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PDF file - 3 MB, Quantitative cellular target profiling of TAK-901 using affinity chromatography.

Aim To evaluate the virologic responses and clinical course of daclatasvir plus asunaprevir treatment in non-hemodialysis (non-HD) and hemodialysis (HD) patients infected with genotype 1 hepatitis C virus (HCV). Methods A total of 1113 non-HD patients and 67 HD patients were assessed. To evaluate pretreatment factors contributing to sustained virological response at 12 weeks (SVR12), univariate and multivariate analyses were carried out. To adjust for differences in patient background, propensity score matching was undertaken. Results The overall SVR12 rates were 91.6% in non-HD patients and 95.5% in HD patients. Compared with non-HD patients, HD patients were younger, were more likely to be male, were less likely to have received interferon-based pretreatment, had a lower viral load, and had lower levels of alanine transaminase, hemoglobin, and α-fetoprotein. Multivariate analysis revealed that viral load, α-fetoprotein, L31 substitution negative, and Y93 substitution negative were independent predictive factors for SVR12 in non-HD patients. The proportion of patients with undetectable HCV-RNA during the initial 4 weeks was significantly higher in HD patients than in non-HD patients. The SVR12 rate was clearly higher in HD patients than in non-HD patients, although the difference was not statistically significant. After propensity score matching to adjust for viral load, α-fetoprotein, L31 substitution, and Y93 substitution, these trends disappeared. Conclusions For treatment of HCV genotype 1 infection, daclatasvir plus asunaprevir is useful not only in non-HD patients but also in HD patients. Viral load, α-fetoprotein levels, L31 substitution, and Y93 substitution influence treatment course and outcome.

AIM The present study aimed to determine the real-world efficacy and safety of the non-structural protein (NS)5A inhibitor elbasvir (EBR) combined with the NS3/4A protease inhibitor grazoprevir (GZR) in patients with hepatitis C virus (HCV) genotype 1 (GT1) infection. METHODS This study retrospectively evaluated the rate of sustained virologic response at 12 weeks post-treatment (SVR12) and the safety of EBR/GZR treatment in 159 men and 194 women with a median age of 72 years, and it assessed factors associated with the SVR12 rate. The attending physicians were responsible for selecting candidate patients for EBR/GZR in this retrospective study. RESULTS Treatment outcomes for EBR/GZR were good in direct-acting antiviral (DAA)-naive patients, of whom 99.4% achieved SVR. Of 353 patients, 10 (2.9%) had treatment failure. Of these patients, eight previously underwent DAA therapy, and the remaining two had NS5A-L31/Y93 double mutation. The SVR rate was 50% (8/16 patients) in patients who previously underwent DAA therapy, and 18.2% (2/11 patients) in patients with NS5A-L31/Y93 double mutation. On multivariate logistic regression analysis, NS5A-Y31/Y93 double mutation (odds ratio 356.3; 95% confidence interval, 23.91-16 940; P

The guideline committee of Japanese Society for Dialysis Therapy (JSDT), chaired by Dr Ohira, has published an original Japanese guideline, ‘Guidelines for Vascular Access Construction and Repair for Chronic Hemodialysis’. The guideline was created mainly because of the existence of numerous factors characteristic of Japanese hemodialysis therapy, which are described in this report, and because we recognized the necessity for standardization in vascular access-related surgeries. This guideline consists of 10 chapters, each of which includes guidelines, explanations or comments and references. The first chapter discusses informed consent of vascular access (VA)-related surgeries, which often resulted in trouble between dialysis staff and patients. The second chapter describes the fundamentals of VA construction and timing of the introduction of hemodialysis with emphasis on the avoidance of catheter indwelling if at all possible. In the third chapter, arteriovenous fistula (AVF) construction and management are discussed from the viewpoint of the most preferable type of VA. The fourth chapter deals with arteriovenous grafts (AVG) which has recently increased in clinical applications. The factors which improve the AVG patency rate are discussed and postoperative management methods are emphasized to avoid possible complications. The fifth chapter deals with short and long-term vascular catheters. It is emphasized that these methods are definitely effective but, at the same time, are apt to be associated with several serious complications and might result in vascular damage. In the sixth chapter, superficialization of an artery is explained. This was originally for emergency use or backup but has been used permanently in 2–3% of Japanese hemodialysis patients. In the seventh chapter, methods for the use of VA are described and the buttonhole method is referred to as one of the options for patients who complain of intense pain at every cannulation. In the eighth chapter, the importance of continuous monitoring is stressed for maintaining appropriate function of VA. As a rule, the internal shunt type VA (AVF, AVG) places a burden on cardiac function. Thus, in the ninth chapter, it is stressed that VA construction, maintenance and repair should always be carried out with consideration of cardiac function which is not constant but variable. The 10th chapter forms one of the cores of this guideline and deals with repair and timing of VA. It is shown how to select a surgical or interventional repair method. In the final 11th chapter, VA types and resultant morbidity and mortality of hemodialysis patients are reviewed.

Background and aim This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort. Methods This multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively. Results AFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients. Conclusions There were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.

To evaluate the virologic responses and clinical course of daclatasvir plus asunaprevir treatment in non-hemodialysis (non-HD) and hemodialysis (HD) patients infected with genotype 1 hepatitis C virus (HCV).A total of 1113 non-HD patients and 67 HD patients were assessed. To evaluate pretreatment factors contributing to sustained virological response at 12 weeks (SVR12), univariate and multivariate analyses were carried out. To adjust for differences in patient background, propensity score matching was undertaken.The overall SVR12 rates were 91.6% in non-HD patients and 95.5% in HD patients. Compared with non-HD patients, HD patients were younger, were more likely to be male, were less likely to have received interferon-based pretreatment, had a lower viral load, and had lower levels of alanine transaminase, hemoglobin, and α-fetoprotein. Multivariate analysis revealed that viral load, α-fetoprotein, L31 substitution negative, and Y93 substitution negative were independent predictive factors for SVR12 in non-HD patients. The proportion of patients with undetectable HCV-RNA during the initial 4 weeks was significantly higher in HD patients than in non-HD patients. The SVR12 rate was clearly higher in HD patients than in non-HD patients, although the difference was not statistically significant. After propensity score matching to adjust for viral load, α-fetoprotein, L31 substitution, and Y93 substitution, these trends disappeared.For treatment of HCV genotype 1 infection, daclatasvir plus asunaprevir is useful not only in non-HD patients but also in HD patients. Viral load, α-fetoprotein levels, L31 substitution, and Y93 substitution influence treatment course and outcome.

In this paper, we report the development of a new polyphenol, NF7177, applied to the Spin-On Carbon Hardmask and the thermosetting properties. The new polyphenol derivatives were easily synthesized by the condensation of aldehydes and dihydroxybiphenyl compounds. We found new polyphenol NF7177 was showed the good applicability to the raw material for the Spin-On Carbon Hardmask [1]. It was indicated that the heat resistance of NF7177 was due to cross-linking based on dehydration reaction. Furthermore the thermosetting properties seem to be depend on the number and position of OH group.

微小変化群のネフローゼ症候群に合併した急性腎障害に対して血漿交換が著効した2例を経験したので報告する．症例1は39歳男性，症例2は33歳女性である．2例とも，メチルプレドニゾロンのパルス療法を行ったが，急性腎障害となり血液濾過透析が必要になった．血清アルブミン濃度は，症例1が1.8mg/dL，症例2が1.6mg/dLといずれも低値であった．アルブミンの静脈内投与は急性腎障害に対していずれも無効であった．3回の血液濾過透析を施行したが，急性腎障害が改善しないため5％アルブミン溶液による血漿交換を行った．血漿交換の終了時期には尿量は著増し，その後急速に腎機能は改善し，その後の血液濾過透析は不要となった．腎生検所見は微小変化群の所見であり，著明な足突起の癒合を伴っており，急性尿細管壊死の所見は認めなかった．蛋白尿は血漿交換後に症例1では3日後から，症例2では翌日から減少し始めた．血漿交換の急性腎障害に対する有効性は単に重症の低アルブミン血症の補正のみでは説明は困難であると考えられた．血液中に存在する何らかの病因物質の除去とステロイドパルス療法との相乗効果が関与していた可能性が示唆された．

This paper presents a novel method for movie affective scene classification that outputs the emotion (in the form of labels) that the scene is likely to arouse in viewers. Since the affective preferences of users play an important role in movie selection, affective scene classification has the potential to develop more attractive user-centric movie search and browsing applications. Two main issues in designing movie affective scene classification are considered. One is “how to extract features that are strongly related to the viewer's emotions”, and the other is “how to map the extracted features to the emotion categories”. For the former, we propose a method to extract emotion-category-specific audio-visual features named affective audio-visual words (AAVWs). For the latter issue, we propose a classification model named latent topic driving model (LTDM). Assuming that viewers' emotions are dynamically changed by the movie scene sequences, LTDM models emotions as Markovian dynamic systems driven by the sequential stimuli of the movie content. Experiments on 206 movie scenes extracted from 24 movie titles and the corresponding labels of eight emotion categories given by 16 subjects show that our method outperforms conventional approaches in terms of the subject agreement rate.

In-situ test of bearing capacity test at six sites were carried out on the steel pipe tapered piles. This paper presents the outline of the loading tests and results of the tests and so on. From the studies, it is found out that the tapered pile has the advantage of the straight pile in the vertical response.

Long term loading test of the decreasing effect of settlement about small building foundations using tapered pile were conducted. We used basis reinforced with tapered pile and straight pile. This paper presents the outline of the loading tests and results of the tests and so on. From the studies, analyzes about settlement of foundation and the load distribution ratio of base slab and pile.

An automatic fault-recorder installed in a substation of Chubu Electric Power Company detected a peculiar phenomenon that bus-bar voltage fell to around 20-30% of the nominal value for a short time (about 8-10 cycles) though electric current didn't change during the period. The phenominon was recorded several times.In this paper, we analyzed the origin of this phenomenon and conducted simulations by EMTP. As a result, we estimated that this phenomenon occurred by the saturation of VT (voltage transformer), and this saturation caused by lightning strokes to the transmission line with line arresters, which have been increasingly installed in recent years. Moreover, we evaluated the influence of the phenomenon to protection relays.

Toughness of CrMoV cast steel for steam turbine casings operated at elevated temperature can be degraded during the operation. It is important to measure the degradation under operation to estimate the damage and the maintenance interval. However, conventional testing methods for fracture toughness require large specimens and it is impractical for successive operation after sampling these specimens. In this report, a new small punch test method to evaluate the fracture toughness at high temperature is proposed. Small punch specimens with fatigue pre-cracks were used in this test method. The crack extension from the pre-crack was detected by electric potential drop method and the plastic strain energy required for crack extension is calculated by FEM analysis. The fracture toughness of degraded CrMoV cast steel was estimated using this method and the values showed a good correlation with those obtained by the conventional test method with CT specimen.

Objective: In FDG-PET examinations, optimization of the injected dose and duration of acquisition are important in determining the physical performance of PET or the PET/CT scanner. This study was intended to elucidate the influence of count rate on image quality. Methods: Three PET/CT scanners (Biograph sensation 16, Discovery ST, and Aquiduo) were used in this study. Body and scatter phantoms (NEMA 2001) and a cylindrical phantom (for QC use) were also used. Data acquisition was performed repeatedly for about 6 h to achieve a fixed 15 million counts of true plus scatter. The count rate performance and image quality (signal-to-noise ratio and contrast) of each frame were analyzed after data acquisition. The relationship between the count rate and image quality was also analyzed. Results: A positive correlation between the random fraction (ratio of random to prompt count rate) and signal-to-noise ratio was found in all PET/CT scanners, but with differing effects of the count rate’s influence on image quality. Image contrast was not correlated with count rate. Conclusion: Acquisition parameters must be determined by considering each scanner’s effect on how count rate influences image quality.

Backgrounds & Aims We aimed to clarify the characteristics of resistance-associated substitutions (RASs) after treatment failure with NS5A inhibitor, daclatasvir (DCV) in combination with NS3/4A inhibitor, asunaprevir (ASV), in patients with chronic hepatitis C virus genotype 1b infection. Methods This is a nationwide multicenter study conducted by the Japanese Red Cross Liver Study Group. The sera were obtained from 68 patients with virological failure after 24 weeks of DCV/ASV treatment. RASs in NS5A and NS3 were determined by population sequencing. Results The frequency of signature RASs at position D168 of NS3 was 68%, and at positions L31 and Y93 of NS5A was 79 and 76%, respectively. The frequency of dual signature RASs in NS5A (L31-RAS and Y93-RAS) was 63%. RASs at L28, R30, P32, Q54, P58, and A92 in addition to dual signature RAS were detected in 5, 5, 1, 22, 2, and 0 patients, respectively. In total, triple, quadruple, and quintuple RASs in combination with dual signature RAS were detected in 35, 10, and 1.5% patients, respectively. These RASs were detected in patients without baseline RASs or who prematurely discontinued therapy. Co-existence of D168 RAS in NS3 and L31 and/or Y93 RAS in NS5A was observed in 62% of patients. Conclusion Treatment-emergent RASs after failure with DCV/ASV combination therapy are highly complex in more than 50% of the patients. The identification of complex RAS patterns, which may indicate high levels of resistance to NS5A inhibitors, highlights the need for RAS sequencing when considering re-treatment with regimens including NS5A inhibitors.