decreases in-hospital mortality in AHFS patients, particularly those with lower SBP or receiving inotropic therapy, suggesting that real-world PAC use could improve AHFS management.

Hyponatremia is known to be a poor prognostic factor in patients hospitalized with heart failure (HF), however not well studied in Japan. The aims of this study were to characterize hyponatremic hospitalized patients with HF and to clarify the relations between hyponatremia and detailed in-hospital outcomes in Japan. Among 4,837 hospitalized patients with HF enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, patient characteristics and in-hospital mortality in those with hyponatremia were examined. Hyponatremia (sodium

Recently we reported novel noninvasive scoring systems for diagnosing nonalcoholic steatohepatitis (NASH) and related fibrosis, namely FM-NASH index and FM-fibro index. They are highly accurate, however, they contain some items not widely used in clinical practice and require six or more items to diagnose both NASH and related fibrosis. By focusing on widely used items, we tried to identify convenient markers in common with the both diagnoses. To explore the markers for NASH and related fibrosis in nonalcoholic fatty liver disease (NAFLD) patients, we used data of 24 clinical items in our previous report. By logistic regression analysis, we identified items suitable for the both diagnoses. We then evaluated their accuracies by area under the receiver operator characteristic curves (AUROCs) on independent validation data. We identified the combination of type IV collagen 7S and aspartate aminotransferase (AST) as the predictor both for NASH and related fibrosis. We developed a scoring system based on the combination and evaluated the prediction accuracy: the AUROCs for training/validation data sets are 0.857/0.769 for NASH and 0.918/0.842 for NASH-related fibrosis. The former was higher than that of NAFIC score, and the latter was higher than those of existing fibrosis markers: BARD score, FIB-4 index and NAFLD fibrosis score but lower than FM-fibro index. The scoring system using type IV collagen 7S and AST named CA index can predict both NASH and related fibrosis in NAFLD patients with sufficient accuracy and could be a convenient diagnostic and screening tool for NASH and related fibrosis. The scoring system needs to be validated in independent larger populations from multiple clinical centers.

The Japan Society of Diabetes Mellitus reported that the leading cause of death in patients with diabetes mellitus (DM) was chronic liver disease; however, there are limited studies investigating the cause of liver injury in these patients. Our study aimed to clarify the clinicopathological features of liver injury and the characteristics of nonalcoholic fatty liver disease (NAFLD) in DM patients. In total, 5,642 DM patients and 365 histologically proven NAFLD patients were enrolled. Clinical and laboratory parameters and liver biopsy results were, respectively, recorded and analyzed for the two sets of patients. Positivity rates for Hepatitis B surface antigens (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV Ab) were 1.7 and 5.1 %, respectively. The proportion of drinkers consuming 20–59 g and ≥60 g alcohol daily was 14.9 and 4.3 %, respectively. The percentage of DM patients with elevated serum alanine aminotransferase (ALT) levels (≥31 IU/L) was 28.6 %. Alcohol consumption had no significant effect on serum ALT levels. Seventy-two percent of HBsAg-positive patients were serum hepatitis B virus (HBV)-DNA negative, whereas 10 % exhibited high levels of the same (>4.0 log copies/ml). Thirty-eight percent of anti-HCV Ab-positive patients were serum HCV-RNA negative. Among the NAFLD patients, the frequencies of NASH and advanced stage NASH were significantly higher in male DM patients than in male patients without DM. Although HBsAg- and anti-HCV Ab-positivity rates were high in our Japanese DM patients, a majority of liver injuries could be associated with NAFLD/nonalcoholic steatohepatitis.

While recent guidelines for the treatment of acute heart failure syndromes (AHFS) recommend pharmacotherapy with vasodilators in patients without excessively low blood pressure (BP), few reports have compared the relative efficiency of vasodilators on hemodynamics in AHFS patients. The present study aimed to assess the differences in hemodynamic responses between intravenous carperitide and nicorandil in patients with AHFS. Thirty-eight consecutive patients were assigned to receive 48-h continuous infusion of carperitide (n = 19; 0.0125-0.05 μg/kg/min) or nicorandil (n = 19; 0.05-0.2 mg/kg/h). Hemodynamic parameters were estimated at baseline, and 2, 24, and 48 h after drug administration using echocardiography. After 48 h of infusion, systolic BP was significantly more decreased in the carperitide group compared with that in the nicorandil group (22.1 ± 20.0 % vs 5.3 ± 10.4 %, P = 0.003). While both carperitide and nicorandil significantly improved hemodynamic parameters, improvement of estimated pulmonary capillary wedge pressure was greater in the carperitide group (38.2 ± 14.5 % vs 26.5 ± 18.3 %, P = 0.036), and improvement of estimated cardiac output was superior in the nicorandil group (52.1 ± 33.5 % vs 11.4 ± 36.9 %, P = 0.001). Urine output for 48 h was greater in the carperitide group, but not to a statistically significant degree (4203 ± 1542 vs 3627 ± 1074 ml, P = 0.189). Carperitide and nicorandil were differentially effective in improving hemodynamics in AHFS patients. This knowledge may enable physicians in emergency wards to treat and manage patients with AHFS more effectively and safely.

A small-size on-chip transformer-based digital isolator for power control systems is proposed. With a proposed pulse generation and detection scheme that enables a 5 V standard CMOS transistor to utilize GHz-band signals, transformer area is reduced to 1/4-1/8 that of conventional transformers. A test chip achieves a 2.5 kV isolation voltage, a 35 kV/us CMR, a 1.6 mA static current and a 250 Mbps data rate, all which are equal to or superior to those of optocouplers or conventional digital isolators. The developed technology greatly reduces the number of chips in power control systems by allowing integration of multiple isolators in a CMOS chip together with microcontrollers or gate drivers. Moreover, the high-speed low-power capability expands the application potential to include isolated serial links, controller area network (CAN), FlexRay, medical devices, displays, sensors, etc.

We herein describe a 45-year-old man with posterior neck pain and severe dysphagia secondary to retropharyngeal calcific tendinitis. Brain stem infarction as a result of vertebral artery dissection was suspected, but head magnetic resonance imaging showed no acute ischemic lesion. Sagittal T2-weighted neck magnetic resonance imaging showed a retropharyngeal fluid collection from C2 to C8, and neck computed tomography showed calcification at the tendon of the longus colli muscle. Based on these characteristic imaging findings, retropharyngeal calcific tendinitis was diagnosed. Neurologists should remember that retropharyngeal calcific tendinitis can cause neck pain and severe dysphagia, and mimic brain stem infarction as a result of vertebral artery dissection.

We propose a three-terminal nanometer metal switch that utilizes a solid electrolyte where a nanoscale metal filament is stretched and retracted. Its operating principle is based on electrochemical reaction and ion migration in the electrolyte. The fabricated device is composed of a solid electrolyte layer (Cu2S), a gate (Cu), a source (Cu), and a drain (Pt). After the Cu filament is formed between the source and the drain by applying the drain voltage, repeatable on/off switching in the drain current is obtained by controlling the gate voltage. The on/off current ratio can be as high as 105, and the programmable cycle is around 50. Each state can be kept for up to 40 days. Since the gate is separated from the current path, the switching current can be reduced to 10 μA, which is two orders of magnitude smaller than that of a two-terminal switch. In this paper, we present the operating principle and electrical characteristics of the three-terminal switches, and discuss how suitable they are for reconfigurable circuits. © 2011 Wiley Periodicals, Inc. Electron Comm Jpn, 94(4): 55–61, 2011; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.10214

Depressive symptoms have been linked to faster progression to AIDS in HIV-positive individuals. The purpose of this correlational, cross-sectional study was to examine the prevalence and predictors of depressive symptoms among postpartum women in Thailand who are HIV-positive. Data were collected at postpartum outpatient units in four hospitals in Thailand from June 2005 to December 2007. Eighty-five HIV-positive postpartum women completed questionnaires on depressive symptoms, self-esteem, emotional support, physical symptoms, infant health status, and demographics. Results showed that 74.1% of the participants reported depressive symptoms. Self-esteem, infant health status, and education were negatively associated with depressive symptoms. Because of the high rates of depression in our study, all HIV-positive postpartum women in Thailand should be screened for depressive symptoms.

Dicode partial response signaling system over inductively-coupled channel has been developed to achieve higher data rate than self-resonant frequencies of inductors. The developed system operates at five times higher data rates than conventional systems with the same inductor. A current-mode equalization in the transmitter designed in a 90-nm CMOS successfully reshapes waveforms to obtain dicode signals at the receiver. For a 5-Gb/s signaling through the coupled inductors with a 120-µm diameter and a 120-µm distance, 20-mV eye opening was observed. The power consumption value of the transmitter was 58mW at the 5-Gb/s operation.

A 4-phase clock generator, which can dynamically change clock frequencies, duty ratios and I/Q balance, is proposed for on-chip timing margin testing. The clock generator macro is integrated into the microprocessor chip of the supercomputer SX-9, which is fabricated with a 65nm CMOS technology. It demonstrates frequency syntheses of 1.68GHz to 3GHz range, an instant frequency change capability for timing margin testing, duty ratio and I/Q balance adjustments of -12.5ps to 9.4ps with a 3.125ps step resolution.

With rapid advance of construction technology, buildings have become much larger and higher. East Asian cities also have a forest of superhigh-rise buildings backed by their economic development. With many buildings, cities changed their skylines and superhigh-rise buildings with characteristic appearance are now regarded as the landmark of the city. As superhigh-rise buildings are built by fully integrating state-of-the-art construction technology, construction of superhigh-rise buildings and formation of cities having those tall buildings represent the technological or economic strength of the nation. In fact many people believe they are the symbol of the nation. To give some examples of superhigh-rise building fires in recent years, there are cases including destruction of World Trade Center by terrorism in New York, USA in 2001, Windsor building fire in Madrid, Spain in 2005 and CCTV high-rise building fire in Beijing, China in 2009 among others. As seen in these examples, fires in superhighrise buildings often burnt down and entirely destroyed the building, and yet the overcrowding trend of cities seems to continue. Under such circumstances, South Korea entered the rush to build superhigh-rise residential buildings in 1990s mainly in Seoul starting with the construction of 30-story residential building in early 1990s. Eventually in 2000s, buildings principally designed for residential use including superhigh-rise residential and commercial complexes or officetels (buildings with units that can be used as either office or house) became higher than 70 stories. South Korea shows different tendency from other advanced nations in situations that led to build superhigh-rise buildings. The reasons are described here.

Duobinary signaling has been introduced into asymmetric multi-chip communications such as DRAM or display interfaces, which allows a controlled amount of ISI to reduce signaling bandwidth by 2/3. A x2 oversampled equalization has been developed to realize Duobinary signaling. Symbol-rate clock recovery form Duobinary signal has been developed to reduce power consumption for receivers. A Duobinary transmitter test chip was fabricated with 90-nm CMOS process. A 3.5dB increase in eye height and a 1.5 times increase in eye width was observed.

The evaluation of cranial nerves in magnetic resonance imaging (MRI) at early developmental stage has not been established in amyotrophic lateral sclerosis (ALS). A 23-year-old man with familial ALS developed peripheral facial nerve palsy, and showed the striking gadolinium enhancement on MRI in those nerves at an early stage. His symptoms progressed rapidly and he died approximately 3 months after onset. We identified a missense mutation in exon 1 of the Cu/Zn superoxide dismutase gene (SOD-1), resulting in a Cys6Gly (C6G) amino acid substitution. Based on the rapid progression and neurotoxicity resulting from SOD-1 protein aggregation, the gadolinium enhancement of facial nerves might be caused by the rapid Wallerian degeneration and blood–brain barrier disruption at the early phase of progression.

a Division of Cardiology, Sensoji Hospital, Tokyo, Japan b Internal Medicine, Cardiology, and Intensive Care Unit, Nippon Medical School Musashi-Kosugi Hospital, Kanagawa, Japan c Department of Cardiovascular Medicine, Edogawa Hospital, Tokyo, Japan d Department of Cardiology, Osaka University Graduate School of Medicine, Osaka, Japan e Department of Internal Medicine, Nippon Medical School, Tokyo, Japan f Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan

A small-size inductive-coupling dc voltage transceiver for highly-parallel wafer-level testing is experimentally demonstrated in 90-nm CMOS technology, which can reduce the total cost of a low-price IC by 18%. In order to carry out dc tests, the proposed transceiver outputs dc voltage to the die-under-test (DUT) without any area-consuming digital circuits. In addition, digital calibration with digital feedback channel which calibrates the output dc voltage enables the removal of calibration circuits on the DUT. All of the circuits for dc tests are implemented into the area of an inductor (100 μm ×100 μm). The proposed dc voltage transmission is successfully demonstrated with 6-bit resolution.

Background— Late vascular responses after implantation of drug-eluting stents may play a key role in steadily increasing occurrence of very late stent thrombosis have not yet been fully investigated in human beings. Methods and Results— Serial optical coherence tomography observations at 2 and 4 years were collected for 17 patients treated with 21 sirolimus-eluting stents. Corresponding 376 cross sections within single-stent segments at intervals of 1 mm were selected for analyses, and neointimal thickness on each strut was measured. Extrastent lumen (ESL) was defined as an external lumen of the stent. Area and angle of ESL were measured. A total of 3369 and 3221 struts were identified at 2 and 4 years, respectively. From 2 to 4 years, mean neointimal thickness increased (76.8±75.6 μm versus 123.0±102.5 μm; P P =0.002). Although prevalence of patients that had ESL was similar (59% of 2 years versus 65% of 4 years; P =1.0), the cross sections with ESL increased (9.6% versus 15.2%; P =0.02). Moreover, area and angle of ESL increased from 2 to 4 years (0.28±0.27 mm 2 versus 0.62±0.68 mm 2 and 16.6±5.4° versus 65.1±38.4°; P P =1.0). All thrombi were identified in patients who had cross sections with ESL. Conclusions— The current serial optical coherence tomography study showed an augmentation of neointimal growth at the late phase of sirolimus-eluting stent implantation. ESL may contribute to thrombus formation and ESL of sirolimus-eluting stents expanded from 2 to 4 years.

A 27-Mbps, frequency-division multiplexing (FDM) receiver was developed. The 3-channel FDM signal is demodulated in the receiver with a traveling subband demodulator using intra-symbol intermittent demodulation for each subband, which does not require an analog-to-digital converter/fast Fourier transform. Also, the receiver sustains a sensitivity of -55 dBm comparable to that of, e.g., Bluetooth standards (-70 dBm) with respect to 14-dB sensitivity degradation caused by signal bandwidth enhancement, with receiver power dissipation of 3 mW. Furthermore, we have successfully demonstrated energy-exploitation capability from the power of unused FDM signals and interference.

Advanced SoC chips used in multimedia devices such as mobile phones have a number of dedicated functional IP cores, including 3D graphics and video codec, and require local memories with high bit density. Each IP core is connected to closely positioned local memories for fast access and wide bandwidth. The simultaneous operation of all of IP cores on a chip is an extremely rare situation and we anticipate that future integration of more IP cores onto a chip will increase the average number of sleeping IP cores at any given time. Therefore, current chip architectures that allocate local memories to individual IP cores will become increasingly inefficient in thier use of memory resources. In contrast to this, is the use of an off-chip external memory shared by a number of IP cores.