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Showing posts with label svr durability. Show all posts
Mortality in Hepatitis C Populations: Another Battle Against Drugs and Alcohol.
Under Hot News
AIDS Rev. 2017 Jan-Mar;19(1):54-55.
Burns JE1.
1Department of Infectious Diseases, University Hospital Crosshouse, Kilmarnock, Scotland.
In the era of efficacious and well-tolerated treatment for chronic hepatitis C virus (HCV) infection, there is an expanding population of individuals who achieve viral eradication. This in turn has generated a need to determine the impact of liver-related morbidity and mortality, particularly liver decompensation and hepatocellular carcinoma, in populations achieving sustained viral response (SVR), and how they correlate with that of the general population.
|Full Article in PDF|
Posted by HCV New Drugs at Friday, February 10, 2017 No comments: Links to this post
File Under alcohol consumption, svr durability
Late Relapse After Hepatitis C Virus Treatment Is Rare
Clin Infect Dis 2017 Jan 1; 64:44. Sarrazin C et al. - Late Relapse Versus Hepatitis C Virus Reinfection in Patients With Sustained Virologic Response After Sofosbuvir-Based Therapies .
Articles in Press - Journal of Hepatology
Hepatitis C "true" late relapse beyond 48 weeks of sustained virologic response after direct acting antiviral therapy
Thomas Klag, Julia Dietz, Christoph R. Werner, Julia M. Schwarz, Ulrich M. Lauer, Robert Beck, Nisar P. Malek, Christoph Sarrazin, Christoph P. Berg
DOI: http://dx.doi.org/10.1016/j.jhep.2017.01.002
Publication stage: In Press Corrected Proof
Published online: January 9, 2017
Article Summary Source - NEJM Journal Watch
Neil M. Ampel, MD reviewing Sarrazin C et al. Clin Infect Dis 2017 Jan 1.
Few patients treated with a sofosbuvir-containing regimen for hepatitis C virus infection had late recurrent viremia, and most occurrences appeared to be reinfections.
Neil M. Ampel, MD
Use of direct antiviral agents (DAAs) for the treatment of hepatitis C virus (HCV) infection has been associated with sustained viral suppression by 12 weeks after therapy (SVR12) in >90% of patients. Because HCV infection does not confer full protective immunity, it is important to determine the frequency of recurrences after SVR12 is achieved and to distinguish between posttreatment relapse and reinfection.
To explore these issues, researchers in Germany, Russia, France, and the U.S. conducted an industry-supported study, examining samples from 11 phase III trials that used the NS5B inhibitor sofosbuvir, alone or in combination. To distinguish late relapse from reinfection, they conducted NS5B deep sequencing analysis, short-fragment NS5B population sequencing, and phylogenetic analyses.
Among 3004 patients, only 12 (0.4%) were found to have detectable HCV RNA by 24 weeks after SVR12. Deep genetic sequencing and phylogenetic analyses revealed that 5 of these 12 patients had HCV with minimal genetic changes in the NS5B sequence, suggesting that the recurrence was due to relapse. In the other 7, the sequences prior to and after DAA therapy were significantly unrelated, indicating reinfection.
This well-performed study indicates that absence of detectable HCV RNA by 12 weeks after DAA therapy is a good measure of SVR. It also demonstrates that most cases of recurrence are due to reinfection. Unfortunately, the tools needed to distinguish reinfection from relapse are not generally available to clinicians, suggesting the need for longer follow-up of patients after DAA therapy and better strategies to prevent reinfection.
Late Relapse Versus Hepatitis C Virus Reinfection in Patients With Sustained Virologic Response After Sofosbuvir-Based Therapies
Posted by HCV New Drugs at Wednesday, January 04, 2017 No comments: Links to this post
File Under relapse, svr, svr durability, SVR24-SVR12-SVR4
Getting Up to Speed on HCV Therapies - Experts discuss HCV before, during and after treatment.
Good day folks, if you have been diagnosed with HCV and either considering treatment, on treatment or have completed treatment you may benefit greatly from viewing this easy to follow video program over at Clinical Care Options.
The presentation; "Getting Up to Speed on HCV Therapies"offers a look see at various HCV patient scenarios. Experts discuss the use of current HCV therapies before, during and after treatment.
As an example in the first video "Treatment for HCV" a noncirrhotic 50-year-old genotype 1a patient who would prefer to be treated with sofosbuvir/ledipasvir is reviewed. In the second module it's all about pre-treatment considerations in patients taking other medications. Next up an overview of adherence during treatment and finally in the post-treatment section "Cure" is defined. In addition experts discuss the benefit of SVR in relation to reducing liver-related mortality in persons with advanced liver damage. Closing with the importance of follow up care, testing, liver wellness, and alcohol use.
Sit back and view experts; Sherilyn C. Brinkley, MSN, CRNP; Elizabeth K. Goacher, PA-C, MHS; Jennifer Katzianer, PharmD, BCPS; and Andrew J. Muir, MD, discuss the following topics
Considerations Influencing Choice of Oral Therapy for HCV Infection
Pretreatment Support for HCV-Infected Patients
On-Treatment Management of HCV Therapy
Posttreatment Care Following HCV Cure
During the presentation participants can easily skip follow up questions by clicking the "NEXT" button located at the bottom of the page or click on the "Table of Contents" to continue with the activity.
Free registration is required, begin here, view video module, here.
Posted by HCV New Drugs at Sunday, April 03, 2016 No comments: Links to this post
File Under HCV-Education, newly diagnosed, svr, svr durability
Hepatitis C Virus Relapse Uncommon After Sustained Virological Response
By Will Boggs MD
NEW YORK (Reuters Health) - Late relapse of hepatitis C virus (HCV) infection is very uncommon after achieving a sustained virological response (SVR), according to a systematic review and meta-analysis including more than 9,000 patients.
SVR at 12 or 24 weeks after completion of antiviral therapy is associated with an improved prognosis, compared with no treatment or failed therapy.
Bryony Simmons from Imperial College London, U.K., and colleagues used data from 59 studies of post-SVR recurrence to provide recurrence rates for three risk groups of HCV-infected patients: low-risk patients (with monoinfection and no recognized risk factors for reinfection); high-risk patients (with monoinfection and at least one identified risk factor for reinfection, such as injecting drug users and prisoners); and coinfection with HCV and HIV.
For the low-risk group, the pooled estimate was 0.82/1,000 person-years of follow-up (PYFU) for late relapse and 0.00/1,000 PYFU for reinfection, which yielded five-year rates of 0.40% for late relapse and 0.00% for reinfection.
The high-risk group had an even lower rate of late relapse (0.00/1,000 PYFU), but the pooled estimate for reinfection was far higher (19.06/1,000 PYFU). The risk of reinfection was highest for prisoners (45.48/1,000 PYFU), the researchers report in Clinical Infectious Diseases, online January 19.
Late relapse rates were also low for those with HCV/HIV coinfection (0.00/1,000 PYFU), and reinfection rates were high (32.02/1,000 PYFU).
Combining these outcomes, five-year recurrence rates remained very low for low-risk patients (0.95%), but were higher for high-risk patients (10.67%) and HCV/HIV coinfected patients (15.02%).
"Thus, despite higher recurrence rates in those with identified ongoing risk behaviors and/or HIV infection, SVR is durable, and the great majority of patients have SVR at 5 years post-treatment," the researchers note.
"The current analysis suggests that the greater recurrence risk in the high-risk and HIV coinfected populations is driven by an increased likelihood of reinfection, highlighting the need for prevention campaigns targeted at individuals who continue to place themselves at high-risk of HCV re-exposure," they write.
It's important to note that most studies included in the analysis evaluated recurrence after treatment with interferon-based therapies, which are being supplanted by interferon-free regimens.
Dr. Havard Midgard from Akershus University Hospital in Lørenskog, Norway, who was not involved in the new work, told Reuters Health by email that the "results are consistent with a very recent study published by our group, which was not included in this review. We performed a 7-year follow-up of 138 Norwegian patients who had obtained SVR in a treatment study in 2004-06. Of 94 individuals with a history of injection drug use (IDU) prior to treatment, 37 had relapsed to IDU after treatment. We identified 10 cases of persistent reinfection, all of which occurred in the subgroup who had relapsed to IDU post SVR."
"Scaling up HCV treatment among people who inject drugs (PWID) is essential to control the HCV epidemic, and I think it is 'the nature of the game' that some individuals will get reinfected," Dr. Midgard said. "However, the issue should be addressed systematically when providing HCV care for high-risk groups. To prevent infection, HCV treatment in PWID should be linked to harm reduction (opioid substitution therapy and needle and syringe program), and individuals should be educated about the risk of reinfection associated with sharing of needles and all kinds of injections paraphernalia."
"Although reinfection might compromise treatment outcomes at the individual level, treating HCV in high-risk individuals may actually prove great prevention benefits at the population level," Dr. Midgard concluded. "As high-risk transmitters are 'kept out of the pool,' onwards transmission will be prevented for a shorter or longer period. In a public health perspective, high-risk individuals should thus be targeted and prioritized for treatment. This approach is now highlighted in international guidelines for HCV treatment."
Simmons did not respond to a request for comments.
SOURCE: bit.ly/1TgbsET
Clin Infect Dis 2016.
Posted by HCV New Drugs at Wednesday, February 17, 2016 No comments: Links to this post
File Under HCV News, svr durability
Is cure of hepatitis C with medications possible? What defines a cure?
Is cure of hepatitis C with medications possible?
What defines a cure?
By Donald Jensen, MD
Hepatitis Expert
The term 'cure' is such a powerful word with such important implications that liver specialists and virologists avoided using it for decades to describe one outcome of hepatitis C therapy (WebMD). The hepatitis C virus is virus that needs to continue to replicate in the liver to survive. There is no ability of HCV to become dormant or go into a state of suspended animation. Therefore, if HCV is suppressed with treatment for a sufficient period of time, the virus cannot survive.
Posted by HCV New Drugs at Thursday, November 12, 2015 No comments: Links to this post
File Under HCV News, svr, svr durability
SVR durability using new interferon-free DAAs in comparison to SVR with interferon-based regimens
In this month's issue of HCV Next, Michael S. Saag, MD., writes about SVR durability using new all-oral, interferon-free DAAs in comparison to SVR with interferon-based regimens, noting some experts suggest there may be a difference.
Here is the editorial;The Unintended Consequences of Conservatism
Each issue of "HCV Next" offers information on a range of topics which include hepatitis C therapies, side effects, drug/drug interaction, guidelines, fatty liver disease and more.
Check out the following articles that appeared in the May 2015 print edition of HCV Next published online at Healio.
The Unintended Consequences of Conservatism
Why should we doubt that SVR due to DAA therapy is any different than an SVR obtained with interferon-based therapy?
A Conversation with Andrea L. Cox, MD, PhD
Business is Booming: Weighing the Wisdom of Expanded HCV Screening
Many organizations, including the CDC, have endorsed expanding widespread screening for hepatitis C virus, but experts writing in The BMJ warn that physicians should resist screening until more evidence on the risk-benefit ratio and long-term clinical improvements with antiviral therapy becomes available.
HCV Genotype 4: A Global Challenge
A number of recent studies demonstrated that, when treated with direct-acting antivirals, there were comparable response rates in patients with hepatitis C virus genotype 4 as those reported for other genotypes. That is, upward of 95%. However, experts remain confounded by a host of obstacles that stand in the way of marginalizing — or eradicating — hepatitis C virus genotype 4.
Model Accurately Predicts Rapid Response in HCV at 4 Weeks
Multiple variables, including IL28B genotype with viral load, HCV genotype, Forns' Index and HIV coinfection were used to construct a model that accurately predicted virological response at 4 weeks in patients with hepatitis C virus infection treated with pegylated interferon alfa-2a and ribavirin, according to study data.
PAD Risk Higher for Patients with HCV
Hepatitis C virus infection was associated with a greater risk for peripheral arterial disease, or PAD, in Taiwanese patients, with a nearly 12-fold increased risk in patients older than 65 years, according to study data published in theJournal of Hepatology.
HCV Eradication Leads to Improved Mixed Cryoglobulinemia
In a prospective cohort study, patients who experienced hepatitis C virus infection clearance after treatment with pegylated interferon and ribavirin also had improved mixed cryoglobulinemia, according to data published in Hepatology.
The Impact of NAFLD on Chronic HCV Progression, Treatment Response
Dina Halegoua-De Marzio, MD
HCV and Metabolic Syndrome
Studies have shown that HCV may directly influence glucose metabolism, increase the risk for diabetes and predispose patients to obesity. Beyond the metabolic factors, patients with chronic HCV and insulin resistance may have higher viral loads based on retrospective studies.
FDA Warns of Hepatic Failure, Bradycardia with Simeprevir
The FDA has approved changes to the warnings and precautions label for simeprevir for the treatment of hepatitis C virus infection, indicating that it can cause hepatic decompensation and failure, and serious symptomatic bradycardia when co-administered with sofosbuvir and amiodarone, according to a news release from the FDA.
Rapid HCV Test gets European Approval
FDA Grants New Breakthrough Therapy Designations for Grazoprevir/Elbasvir
The FDA originally granted breakthrough therapy designation for the drug combination in October 2013. However, in February, Merck announced the FDA's intent to rescind that designation due to the availability of other new drugs for HCV. The new breakthrough designations for grazoprevir and elbasvir (MK-5172, MK-8742; Merck) are geared towards treating patients with chronic HCV genotype 1 with end-stage renal disease on hemodialysis and patients with chronic HCV genotype 4, according to the release.
Japan Approves Sofosbuvir for HCV Genotype 2
The Japanese Ministry of Health, Labour and Welfare has approved sofosbuvir to suppress viremia in patients with chronic hepatitis C virus genotype 2 infection, with or without compensated cirrhosis, according to a press release from the drug maker.
Posted by HCV New Drugs at Monday, May 18, 2015 No comments: Links to this post
File Under HCV next, HCV-Education, svr, svr durability
Long-term follow-up of successful hepatitis C virus therapy: waning immune responses and disappearance of liver disease are consistent with cure
Download full text article @ NATAP
Alimentary Pharmacology & Therapeutics March 2015
M. Hedenstierna*,, O. Weiland*,, A. Brass, D. Bankwitz, P. Behrendt, I. Uhnoo, S. Aleman**, K. Cardell,
A. Fryden, G. Norkrans, A. Eilard, H. Glaumann, T. Pietschmann, M. Sallberg & E. D. Brenndorfer
*Department of Infectious Diseases, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Institute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.
Department of Infectious Diseases, Akademiska University Hospital, Uppsala, Sweden.
**Department of Gastroenterology and Hepatology, Karolinska University Hospital Solna and Huddinge, Stockholm, Sweden.
Department of Infectious Diseases, University Hospital, Linkoping, Sweden. Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden.
Clinical Pathology and Cytology, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
A sustained viral response (SVR) after interferon-based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work-up with highly sensitive HCV RNA detection, and the determination of immune responses.
To determine clinical, histological, virological and immunological markers 5-20 years after SVR.
In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV-specific T-cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3-specific antibodies and virus neutralisation.
Liver disease regressed significantly in all patients, and 51 were HCV RNA-negative in all tissues tested. There was an inverse association between liver disease, HCV-specific T-cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5-9 years after SVR. All three had HCV-specific T cells and NS3 antibodies, but no cross-neutralising antibodies.
Our combined data confirm that a SVR corresponds to a long-term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease.
Full Text Available @ NATAP
Posted by HCV New Drugs at Friday, April 17, 2015 No comments: Links to this post
Sustained virological response after treatment in chronic hepatitis C - five year follow up
Sustained virological response after treatment in patients with chronic hepatitis C infection - a five year follow up
DOI: http://dx.doi.org/10.3329/bmrcb.v39i1.15791
Rahman MZ1, Ahmed DS1, Masud H1, Parveen S2, Rahman MA1, Chowdhury MS1, Barua R1, Ishaque SM1 1Department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, 2Department of Paediatrics, BSMMU, Dhaka.
Peginterferon α-2a and ribavirin combination therapy achieves a sustained virological response (SVR) in patients with chronic hepatitis C. Little is know about long-term durability of hepatitis C virus – Ribonucleic acid (HCV-RNA) negativity in patient treated with pegylated interferon and ribavirin therapy.
Aim of this study was to evaluate the durability of virologic response in patients with SVR to anti-viral therapy treated at our centre. A total of 52 patients with chronic hepatitis C virus infection who had obtained SVR after Peginterferon α-2a and ribavirin combination therapy were followed up to 5 years with annual HCV-RNA testing. During this follow up period, 4 of 52 patients with initial SVR developed late relapse of hepatitis C virus infection. Relapse was more common in patients who has cirrhosis (3/6 [50%]) vs (1/46 [2.17%]) without cirrhosis.
In conclusion, SVR is durable in most patients, but some patients do have late relapse; long term follow up may be particularly important in a subset of patients with hepatitis C virus infection who have liver cirrhosis.
Discussion Only
Full text available here, or Download PDF file here
Infection with hepatitis C virus is a leading cause of liver disease worldwide1,2. Progression to chronic hepatitis C occurs in most people acutely infected with HCV and persistent infection is an important cause of cirrhosis, end stage liver disease and hepatocellular carcinoma. Thus, early detection and treatment is of great importance. The goal of treatment is to prevent complications of HCV infection3,4.
There have been substantial improvements in the success of HCV treatment and there are currently several treatment regimens approved by the FDA. In randomized clinical trials, the highest overall SVR rated have been achieved with the combination of weekly subcuataneous injection of long acting peginterferon α-2a and daily oral ribavirin, which represents the current standard of care12-14. Nevertheless, little is known on the outcome of patients treated with PEG-IFN/ribavirin combination therapy.
Recently, swain et al. evaluated the durability of SVR after the treatment with peginterferon α-2a ± ribavirin in 845 patients, who had participated in pivotal trials15 and achieved SVR.
Only in seven patients (<1%), HCV-RNA was detected (after 391-1076 days of treatment). All these data indicate that the late relapse after SVR in chronic hepatitis C patients following anIFN-based anti-viral therapy is rare16-19.
This is the first study from Bangladesh on long term outcomes of anti-viral therapy for chronicHCV infection.
Our study shows that SVR is durable in a majority of patients but late relapses do occur. These relapses occur more commonly in patients with cirrhosis. Our study revealed late relapses in 7.69% over 5 year follow up. One reason for high late relapse in our study could be due to presence of poor baseline predictors of response: obesity i.e., BMI>30 (n=3), alcohol intake (n=1) and cirrhosis (n=3). In addition, on retrospective analysis we found that mean dose of ribavirin and peginterferon used in these patients was suboptimal as dose reductions were required more frequently due to severe adverse effects.
A theoretical explanation for late relapse could be persistence of undetected occult hepatitis C virus in hepatocytes, PBMCs, lymphocytes or macrophages.
There are several limitations of the study. Liver biopsy was not done. So histological relapse could not be seen. Similarly, retesting of genotype/sequencing was not done and possibility of reinfection cannot be ruled out.
SVR once achieved is sustained in majority of patients. The treating hepatologist need to be aware of occurrence of late relapses in patients with chronic HCV infection with cirrhosis.
Full Text - Download this PDF file
Of Interest - July 2013
Durability of sustained virologic response in chronic hepatitis C.
Posted by HCV New Drugs at Thursday, August 08, 2013 No comments: Links to this post
Gut Liver. 2013 Jul;7(4):458-61. doi: 10.5009/gnl.2013.7.4.458. Epub 2013 Jun 20.
Durability of sustained virologic response in chronic hepatitis C
Uyanikoglu A, Kaymakoglu S, Danalioglu A, Akyuz F, Ermis F, Pinarbasi B, Demir K, Besisik F, Cakaloglu Y.
Department of Gastroenterology, Harran University Faculty of Medicine, Sanliurfa, Turkey.
BACKGROUND/AIMS:
The aim of this study is to investigate the rate of sustained virologic response (SVR) in chronic hepatitis C patients receiving antiviral treatment.
The files of patients with chronic hepatitis C treated with interferon±ribavirin between 1995 and 2009 were reviewed retrospectively. Six months after the end of treatment, patients with negative hepatitis C virus (HCV)-RNA (<50 IU/mL, as determined by the polymerase chain reaction method) were enrolled in the study.
The mean age of 196 patients (89 males) was 46.13±11.10 years (range, 17 to 73 years). In biopsies, the mean stage was 1.50±0.94; histological activity index was 7.18±2.43. In total, 139 patients received pegylated interferon (IFN)+ribavirin, 21 patients received classical IFN+ribavirin, and 36 patients received IFN alone. The HCV genotypes of 138 patients were checked: 77.5% were genotype 1b, and 22.5% were other genotypes. After achievement of SVR, the median follow-up period was 33.5 months (range, 6 to 112 months), and in this period relapse was only detected in two patients (1.02%) at 18 and 48 months after treatment.
In total, 98.9% of patients with SVR in chronic hepatitis C demonstrated truly durable responses over the long-term follow-up period of 3 years; relapsed patients had intermittent or low-grade viremia.
Chronic hepatitis C, Interferons
Full Text Available Here
Regular and long-term follow-up of patients with SVR was not well documented. The current study evaluates the long term results of SVR. In standard interferon or IFN/ribavirin combination therapies, HCV-RNA was negative for 92% to 100% of patients during the follow-up of 1 to 12 years following SVR in patients with chronic hepatitis C.
Recent studies reported that cure for HCV infection was achieved with SVR. Additionally, histological improvement was detected in 94% of the patients and persistently normal ALT levels were detected in 93%.
Our results also confirmed these data and HCV-RNA level was not detectable in the long term for 99.4% of the patients. ALT was determined to be within normal limits for 153 patients (94%) in the final control.
The available data was relatively less for PEG-IFN/ribavirin combination. In a study by Swain et al follow-up of 845 patients who achieved SVR with interferon alpha 2a±ribavirin revealed that HCV-RNA was detected in only seven patients (<1%) within 391 to 1,076 days after treatment. For treatments based on PEG-IFN, it was concluded that late relapse was rare after achievement of SVR. More than half (65%) of our patients received PEG-IFN/ribavirin treatment, with results supporting this study. PEG-IFN + ribavirin treatment appears to have good long term results.
In chronic hepatitis C treatment, it is still uncertain whether complete elimination is achieved as a result of the treatment or whether a small number of viruses persist. In former studies using less sensitive tests, 95% of the patients with SVR had undetectable levels of HCV-RNA in the liver within 1 to 2 years after treatment. Only two of the seven patients with HCV-RNA detected in the liver after treatment relapsed after 4 years. In another study, none of the 17 patients with negative HCV-RNA detected in the liver after treatment relapsed at the end of 12 years.
On the other hand, only two of the 17 patients with negative HCV-RNA resulting from IFN+ribavirin had negative HCV-RNA in all of their body components including hepatocyte, serum, peripheral blood mononuclear cell, lymphocyte, and macrophage cultures. This suggests that there is a probability of relapse after many years.
The clinical significance of low-level HCV-RNA persistence is unknown and further studies must be performed for this issue. For two of our 196 patients with SVR, HCV-RNA was determined to be positive at a low level at months 18 and 48; however, when both observations were repeated after 3 months they were noted to be negative. The exact reason for transient positivity of HCV-RNA was not clear. It was determined that patients with SVR demonstrated truly durable viral responses and relapsed patients had intermittent and low-grade viraemia.
SVR presumably prevents HCC development. None of our patients with SVR demonstrated HCC on long term follow-up. Improvements in liver fibrosis, biochemical indicators, fatigue, and life quality
were detected with SVR. In our batch, no data was available concerning improvements in fibrosis, as there were no adequate end-of-therapy control liver biopsies.
When pretreatment ALT levels were compared with ALT on the last control (101.72±78.84 IU/mL [range, 12 to 465 IU/mL] vs 22.52±11.73 IU/mL [range, 8 to 84 IU/mL]), further improvement was observed (p<0.05).
In conclusion, it was found that patients with SVR in chronic hepatitis C demonstrated truly durable responses in the long term follow-up period of 3 years on average and that there was no complication related with liver disease throughout this period
Gut and Liver 2013 Jul; 7(4): 458-461/ Download Full Text
Posted by HCV New Drugs at Wednesday, July 31, 2013 No comments: Links to this post
File Under hcv abstracts, HCV News, svr, svr durability
SVR after triple therapy maintained long-term durability in HCV patients
Rutter K. Aliment Pharmacol Ther. 2013;38:118-123.
Source - Healio
Nearly all patients with chronic hepatitis C who achieved sustained virologic response to therapy with pegylated interferon, ribavirin and direct-acting antivirals continued to have undetectable HCV RNA over long-term follow-up in a recent study.
Researchers followed 103 white patients with chronic HCV who had participated in randomized, controlled trials or an extended access program in which they achieved sustained virologic response (SVR) at 24 weeks after completing combination therapy with peginterferon alfa-2a and ribavirin and a direct-acting antiviral (DAA). Evaluated DAAs included protease inhibitors (90.3% of cases), NS5B polymerase inhibitors (6.8%) and both in combination (2.9%). Patients were followed for a median of 21 months after achieving SVR (range 7 to 64 months).
The cohort included 80 treatment-naive patients, 17 who had been nonresponsive and six who had relapsed during prior therapy. Nearly all patients were infected with HCV genotype 1, including 34 with genotype 1a and 67 with 1b, while two patients had genotype 4.
Relapse occurred in two patients who had genotype 1b and had been treated with faldaprevir. Both patients achieved undetectable HCV RNA levels at 4 weeks, and cloning sequencing after relapse indicated identical sequences to those observed at baseline. Viral resistance was unseen in either case.
One treatment-naive, noncirrhotic woman who relapsed had detectable HCV RNA 8 months after therapy cessation, which increased to pretreatment levels in subsequent months. Retreatment with 24 weeks of peginterferon, ribavirin and telaprevir resulted in undetectable RNA levels. The second relapser, a treatment-naive cirrhotic man, had detectable HCV RNA 12 months after therapy ended that returned to pretreatment levels shortly after detection.
"To the best of our knowledge, this is the first study reporting long-term virological outcomes in patients with hepatitis C after successful antiviral triple therapy," the researchers wrote. "Our study shows that HCV eradication by triple therapy remains durable and confirms an excellent long-term prognosis of HCV patients with SVR. To assess the long-term clinical benefit of triple therapy, studies with a longer follow-up and larger patient numbers are needed."
Disclosure: See the study for a full list of relevant disclosures.
William Carey
Sustained virological response, historically, has been tantamount to a cure in patients who are treated for hepatitis C. The problem, of course, is that with every change in therapy, it's necessary to validate that the concept of SVR - no virus detectable in the blood 6 months after stopping treatment - actually applies. It applies for pegylated interferon and ribavirin, and now we're seeing evidence that it also applies when we're using direct-acting antiviral agents in addition.
[This is] an important study to do. I think the strength of it is that it has at least a moderate number of patients, over 100, and they found, not surprisingly, that SVR 24 weeks after stopping treatment seems to be associated with permanent eradication of detectable virus. Again, this is not surprising, but still an important detail that needs to be hammered out, and the study goes a long way toward doing that.
The limitations of the study are that they looked at many different direct-acting agents, and so the number of patients treated with any particular direct-acting agent is somewhat limited. This really comes into focus when we look at the two breakthrough patients: They were both treated with the same drug. So [the study] raises, but doesn't answer the question: "Is faldaprevir different than the other agents that were tested?" It's really impossible to say, because the numbers are too small, but it raises the question of whether this agent is going to be associated with a higher rate of breakthrough than the other agents tested here.
Instead of 100 patients, I'd like to see 1,000, and certainly there are many many hundreds of patients who have been in randomized trials, and this data is or will soon become available. So I think that this is a good beginning, but we just need to see larger numbers, and we need to see numbers that are specific to each and every direct-acting antiviral drug.
William Carey, MD
Professor of medicine, Cleveland Clinic Liver College of Medicine
Founding member, Cleveland Clinic Hepatology section
Disclosures: Dr. Carey reported no relevant financial disclosures.
http://www.healio.com/infectious-disease/hepatitis-resource-center-2013/svr-after-triple-therapy-maintained-long-term-durability-in-hcv-patients
Posted by HCV New Drugs at Thursday, June 20, 2013 No comments: Links to this post
File Under boceprevir-victrelis, faldaprevir, HCV News, svr, svr durability, telaprevir-incivek
Hepatitis C:Impact of a sustained virological response on the long-term outcome
Impact of a sustained virological response on the long-term outcome of hepatitis C
Alfredo Alberti
Article first published online: 4 JAN 2011
© 2011 John Wiley & Sons A/S
A sustained virological response (SVR), defined as undetectable hepatitis C virus (HCV)-RNA 24 weeks after withdrawal from therapy (SVR-24w), is the primary endpoint of antiviral therapy in chronic hepatitis C. There is solid evidence that patients who reach this target will remain virus free during long-term follow-up, with a risk of late HCV recurrence of <2>
However, most available data suggest that SVR following antiviral therapy reduces the risk of progression to cirrhosis and may prevent the development of severe liver complications and improve survival, at least in successfully treated patients who have already progressed to significant liver fibrosis or early cirrhosis. Outcome modelling suggests that these effects might also include HCV patients treated with milder forms of liver damage. The primary endpoint of antiviral therapy for chronic hepatitis C is achieving sustained virological response (SVR), defined as undetectable hepatitis C virus (HCV)-RNA in serum 24 weeks after stopping antiviral therapy (SVR-24w). This is the endpoint used in all clinical trials to assess therapeutic interventions as well as by clinicians treating patients.
This is because a large body of evidence exists that SVR-24w is an excellent surrogate endpoint to identify a permanent virological cure in most patients, with a clear clinical benefit in many of them. While it has been fairly easy to show that SVR-24w is associated with an extremely low risk of persistent HCV or recurrence during longer follow-up, data on the impact of SVR for more specific clinical endpoints have been limited by the heterogeneity of the initial presentation and rate and speed of chronic hepatitis C disease progression. It is clear from studies on the natural history of HCV that a minority of patients with chronic infection develop significant life-long clinical complications, and it is also well known that current clinical practice has extended the indication to start antiviral therapy to patients with the mild or moderate hepatitis C, whose risk of progression is often difficult to define.
When these patients receive antiviral therapy, data show that SVR improves quality of life and reduces the risk of histological progression. Although there is no direct evidence, outcome modelling suggests that there may be significant effects on clinical complications and survival in a subgroup of patients at risk of more rapid disease progression. On the other hand, solid evidence shows that the risk of developing end-stage liver disease, portal hypertension and hepatocellular carcinoma (HCC) is reduced in patients with more advanced liver disease or cirrhosis who achieve SVR with antiviral therapy. In this chapter, we briefly discuss the data on the impact of SVR on long-term HCV eradication as well as on biochemical, histological and clinical outcomes in patients with hepatitis C depending on the phase of liver disease when therapy was begun.
There is good evidence that HCV permanently disappears from serum when antiviral therapy is successful. Most experts consider this to be the expression of complete and permanent viral eradication, while data on a persistent occult form of HCV in the liver and/or peripheral blood mononuclear cells (PBMC) are not fully convincing. Because HCV-RNA may be negative in serum during and at the end of antiviral therapy and reactivate after treatment withdrawal in a subgroup of patients with incomplete clearance (relapsers), viral negativity must be confirmed during off-therapy follow-up to confirm a definitive cure of hepatitis C. SVR is the primary goal of antiviral therapy in chronic hepatitis C and is classically defined as the absence, by the most sensitive polymerase chain reaction assay, of HCV-RNA in serum, 24 weeks after therapy has been withdrawn (SVR-24w) (1). This has been the definition since standard interferon (IFN) monotherapy was implemented and remained valid for IFN plus ribavirin combination therapy and more recently for pegylated interferon (PEG-IFN) plus ribavirin combination regimens. The SVR-24w definition of response to therapy will be maintained when new strategies of HCV treatment, including direct antiviral agents, are introduced into clinical practice. Indeed, most published studies as well as extensive clinical experience show that an absence of HCV-RNA in serum 6 months after therapy is the best indicator of HCV clearance, whatever the HCV genotype, patient characteristics, type and duration of treatment. This has been confirmed in several studies evaluating the long-term virological profile in large cohorts of patients treated with different schedules of IFN-based therapies and tested for HCV recurrence several months or years after having achieved SVR-24w.
Recently, Welker and Zeuzem (2) reviewed available data on the rates of late virological relapse in hepatitis C patients treated with IFN (or PEG-IFN) therapy with a sustained response based on the 24 week off-therapy rule. The authors identified 44 studies, including more than 4200 patients who had been followed up to 108 months after the end of therapy. Overall, late virological relapses were rare (3%). There was considerable heterogeneity among the different studies, with some of the smaller series reporting the highest rates of HCV recurrence. On the other hand, the larger series and those with the most stringent criteria to define SVR conclude that negative HCV-RNA in serum 24 weeks after the end of therapy is associated with a durable response and no recurrence of HCV during follow-up in more than 98% of cases.
Some studies have suggested that HCV-RNA may persist in the liver and/or in PBMC in patients who achieve SVR after antiviral therapy and with undetectable HCV-RNA in serum (3, 4). The significance of these findings is uncertain but most available data suggest that they are not clinically significant, at least in the immunocompetent host.
Thus, patients achieving SVR-24w with antiviral therapy can be considered clinically cured of viral infection, with an extremely low risk of late virological recurrence. If this occurs, reinfection rather than a 'true' relapse could be suspected and should be evaluated carefully.
Recently, it has been proposed that a 12-week post-treatment follow-up might be as relevant as 24 weeks to determine the sustained virological response in patients with hepatitis C virus receiving PEG-IFN and ribavirin (5).
Alanine transaminase (ALT)/aspartate aminotransferase (AST) levels markedly improve in most patients who achieve SVR with antiviral therapy and permanently normalize in many (6, 7). The mean ALT and AST activities after therapy are significantly lower than the pretreatment baseline levels even in HCV carriers who began antiviral therapy with 'normal' ALT levels (8). Indeed, eradication of HCV by antiviral therapy in these cases is associated with a significant improvement in liver enzyme levels, which decrease from pretreatment 'high normal' to post-treatment 'low normal' levels. These findings suggest the presence of ongoing marginal liver disease activity even in HCV carriers with 'normal' range ALT levels, in agreement with histological findings of inflammation and fibrosis in around 15–25% of these patients (9).
On the other hand, liver enzymes may not normalize completely in patients with cirrhosis who achieve SVR. The discrepancy between biochemical and virological outcomes does not exclude a clinical benefit and is probably a sign of profound irreversible changes in hepatocyte metabolism from advanced cirrhosis.
As a general rule, other causes of liver damage (coinfections, alcohol, drugs, metabolic abnormalities) should be investigated in patients who achieve SVR with antiviral therapy but still have elevated ALT and/or AST.
Many studies have described the histological outcome following antiviral therapy for chronic hepatitis C and have clearly identified some major differences among non-responders, partial responders, relapsers and sustained responders (10–15). Although the benefit to disease activity and progression with a partial or a transient virological response remains controversial, these studies clearly confirm that SVR is associated with histological improvement in disease activity and associated fibrosis. Liver steatosis is also improved when it is directly linked to HCV as for HCV-3.
The type and degree of histological benefit after SVR is highly dependent on pretreatment activity, the stage of liver disease and the interval between end of therapy and liver biopsy. Improvement in liver inflammation is more evident when a liver biopsy is obtained years rather than months after the end of therapy. The effect of time is even more evident for the regression of liver fibrosis. Available studies indicate that liver inflammation resolves in most, if not all, patients after SVR while improvement in fibrosis (regression) is found in 25–80%, worsening (progression) in only 0–12, and 16–68% remain stable. These results are significantly different from those in patients who do not achieve SVR. Table 1 describes some studies that have evaluated histological outcome after SVR using paired liver biopsies before and at different intervals after antiviral therapy. Available cumulative data on progression to cirrhosis have indicated that the risk after 1–10 years is reduced from 7–10% in non-responders to 0.5–1% in sustained responders, although it should be emphasized that patients who achieve SVR might have a milder and less progressive form of liver disease compared with non-responders.
Table 1. Histological changes in the liver in patients achieving sustained virological response during antiviral therapy for chronic hepatitis C Authors
Click to Enlarge Table 1
Reversal of histological cirrhosis has been reported in patients achieving SVR with antiviral therapy. Although in most patients the benefit was limited to regression to METAVIR stage 3, i.e. advanced fibrosis with bridging, a histological sampling error cannot be excluded, other patients have been shown to achieve more marked and permanent histological benefit with regression from signs of cirrhosis to minimal-mild fibrosis.
Recent non-invasive markers of liver fibrosis, such as the FibroTest and FibroScan, have become important new tools for the management of patients with chronic hepatitis C. Results in patients receiving antiviral therapy have confirmed a marked improvement in liver fibrosis indexes following SVR (16, 17). Further validation for the optimized use of these methods during and after antiviral therapy is ongoing in several centres
Sustained virological response and clinical outcomes
Morbidity and mortality in chronic hepattis C infection are mainly associated with the complications of cirrhosis and the development of HCC, as well as an increased risk in liver-related deaths. It is therefore essential to assess the impact of SVR on these clinical outcomes. Because of the heterogeneity of the clinical presentation of chronic HCV infection, the slow and unpredictable progression and the lack of longitudinal studies of adequate size and duration, the impact of antiviral therapy and SVR on liver-related complications and mortality has been difficult to determine, especially in patients with milder forms of HCV-related liver disease. Although the endpoint of SVR is clearly associated with reduced histological disease progression in these patients, there is no clear evidence that this will result in reduced morbidity and mortality. At present, many patients with mild chronic hepatitis C are treated with antiviral therapy, especially younger patients or those infected with easy to clear HCV genotypes.
High SVR rates are achieved in these patients and outcome modelling also suggests that successful antiviral therapy could reduce the clinical burden of their disease. On the other hand, there are also convincing results associating a marked improvement in quality of life with SVR after antiviral therapy. This effect is largely independent of the stage of disease when treatment is begun (18). The clinical benefit associated with HCV clearance at any stage of chronic HCV infection is supported by recent results in a large population-based survey by Omland and Krarup (19), showing that overall life-long mortality as well as liver-and HCC-related mortality were significantly lower in HCV patients who showed a clearance of viraemia than in those with chronic viraemia.
Unlike the data for patients with milder forms of chronic hepatitis C, several studies have clearly shown that antiviral therapy with SVR is associated with a marked improvement in clinical outcomes in patients with advanced fibrosis or compensated cirrhosis. Indeed, most studies show that ascites, hepatic encephalopathy, jaundice or gastrointestinal bleeding are extremely rare after SVR has been achieved. Development of hepatocellular carcinoma is also significantly reduced, but patients with cirrhosis who clear HCV during antiviral therapy are still at a risk of developing HCC. Although the risk is certainly much lower than in age/gender/race-matched patients with active disease, continued monitoring is recommended
One of the most recent reports on the impact of combination PEG-IFN and ribavirin therapy on clinical outcome and complications in patients with chronic hepatitis C and advanced fibrosis is that of Cardoso et al. (20). These authors describe long-term outcomes in 307 patients with chronic hepatitis C and advanced fibrosis (127 cases) or cirrhosis (180 cases) treated with PEG-IFN plus ribavirin and followed up for a mean 3–5 years after treatment. SVR-24w was found in 33% of the cases, with no significant differences between patients with advanced fibrosis (37%) and cirrhosis (30%). During follow-up, the incidence of liver-related complications, HCC and liver-related deaths per 100 person – years was 0.63, 1.24 and 0.61, respectively, in patients with SVR and 4.16, 5.85 and 3.66, respectively, in patients without SVR. The difference for each outcome was statistically significant P less then 0.001
These results confirm those of several previous studies based on cohorts of patients treated with standard IFN, standard IFN plus ribavirin or PEG-IFN plus ribavirin, showing that antiviral treatment provides a definitive clinical advantage to patients with compensated cirrhosis who tolerate treatment and achieve an SVR. Another recent study published by Bruno et al. (21) reported the effect of antiviral therapy and SVR on portal hypertension in HCV patients with cirrhosis. The authors reported results in 218 patients with cirrhosis who were untreated or treated with IFN--based therapy and followed up for a median 11.4 years. All patients had compensated cirrhosis when therapy began without oesophageal varices. Endoscopic monitoring was performed at 3-year intervals.
None of the patients who achieved SVR developed oesophageal varices during follow-up compared with 32% of untreated patients and 39% of treated patients who did not achieve SVR, showing that SVR clinically improved the development of portal hypertension. In conclusion, SVR improves the clinical outcomes in patients with chronic hepatitis C and advanced fibrosis or compensated cirrhosis. On the other hand, most studies assessing whether a partial response or long-term maintenance therapy with PEG-IFN without viral eradication is beneficial have failed to demonstrate any significant improvement in clinical outcomes (22, 23).
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This is a class designed for those who have already had a minimal exposure to the Italian language and it is taught in an enjoyable and communicative way. Please, call 473 0832 for an assessment of your Italian level.
Please, contact the teacher also if you cannot make it to the scheduled time, as class time could be rearranged, or if you would like individual lessons. This is a continuing class, run in cycles of 8 lessons each, so feel free to contact the teacher to join the class at any time.
The instructor is Antonella Vecchiato, a native speaker of Italian born and raised in Venice. She is a trained linguist (PhD in Linguistics, University of Southern California), and has over 20 years of teaching experience from beginners to advanced courses in universities (USC, Otago), community (Adult Community Education programmes at Logan Park and Bayfield High Schools), and private classes. Antonella is also one of the founders and the current chair of the Dunedin Italian community group, La Piccola Italia, and passionate about introducing the Italian language and culture to Dunedin.


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If you have audio, you might be interested to know about our background music. This was a song sung by the tax rebels and pro-democracy forces in Central Europe during the years 1524-1526. One of the verses of the song comes from an even earlier tax rebellion, in 1381.


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Steered Mixture-of-Experts (SMoE) is a novel framework for representing multidimensional image modalities. In this paper, we propose a coding methodology for SMoE models that is readily extendable to any dimensional SMoE model, thus representing any image modality of any dimension. We evaluate the coding performance of SMoE models of light field video, a 5D image modality, i.e. time, two angular, and two spatial dimensions. The coding consists of the exploiting the redundancy between the parameters of SMoE models, i.e. a set of multivariate Gaussian distributions. We compare the performance of three multi-view HEVC (MV-HEVC) configurations that differ in terms of random access. Each subaperture view from the light field video is interpreted as a single view in MV-HEVC. Experiments validate that excellent coding performance compared to MV-HEVC for low- to midrange bitrates in terms of PSNR and SSIM with bitrate savings up to 75%.
In this paper, we address the handling of independently moving objects (IMOs) in automatic 2D to stereoscopic 3D conversion systems based on structure-from-motion (SfM) techniques. Exploiting the different viewing positions of a moving camera, these techniques yield excellent 3D results for static scene objects. However, the independent motion of any foreground object requires a separate conversion process. We propose a novel segmentation approach that estimates the occluded static background and segments the IMOs based on advanced change detection. The background estimation is achieved applying 2D registration and blending techniques, representing an approximation of the underlying scene geometry. The segmentation process itself uses anisotropic filtering applied on the difference image between original frame and the estimated background frame. In order to render the segmented objects into the automatically generated 3D scene properly, a small amount of user interaction will be necessary, e.g. an assignment of intra-object depth or the object's absolute z-position. Experiments show that the segmentation method achieves accurate mask results for a variety of scenes, similar to the masks obtained manually using state-of-the-art rotoscoping tools. Though, this work contributes to the extension of SfM-based automatic 3D conversion methods for the application on dynamic scenes.
For object analysis in videos such as in video surveillance systems, the preliminary segmentation step is very important. Many segmentation methods using static camera have been proposed in the last decade, but they all suffer in occurrance of object reflection especially on the ground, i.e. reflected regions are also segmented as foregrounds. We present a new method which detects the border between the real object and its reflection. Experiments show that an outstanding improvement of segmentation results are obtained by removing the reflection part of the over-segmented objects.
Forward error correction (FEC) improves the quality of compressed video transmitted through a lossy network for real-time applications such as video streaming. The FEC techniques are generally applied on source video packets at the frame level. In this paper, we propose a technique where the FEC is applied on source packets at the group-of-pictures (GoP) level assuming an MPEG-like compression scheme. We derive analytically an estimate of the average playable frame rate for a given packet loss probability. Our analysis over a range of network conditions indicates that in most practical network conditions, the proposed technique provides a larger playable frame rate compared to the frame-level FEC technique. This analysis results are also validated by video streaming simulations conducted on the NS-2 network simulator.
Speaker change detection (SCD) is a preliminary step for many audio applications such as speaker segmentation and recognition. Thus, its robustness is crucial to achieve a good performance in the later steps. Especially, misses (false negatives) affect the results. For some applications, domain-specific characteristics can be used to improve the reliability of the SCD. In broadcast news and discussions, the cooccurrence of shot boundaries and change points provides a robust clue for speaker changes. In this paper, two multimodal approaches are presented that utilize the results of a shot boundary detection (SBD) step to improve the robustness of the SCD. Both approaches clearly outperform the audio-only approach and are exclusively applicable for TV broadcast news and plenary discussions.
We present a robust and computational low complex method to estimate the physical camera parameters, intrinsic and extrinsic, for scene shots captured by cameras applying pan, tilt, rotation, and zoom. These parameters are then used to split a sequence of frames into several subsequences in an optimal way to generate multiple sprites. Hereby, optimal means a minimal usage of memory while keeping or even improving the reconstruction quality of the scene background. Since wide angles between two frames of a scene shot cause geometrical distortions using a perspective mapping it is necessary to part the shot into several subsequences. In our approach it is not mandatory that all frames of a subsequence are adjacent frames in the original scene. Furthermore the angle-based classification allows frame reordering and makes our approach very powerful.
Image and video-based rendering technologies are receiving growing attention due to their photo-realistic rendering capability in free-viewpoint. However, two major limitations are ghosting and blurring due to their sampling-based mechanism. The scene geometry which supports to select accurate sampling positions is proposed using global method (i.e. approximate depth plane) and local method (i.e. disparity estimation). This paper focuses on the local method since it can yield more accurate rendering quality without large number of cameras. The local scene geometry has two difficulties which are the geometrical density and the uncovered area including hidden information. They are the serious drawback to reconstruct an arbitrary viewpoint without aliasing artifacts. To solve the problems, we propose anisotropic diffusive resampling method based on tensor theory. Isotropic low-pass filtering accomplishes anti-aliasing in scene geometry and anisotropic diffusion prevents filtering from blurring the visual structures. Apertures in coarse samples are estimated following diffusion on the pre-filtered space, the nonlinear weighting of gradient directions suppresses the amount of diffusion. Aliasing artifacts from low density are efficiently removed by isotropic filtering and the edge blurring can be solved by the anisotropic method at one process. Due to difference size of sampling gap, the resampling condition is defined considering causality between filter-scale and edge. Using partial differential equation (PDE) employing Gaussian scale-space, we iteratively achieve the coarse-to-fine resampling. In a large scale, apertures and uncovered holes can be overcoming because only strong and meaningful boundaries are selected on the resolution. The coarse-level resampling with a large scale is iteratively refined to get detail scene structure. Simulation results show the marked improvements of rendering quality.
This paper presents a novel approach for automatic and robust object detection. It utilizes a component-based approach that combines techniques from both statistical and structural pattern recognition domain. While the component detection relies on Haar-like features and an AdaBoost trained classifier cascade, the topology verification is based on graph matching techniques. The system was applied to face detection and the experiments show its outstanding performance in comparison to other face detection approaches. Especially in the presence of partial occlusions, uneven illumination and out-of-plane rotations it yields higher robustness.
A new segmentation approach usable for fixed or motion compensated camera is described. Instead of the often used RGB color space we operate with the invariant Gaussian color model proposed by Geusebroek and temporal information which eliminates unsteady regions surrounded by the moving objects. The Gaussian color model has never been used in video segmentation. Comparison with some state of the art methods in which both subjective and objective evaluation are applied proof the good performance of the proposed method.
In the case of a static or motion compensated camera, static background segmentation methods can be applied to segment the interesting foreground objects from the background. Although a lot of methods have been proposed, a general assessment of the state of the art is not available. An important issue is to compare various state of the art methods in terms of quality (accuracy) and computational complexity (time and memory consumption). A representative set of recent techniques is chosen, implemented and compared to each other. An extensive set of videos is used to achieve comprehensive results. Both indoor and outdoor videos with different environmental conditions are used. While visual analysis is used for subjective assessment of the quality, pixel based measures based on available ground truth data are used for the objective assessment. Furthermore the computational complexity is estimated by measuring the elapsed time and memory requirements of each algorithm. The paper summarizes the experiments and considers the assets and drawbacks of the various techniques. Moreover, it will give hints for selecting the optimal approach for a specific environment and directions for further research in this field.
In this paper, we present an automatic extraction of goal events in soccer videos by using audio track features alone without relying on expensive-to-compute video track features. The extracted goal events can be used for high-level indexing and selective browsing of soccer videos. The detection of soccer video highlights using audio contents comprises three steps: 1) extraction of audio features from a video sequence, 2) event candidate detection of highlight events based on the information provided by the feature extraction Methods and the Hidden Markov Model (HMM), 3) goal event selection to finally determine the video intervals to be included in the summary. For this purpose we compared the performance of the well known Mel-scale Frequency Cepstral Coefficients (MFCC) feature extraction method vs. MPEG-7 Audio Spectrum Projection feature (ASP) extraction method based on three different decomposition methods namely Principal Component Analysis( PCA), Independent Component Analysis (ICA) and Non-Negative Matrix Factorization (NMF). To evaluate our system we collected five soccer game videos from various sources. In total we have seven hours of soccer games consisting of eight gigabytes of data. One of five soccer games is used as the training data (e.g., announcers' excited speech, audience ambient speech noise, audience clapping, environmental sounds). Our goal event detection results are encouraging.
Multiple Description Video Coding (MDC) and Layered Coding (LC) are both error-resilient source coding techniques used for transmission over error-prone channels. Both techniques generate multiple streams. The streams generated by MDC correspond to different descriptions of the same source whereas the streams produced by LC are differentiated as base and enhancement layer streams. Moreover whereas the MDC streams are independently decodable the decoding of the enhancement layer stream is dependent on the decoding of the base layer stream. In this work we concentrate on specific MDC and LC schemes, i.e. Multi-State Video Coding (MSVC) and Temporal Layered Coding (TLC). MSVC was introduced by John Apostolopoulos and it was showed that if each frame is transmitted in a separate packet and if motion information for each lost frame is also lost, MSVC outperforms Single Layer Coding (SC) in recovering from single as well as burst losses. Here we compared MSVC with TLC as an extension of SC based on transmission simulations over lossy channels under the assumption that the motion vectors are always available. Using different coding modes and specific reconstruction methods average reconstructed frame PSNR (peak signal to noise ratio) is measured and compared. Results show that when motion vectors are received TLC performs better than MSVC for every coding option tested. The performance difference is bigger for low motion sequences.
This paper presents a novel approach to human body posture recognition based on the MPEG-7 contour-based shape descriptor and the widely used projection histogram. A combination of them was used to recognize the main posture and the view of a human based on the binary object mask obtained by the segmentation process. The recognition is treated as a typical pattern recognition task and is carried out through a hierarchy of classifiers. Therefore various structures both hierachical and non-hierarchical, in combination with different classifiers, are compared to each other with respect to recognition performance and computational complexity. Based on this an optimal system design with recognition rates of 95.59% for the main posture, 77.84% for the view and 79.77% in combination is achieved.
In this paper, we present a classification and retrieval technique targeted for retrieval of home video abstract using dimension-reduced, decorrelated spectral features of audio content. The feature extraction based on MPEG-7 descriptors consists of three main stages: Normalized Audio Spectrum Envelope (NASE), basis decomposition algorithm and basis projection, obtained by multiplying the NASE with a set of extracted basis functions. A classifier based on continuous hidden Markov models is applied. For retrieval with accurate performance the system consists of a two-level hierarchy method using speech recognition and sound classification. For the measure of the performance we compare the classification results of MPEG-7 standardized features vs. Mel-scale Frequency Cepstrum Coefficients (MFCC). Results show that the MFCC features yield better performance compared to MPEG-7 features.
In this paper, dimension-reduced, decorrelated spectral features for general sound recognition are applied to segment conversational speech of both broadcast news audio and panel discussion television programs. Without a priori information about number of speakers, the audio stream is segmented by a hybrid metric-based and model-based segmentation algorithm. For the measure of the performance we compare the segmentation results of the hybrid method versus metric-based segmentation with both the MPEG-7 standardized features and Mel-scale Frequency Cepstrum Coefficients (MFCC). Results show that the MFCC features yield better performance compared to MPEG-7 features. The hybrid approach significantly outperforms direct metric based segmentation.
Multiple State Video Coding (MSVC) is a Multiple Description Coding Scheme where the video is coded into multiple independently decodable streams, each with its own prediction process and state. The system subject to this work is composed of two subsystems: 1- multiple state encoding/decoding, 2- path diversity transmission system. In  we discussed how to optimize the rate allocation of such a system while maximizing the average reconstructed frame PSNR at the decoder and minimizing the PSNR variations between the streams given the total bitrate RT and the balanced (equal loss probabilities) or unbalanced (unequal) loss probabilities p1 and p2 over the two paths. In our current work we establish a theoretical framework to estimate the rate-(decoder) distortion (R-Dd) function and have taken into account the MSVC-structure, the rate allocation, channel impairments and reconstruction strategies respectively. The video sequence is modeld as an AR(1) source and the distortion associated with each reconstructed frame in both threads is a lossy transmission environment is estimated recursively depending on the system parameters.
Multiple Description Coding is a forward error correction scheme where two or more descriptions of the source are sent to the receiver over different channels. If only one channel is received the signal can be reconstructed with distortion D1 or D2. On the other hand, if both channels rae received the combined information is used to achieve a lower distortion D0. Our approach is based on the Multiple State Video Coding with the novelty that we achieve a flexible unbalance rate of the two streams by varying the quantization step size while keeping the original frame rate constant. The total bitrate Rτ is fixed which is to be allocated between the two streams. If the assigned bitratres are not balanced there will be PSNR variations between neighboring frames after reconstruction. Our goal is to find the optimal rate allocation while maximizing the average reconstructed frame PSNR and minimizing the PSNR variations given the total bitrate Rτ and the packet loss probabilities p1 and p2 over the two paths. The reconstruction algorithm is also taken into account in the optimization process. The paper will report results presenting optimal system designs for balanced but also for unbalanced path conditions.
n this paper we address the user-navigation through large volumes of image data. Similarity-measures based on different MPEG-7 descriptors are introduced and multidimensional scaling is employed to display images in three dimensions according to their mutual similarities. With such a view the user can easily see similarity relations between images and understand the structure of the database. In order to cope with large volumes of images a k-means clustering technique is introduced which identifies representative image samples for each cluster. Representative images (up to 100) are then displayed in three dimensions using multidimensional scaling structuring. The clustering technique proposed produces a hierarchical structure of clusters - similar to street maps with various resolutions of details. The user can zoom into various cluster levels to obtain more or less details if required. Further a new query refinement method is introduced. The retrieval process is controlled by learning from positive examples from the user, often called the relevance feedback of the user. The combination of the three techniques 3D-visualization, relevance feedback and the hierarchical structure of the image database leads to an intuitive browsing environment. The results obtained verify the attractiveness of the approach for navigation and retrieval applications.
In this paper we address the user-navigation through large volumes of image data. A similarity-measure based on MPEG-7 color histograms is introduced and Multidimensional Scaling concepts are employed to display images in two dimensions according to their mutual similarities. With such a view the user can easily see relations and color similarity between images and understand the structure of the data base. In order to cope with large volumes of images a modified version of k-means clustering technique is introduced which identifies representative image samples for each cluster. Representative images (up to 100) are then displayed in two dimensions using MDS structuring. The modified clustering technique proposed produces a hierarchical structure of clusters--similar to street maps with various resolutions of details. The user can zoom into various cluster levels to obtain more or less details if required. The results obtained verify the attractiveness of the approach for navigation and retrieval applications.
A layered Pyramid image coding scheme suitable for interworking of videoconferencing and videophone services is presented in this paper. The scheme proposed takes advantage of inter-layer embedded motion prediction to compress image data on the upper Pyramid enhancement layer. As an important advantage of this scheme we have preserved independence of the coding in the two layers using embedded motion compensation. Thus no information about the coding procedure on the lower resolution layer is needed to encode the upper layer enhancement information. The results are encouraging, showing that the scheme reconstructs images of both CIF and QCIF resolution with good quality and that the scheme is more data efficient than a comparable Simulcast approach.


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FROM PANEL TO PANEL • Fewest Mistakes Win! (Dragon Hoops by Gene Luen Yang)
April 8, 2020 • Cee • Comics
Dragon Hoops by Gene Luen Yang • March 17, 2019 • First Second
Twitter | Goodreads | Amazon | Barnes & Noble | The Book Depository | Indiebound | Indigo | Library
Gene understands stories—comic book stories, in particular. Big action. Bigger thrills. And the hero always wins. But Gene doesn't get sports. As a kid, his friends called him "Stick" and every basketball game he played ended in pain. He lost interest in basketball long ago, but at the high school where he now teaches, it's all anyone can talk about. The men's varsity team, the Dragons, is having a phenomenal season that's been decades in the making. Each victory brings them closer to their ultimate goal: the California State Championships. Once Gene gets to know these young all-stars, he realizes that their story is just as thrilling as anything he's seen on a comic book page. He knows he has to follow this epic to its end. What he doesn't know yet is that this season is not only going to change the Dragons's lives, but his own life as well.
I received this graphic novel for free from First Second for review consideration. This does not affect my opinion of the book or the content of my review.
First sentence: "I've hated sports ever since I was a little kid. Especially basketball."
For all you people who are usually uninterested in basketball (like I am), prepare to become a fan because of Dragon Hoops!
This graphic memoir captivated my attention with the very real people that Gene Luen Yang focus on, the history of basketball through different cultures, and the process Yang goes through to create an accurate portrayal of the events. It'll convince you that you need to be in the front row for all the action at Bishop O'Dowd High School.
Dragon Hoops explores an Oakland high school basketball teams journey to win the basketball state championship.
Set in Bishop O'Dowd High School in Oakland, Yang focuses on this basketball team who have reached the finals of the California state championship, but have never won. 2015 would be different though—it will be the year they win because of the all-star team of players that readers will get to know throughout the graphic memoir.
Yang focuses on a few key players—Coach Lou, Ivan Rabb, Paris Austin, Oderah and Arinze Chidom, Jeevin Sandhu, Alex Zhao, and Austin Walker—and the games that led to their journey to the state championship. He writes these beautiful scenes of these players and their struggles to be where they are at in the book. Readers will get that fire that these characters felt on their journey. It's in the power of Yang's storytelling and drawings. He draws these characters and the basketball games in a way that makes you feel like you're sitting in the front row, and you'll jump out of your seat cheering along.
You get basketball history and its impact on different cultures.
Not only does Yang portray the events leading up to the state championship, he discusses the history of basketball and the impact it has on different types of people and different cultures. Readers learn about how basketball was created, the key basketball players that changed the game like Marques Haynes and George Mikan, the tensions between black and white players when they started playing together, how the Harlem Globetrotters started, how basketball impacted women, how it impacted cultures outside the West, and so on.
I love that these personal stories are framed with history about basketball. It's a way to make you understand why it's an important part of history and why it's important to a lot of people throughout the world.
Dragon Hoops is not only a basketball story; it's a story about Gene Luen Yang's struggle to juggle his life—family, teaching, and making comics—and figure out how he can portray these player's experiences accurately.
There are struggles on and off the court, and for Yang, that's exactly what it feels like minus the basketball. Those moments of struggle that Yang experiences throughout the book—where he has to juggle different aspects of his life and wondering whether to accept a life-changing offer that will affect his future as a comics person—is so well done. It's never distracting; it's rather a reminder that Yang is also on a journey of his own. Basketball is not his life; comics and his family is. Yang has a lot of obligations that pull him in different directions, and it shows with the way he portrays the events and the discussions via the way he talks aloud and with his wife. It's very enlightening and real.
There are moments where Yang steps back from the story to discuss the comic aspect of creating this story.
Yang shows he's very self aware of accurately portraying these characters and their stories in a respectful manner. I love that he discusses his creative process throughout the book. He wonders whether to include certain things or exclude them due to the toughness of the subject matter. He explains the reason why he drew the way he did like the hair of Jeevin Sandhu, the Punjabi basketball player, to set him apart from the Black players. He shows he takes concerns and criticisms to heart, and revises it in real time. There are some embellishments and moments that didn't exist to move the story along, but that's the beauty of a graphic memoir. It is rooted in truth.
Who should read Dragon Hoops? Everybody. Sports fan. Non-basketball fans. People who want to learn a bit about basketball on a comic format.
Should you read Dragon Hoops? Yes! You'll be rooting for the Dragons too!
Tags:gene luen yang • graphic memoir
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redpajama_set_name: RedPajamaCommonCrawl


Studies of Architecture, Urbanism and Environmental Sciences Journal (abbreviation: SAUES) is a bi-annual, international, academic publication by Hakim Sabzevari University focusing on the theoretical, practical and research aspects of the fields of architecture, urbanism, and environmental sciences. SAUES is accessible online under Open Access terms and conditions of the Creative Commons Attribution 4.0 International (CC-BY 4.0) license. The journal aims to provide a scientific forum for gathering distinguished scholars, academics, experts and students interested in interdisciplinary, applied and operational research and practices to share their latest most innovative ideas for resolving the challenges facing today's societies. In other words, the journal aims to build a bridge between theory and practice and connects different viewpoints of resolving challenges and urban problems. Hence, we extend our hand to all scientific communities and individuals concerned in any way with building a lively city or an environment having a high quality of residential standards.


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Bird flu takes steep toll on farmers, consumers
By Adriana Diaz
June 12, 2015 / 7:11 PM / CBS News
The spread of the virus has disrupted the poultry industry's entire supply chain
The spread of the virus has disrupted the pou... 01:57
REMBRANDT, Iowa - Poultry farmers in the U.S. are struggling to contain a crisis triggered by the spread of bird flu.
Dave Rettig, owner of Rembrandt Enterprises in Iowa, in the heart of America's egg producing region. He could only talk to CBS News outside his facility, because it's under quarantine
Rettig's production has dropped 60 percent. He's lost more than 8 million hens to bird flu in less than four weeks, resulting in tens of millions of dollars in losses and forcing hundreds of layoffs.
The bird flu has been detected in 13 states s... 01:53
Nationwide, nearly 49 million birds in 21 states are gone, about a 10 percent drop in egg production. according to the USDA.
It's the worst moment his industry has ever experienced, Rettig says.
"There's nothing that can come close to it," he told us. "Absolutely nothing."
Scientists aren't sure how the virus is spreading. But Rettig calls it a tsunami that's rippling through the egg supply chain, from farms to food companies to truckers.
Loren Bosma owns a trucking company that hauls for Rembrandt. He says chicken-related hauls make up more than 98 percent of his business. Since bird flu hit, orders are down and his revenue has been cut in half. He hopes he doesn't have to lay off workers but admits the future will be challenging.
"My goal is not, but you know, right now I've got to look at the big picture, once I know what the picture is," said Bosma. "Everybody is probably going to have to cut back, but... There could be some short-term layoffs."
The short supply has already driven up prices by an average of 17 cents a dozen, meaning the cost of flu has spread from farm to table.
New evidence revealed in Trump fraud probe
CBS Evening News, January 19, 2022
Reporter Alison Parker and cameraman Adam Ward of Virginia station WDBJ-TV were gunned down on live television Wednesday morning
Man arrested in UCLA grad student stabbing
First published on June 12, 2015 / 7:11 PM


text:
MEET THE FRASERS
VERY CAVALLRI
DATING #NOFILTER
NIGHTLY POP
THE MARILYN DENIS SHOW
You Have to Hear Camila Cabello's Google-Translated Version of Billie Eilish's "Bad Guy"
by Elyse Dupre | Fri., Dec. 6, 2019 4:59 AM
Andrew Lipovsky/NBC
You've never heard Billie Eilish's "bad guy" sung like this before.
Camila Cabello performed a Google-Translated version of the Grammy-nominated hit on Thursday's episode of The Tonight Show. Although, the technological transcription wasn't perfect.
For instance, instead of singing, "So you're a tough guy/Like it really rough guy," the 22-year-old artist sang "An evil young boy/That sounds like a bumpy boy." Similarly, she sang, "My text is evil/Your mom gets kind of weird/My daughter's a desert/Eliminate your dad" instead of the real lyrics, "I'm that bad type/Make your mama sad type/Make your girlfriend mad tight/Might seduce your dad type."
Jimmy Fallon also sang a Google-Translated version of Smash Mouth's "All Star." Instead of singing, "Hey now/You're a rock star/Get the show on/Get paid," the late-night host belted, "Ahoy/You're the stone man/Entertain me/Have cash."
At the end of these performances, the dynamic duo sang a duet of Shaggy's "It Wasn't Me."
Camila Cabello on BF Shawn Mendes: We Collaborate in Life
Watch the video to hear the renditions.
Cabello wasn't the first celebrity to sing a Google-Translated song on The Tonight Show. Anne Hathaway, Kelly Clarkson and Rebel Wilson have tried it, as well.
Camila Cabello Explains Why "Senorita" Took So Long
Of course, if fans want to hear some of Cabello's original songs, they can listen to her new album Romance, which is out now.
Get to Know Tank and the Bangas, Best New Artist Nominee at This Year's Grammys
How to Watch the 2020 Grammys on TV and Online
Secret Tattoos and an Affair That Nearly Killed Her: Inside Dolly Parton's Endlessly Fascinating World
Céline Dion Pays Touching Tribute to Late Mother Onstage at Concert
Luis Fonsi Thanks Both New & Old Fans for ''Celebrating Latin Music'' Ahead of the 2020 Grammys
Luis Fonsi & "Despacito": 20-Year Journey to 2020 Grammys
TAGS/ Camila Cabello , Billie Eilish , Jimmy Fallon , The Tonight Show , , Music , Celebrities , Top Stories , Apple News
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This mammoth wine of unparalleled length and complexity, this '14 Château is loaded with dark cherry, violets and hints of earth. Rich, sappy Pinot Noir fruit is underlain by an almost weightless body. The grapes for this wine enjoy temperature-controlled fermentation, and the wine ages in barrel for 14 to 18 months before bottling.


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Nicholas Raymond Guydosh, Ph.D.
Stadtman Investigator
Section on mRNA Regulation and Translation, Laboratory of Biochemistry and Genetics
Building 8, Room 220
8 Center Dr
nicholas.guydosh@nih.gov
We seek to discover how cells control the expression of genes during translation by the ribosome. We're interested in both the mechanisms that underlie the basic steps of translation—particularly termination and recycling—and how these processes are regulated to carry out cellular functions.
The translation of the genetic code is a highly regulated process that is fundamental to life. All cells have evolved elaborate mechanisms for determining which RNA messages get translated, how frequently and where they are translated, and whether errors occur. We employ multi-disciplinary approaches such as ribosome profiling, biochemical techniques, and computational tools to investigate how translation is regulated to control the expression of genes in yeast and mammalian cultured cells. We're also developing single-molecule fluorescence methods to address mechanistic questions about ribosome function.
We recently discovered that failure to properly remove (recycle) ribosomes from mRNAs at stop codons leads to reinitiation of translation in 3'UTRs and the production of short peptides. We're now investigating the mechanism of this non-canonical process and potential functions for the peptide products in helping cells respond to stress, such as nutrient starvation and viral infection. We're also interested in the "rescue" process that takes place when ribosomes arrest after translation of particular sequences, such as the poly(A) tail of prematurely polyadenylated mRNAs.
We're also pursuing general questions of how translation is coupled to mRNA decay and protein localization.
Applying our Research
The ribosome is central to gene expression so our basic work on ribosome function is critical for developing models of disease. In particular, we are examining how changes in the translational machinery during viral infection lead to the production of non-canonical peptides that can be used during the innate immune response. We are also looking at how environmental stress and changes in nutrient levels alter the translational program of a cell. Outcomes of this research will help guide the development of new therapies in the areas of infectious disease, aging, and cancer.
Postdoctoral Fellow, Johns Hopkins University School of Medicine, 2009-2016
Ph.D., Stanford University, 2009
M.Phil, University of Cambridge, 2003
A.B., Harvard University, 2001
Young DJ, Makeeva DS, Zhang F, Anisimova AS, Stolboushkina EA, Ghobakhlou F, Shatsky IN, Dmitriev SE, Hinnebusch AG, Guydosh NR. Tma64/eIF2D, Tma20/MCT-1, and Tma22/DENR Recycle Post-termination 40S Subunits In Vivo. Mol Cell. 2018.
Young DJ, Guydosh NR, Zhang F, Hinnebusch AG, Green R. Rli1/ABCE1 Recycles Terminating Ribosomes and Controls Translation Reinitiation in 3'UTRs In Vivo. Cell. 2015;162(4):872-84.
Guydosh NR, Kimmig P, Walter P, Green R. Regulated Ire1-dependent mRNA decay requires no-go mRNA degradation to maintain endoplasmic reticulum homeostasis in <i>S. pombe</i>. Elife. 2017;6.
Guydosh NR, Green R. Dom34 rescues ribosomes in 3' untranslated regions. Cell. 2014;156(5):950-62.
Guydosh NR, Green R. Translation of poly(A) tails leads to precise mRNA cleavage. RNA. 2017;23(5):749-761.
Biomedical Engineering and Biophysics
View additional Principal Investigators in Biomedical Engineering and Biophysics
View additional Principal Investigators in Computational Biology
View additional Principal Investigators in RNA Biology
This page was last updated on June 25th, 2019


Welp… It's that time again. We humbly present to you, dear reader (and listener) the fourth Metro Silicon Valley podcast, which we are tentatively calling SV411. In this 'cast, Metro Managing Editor Josh Koehn and A&E Editor Nick Veronin discuss this week's issue.
All Hallows' eve falls on a Monday this year, but that doesn't mean the parties are packing it in. Check out this list of haunted houses, masquerade balls, costume contests and Dia de Los Muertos celebrations.


Bradley Cooper and Lady Gaga were nominated for best actor & actress for 'A Star Is Born'.
Almost every official portrait or statue of Nehru across India shows Nehru wearing a rose it.
The decision is applicable for both non-SSI (small scale industry) and SSI-manufactured drugs.


On our way to Svaneti, we will visit an Enguri Water Reservoir – the biggest hydroelectric power station in Caucasus. From there to Svaneti road goes through the picturesque nature and is very good for adrenaline lovers. The final destination is Mestia, capital city of the region. From Mestia we will take an off-road cars to explore the glaciers, forests and Caucasus mountains. There are places reachable only by pathway, so we will have to walk. It's a real gift for the lovers of adventure, nature and active rest..
Later we will take a lift to the mount Zuruldi at an altitude of 2400 m above the sea level to take a look on the Caucasus mountains, Mt. Ushba which peak is covered with snow all year long. You will be delighted by the nature around you and full with these emotions we will return to the azure costs of the black sea – to Batumi.