Era of direct acting anti-viral agents for the treatment of hepatitis C

Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents(DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article.

Are metabolic factors still important in the era of direct antiviral agents in patients with chronic hepatitis C?

The high rate of sustained viral response(SVR)to boceprevir or telaprevir-based triple therapy in hepatitis C(HCV)-related,non-cirrhotic na ve patients or relapsers to previous antiviral treatment leads clinicians to believe that the impact of metabolic host factors on SVR is minimal when triple therapy is used,unlike what is observed with the peginterferon and ribavirin schedules.This concept is strongly expressed by some opinion leaders on the basis of the data derived from subanalyses of registrative trials as well as from a post-hoc analysis of the phaseⅡC208 clinical trial.The perception of unrestrainable therapeutic success with the use of newer,more powerful antivirals is now reinforced by the brilliant results obtained with sofosbuvir,an HCV NS5B polymerase inhibitor,as well as by the data from the phaseⅡandⅢstudies on the various combinations of second-generation NS3/4A inhibitors and NS5A and/or NS5B inhibitors.However,a great deal of concern has emerged from the real world scenario in which patients are often older and have more comorbidities than patients in the"world of trials".Furthermore,many of them have advanced fibrosis and previous failure with peginterferon and ribavirin treatment.Some data from the recent literature suggest that the host metabolic factors may play a minor but non-negligible role in these difficult-to-treat patients,an issue that will hopefully be investigated in further studies.This editorial aims to provide a detailed analysis of the role that host metabolic factors played in the past and what role they may play in the era of direct antiviral agents.

Hepatitis C virus reinfection after liver transplantation: Is there a role for direct antiviral agents?

Recurrence of hepatitis C virus(HCV)infection following liver transplantation(LT)is almost universal and can accelerate graft cirrhosis in up to 30%of patients.The development of effective strategies to treat or prevent HCV recurrence after LT remains a major challenge,considering the shortage of donor organs and the accelerated progression of HCV in LT recipients.Standard antiviral therapy with pegylated-interferon plus ribavirin is the current treatment of choice for HCV LT recipients,even though the combination is not as effective as it is in immunocompetent patients.A sustained virological response in the setting of LT improves patient and graft survival,but this is only achieved in 30%-45%of patients and the treatment is poorly tolerated.To improve the efficacy of pre-and post-transplant antiviral therapy,a new class of potent direct-acting antiviral agents (DAAs)has been developed.The aim of this review is to summarize the use of DAAs in LT HCV patients.PubMed,Cochrane Library,MEDLINE,EMBASE,Web of Science and clinical trial databases were searched for this purpose.To date,only three clinical studies on the topic have been published and most of the available data are in abstract form.Although a moderately successful early virological response has been reported,DAA treatment regimens were associated with severe toxicity mitigating their potential usefulness.Moreover,the ongoing nature of data,the lack of randomized studies,the small number of enrolled patients and the heterogeneity of these studies make the results largely anecdotal and questionable.In conclusion,large welldesigned clinical studies on DAAs in HCV LT patients are required before these drugs can be recommended after transplantation.

Effect of reducing agents on reducing atmosphere in coal-based direct reduction of beach titanomagnetite

Beach titanomagnetite(TTM)provides a cheap alternative source of Fe and Ti,but this ore is difficult to process to make suitable concentrates for the blast furnace.Recently studies showed that it is feasible to separate Fe and Ti by coal-based direct reduction.In this study,beach TTM was selected as the research object,the effects of reducing agents on reducing atmosphere in coal-based direct reduction of beach TTM were analyzed,and the role of volatiles was also studied.The results showed that when bitumite and coke were used as reducing agents of TTM,the CO produced from volatiles was involved in the reduction reaction,and the generated CO_(2) provided the raw material for the reaction of TTM.The reduction effect of bitumite was better than that of coke.The reason is that bitumite+TTM had a higher gas generation rate and produced a higher CO partial pressure,while coke+TTM had a lower gas generation rate and produced a lower CO partial pressure.When graphite was used as a reducing agent,there was a solid-solid reaction in the early stage in the reaction.With the continuous accumulation of CO_(2),the Boudouad reaction started and accelerated.Graphite+TTM also produced a higher CO partial pressure.

Global behavior of dynamical agents in directed network

This paper investigates the global behavior of controlled dynamical agents in directed networks. The agents are Lyapunov stable, are distributed in a line, and communicate through a directed network. The communication topology of the network is characterized by a directed graph and the control protocol is designed in simple linear decentralized feedback law. We study the different conditions under which agents will achieve aggregation, and critical and divergent trajectories, respectively. Our investigation on the dynamical agent system under network is extended to the time-delay network case. Furthermore, we study the case with two pre-specified virtual leaders in the system. Numerical simulations are given and demonstrate that our theoretical results are effective.

Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study

BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC)and mortality is less well established.AIM To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with DAAs.METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy.The study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HCV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be confounders.RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%CI:15-136,P<0.001).Considering the combined endpoint of HCC or death from any cause,the hazard ratio(HR)for the SVR patients was 0.070(95%CI:0.025-0.194,P<0.001).Other independent predictors of HCC or death were low HCV viremia(HR:0.808,P=0.030),low platelet count(HR:0.910,P=0.041),and presence of mixed cryoglobulinemia(HR:3.460,P=0.044).Considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521,P<0.001)and high platelet count(HR:1.019,P=0.026).Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR:5.982,P=0.028 and HR:5.633,P=0.047,respectively).CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death.A residual risk of HCC persists in patients with advanced liver disease or with complications,such as mixed cryoglobulinemia or renal failure.

Outcomes assessment of hepatitis C virus-positive psoriatic patients treated using pegylated interferon in combination with ribavirin compared to new Direct-Acting Antiviral agents

AIM To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C(CHC) treated with new Direct-Acting Antiviral agents(DAAs) compared to pegylated interferon-2α plus ribavirin(P/R) therapy.METHODS This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus(HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017. The patients were divided into two groups: patients that underwent therapy with DAAs and patients that underwent HCV treatment with P/R. Patients were assessed by a dermatologist for psoriasis symptoms, collecting Psoriasis Area Severity Index(PASI) scores and the Dermatology Quality of Life Index(DLQI). PASI and DLQI scores were evaluated 24 wk after the end of HCV treatment and were assumed as an outcome of the progression of psoriasis. Switching to a different b DMARD was considered as an inadequate response to biological therapy. The dropout of HCV therapy and sustained virological response(SVR) were considered as outcomes of HCV therapy.RESULTS Fifty-nine psoriatic patients in biological therapy underwent antiviral therapy for CHC. Of this, 27 patients were treated with DAAs and 32 with P/R. After 24 wk post treatment, the DLQI and the PASI scores were significantly lower(P < 0.001 and P < 0.005, respectively) in the DAAs group compared with P/R group. None of the patients in the DAAs group(0/27) compared to 8 patients of the P/R group(8/32) needed a shift in biological treatment.CONCLUSION DAAs seem to be more effective and safe than P/R in HCV-positive psoriatic patients on biological treatment. Fewer dermatological adverse events may be due to interferon-free therapy.

Mechanism of phosphorus removal in beneficiation of high phosphorous oolitic hematite by direct reduction roasting with dephosphorization agent

High phosphorous oolitic hematite ore is one of typical intractable iron ores in China, and the conventional beneficiation methods are found to be impracticable to , remove phosphorus from the ore effectively. Better beneficiation index were gotten by direct reduction roasting with dephosphorization agent followed by two stages of grinding and magnetic separation. P content decreases from 0.82% in the raw ore to 0.06% in the magnetic concentrate, and the total iron grade increases from 43.65% to 90.23%, the recovery of iron can reach 87%. Mechanisms of phosphorus removal in the beneficiation of high phosphorous oolitic hematite ore by direct reduction roasting with dephosphorization agent were studied using XRD, SEM and EPMA. The results showed that about 20% of the apatite in the raw ore transferred into phosphorus and volatilized with the gas in the process of reduction roasting, while the rest 80% apatite was not involved in the reaction of generation of phosphorus, and remained as apatite in the roasted products, which was removed to tailings by grinding and magnetic separation. A small amount of phosphorus existed in the magnetic concentrate as apatite. The oolitic texture of raw ore was partly changed during roasting, resulting in the formation of nepheline in the reaction between the dephosphorization agent, SiO2 and Al2O3 in the raw ore, which greatly improved the liberation degree of minerals in the roasted products, and it was beneficial to the subsequent grinding and magnetic separation.

Experimental investigation on basic law of rock directional fracturing with static expansive agent controlled by dense linear multi boreholes

Directional rupture is one of the difficult problems in deep rock mechanics and engineering.A directional fracturing method with static expansive agent controlled by dense linear multi boreholes is proposed.A physical experiment is designed and performed to investigate the basic laws of this method.The fracture initiation and propagation process,and the mechanism of directional fracturing are analyzed.The results indicate that a directional fracture is formed along the direction of boreholes layout through directionally fracturing with static expansive agents controlled by the dense linear multi boreholes.According to the variation of strain and the distribution of associated acoustic emission(AE)events and energy,the experiment can be divided into three stages.In the first stage,the static expansive agent expand slowly with no fracturing inside the rock.In the second stage,some initial micro-fracturing occurs inside the rock.In the third stage,a wide range of fracturing occurs inside the sample.The internal micro-fracturing planes are connected to form a macro-fracture.Finally,it propagates to the surface of the sample.The directional fracturing plane presents a relatively smooth plane with little bias but much local fluctuation.

Synthesis of Hierarchically Porous FAU/γ-Al2O3 Composites with Different Morphologies via Directing Agent Induced Method

Zeolite FAU composites with a macro/meso-microporous hierarchical structure were hydrothermally synthesized using macro-mesoporous γ-Al_2O_3 monolith as the substrate by means of the liquid crystallization directing agent(LCDA) induced method. No template was needed throughout the synthesis processes. The structure and porosity of zeolite composites were analyzed by means of X-ray powder diffraction(XRD), scanning electron microscopy(SEM) and N_2adsorption-desorption isotherms. The results showed that the supported zeolite composites with varied zeolitic crystalline phases and different morphologies can be obtained by adjusting the crystallization parameters, such as the crystallization temperature, the composition and the alkalinity of the precursor solution. The presence of LCDA was defined as a determinant for synthesizing the zeolite composites. The mechanisms for formation of the hierarchically porous FAU zeolite composites in the LCDA induced synthesis process were discussed. The resulting monolithic zeolite with a trimodal-porous hierarchical structure shows potential applicability where facile diffusion is required.

Eco-friendly synthesis of high silica zeolite Y with choline as green and innocent structure-directing agent

Zeolite synthesis in contemporary chemical industries is predominantly conducted using organic structure‐directing agents(OSDAs),which are chronically hazardous to humans and the environment.It is a growing trend to develop an eco‐friendly and nuisanceless OSDA for zeolite synthesis.Herein,choline is employed as a non‐toxic and green OSDA to synthesize high silica Y zeolite with SiO2/Al2O3 ratios of 6.5–6.8.The prepared Y zeolite samples exhibited outstanding(hydro)thermal stability at ultrahigh temperature owing to the higher SiO2/Al2O3 ratio.The XRF,SEM,29Si‐NMR and 13Na+results suggested that choline plays a structure‐directing role in the synthesis of Y zeolite,while the feed molar fraction of Na+is a crucial determinant for the framework SiO2/Al2O3 ratio and the crystal morphology.

Hierarchical SAPO-11 Molecular Sieve for n-Alkane Hydroisomerization Synthesized by Directing Agent Method

Silicoaluminophosphates SAPO-11 molecular sieves with small particle size and hierarchical pores were synthesized using the directing agent method.The effect of crystallization time on the particle structure,morphology,pore structure properties,and acid properties of SAPO-11 molecular sieves were investigated.Unlike the SAPO-11 molecular sieves synthesized with the conventional method,the results of XRD,SEM,BET and NH3-TPD analyses showed that the SAPO-11 molecular sieves synthesized by the directing agent method in a shorter crystallization time exhibited fine and uniform morphology.By increasing the crystallization time,the particle size of SAPO-11 molecular sieve was significantly reduced,and the mesoporous structure(intercrystalline pores)was formed.Furthermore,the external specific surface area and the total specific surface area reached 81.7 m^2/g and 192.0 m^2/g,respectively,which effectively reduced the pore mass transfer resistance and significantly increased the number of acid sites.The results of n-dodecane hydroisomerization revealed that the Pt/SAPO-11 prepared with the novel method exhibited higher catalytic activity and better hydroisomerization selectivity than that synthesized by the conventional hydrothermal method.Thus,the small particle molecular sieve showed a promising industrial application prospect to be used as catalyst support.

Electrodeposition of SnO_2 nanocrystalline thin film using butyl-rhodamine B as a structure-directing agent

Porous SnO2 nanocrystalline thin films were successfully electrodeposited from an oxygen-saturated acid aqueous solution of SnCl2 containing different concentrations of butyl-rhodamine B（BRhB） at 70℃.BRhB with substitute of amidocyanogen can be dissolved in the acid deposition solution,where HCl was added to suppress hydrolysis of SnCl2.So it was used as a structure-directing agent to promote the crystal growth of SnO_2.The formed porous morphology and tetragonal rutile crystalline structure of the electrodeposited thin films were controlled by the addition of BRhB with different amounts.

Hepatitis C and renal transplantation in era of new antiviral agents

Data from World Health Organization estimates that the hepatitis C virus(HCV) prevalence is 3% and approxi-mately 71 million persons are infected worldwide. HCV infection is particularly frequent among patients affected by renal diseases and among those in dialysis treatment. In addition to produce a higher rate of any cause of death, HCV in renal patients and in renal transplanted patients produce a deterioration of liver disease and is a recognized cause of transplant glomerulopathy, new onset diabetes mellitus and lymphoproliferative disorders. Treatment of HCV infection with interferon alpha and/or ribavirin had a poor efficacy. The treatment was toxic, expensive and with limited efficacy. In the post-transplant period was also cause of severe humoral rejection. In this review we have highlighted the new direct antiviral agents that have revolutionized the treatment of HCV both in the general population and in the renal patients. Patients on dialysis or with low glomerular filtration rate were particularly resistant to the old therapies, while the direct antiviral agents allowed achieving a sustained viral response in 90%- 100% of patients with a short period of treatment. This fact to date allows HCV patients to enter the waiting list for transplantation easier than before. These new agents may be also used in renal transplant patients HCV -positive without relevant clinical risks and achieving a sustained viral response in almost all patients. New drug appears in the pipeline with increased profile of efficacy and safety. These drugs are now the object of several phases Ⅱ, Ⅲ clinical trials.

Bounded consensus tracking of second-order multi-agent systems with sampling delay under directed networks

The bounded consensus tracking problems of second-order multi-agent systems under directed networks with sam- pling delay are addressed in this paper. When the sampling delay is more than a sampling period, new protocols based on sampled-data control are proposed so that each agent can track the time-varying reference state of the virtual leader. By using the delay decomposition approach, the augmented matrix method, and the frequency domain analysis, necessary and sufficient conditions are obtained, which guarantee that the bounded consensus tracking is realized. Furthermore, some numerical simulations are presented to demonstrate the effectiveness of the theoretical results.

A Dynamic Organic Structuring-Directing Agent for Pure-Silica-Zeolite AST and LTA Syntheses

Pure-silica-zeolite (PSZ ) 著名计算机生产厂商和 LTA 被使用一样的指导结构的代理人(SDA ) 成功地综合分子，但是在不同集中。动态器官的 SDA 被建议讨论在著名计算机生产厂商和 LTA 之间的阶段辨别的机制。数据建议进在不同集中由的更暗淡或更整齐的建筑群自我装配的 SDA 分子罐头 - 相互作用，和这些差别能被利用有选择地综合 PSZ 著名计算机生产厂商或 LTA。从 Liebau 的规则的这些偏差显示在在溶液的 SDA 化学，结构，和顺序的小面值硬币能在沸石合成的结构选择上有大影响。

考虑盐度影响的粉煤灰固化软土直剪试验

采用粉煤灰作为固化剂,制备了多组粉煤灰固化软土试样,其孔隙水中盐度分别为0%、2%、4%和6%,养护龄期分别为3 h、7 d和28 d.通过开展室内直剪试验,探讨盐度对粉煤灰固化软土强度特性的影响.试验结果表明:竖向固结压力为50 kPa时,粉煤灰固化软土的剪应力与剪切位移关系曲线呈现软化型,而在竖向固结压力为200 kPa时曲线呈现硬化型;高盐度试样具有较低的峰值剪应力和残余强度,表明高盐度对粉煤灰固化软土强度特性具有不利的影响;随着盐度增加,各养护龄期下软土试样的抗剪强度、黏聚力和内摩擦角的曲线均呈现近似线性下降的趋势,主要原因在于盐度的增加抑制了粉煤灰中活性成分的水化反应.

基于多Agent的电动汽车底盘智能控制系统框架

为了解决传统集成控制框架灵活性和可扩展性不足以及传统汽车底盘控制系统不适用于新型分布式轮毂电机驱动纯电动汽车的问题,提出了基于多Agent的四轮独立驱动纯电动汽车的底盘智能动态综合控制系统框架,分析了框架各个层次的功能和相互关系。以底层控制层中直接横摆力矩控制Agent为例,搭建控制器Agent模型。在MATLAB/Simulink和Carsim联合仿真环境中对前轮转向角阶跃输入工况进行仿真试验。仿真结果表明,搭建的控制器Agent较好地实现了预期的动力学控制目标,有效改善了车辆的横向操纵稳定性能,奠定了控制框架的基础。

基于Agent的微型工厂加工过程仿真研究

文章开展了针对以准分子激光直写刻蚀加工方法为主要加工手段,以微集成机构(Integrated Mechanism,IM)为产品对象的桌面式微型工厂(Micro-factory)加工过程仿真的研究,得出基于Agent的方法对微型工厂中的激光加工过程进行仿真是较为有效方法的结论,指出基于Agent加工过程的仿真模型包括建立设备模型、产品模型和工艺模型等几个方面,并讨论了采用Agent方法进行加工过程仿真的分析和实现方法。

一个通用移动agent仿真平台的设计与实现

对移动agent在广域网中的运行情况进行仿真从而评价其算法的性能是优化移动agent应用设计的关键问题之一。在前期工作基础上,采用直接执行仿真方法,设计并实现的通用移动agent仿真平台SimulAglets。实验结果表明,该平台可对复杂的移动agent算法进行有效的模拟,仿真结果与理论建模和专用仿真程序得到的结果完全相符。