The goal of therapy in chronic hepatitis c virus(HcV) infection is sustained virological response(SVR) which reflects HcV eradication. Treatment against HcV has dramatically improved with the recent availability of di...
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The goal of therapy in chronic hepatitis c virus(HcV) infection is sustained virological response(SVR) which reflects HcV eradication. Treatment against HcV has dramatically improved with the recent availability of direct-acting antivirals(DAAs) including sofosbuvir, simeprevir, daclatasvir, ledipasvir/sofosbuvir, paritaprevir/ombitasvir and dasabuvir. carefully selected combinations of these DAAs offer the potential for highly effective all-oral safe regimens even for patients with decompensated cirrhosis or liver transplant(LT) recipients. Like all current protease inhibitors, simeprevir and paritaprevir should not be used in patients with child ccirrhosis, while sofosbuvir and ledipasvir/sofosbuvir should not be given in patients with severe renal impairment and glomerular filtration rate less than 30 m L/min. Drug-drug interactions may still occur with the current DAAs particularly in postLT patients, in whom simeprevir should not be coadministered with cyclosporine and dose adjustments of calcineurin inhibitors are required in case of regimens including the ritonavir boosted paritaprevir. Phase Ⅱ clinical trials and real life cohort studies have shown that sofosbuvir based combinations are safe and can achieve improvements of clinical status, high SVR rates and even prevention of post-LT HcV recurrence in patients with decompensated cirrhosis or LT-candidates. In the post-LT setting, sofosbuvir based regimens and the combination of paritaprevir/ombitasvir and dasabuvir have been reported to be safe and achieve high SVR rates, similar to those in non-transplantpatients, being effective even in cases with cholestatic fibrosing hepatitis. Ongoing clinical trials and rapidly emerging real life data will further clarify the safety and efficacy of the new regimens in these settings.
Hepatitis c virus(HcV)-specificcytotoxic T cell(cTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onse...
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Hepatitis c virus(HcV)-specificcytotoxic T cell(cTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onset, being unable to get rid of HcV. The role of this response in contributing to sustained viral response(SVR) after anti-HcV is controversial. Recent studies show that after successful interferon-based anti-HcV treatment, HcV traces are still detectable and this correlates with a peak of HcV-specificcTL response activation, probably responsible for maintaining SVR by subsequent complete HcV clearing. Moreover, SVR patients' serum is still able to induce HcV infection in na?ve chimpanzees, suggesting that the infection could be under the control of the immune system after a successful treatment, being transmissible in absence of this adaptive response. At least theoretically, treatmentinduced viral load decrease could allow an effective HcV-specificcTL response reestablishment. This effect has been recently described with anti-HcV interferonfree regimes, based on direct-acting antivirals. Nevertheless, this is to some extent controversial with interferon-based therapies, due to the detrimental immunoregulatory α-interferon effect on T cells. Moreover, HcV-specificcTL response features during anti-HcV treatment could be a predictive factor of SVR that could have clinical implications in patient management. In this review, the recent knowledge about the role of HcV-specificcTL response in the development of SVR after anti-HcV treatment is discussed.
Hepatitis c virus(HcV) is a major global health problem with high morbidity and mortality. About 185 million people are living with HcV,of which 80% are living in low and middle income countries. With the development ...
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Hepatitis c virus(HcV) is a major global health problem with high morbidity and mortality. About 185 million people are living with HcV,of which 80% are living in low and middle income countries. With the development of new highly effective treatments for HcV,it is considered that the eradication of HcV may only be one step away. The major problem with new treatment options is its high price. The price of sofosbuvir-based treatment for one patient in the United States is US$85000-110000,while the actual production cost of a 12 wk direct-acting antiviral regimen is less than US$250. Another major hindrance in HcV eradication is the lack of quality management of blood transfusion screens. Due to the lack of HcV screening,75% of people in the United States with HcV infection are unaware of their positive HcV status. The control of massive HcV pandemic will require a significant financial investment,political will,and support from medical,pharmaceutical,and civil organizations around the globe.
Over the past decade, AIM has developed a family of compact, highly reliable cryocoolers to meet the demands of various customers and its products. These developments mainly focused on the improvement and optimization...
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ISBN:
(数字)9781510626706
ISBN:
(纸本)9781510626706
Over the past decade, AIM has developed a family of compact, highly reliable cryocoolers to meet the demands of various customers and its products. These developments mainly focused on the improvement and optimization of size, weight, power consumption and cost (SWaP,c). In particular, efforts have been made to meet the requirements for ultra-compact camera cores using high operating temperature (HOT)-IR sensors as well as for high performance IR-modules using the latest digital ROIc technology. Design features and performance data of the most recent cryocooler and cooler electronics developments will be presented. Technical details introduced to meet demanding customer requirements will be discussed.
This paper presents an improved Othello game solver using the Hardware/Software co-Design approach. Enhancements in Data communication, Searching Algorithm, and Evaluation function have been made to beat the prevalent...
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ISBN:
(纸本)9781728127880
This paper presents an improved Othello game solver using the Hardware/Software co-Design approach. Enhancements in Data communication, Searching Algorithm, and Evaluation function have been made to beat the prevalent implementations. A novel 64-bit communication model is proposed which transfers the current board position from the Processing System to the Programmable Logic through a 64-bit change board, instead of the complete 128-bit board. The proposal uses NegaScout searching algorithm along with Transposition Table and Node Ordering;and features like Opening Book, Killer Heuristics, and Bitboards. An Adaptive Evaluation function assigns variable weights to Mobility, Stability, corner Occupancy, and Disc Differential depending upon the game stage. At a search depth of eight, the proposed communication model improves the communication overhead by 19.5%. Overall, the proposed design demonstrates 75.06% improved performance as compared to the prevalent implementation, and 6.53 times faster than its software implementation on the same platform.
Hepatitis c virus(HcV) genotypes 4, 5 and 6 are mainly present in Africa, the Middle East and Asia and they have been less extensively studied with respect to epidemiology, natural disease history and therapeutic endp...
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Hepatitis c virus(HcV) genotypes 4, 5 and 6 are mainly present in Africa, the Middle East and Asia and they have been less extensively studied with respect to epidemiology, natural disease history and therapeutic endpoints. Response rates to a 48-wk combined peginterferon/ribavirin treatment range to 40%-69% for HcV 4, 55%-60% for HcV 5 and 60%-90% for HcV 6. Response-guided schedules are recommended to optimize the outcomes of peginterferon/ribavirin treatment in HcV 4 and, in form of preliminarydata, for HcV 6, but no data are yet available to support such an individualization of therapy for HcV 5. Recently, the direct-acting antivirals(DAAs) with pan-genotypic activities simeprevir, sofosbuvir and daclatasvir have been recommended in triple regimens with peginterferon/ribavirin for the treatment of HcV genotypes 4 to 6 infections. In the future, DAA-based interferon-free therapies are awaited to drastically improve treatment outcomes in HcV. However, efforts to improve treatment outcomes with peginterferon/ribavirin should continue, as the HcV 4-6 infected population is mainly based in resource-limited settings with restricted access to the costly DAAs.
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