Hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in genotype-4 chronic hepatitis C patients.

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Helal, Gouda Kamel; Gad, Magdy Abdelmawgoud; Abd-Ellah, Mohamed Fahmy; Eid, Mahmoud Saied

2016-12-01

The therapeutic effect of pegylated interferon (peg-IFN) alfa-2a combined with ribavirin (RBV) on chronic hepatitis C Egyptian patients is low and further efforts are required to optimize this therapy for achievement of higher rates of virological response. This study aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) in combination with pegylated interferon plus ribavirin on early virological response (EVR) in chronic hepatitis C Egyptian patients. Naïve 120 Egyptian patients with chronic hepatitis C virus infection were divided into two groups. Group 1 have administered the standard of care therapy (pegylated interferon alfa-2a plus ribavirin) for 12 weeks, (n = 60). Group 2 have administered hydroxychloroquine plus standard of care therapy for 12 weeks, (n = 60). Therapeutics included hydroxychloroquine (200 mg) oral twice daily, peginterferon alfa-2a (160 μg) subcutaneous once weekly and oral weight-based ribavirin (1000-1200 mg/day). Baseline characteristics were similar in the two groups. The percentage of early virological response was significantly more in patients given the triple therapy than in patients given the standard of care [54/60 (90%) vs. 43/60 (71.7%); P = 0.011; respectively]. Biochemical response at week 12 was also significantly higher in patients given the triple therapy compared with the standard of care [58/60 (96.7%) vs. 42/60 (70%); P hydroxychloroquine to pegylated interferon plus ribavirin improves the rate of early virological and biochemical responses in chronic hepatitis C Egyptian patients without an increase in adverse events. J. Med. Virol. 88:2170-2178, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention?

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Gurusamy, Kurinchi S; Wilson, Edward; Koretz, Ronald L

2013-01-01

Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.......Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs....

On the front line of HIV virological monitoring: barriers and facilitators from a provider perspective in resource-limited settings.

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Rutstein, S E; Golin, C E; Wheeler, S B; Kamwendo, D; Hosseinipour, M C; Weinberger, M; Miller, W C; Biddle, A K; Soko, A; Mkandawire, M; Mwenda, R; Sarr, A; Gupta, S; Mataya, R

2016-01-01

Scale-up of viral load (VL) monitoring for HIV-infected patients on antiretroviral therapy (ART) is a priority in many resource-limited settings, and ART providers are critical to effective program implementation. We explored provider-perceived barriers and facilitators of VL monitoring. We interviewed all providers (n = 17) engaged in a public health evaluation of dried blood spots for VL monitoring at five ART clinics in Malawi. All ART clinics were housed within district hospitals. We grouped themes at patient, provider, facility, system, and policy levels. Providers emphasized their desire for improved ART monitoring strategies, and frustration in response to restrictive policies for determining which patients were eligible to receive VL monitoring. Although many providers pled for expansion of monitoring to include all persons on ART, regardless of time on ART, the most salient provider-perceived barrier to VL monitoring implementation was the pressure of work associated with monitoring activities. The work burden was exacerbated by inefficient data management systems, highlighting a critical interaction between provider-, facility-, and system-level factors. Lack of integration between laboratory and clinical systems complicated the process for alerting providers when results were available, and these communication gaps were intensified by poor facility connectivity. Centralized second-line ART distribution was also noted as a barrier: providers reported that the time and expenses required for patients to collect second-line ART frequently obstructed referral. However, provider empowerment emerged as an unexpected facilitator of VL monitoring. For many providers, this was the first time they used an objective marker of ART response to guide clinical management. Providers' knowledge of a patient's virological status increased confidence in adherence counseling and clinical decision-making. Results from our study provide unique insight into provider

Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults

DEFF Research Database (Denmark)

Marzolini, Catia; Sabin, Caroline; Raffi, François

2015-01-01

OBJECTIVE: The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens...... individuals had significantly higher CD4 cell count at baseline, CD4 cell recovery at 6 and 12 months after EFV initiation was comparable to normal-weight individuals. CONCLUSION: Virological and immunological responses to initial EFV-containing regimens were not impaired in heavy individuals, suggesting...

New-onset ascites as a manifestation of virologic relapse in patients with hepatitis C cirrhosis

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Chua DL

2014-01-01

Full Text Available Deborah Lim Chua, Thomas Hahambis, Samuel H SigalDivision of Gastroenterology, Department of Medicine, New York University School of Medicine, New York, NY, USABackground: Chronic hepatitis C is the most common cause of cirrhosis in industrialized countries. Successful treatment of chronic hepatitis C in patients with advanced fibrosis or cirrhosis has significant benefits, including improvements in inflammation, fibrosis, and portal hypertension, with prevention of esophageal varices and clinical decompensation.Case: In this report, we present two patients with well-compensated hepatitis C cirrhosis who achieved an end-of-treatment response on a direct-acting antiviral therapy-based triple regimen for hepatitis C virus, but subsequently presented with new-onset ascites associated with virologic relapse.Conclusion: We propose that the development of ascites in this setting is due to the adverse impact of inflammation of the virologic relapse on portal hypertension. Our observation that ascites formation can be a manifestation of virologic relapse has potentially important clinical implications, as it highlights not only the importance of close monitoring of cirrhotic patients after achieving end-of-treatment response but also the impact of active inflammation on the severity of portal hypertension.Keywords: chronic hepatitis C, cirrhosis, virologic relapse, portal hypertension, ascites

Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response

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Dalgard, Olav; Bjøro, Kristian; Larsen, Helmer Ring

2008-01-01

A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428...

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin.

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Coelho-Borges, Silvia; Cheinquer, Hugo; Wolff, Fernando Herz; Cheinquer, Nelson; Krug, Luciano; Ashton-Prolla, Patricia

2012-01-01

Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks. Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test). Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

Regional changes over time in initial virologic response rates to combination antiretroviral therapy across Europe

DEFF Research Database (Denmark)

Bannister, Wendy P; Kirk, Ole; Gatell, Jose M

2006-01-01

BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS: Vi...... rates Udgivelsesdato: 2006/6...

Association between insulin resistance and sustained virologic response in hepatitis C treatment, genotypes 1 versus 2 and 3: systematic literature review and meta-analysis.

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Laurito, Marcela Pezzoto; Parise, Edison Roberto

2013-01-01

Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCV-RNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% CI: 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin

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Silvia Coelho-Borges

2012-03-01

Full Text Available CONTEXT: Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. OBJECTIVE: To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. METHODS: A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2 and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week and ribavirin (1.000 mg, daily for 24 weeks. RESULTS: Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis and BclI (H63D mutation analysis in 16 (37% patients, all heterozygous (11 H63D, 2 C282Y and 3 both. Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41% of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test. CONCLUSION: Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

Clinical, immunological and virological response to different antiretroviral regimens in a cohort of HIV-2-infected patients

NARCIS (Netherlands)

van der Ende, Marchina E.; Prins, Jan M.; Brinkman, Kees; Keuter, Monique; Veenstra, Jan; Danner, Sven A.; Niesters, Hubert G. M.; Osterhaus, Albert D. M. E.; Schutten, Martin

2003-01-01

Objective: To assess the clinical, immunological and virological response and the emergence of resistance towards antiretroviral therapy (ART) in a cohort of HIV-2-infected patients. Design: Observational study. Patients: HIV-2-infected patients residing in the Netherlands. Results: From 1995 to

Lower liver stiffness in patients with sustained virological response 4 years after treatment for chronic hepatitis C

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Andersen, Ellen Sloth; Moessner, Belinda Klemmensen; Christensen, Peer Brehm

2011-01-01

Transient elastography (TE) is a noninvasive and well validated method for measurement of liver stiffness. The aim of this study was to use TE to evaluate whether patients with sustained virological response (SVR) have lower liver stiffness than patients with non-SVR after treatment for chronic...

Patient Characteristics Associated with HCV Treatment Adherence, Treatment Completion, and Sustained Virologic Response in HIV Coinfected Patients

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Glenn Wagner

2011-01-01

Full Text Available Background. Hepatitis C (HCV treatment efficacy among HIV patients is limited by poor treatment adherence and tolerance, but few studies have examined the psychosocial determinants of treatment adherence and outcomes. Methods. Chart abstracted and survey data were collected on 72 HIV patients who had received pegylated interferon and ribavirin to assess correlates of treatment adherence, completion, and sustained virologic response (SVR. Results. Nearly half (46% the sample had active psychiatric problems and 13% had illicit drug use at treatment onset; 28% reported <100% treatment adherence, 38% did not complete treatment (mostly due to virologic nonresponse, and intent to treat SVR rate was 49%. Having a psychiatric diagnosis was associated with nonadherence, while better HCV adherence was associated with both treatment completion and SVR. Conclusions. Good mental health may be an indicator of HCV treatment adherence readiness, which is in turn associated with treatment completion and response, but further research is needed with new HCV treatments emerging.

Declining sustained virological response in hepatitis c

International Nuclear Information System (INIS)

Batool, U.; Qureshi, S.

2006-01-01

Objective: To determine the response of treatment with standard interferon and Ribazole in treatment naive hepatitis C infected patients, with different grades of activity. Design: A quasi-experimental study. Place and Duration of Study: This study was carried out at the Department of Medicine, KRL General Hospital, Islamabad, from January 2001 to September 2004. Patients and Methods: A total of 300 patients were enrolled. All patients were anti-HCV positive confirmed by device method, PCR positive and had 3a genotype. A specially-designed proforma containing the patient profile, family transmission, and baseline laboratory values was filled. All patients were treated according to a set protocol of Interferon plus ribavirin therapy (IFN alpha 2a, 3MU t.i.w 24 weeks plus ribavirin 1000 to 1200 mg/day) for six months. Chi-square tests were used to analyze the data. Primary end point was a sustained virological response (SVR) that is response assessed after six months of completion of treatment. Results: Over a period of four years response rates to standard Interferon plus Ribazole therapy were studied. Out of the total 300 patients data was available for 161 patients as 60 patients were excluded and 79 patients are currently under treatment. Treatment was stopped in 3 patients due to serious side effects. In the 161 patients, 135 (83.8%), achieved response at the end of treatment at six months; End of Treatment Complete Response (EOTCR); and 26 (16.14%) were non-responders (NR). Out of the complete responders, 68 patients had been followed completely up to six months after the treatment to asses Sustained Viral Response (SVR) defined as undetectable HCV RNA in serum at the end of six months post treatment follow-up. Sustained viral response was seen in 46 patients Le. 68% ( CI: 57-79%) and 22(32.3%) were relapsers (those who developed recurrence of viremia after having achieved eradication at the end of six months treatment). Response rates are co-related with

Finding our roots and celebrating our shoots: Plant virology in Virology, 1955-1964.

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Scholthof, Karen-Beth G

2015-05-01

To celebrate the sixtieth anniversary of Virology a survey is made of the plant viruses, virologists and their institutions, and tools and technology described in the first decade of plant virus publications in Virology. This was a period when plant viruses increasingly became tools of discovery as epistemic objects and plant virology became a discipline discrete from plant pathology and other life sciences. Copyright © 2015 Elsevier Inc. All rights reserved.

Predictors of sustained virological response in Greek and Egyptian patients with hepatitis C genotype 4: does ethnicity matter?

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Papastergiou, Vasilios; Dimitroulopoulos, Dimitrios; Skorda, Lamprini; Lisgos, Philippos; Ketikoglou, Ioannis; Kostas, Nikolaos; Karatapanis, Stylianos

2012-08-01

Hepatitis C virus genotype 4 (HCV-4) is spreading beyond Africa and the Middle East but data regarding treatment with pegylated interferon alpha and ribavirin of European populations infected with HCV-4 remains limited. Interestingly, European (vs. Egyptian) origin has been associated with lower sustained virological response rates. Hence the aim of this study was to investigate the treatment outcomes of Greek (vs. Egyptian), treatment-naïve patients infected with HCV-4 (subtype a) and to identify factors influencing response rates. One hundred seventy-seven consecutive patients (mean age: 44.6 ± 10.2, males: 143/177; 80.8%, Egyptians: 76/177; 42.9%) treated over a 7-year period at the Hepatology clinics of three tertiary care hospitals in Greece were retrospectively evaluated. Overall, sustained virological response was achieved in 75/177 (42.4%) of the cohort without a significant difference between the two ethnic groups [Greek: 44/101 (43.6%); Egyptian 31/76 (40.8%), P = 0.7598]. In multivariate analysis, it was found that ethnicity was not associated with an impaired response but age ≥45 years [odds ratio (OR): 0.4225, 95% confidence interval (CI): 0.2135-0.8133; P = 0.0134], diabetes (OR: 0.2346, 95% CI: 0.0816-0.0674; P = 0.0071), advanced liver fibrosis (OR: 0.3964, 95% CI: 0.1933-0.8133; P = 0.0116), and treatment suspension (OR: 0.1738, 95% CI: 0.0482-0.6262; P = 0.0075) showed an independent negative association with response to antiviral treatment. In contrast to previous European data suggesting Egyptian ethnicity to be a positive predictor for a sustained virological response, there was no influence of Greek versus Egyptian ethnicity on treatment outcomes. Higher age, advanced liver fibrosis, and diabetes have been shown to reduce significantly response rates in patients infected with HCV-4. Copyright © 2012 Wiley Periodicals, Inc.

High exposure to nevirapine in plasma is associated with an improved virological response in HIV-1-infected individuals

NARCIS (Netherlands)

Veldkamp, A. I.; Weverling, G. J.; Lange, J. M.; Montaner, J. S.; Reiss, P.; Cooper, D. A.; Vella, S.; Hall, D.; Beijnen, J. H.; Hoetelmans, R. M.

2001-01-01

OBJECTIVE: To explore relationships between exposure to nevirapine and the virological response in HIV-1-infected individuals participating in the INCAS trial. METHODS: The elimination rate constant of plasma HIV-1 RNA (k) was calculated during the first 2 weeks of treatment with nevirapine,

Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue based regimens in ART-naïve and experienced patients

DEFF Research Database (Denmark)

Silberstein, F; Cozzi-Lepri, A; Ruiz, L

2007-01-01

BACKGROUND: A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated. METHODS: We studied 590 patients from EuroSIDA who started ...... were observed in patients with M41L/T215Y and mixed TAM profiles detected before the initiation of cART. CONCLUSIONS: This study provides evidence that the detection of polymorphism F214L is associated with a favorable virological response to TA-based cART.......BACKGROUND: A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated. METHODS: We studied 590 patients from EuroSIDA who started TA...... therapy for the first time as part of potent combination antiretroviral therapy (cART) and who were tested for genotypic resistance within the past 6 months. End points were median reduction in the week 24 viral load and time to virological failure (2 consecutive VL measurements >400 copies/mL after...

Prediction of week 4 virological response in hepatitis C for making decision on triple therapy: the Optim study.

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Manuel Romero-Gómez

Full Text Available Virological response to peginterferon + ribavirin (P+R at week 4 can predict sustained virological response (SVR. While patients with rapid virological response (RVR do not require triple therapy, patients with a decline <1 log10 IU/ml HCVRNA (D1L should have treatment discontinued due to low SVR rate.To develop a tool to predict first 4 weeks' viral response in patients with hepatitis C genotype 1&4 treated with P+R.In this prospective and multicenter study, HCV mono-infected (n=538 and HCV/HIV co-infected (n=186 patients were included. To develop and validate a prognostic tool to detect RVR and D1L, we segregated the patients as an estimation cohort (to construct the model and a validation cohort (to validate the model.D1L was reached in 509 (80.2% and RVR in 148 (22.5% patients. Multivariate analyses demonstrated that HIV co-infection, Forns' index, LVL, IL28B-CC and Genotype-1 were independently related to RVR as well as D1L. Diagnostic accuracy (AUROC for D1L was: 0.81 (95%CI: 0.76 ̶ 0.86 in the estimation cohort and 0.71 (95%CI: 0.62 ̶ 0.79 in the validation cohort; RVR prediction: AUROC 0.83 (95%CI: 0.78 ̶ 0.88 in the estimation cohort and 0.82 (95%CI: 0.76 ̶ 0.88 in the validation cohort. Cost-analysis of standard 48-week treatment indicated a saving of 30.3% if the prognostic tool is implemented.The combination of genetic (IL28B polymorphism and viral genotype together with viral load, HIV co-infection and fibrosis stage defined a tool able to predict RVR and D1L at week 4. Using this tool would be a cost-saving strategy compared to universal triple therapy for hepatitis C.

Quantum virology : improved management of viral infections through quantitative measurements

NARCIS (Netherlands)

Kalpoe, Jaijant Satishkumar

2007-01-01

Real-time monitoring of PCR has strongly supported the increased diagnostic use of nucleic acid detection assays in clinical virology. Particularly the improvements in the ability to quantify target nucleic acid sequences offer new opportunities in the management of viral infections. Real-time PCR

Interferon-γ-inducible protein-10 in chronic hepatitis C: Correlations with insulin resistance, histological features & sustained virological response.

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Crisan, Dana; Grigorescu, Mircea Dan; Radu, Corina; Suciu, Alina; Grigorescu, Mircea

2017-04-01

One of the multiple factors contributing to virological response in chronic hepatitis C (CHC) is interferon-gamma-inducible protein-10 (IP-10). Its level reflects the status of interferon-stimulated genes, which in turn is associated with virological response to antiviral therapy. The aim of this study was to evaluate the role of serum IP-10 levels on sustained virological response (SVR) and the association of this parameter with insulin resistance (IR) and liver histology. Two hundred and three consecutive biopsy proven CHC patients were included in the study. Serum levels of IP-10 were determined using ELISA method. IR was evaluated by homeostasis model assessment-IR (HOMA-IR). Histological features were assessed invasively by liver biopsy and noninvasively using FibroTest, ActiTest and SteatoTest. Predictive factors for SVR and their interrelations were assessed. A cut-off value for IP-10 of 392 pg/ml was obtained to discriminate between responders and non-responders. SVR was obtained in 107 patients (52.70%). Area under the receiver operating characteristic curve for SVR was 0.875 with a sensitivity of 91.6 per cent, specificity 74.7 per cent, positive predictive value 80.3 per cent and negative predictive value 88.7 per cent. Higher values of IP-10 were associated with increasing stages of fibrosis (P<0.01) and higher grades of inflammation (P=0.02, P=0.07) assessed morphologically and noninvasively through FibroTest and ActiTest. Significant steatosis and IR were also associated with increased levels of IP-10 (P=0.01 and P=0.02). In multivariate analysis, IP-10 levels and fibrosis stages were independently associated with SVR. Our findings showed that the assessment of serum IP-10 level could be a predictive factor for SVR and it was associated with fibrosis, necroinflammatory activity, significant steatosis and IR in patients with chronic HCV infection.

Virological and immunological response to antiretroviral regimens containing maraviroc in HIV type 1-infected patients in clinical practice: role of different tropism testing results and of concomitant treatments.

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Rossetti, Barbara; Bianco, Claudia; Bellazzi, Lara Ines; Bruzzone, Bianca; Colao, Grazia; Corsi, Paola; Monno, Laura; Pagano, Gabriella; Paolucci, Stefania; Punzi, Grazia; Setti, Maurizio; Zazzi, Maurizio; De Luca, Andrea

2014-01-01

We assessed the immunovirological response to antiretroviral regimens containing maraviroc in HIV-infected viremic patients with viral tropism predicted by different assays. We selected antiretroviral treatment-experienced HIV-1-infected patients initiating regimens containing maraviroc after different phenotypic or genotypic viral tropism assays, with at least one HIV-1 RNA determination during follow-up. Survival analysis was employed to assess the virological response as time to HIV-1 RNA immunological response as time to a CD4 cell count increase of ≥ 100/μl from baseline. Predictors of these outcomes were analyzed by multivariate Cox regression models. In 191 treatments with maraviroc, virological response was achieved in 65.4% and the response was modestly influenced by the baseline viral load and concomitant drug activity but not influenced by the type of tropism assay employed. Immunological response was achieved in 58.1%; independent predictors were baseline HIV-1 RNA (per log10 higher: HR 1.29, 95% CI 1.05-1.60) and concomitant therapy with enfuvirtide (HR 2.05, 0.96-4.39) but not tropism assay results. Of 17 patients with baseline R5-tropic virus and available tropism results while viremic during follow-up on maraviroc, seven (41%) showed a tropism switch to non-R5 virus. A significant proportion of experienced patients treated with regimens containing maraviroc achieved virological response. The tropism test type used was not associated with immunovirological response and concomitant treatment with enfuvirtide increased the chance of immunological response. More than half of virological failures with maraviroc were not accompanied by tropism switch.

Rapid virological response assessment by Abbott RealTime hepatitis C virus assay for predicting sustained virological responses in patients with hepatitis C virus genotype 1 treated with pegylated-interferon and ribavirin

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Pei-yuan Su

2016-07-01

Full Text Available The lower limits of virus detection of hepatitis C virus (HCV RNA detection assays are continuously improving. We aimed to assess the utility of more precise definition of 4th week viral load [rapid virological response (RVR] in predicting sustained virological response (SVR in HCV genotype 1 patients treated with pegylated-interferon (PEG-IFN and ribavirin. Clinical data of treatment-naïve HCV genotype 1 patients were retrospectively collected from 2009 to 2014. Patients were grouped according to 4th week viral load as follows: undetectable (n = 90 and detectable but not quantifiable (< 12 IU/mL, n = 27. All patients received PEG-IFNα-2a or -2b and ribavirin for 24 weeks. Serum HCV RNA levels were measured by Abbott RealTime (ART; Abbott Molecular, Abbott Park, IL, USA HCV assay. SVR was 95.5% and 63% in the undetectable group and < 12 IU/mL group of 4th week viral load, respectively. The between-group difference in SVR was significant (p < 0.001. We determined 4th week viral load was independently associated with SVR (odds ratio = 19.28; p = 0.002 and a good predictor of SVR [area under the curve (AUC = 0.775; p = 0.001]. ART HCV assays had a stronger SVR predictive value in HCV genotype 1 patients, indicating that only the undetectable group of 4th week viral load patients measured by ART HCV assay should be considered for shorter treatment time (24 weeks with PEG-IFN and ribavirin.

Virologic outcome among patients receiving antiretroviral therapy at five hospitals in Haiti.

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Frantz Jean Louis

Full Text Available Viral load (VL assessment is the preferred method for diagnosing and confirming virologic failure for patients on antiretroviral therapy (ART. We conducted a retrospective cross-sectional study to evaluate the virologic suppression rate among patients on ART for ≥6 months in five hospitals around Port-au-Prince, Haiti.Plasma VL was measured and patients with VL <1,000 copies/mL were defined as virologically suppressed. A second VL test was performed within at least six months of the first test. Factors associated with virologic suppression were analyzed using logistic regression models accounting for site-level clustering using complex survey procedures.Data were analyzed for 2,313 patients on ART for six months or longer between July 2013 and February 2015. Among them, 1,563 (67.6% achieved virologic suppression at the first VL test. A second VL test was performed within at least six months for 718 (31.0% of the patients. Of the 459 patients with an initial HIV-1 RNA <1,000 copies/mL who had a second VL performed, 394 (85.8% maintained virologic suppression. Virologic suppression was negatively associated with male gender (adjusted odds ratio [aOR]: 0.80, 95% CI: 0.74-0.0.86, 23 to 35 months on ART (aOR:0.72[0.54-0.96], baseline CD4 counts of 201-500 cells/mm3 and 200 cells/mm3 or lower (aORs: 0.77 [0.62-0.95] and 0.80 [0.66-0.98], respectively, poor adherence (aOR: 0.69 [0.59-0.81], and TB co-infection (aOR: 0.73 [0.55-0.97].This study showed that over two-thirds of the patients in this evaluation achieved virologic suppression after ≥ six months on ART and the majority of them remained suppressed. These results reinforce the importance of expanding access to HIV-1 viral load testing in Haiti for monitoring ART outcomes.

Effect of HIV type 1 subtype on virological and immunological response to combination antiretroviral therapy: evidence for a more rapid viral suppression for subtype A than subtype B-infected Greek individuals.

Science.gov (United States)

Paraskevis, Dimirios; Touloumi, Giota; Bakoyannis, Giorgos; Paparizos, Vassilios; Lazanas, Marios; Gargalianos, Panagiotis; Chryssos, Georgios; Antoniadou, Anastasia; Psichogiou, Mina; Panos, Georgios; Katsarou, Olga; Sambatakou, Helen; Kordossis, Theodoros; Hatzakis, Angelos

2013-03-01

Whether response to combination antiretroviral therapy (cART) differs between those infected with HIV-1 subtype A or B remains unclear. We compared virological and immunological response to cART in individuals infected with subtype A or B in an ethnically homogeneous population. Data derived from the Athens Multicenter AIDS Cohort Study (AMACS) and analysis were restricted to those of Greek origin. Time to virological response (confirmed HIV-RNA 500 copies/ml at any time or no response by month 6) were analyzed using survival models and CD4 changes after cART initiation using piecewise linear mixed effects models. Of the 571 subjects included in the analysis, 412 (72.2%) were infected with subtype B and 159 (27.8%) with subtype A. After adjusting for various prognostic factors, the rate of virological response was higher for those infected with subtype A versus B (adjusted HR: 1.35; 95% CI: 1.08-1.68; p=0.009). Subtype A was also marginally associated with a lower hazard of virological failure compared to subtype B (HR=0.73; 95% CI: 0.53-1.02; p=0.062). Further adjustment for treatment adherence did not substantially changed the main results. No significant differences were observed in the rates of CD4 increases by subtype. The overall median (95% CI) CD4 increase at 2 years of cART was 193 (175, 212) cells/μl. Our study, based on one of the largest homogeneous groups of subtype A and B infections in Europe, showed that individuals infected with subtype A had an improved virological but similar immunological response to cART compared to those infected with subtype B.

Mapping of the US Domestic Influenza Virologic Surveillance Landscape.

Science.gov (United States)

Jester, Barbara; Schwerzmann, Joy; Mustaquim, Desiree; Aden, Tricia; Brammer, Lynnette; Humes, Rosemary; Shult, Pete; Shahangian, Shahram; Gubareva, Larisa; Xu, Xiyan; Miller, Joseph; Jernigan, Daniel

2018-07-17

Influenza virologic surveillance is critical each season for tracking influenza circulation, following trends in antiviral drug resistance, detecting novel influenza infections in humans, and selecting viruses for use in annual seasonal vaccine production. We developed a framework and process map for characterizing the landscape of US influenza virologic surveillance into 5 tiers of influenza testing: outpatient settings (tier 1), inpatient settings and commercial laboratories (tier 2), state public health laboratories (tier 3), National Influenza Reference Center laboratories (tier 4), and Centers for Disease Control and Prevention laboratories (tier 5). During the 2015-16 season, the numbers of influenza tests directly contributing to virologic surveillance were 804,000 in tiers 1 and 2; 78,000 in tier 3; 2,800 in tier 4; and 3,400 in tier 5. With the release of the 2017 US Pandemic Influenza Plan, the proposed framework will support public health officials in modeling, surveillance, and pandemic planning and response.

Paediatric Virology as a new educational initiative: An interview with Nobelist Professor of Virology Harald zur Hausen.

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Mammas, Ioannis N; Spandidos, Demetrios A

2017-10-01

Born in Gelsenkirchen-Buer in Germany on March 11th, 1936, Professor Harald zur Hausen, Emeritus Professor of Virology at the University of Freiburg and 2008 Nobel Prize Laureate in Physiology or Medicine for his discovery of human papillomavirus (HPV), which causes cervical cancer, believes that good knowledge of virological methods and diagnostic possibilities are an asset for all young paediatricians. Professor zur Hausen considers that the creation of an educational platform on Paediatric Virology is definitely very beneficial for young paediatricians, as this will greatly enhance their knowledge in the field of Virology. He very actively advocates the vaccination of boys for the eradication of HPV infection and emphasises that male HPV vaccination should be included into the current vaccination programmes. He would have certainly considered Dr George N. Papanicolaou (Kyme, Island of Euboea, Greece, 1883 - Miami, Florida, USA, 1962) as an excellent candidate for the Nobel Prize, stating that the contribution of Dr Papanicolaou did not find sufficient recognition in the past. In the context of the 3rd Workshop on Paediatric Virology, which will be held in Athens, Greece, on October 7th, 2017, Professor zur Hausen will give his plenary lecture on 'Paediatric Virology and Oncology: Virus persistence and the important first years of life'.

Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals

Science.gov (United States)

Noureddin, Mazen; Wong, Micaela M; Todo, Tsuyoshi; Lu, Shelly C; Sanyal, Arun J; Mena, Edward A

2018-01-01

AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals. METHODS Transient elastography with controlled attenuation parameter (CAP) was used to assess hepatic steatosis post-sustained virological response (SVR); the CAP technology was not available in the United States at study initiation. Liver stiffness/fibrosis was measured before and 47 wk after treatment completion. Patients with genotype 3 and patients with cirrhosis were excluded. RESULTS One hundred and one patients were included in the study. Post-SVR there were decreases from baseline in alanine aminotransferase (ALT) (63.1 to 17.8 U/L), aspartate aminotransferase (51.8 to 21.5 U/L) and fibrosis score (7.4 to 6.1 kPa) (P steatosis on CAP; of these, 6.25% had advanced fibrosis. Patients with steatosis had higher body mass index (29.0 vs 26.1 kg/m2), glucose (107.8 vs 96.6 mg/dL), ALT (20.4 vs 15.3 mg/dL), CAP score (296.3 vs 212.4 dB/m) and fibrosis score (7.0 vs 5.3 kPa); P steatosis had change in fibrosis score post-SVR (7.7 kPa vs 7.0 kPa and 7.0 kPa vs 5.3 kPa); alternatively, (P steatosis continued to have clinically significant stiffness (≥ 7 kPa). CONCLUSION Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR. These patients continue to have elevated mean fibrosis score (≥ 7 kPa) compared to those without fatty liver; some have advanced fibrosis. Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR. PMID:29568207

Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals.

Science.gov (United States)

Noureddin, Mazen; Wong, Micaela M; Todo, Tsuyoshi; Lu, Shelly C; Sanyal, Arun J; Mena, Edward A

2018-03-21

To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals. Transient elastography with controlled attenuation parameter (CAP) was used to assess hepatic steatosis post-sustained virological response (SVR); the CAP technology was not available in the United States at study initiation. Liver stiffness/fibrosis was measured before and 47 wk after treatment completion. Patients with genotype 3 and patients with cirrhosis were excluded. One hundred and one patients were included in the study. Post-SVR there were decreases from baseline in alanine aminotransferase (ALT) (63.1 to 17.8 U/L), aspartate aminotransferase (51.8 to 21.5 U/L) and fibrosis score (7.4 to 6.1 kPa) ( P < 0.05). Post-SVR, 48 patients (47.5%) had steatosis on CAP; of these, 6.25% had advanced fibrosis. Patients with steatosis had higher body mass index (29.0 vs 26.1 kg/m 2 ), glucose (107.8 vs 96.6 mg/dL), ALT (20.4 vs 15.3 mg/dL), CAP score (296.3 vs 212.4 dB/m) and fibrosis score (7.0 vs 5.3 kPa); P < 0.05. Interestingly, compared to baseline, both patients with and without steatosis had change in fibrosis score post-SVR (7.7 kPa vs 7.0 kPa and 7.0 kPa vs 5.3 kPa); alternatively, ( P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness (≥ 7 kPa). Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR. These patients continue to have elevated mean fibrosis score (≥ 7 kPa) compared to those without fatty liver; some have advanced fibrosis. Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.

Determinants of virological failure among patients on highly active antiretroviral therapy in University of Gondar Referral Hospital, Northwest Ethiopia: a case-control study.

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Bayu, Belete; Tariku, Amare; Bulti, Abera Balcha; Habitu, Yohannes Ayanaw; Derso, Terefe; Teshome, Destaw Fetene

2017-01-01

Viral load monitoring is used as an important biomarker for diagnosing treatment failure in patients with HIV infection/AIDS. Ethiopia has started targeted viral load monitoring. However, factors leading to virological failure are not well understood and studied. Thus, the aim of this study was to identify the determinants of virological failure among HIV-infected patients on highly active antiretroviral therapy at the University of Gondar Referral Hospital, Northwest Ethiopia. A case-control study was conducted from May to June 2015. Cases were subjects who had already experienced virological failure; controls were those without virological failure. Data were extracted from 153 cases and 153 controls through chart review. A multivariate logistic regression analysis was carried out to identify factors associated with virological failure, and variables with a p -value failure was observed among patients aged failure. Therefore, evidence-based intervention should be implemented to improve adherence to ART, which in turn helps to boost immunity (CD4) and suppresses viral replication and load. Moreover, attention should be given to younger patients who have had ART for longer periods.

HIV Stigma and Depressive Symptoms are Related to Adherence and Virological Response to Antiretroviral Treatment Among Immigrant and Indigenous HIV Infected Patients

NARCIS (Netherlands)

Sumari-de Boer, I. Marion; Sprangers, Mirjam A. G.; Prins, Jan M.; Nieuwkerk, Pythia T.

2012-01-01

We compared adherence to cART and viro-logical response between indigenous and immigrant HIV-infected patients in the Netherlands, and investigated if a possible difference was related to a difference in the psychosocial variables: HIV-stigma, quality-of-life, depression and beliefs about

Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C.

Science.gov (United States)

Lee, Jae-Won; Kim, Won; Kwon, Eun-Kyung; Kim, Yuri; Shin, Hyun Mu; Kim, Dong-Hyun; Min, Chan-Ki; Choi, Ji-Yeob; Lee, Won-Woo; Choi, Myung-Sik; Kim, Byeong Gwan; Cho, Nam-Hyuk

2017-01-01

Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.

Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study

DEFF Research Database (Denmark)

Bannister, Wendy P; Cozzi-Lepri, Alessandro; Clotet, Bonaventura

2008-01-01

OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients...

Sustained virologic response following HCV eradication in two brothers with X-linked agammaglobulinaemia.

LENUS (Irish Health Repository)

Houlihan, Diarmaid D

2009-08-21

X-linked agammaglobulinaemia (XLA) is a humoral immunodeficiency syndrome characterized from childhood by the absence of circulating B lymphocytes, absent or reduced levels of serum immunoglobulin and recurrent bacterial infections. For many affected patients, regular treatment with immunoglobulin is life saving. Hepatitis C viral (HCV) infection acquired through contaminated blood products is widely described in this patient cohort. The natural history of HCV infection in patients with XLA tends to follow a more rapid and aggressive course compared to immunocompetent individuals. Furthermore, standard anti-viral therapy appears to be less efficacious in this patient cohort. Here we report the cases of two brothers with XLA who contracted HCV through contaminated blood products. They were treated with a six month course of Interferon alpha-2b and Ribavirin. We report a sustained virologic response five years after completing treatment.

Clinical, virological and immunological responses in Danish HIV patients receiving raltegravir as part of a salvage regimen

Directory of Open Access Journals (Sweden)

Frederik N Engsig

2010-05-01

Full Text Available Frederik N Engsig1, Jan Gerstoft1, Gitte Kronborg2, Carsten S Larsen3, Gitte Pedersen4, Anne M Audelin5, Louise B Jørgensen5, Niels Obel11Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark; 2Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; 3Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark; 4Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark; 5Department of Virology, Statens Serum Institute, Copenhagen, DenmarkBackground: Raltegravir is the first integrase inhibitor approved for treatment of HIV-infected patients harboring multiresistant viruses.Methods: From a Danish population-based nationwide cohort of HIV patients we identified the individuals who initiated a salvage regimen including raltegravir and a matched cohort of HIV-infected patients initiating HAART for the first time. We compared these two cohorts for virological suppression, gain in CD4 count, and time to first change of initial regimen.Results: We identified 32 raltegravir patients and 64 HIV patients who initiated HAART for the first time in the period 1 January 2006 to 1 July 2009. The virological and immunological responses in the raltegravir patients were comparable to those seen in the control cohort. No patients in the two cohorts died and no patients terminated raltegravir treatment in the observation period. Time to first change of initial regimen was considerably shorter for HAART-naïve patients.Conclusion: We conclude that salvage regimens including raltegravir have high effectiveness in the everyday clinical setting. The effectiveness of the regimens is comparable to that observed for patients initiating HAART for the first time. The risk of change in the salvage regimens after initiation of raltegravir is low.Keywords: HIV, raltegravir, salvage regime, efficacy, matched cohort

Cost-effectiveness of tenofovir instead of zidovudine for use in first-line antiretroviral therapy in settings without virological monitoring.

Directory of Open Access Journals (Sweden)

Viktor von Wyl

Full Text Available BACKGROUND: The most recent World Health Organization (WHO antiretroviral treatment guidelines recommend the inclusion of zidovudine (ZDV or tenofovir (TDF in first-line therapy. We conducted a cost-effectiveness analysis with emphasis on emerging patterns of drug resistance upon treatment failure and their impact on second-line therapy. METHODS: We used a stochastic simulation of a generalized HIV-1 epidemic in sub-Saharan Africa to compare two strategies for first-line combination antiretroviral treatment including lamivudine, nevirapine and either ZDV or TDF. Model input parameters were derived from literature and, for the simulation of resistance pathways, estimated from drug resistance data obtained after first-line treatment failure in settings without virological monitoring. Treatment failure and cost effectiveness were determined based on WHO definitions. Two scenarios with optimistic (no emergence; base and pessimistic (extensive emergence assumptions regarding occurrence of multidrug resistance patterns were tested. RESULTS: In the base scenario, cumulative proportions of treatment failure according to WHO criteria were higher among first-line ZDV users (median after six years 36% [95% simulation interval 32%; 39%] compared with first-line TDF users (31% [29%; 33%]. Consequently, a higher proportion initiated second-line therapy (including lamivudine, boosted protease inhibitors and either ZDV or TDF in the first-line ZDV user group 34% [31%; 37%] relative to first-line TDF users (30% [27%; 32%]. At the time of second-line initiation, a higher proportion (16% of first-line ZDV users harboured TDF-resistant HIV compared with ZDV-resistant viruses among first-line TDF users (0% and 6% in base and pessimistic scenarios, respectively. In the base scenario, the incremental cost effectiveness ratio with respect to quality adjusted life years (QALY was US$83 when TDF instead of ZDV was used in first-line therapy (pessimistic scenario: US$ 315

Virologic outcomes in early antiretroviral treatment: HPTN 052.

Science.gov (United States)

Eshleman, Susan H; Wilson, Ethan A; Zhang, Xinyi C; Ou, San-San; Piwowar-Manning, Estelle; Eron, Joseph J; McCauley, Marybeth; Gamble, Theresa; Gallant, Joel E; Hosseinipour, Mina C; Kumarasamy, Nagalingeswaran; Hakim, James G; Kalonga, Ben; Pilotto, Jose H; Grinsztejn, Beatriz; Godbole, Sheela V; Chotirosniramit, Nuntisa; Santos, Breno Riegel; Shava, Emily; Mills, Lisa A; Panchia, Ravindre; Mwelase, Noluthando; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Fogel, Jessica M

2017-05-01

The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350-550 cells/mm 3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4  1000 copies/mL > 24 weeks after ART initiation. Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.

Factors influencing the virological testing of cornea donors.

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Röck, Tobias; Beck, Robert; Jürgens, Stefan; Bartz-Schmidt, Karl Ulrich; Bramkamp, Matthias; Thaler, Sebastian; Röck, Daniel

2017-11-01

To assess the influence of donor, environment, and logistical factors on the results of virological testing of blood samples from cornea donors.Data from 670 consecutive cornea donors were analyzed retrospectively. Logistic regression analysis was used to assess the influence of different factors on the results of virological testing of blood samples from cornea donors.The mean annual rate of donors with serology-reactive or not evaluable result was 14.8% (99 of 670) (range 11.9%-16.9%). The cause of donor death by cancer increased the risk of serology-reactive or not evaluable result (P = .0300). Prolonged time between death and post mortem blood removal was associated with a higher rate of serology-reactive or not evaluable result (P donors, sex, and donor age had no significant impact on the results of virological testing of blood samples from cornea donors.The cause of donor death by cancer and a prolonged time between death and post mortem blood removal seem to be mainly responsible for serology-reactive or not evaluable result of blood samples from cornea donors. The percentage of discarded corneas caused by serology-reactive or not evaluable result may be reduced by shortening the period of time between death and post mortem blood removal. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Virological and immunological failure of HAART and associated risk factors among adults and adolescents in the Tigray region of Northern Ethiopia.

Science.gov (United States)

Hailu, Genet Gebrehiwet; Hagos, Dawit Gebregziabher; Hagos, Amlsha Kahsay; Wasihun, Araya Gebreyesus; Dejene, Tsehaye Asmelash

2018-01-01

Human immunodeficiency virus/Acquired immunodeficiency syndrome associated morbidity and mortality has reduced significantly since the introduction of highly active antiretroviral therapy. As a result of increasing access to highly active antiretroviral therapy, the survival and quality of life of the patients has significantly improved globally. Despite this promising result, regular monitoring of people on antiretroviral therapy is recommended to ensure whether there is an effective treatment response or not. This study was designed to assess virological and immunological failure of highly active antiretroviral therapy users among adults and adolescents in the Tigray region of Northern Ethiopia, where scanty data are available. A retrospective follow up study was conducted from September 1 to December 30, 2016 to assess the magnitude and factors associated with virological and immunological failure among 260 adults and adolescents highly active antiretroviral therapy users who started first line ART between January 1, 2008 to March 1, 2016. A standardized questionnaire was used to collect socio-demographic and clinical data. SPSS Version21 statistical software was used for analysis. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated to virological and immunological failure. Statistical association was declared significant if p-value was ≤ 0.05. A total of 30 (11.5%) and 17 (6.5%) participants experienced virological and immunological failure respectively in a median time of 36 months of highly active antiretroviral therapy. Virological failure was associated with non-adherence to medications, aged < 40 years old, having CD4+ T-cells count < 250 cells/μL and male gender. Similarly, immunological failure was associated with non-adherence, tuberculosis co-infection and Human immunodeficiency virus RNA ≥1000 copies/mL. The current result shows that immunological and virological failure is a problem in a setting

The innovation of the subspecialty of Paediatric Virology: An interview with Research Professor of Molecular Virology Anna Kramvis.

Science.gov (United States)

Mammas, Ioannis N; Spandidos, Demetrios A

2017-10-01

Professor Anna Kramvis, Research Professor of Molecular Virology at the University of the Witwatersrand in Johannesburg, South Africa, talks about direct-acting antiviral treatments against hepatitis C virus (HCV), as well as the perspective of the development of an effective vaccine against HCV. She emphasises the necessity of vaccination against hepatitis B virus (HBV), highlighting that it is very important that vaccination should be administered at birth in order to prevent mother-to-child transmission (MTCT) of HBV. Professor Kramvis states that vaccination against HBV is safe and that HBV and HCV infections are not contraindications for breastfeeding. Regarding the challenge of Paediatric Virology, she believes that it is a field that during the last years is increasing exponentially, while she concurs that Paediatric Virology subspecialty will be a popular choice for infectious diseases subspecialists. In the context of the 3rd Workshop on Paediatric Virology, which will be held in Athens on October 7th, 2017, Professor Kramvis will give her key lecture on MTCT of HBV and HCV.

Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue-based regimens in antiretroviral therapy (ART)-naive and ART-experienced patients

DEFF Research Database (Denmark)

Ceccherini-Silberstein, Francesca; Cozzi-Lepri, Alessandro; Ruiz, Lidia

2007-01-01

A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated....

No impact of HIV-1 protease minority resistant variants on the virological response to a first-line PI-based regimen containing darunavir or atazanavir.

Science.gov (United States)

Perrier, Marine; Visseaux, Benoit; Landman, Roland; Joly, Véronique; Todesco, Eve; Yazdanpanah, Yazdan; Calvez, Vincent; Marcelin, Anne-Geneviève; Descamps, Diane; Charpentier, Charlotte

2018-01-01

To evaluate, in a clinical cohort of HIV-1-infected patients, the prevalence of PI minority resistant variants (MRV) at ART baseline and their impact on the virological response to a first-line PI-based regimen. In an observational single-centre cohort, we assessed all ART-naive patients initiating a first-line regimen including two NRTI and one boosted PI, darunavir/ritonavir or atazanavir/ritonavir, between January 2012 and March 2015. Ultra-deep sequencing of the pol gene was performed using Illumina® technology. Protease mutations were identified using the WHO transmitted drug resistance list and major PI resistance mutations (IAS-USA drug resistance mutations list). Ninety-four and 16 patients initiating a darunavir/ritonavir-based regimen and an atazanavir/ritonavir-based regimen, respectively, were assessed. Twenty-eight percent of the patients were HIV-1 subtype B, 39% CRF02_AG and 33% other non-B subtypes. Thirteen patients (13.8%) in the darunavir group and three patients (18.8%) in the atazanavir group experienced a virological failure (VF). Overall, 13 (11.8%) subjects had PI MRV at baseline in the median proportion of 1.3% (IQR = 1.1-1.7). The most prevalent PI MRV were G73C (n = 5) and M46I (n = 3). The proportion of patients harbouring baseline PI MRV was similar between those with virological success (10.6%) and those experiencing VF (18.8%) (P = 0.40). No difference was observed in the rate of PI MRV by viral subtype (P = 0.51) or by PI drug (P = 0.40). This study showed a prevalence of 11.8% of PI MRV among 110 ART-naive subjects, without significant impact on the virological response to a first-line PI-based regimen containing darunavir or atazanavir. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Diagnostic virology laboratory within a microbiology setting.

Science.gov (United States)

Rubin, S J

1984-01-01

The virology section at St. Francis Hospital and Medical Center, Connecticut, is not a separate laboratory division but is a part of the microbiology division and is supervised by the same personnel who supervise bacteriology, mycology, mycobacteriology, and serology. Current volume is over 1,000 cultures yearly with 12 to 24 percent positive. Isolates are confirmed and typed by the Connecticut State Health Department Laboratory. Specimen distribution, percentage positive specimens, and distribution of viral isolates are similar to those reported from microbiology laboratories with separate virology laboratories directed by a full-time doctoral-level virologist. Our seven years' experience demonstrates that a microbiology laboratory without a full-time doctoral-level virologist can provide clinically useful virologic information.

History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change

DEFF Research Database (Denmark)

Reekie, J; Mocroft, A; Ledergerber, B

2010-01-01

OBJECTIVES: HIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategi...

Virological response and safety of 24-week telaprevir alone in Japanese patients infected with hepatitis C virus subtype 1b

Science.gov (United States)

Toyota, J; Ozeki, I; Karino, Y; Asahina, Y; Izumi, N; Takahashi, S; Kawakami, Y; Chayama, K; Kamiya, N; Aoki, K; Yamada, I; Suzuki, Y; Suzuki, F; Kumada, H

2013-01-01

Hepatitis C virus (HCV) subtype 1b, which infects approximately 70% of Japanese carriers, is likely to be more eradicable by a telaprevir regimen than subtype 1a because of the higher genetic barrier of Val36 and Arg155 substitutions. The aims of this exploratory study were to evaluate the virological response and safety of 24-week oral administration of telaprevir alone in chronic HCV subtype 1b infection. Fifteen treatment-naïve patients were treated with telaprevir 750 mg every 8 h for 24 weeks. All patients were Japanese whose median age was 58.0 years (range: 45–68), and six patients (40%) were men. Median baseline HCV RNA level was 6.80 log10 IU/mL (range: 3.55–7.10). The HCV RNA levels decreased to undetectable in five patients (33%) within 8 weeks. Three patients (20%) with negative HCV RNA by Week 4 achieved end of treatment response. One patient (7%) who achieved sustained virological response had a low baseline viraemia of 3.55 log10 IU/mL. Most of the adverse events including anaemia and skin disorders were mild to moderate. Developed variants were T54A and A156V/T/F/Y with or without secondary substitutions rather than V36M ± R155K. Telaprevir alone for 24 weeks in Japanese patients with HCV subtype 1b resulted in an sustained viral response rate of 7% (1/15) and was well tolerated for 24 weeks. These results will support the implementation of further studies on oral combination of telaprevir with other direct-acting antiviral agents in patients infected with HCV subtype 1b. PMID:23383655

Superior virologic and treatment outcomes when viral load is measured at 3 months compared to 6 months on antiretroviral therapy.

Science.gov (United States)

Kerschberger, Bernhard; Boulle, Andrew M; Kranzer, Katharina; Hilderbrand, Katherine; Schomaker, Michael; Coetzee, David; Goemaere, Eric; Van Cutsem, Gilles

2015-01-01

Routine viral load (VL) monitoring is utilized to assess antiretroviral therapy (ART) adherence and virologic failure, and it is currently scaled-up in many resource-constrained settings. The first routine VL is recommended as late as six months after ART initiation for early detection of sub-optimal adherence. We aimed to assess the optimal timing of first VL measurement after initiation of ART. This was a retrospective, cohort analysis of routine monitoring data of adults enrolled at three primary care clinics in Khayelitsha, Cape Town, between January 2002 and March 2009. Primary outcomes were virologic failure and switch to second-line ART comparing patients in whom first VL done was at three months (VL3M) and six months (VL6M) after ART initiation. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard models. In total, 6264 patients were included for the time to virologic failure and 6269 for the time to switch to second-line ART analysis. Patients in the VL3M group had a 22% risk reduction of virologic failure (aHR 0.78, 95% CI 0.64-0.95; p=0.016) and a 27% risk reduction of switch to second-line ART (aHR 0.73, 95% CI 0.58-0.92; p=0.008) when compared to patients in the VL6M group. For each additional month of delay of the first VL measurement (up to nine months), the risk of virologic failure increased by 9% (aHR 1.09, 95% CI 1.02-1.15; p=0.008) and switch to second-line ART by 13% (aHR 1.13, 95% CI 1.05-1.21; p<0.001). A first VL at three months rather than six months with targeted adherence interventions for patients with high VL may improve long-term virologic suppression and reduce switches to costly second-line ART. ART programmes should consider the first VL measurement at three months after ART initiation.

Heterogeneity of HVR-1 quasispecies is predictive of early but not sustained virological response in genotype 1b-infected patients undergoing combined treatment with PEG- or STD-IFN plus RBV.

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Abbate, I; Cappiello, G; Lo Iacono, O; Longo, R; Ferraro, D; Antonucci, G; Di Marco, V; Di Stefano, R; Craxì, A; Solmone, M C; Spanò, A; Ippolito, G; Capobianchi, M R

2003-01-01

ISDR mutation pattern and HVR-1 quasispecies were analyzed in HCV genotype 1b-infected patients treated with either PEG- or STD-IFN plus ribavirin, in order to find virological correlates of therapy outcome. ISDR region analysis, performed at baseline (T0) and at 4 weeks of therapy (T1), indicated that ISDR mutation pattern was not predictive of response to treatment. Moreover, no selection of putative resistant strains in the first month of therapy was observed. Viral load was not correlated with any parameter of HVR-1 heterogeneity. Among the HVR-1 heterogeneity parameters considered, complexity was inversely correlated to viral load decline at T1. In univariate analysis, complexity, proportion of non synonymous substitutions (NS) and NS/S ratio were lower in patients showing virological response at 6 months of treatment. Complexity was the only parameter independently associated with both decline of viral load at T1 and virological response after 6 months, even after adjustment for confounding variables. At the end of treatment or later, these correlations were lost. Evolution pattern of the HVR-1 quasispecies indicated a strong selective pressure in sustained responders, with complete substitution of pre-existing quasispecies, while minor changes occured in non responders. In relapsers both patterns were present at a similar rate. In conclusion, this study shows that HVR-1 heterogeneity may be involved in the early response to combined IFN-RBV therapy. The loss of correlation between viral heterogeneity and therapy outcome at 6 months of therapy, or later, suggests that other factors may play a role in maintaining sustained response to treatment.

Early virologic response and IL28B polymorphisms in patients with chronic hepatitis C genotype 3 treated with peginterferon alfa-2a and ribavirin.

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Scherzer, Thomas-Matthias; Hofer, Harald; Staettermayer, Albert Friedrich; Rutter, Karoline; Beinhardt, Sandra; Steindl-Munda, Petra; Kerschner, Heidrun; Kessler, Harald H; Ferenci, Peter

2011-05-01

Polymorphisms of the IL28B gene (rs12979860 and rs8099917) are associated with high sustained virological response (SVR) rates in HCV genotype 1 patients. This study analyzes the impact of these IL28B polymorphisms on early treatment response (weeks 2 and 4) and SVR in HCV genotype 3 patients. rs12979860 and rs8099917 were analyzed by the Step-OnePlus Real-time PCR system in 71 out of 72 Caucasian HCV genotype 3 patients participating, at our center, in a randomized study comparing 400mg with 800 mg ribavirin/day. HCV RNA was determined at weeks 2 and 4 of 180 μg/week peginterferon alfa-2a/ribavirin treatment. Sixty-nine patients completed the treatment and follow-up. rs12979860 genotyping revealed that 27 (37.5%) patients had C/C, 39 (54.2%) T/C, and 5 (6.9%) T/T. Thirteen patients (18.1%) became HCV RNA negative at week 2 and an additional 30 (41.7%) at week 4 (rapid virologic response; RVR); thus a total of 43 had a RVR (C/C: 77.8%; T/C or T/T: 50.0%). Irrespective of the ribavirin dose, the viral load decline was larger than in those with the T allele (T/C or T/T) (week 2: 4.46; [0.36-6.02] median; [range] vs. 3.50; [0.14-5.62]; log IU HCV-RNA/ml; p<0.001; week 4: 4.97; [1.21-6.20] vs. 4.49; [1.16-6.23]; p=0.003). Despite the faster initial viral response in C/C carriers, SVR rates were not different compared to T-allele carriers. Results of the SNP in the rs8099917 region were similar. IL28B polymorphisms modulate early virologic response to peginterferon/ribavirin treatment. In contrast to HCV genotype 1 patients, no effect on SVR rates was observed in genotype 3 patients. The clinical relevance of an earlier viral decline in C/C patients needs to be determined. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Considerations in choosing a primary endpoint that measures durability of virological suppression in an antiretroviral trial.

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Gilbert, P B; Ribaudo, H J; Greenberg, L; Yu, G; Bosch, R J; Tierney, C; Kuritzkes, D R

2000-09-08

At present, many clinical trials of anti-HIV-1 therapies compare treatments by a primary endpoint that measures the durability of suppression of HIV-1 replication. Several durability endpoints are compared. Endpoints are compared by their implicit assumptions regarding surrogacy for clinical outcomes, sample size requirements, and accommodations for inter-patient differences in baseline plasma HIV-1-RNA levels and in initial treatment response. Virological failure is defined by the non-suppression of virus levels at a prespecified follow-up time T(early virological failure), or by relapse. A binary virological failure endpoint is compared with three time-to-virological failure endpoints: time from (i) randomization that assigns early failures a failure time of T weeks; (ii) randomization that extends the early failure time T for slowly responding subjects; and (iii) virological response that assigns non-responders a failure time of 0 weeks. Endpoint differences are illustrated with Agouron's trial 511. In comparing high with low-dose nelfinavir (NFV) regimens in Agouron 511, the difference in Kaplan-Meier estimates of the proportion not failing by 24 weeks is 16.7% (P = 0.048), 6.5% (P = 0.29) and 22.9% (P = 0.0030) for endpoints (i), (ii) and (iii), respectively. The results differ because NFV suppresses virus more quickly at the higher dose, and the endpoints weigh this treatment difference differently. This illustrates that careful consideration needs to be given to choosing a primary endpoint that will detect treatment differences of interest. A time from randomization endpoint is usually recommended because of its advantages in flexibility and sample size, especially at interim analyses, and for its interpretation for patient management.

Utility of CD4 cell counts for early prediction of virological failure during antiretroviral therapy in a resource-limited setting

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Lawn Stephen D

2008-07-01

Full Text Available Abstract Background Viral load monitoring is not available for the vast majority of patients receiving antiretroviral therapy in resource-limited settings. However, the practical utility of CD4 cell count measurements as an alternative monitoring strategy has not been rigorously assessed. Methods In this study, we used a novel modelling approach that accounted for all CD4 cell count and VL values measured during follow-up from the first date that VL suppression was achieved. We determined the associations between CD4 counts (absolute values and changes during ART, VL measurements and risk of virological failure (VL > 1,000 copies/ml following initial VL suppression in 330 patients in South Africa. CD4 count changes were modelled both as the difference from baseline (ΔCD4 count and the difference between consecutive values (CD4 count slope using all 3-monthly CD4 count measurements during follow-up. Results During 7093.2 patient-months of observation 3756 paired CD4 count and VL measurements were made. In patients who developed virological failure (n = 179, VL correlated significantly with absolute CD4 counts (r = - 0.08, P = 0.003, ΔCD4 counts (r = - 0.11, P P P = 0.99, P = 0.92 and P = 0.75, respectively. Moreover, in a receiver operating characteristic (ROC curve, the association between a negative CD4 count slope and virological failure was poor (area under the curve = 0.59; sensitivity = 53.0%; specificity = 63.6%; positive predictive value = 10.9%. Conclusion CD4 count changes correlated significantly with VL at group level but had very limited utility in identifying virological failure in individual patients. CD4 count is an inadequate alternative to VL measurement for early detection of virological failure.

Hot News: Impact of Low-level Viremia on Treatment Outcomes During ART - Is it Time to Revise the Definition of Virological Failure?

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Poveda, Eva; Crespo, Manuel

2018-01-01

The level of HIV-RNA in plasma (HIV viral load) is the main marker used to monitor the virological response to antiretroviral therapy (ART) in HIV-infected patients. The threshold used to define virological suppression has historically been dictated by the limits of detection of the commercial assays used to quantify the plasma viral load. Thus, as more sensitive assays have proliferated and become more widely available, the definition has shifted from ART is to maintain virological suppression below 200 cop/mL, or even > 1000 cop/mL according to the WHO guidelines for low-income and middle-income countries. Several studies have evaluated the impact of low-level viremia as intermittent episodes (blips) or persistent detectable low-level viremia (50-1000 cop/mL) on treatment outcomes during ART. Some of these studies have suggested a potential role for low-level viremia as a predictor of virological failure, although up to now the data have been insufficient and controversial to guide clinical management. Hermans et al. have recently published the results of a large (n = 70.930 HIV-infected patients) multicenter study (57 clinical sites in South Africa) with a median follow-up for more than 2 years, to evaluate the incidence and impact of low-level viremia (defined as HIV-RNA viral load of 51-999 cop/mL) and its association with virological failure (Hermans et al., Lancet Infect Dis 2018;18:188-97). This large cohort study concludes that overall, patients with low-level viremia are predisposed to subsequent virological failure. The risk of virological failure was 5 times higher for patients with low-level viremia ranging 400-999 cop/mL, and 2 times higher for those with viremia ranging 51-199 cop/mL, compared with patients maintaining viral load suppression (ART should be recognized and considered in clinical decision-making. Furthermore, current WHO guidelines for low-income and middleincome countries should be revised and updated. Although substantial differences

Clinical outcome of HIV-infected patients with sustained virologic response to antiretroviral therapy: long-term follow-up of a multicenter cohort.

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Félix Gutierrez

Full Text Available BACKGROUND: Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. METHODS: Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. RESULTS: Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9% patients died (mortality rate 0.86 per 100 person-years, and 40 (5.3% died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68-10.83]; P = .002, and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02-1.09; P = .001. Initial antiretroviral regimen chosen was not associated with different risk of clinical progression. CONCLUSIONS: Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected.

Immunological responses during a virologically failing antiretroviral regimen are associated with in vivo synonymous mutation rates of HIV type-1 env

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Mens, Helene; Jørgensen, Louise Bruun; Kronborg, Gitte

2009-01-01

BACKGROUND: Little is known about the underlying causes of differences in immunological response to antiretroviral therapy during multidrug-resistant (MDR) HIV type-1 (HIV-1) infection. This study aimed to identify virological factors associated with immunological response during therapy failure...... for analysis. In a longitudinal mixed-effects model, plasma HIV-1 RNA only tended to predict immunological response (P=0.06), whereas minor protease inhibitor (PI) and nucleoside reverse transcriptase (NRTI) mutations at baseline correlated significantly with CD4+ T-cell count slopes (r= -0.56, P=0.04 and r......= -0.64, P=0.008, respectively). Interestingly, synonymous mutations of env correlated inversely with CD4+ T-cell count slopes (r=-0.60; P=0.01) and individuals with codons under positive selection had significantly better CD4+ T-cell responses than individuals without (0.42 versus -5.34; P=0...

Circulating sCD14 is associated with virological response to pegylated-interferon-alpha/ribavirin treatment in HIV/HCV co-infected patients.

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Giulia Marchetti

Full Text Available Microbial translocation (MT through the gut accounts for immune activation and CD4+ loss in HIV and may influence HCV disease progression in HIV/HCV co-infection. We asked whether increased MT and immune activation may hamper anti-HCV response in HIV/HCV patients.98 HIV/HCV patients who received pegylated-alpha-interferon (peg-INF-alpha/ribavirin were retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS, host response to MT (sCD14, CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week 12 of therapy or ≥2 log(10 reduction from baseline after 12 weeks of therapy and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of therapy. Mann-Whitney/Chi-square test and Pearson's correlation were used. Multivariable regression was performed to determine factors associated with EVR/SVR.71 patients displayed EVR; 41 SVR. Patients with HCV genotypes 1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with genotypes 2-3 (p = 0.053 and no cirrhosis (p = 0.052. EVR and SVR patients showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively, but similar T-cell activation compared to Non-EVR (Null Responders, NR and Non-SVR (N-SVR subjects. sCD14 resulted the main predictive factor of EVR (0.145 for each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015. SVR was associated only with HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, p = 0.014.In HIV/HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-INF-alpha/ribavirin, suggesting MT-driven immune activation as pathway of HIV/HCV co-infection and response to therapy.

Timing of pregnancy, postpartum risk of virologic failure and loss to follow-up among HIV-positive women.

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Onoya, Dorina; Sineke, Tembeka; Brennan, Alana T; Long, Lawrence; Fox, Matthew P

2017-07-17

We assessed the association between the timing of pregnancy with the risk of postpartum virologic failure and loss from HIV care in South Africa. This is a retrospective cohort study of 6306 HIV-positive women aged 15-49 at antiretroviral therapy (ART) initiation, initiated on ART between January 2004 and December 2013 in Johannesburg, South Africa. The incidence of virologic failure (two consecutive viral load measurements of >1000 copies/ml) and loss to follow-up (>3 months late for a visit) during 24 months postpartum were assessed using Cox proportional hazards modelling. The rate of postpartum virologic failure was higher following an incident pregnancy on ART [adjusted hazard ratio 1.8, 95% confidence interval (CI): 1.1-2.7] than among women who initiated ART during pregnancy. This difference was sustained among women with CD4 cell count less than 350 cells/μl at delivery (adjusted hazard ratio 1.8, 95% CI: 1.1-3.0). Predictors of postpartum virologic failure were being viremic, longer time on ART, being 25 or less years old and low CD4 cell count and anaemia at delivery, as well as initiating ART on stavudine-containing or abacavir-containing regimen. There was no difference postpartum loss to follow-up rates between the incident pregnancies group (hazard ratio 0.9, 95% CI: 0.7-1.1) and those who initiated ART in pregnancy. The risk of virologic failure remains high among postpartum women, particularly those who conceive on ART. The results highlight the need to provide adequate support for HIV-positive women with fertility intention after ART initiation and to strengthen monitoring and retention efforts for postpartum women to sustain the benefits of ART.

Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA

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Bannister, Wendy P; Ruiz, Lidia; Cozzi-Lepri, Alessandro

2008-01-01

OBJECTIVE: To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) wi...

Virology: The Next Generation from Digital PCR to Single Virion Genomics

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White, Richard A.; Brazelton De Cardenas, Jessica N.; Hayden, Randall T.

2015-10-01

In the past 25 years, virology has had major technology breakthroughs stemming first from the introduction of nucleic acid amplification testing, but more recently from the use of next-generation sequencing, digital PCR, and the possibility of single virion genomics. These technologies have and will improve diagnosis and disease state monitoring in clinical settings, aid in environmental monitoring, and reveal the vast genetic potential of viruses. Using the principle of limiting dilution, digital PCR amplifies single molecules of DNA in highly partitioned endpoint reactions and reads each of those reactions as either positive or negative based on the presence or absence of target fluorophore. In this review, digital PCR will be highlighted along with current studies, advantages/disadvantages, and future perspectives with regard to digital PCR, viral load testing, and the possibility of single virion genomics.

Rapid virological response of telaprevir and boceprevir in a Brazilian cohort of HCV genotype 1 patients: a multicenter longitudinal study

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Borba HHL

2017-01-01

Full Text Available Helena HL Borba,1 Astrid Wiens,1 Laiza M Steimbach,1 Fernanda S Tonin,1 Maria LA Pedroso,2 Cláudia AP Ivantes,3 Fernando Fernandez-Llimos,4 Roberto Pontarolo1 1Pharmaceutical Sciences Postgraduate Research Program, Department of Pharmacy, 2Gastroenterology Service, Hospital de Clínicas, Federal University of Paraná, 3Guidance and Counseling Center, Curitiba City Hall, Curitiba, Paraná, Brazil; 4Department of Social Pharmacy, Faculty of Pharmacy, Research Institute for Medicines, University of Lisboa, Lisbon, Portugal Background: Chronic hepatitis C is a major public health issue, but there is a gap in the literature regarding the effectiveness and safety of direct-acting antiviral agents in the Brazilian population. The main aim of this study was to describe the effectiveness of boceprevir and telaprevir in patients treated at public health care institutions in Brazil.Materials and methods: A prospective longitudinal and multicenter study was conducted in five centers in the State of Paraná between September 2014 and June 2016. Data regarding effectiveness and safety were collected from medical records of patients treated with boceprevir or telaprevir. The effectiveness outcome comprised the rapid virological response (RVR. Multivariate analysis was performed to verify the influence of independent variables (ie, age, gender, baseline viral load on RVR achievement.Results: Data were collected from 117 patients with chronic hepatitis C virus (HCV genotype 1 infection. Fifteen patients received treatment with boceprevir and 102 received telaprevir. The mean age was 51.6 years, 64.1% were male, 44.4% were infected with HCV subtype 1a, 62.4% had a high baseline viral load (≥800,000 IU/mL and 33% were cirrhotic. Furthermore, 79.5% of patients achieved RVR (26.7% in the boceprevir group and 87.3% in the telaprevir group. Multivariate analysis demonstrated that the type of protease inhibitor (boceprevir or telaprevir and the baseline viral load

Characterization of Hepatitis C Virus genotype 3a Hypervariable region 1 in patients achieved rapid virological response to alpha interferon and Ribavirin Combination therapy

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Badar Sadaf

2011-05-01

Full Text Available Abstract Background Hepatitis C virus roots a chronic liver disease. Currently approved treatment strategy includes administration of alpha interferon and ribavirin combined therapy for 24-48 weeks. One of the predictor of sustained virological response is an early virological response to treatment characterized as rapid response. Hyper variable region 1 (HVR1 of E2 protein is responsible for viral entry and acts as a target for neutralizing antibodies. Any mutation in this region would effect virus interaction with target cell and viral persistence. Methods Thirty one clones of six pre-treatment samples subjected to combination therapy were investigated. Three of the patients were rapid responders (R1, R2 and R3 and two were breakthrough responders (BT1 and BT2. Envelope 2 gene was amplified, cloned and sequenced. Amino acid substitution, frequency, composition and antigenic properties of HVR 1 of E2 protein were studied. Results In both rapid responders (R.R (14 amino acid sites and breakthrough responders (BT.R (13 amino acid sites half of the amino acid sites were either conserved or resistant to any physiochemical change due to amino acid substitution. It also indicated that average composition of hydrophilic and basic amino acids were comparatively lower in rapid responders than other samples affecting probable interaction of virus with target cells. A central non antigenic region was constant among the breakthrough responders but differed in length significantly among rapid responders reflecting the adaptive nature of HVR1 to the immune response. Conclusions We observed that although HVR1is quite variable region in HCV 3a patients responding differently to treatment it still maintains its physiochemical properties for its proper functioning and viability.

A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

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Micheli Valeria

2011-06-01

Full Text Available Abstract Background HIV-1 genotypic susceptibility scores (GSSs were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed. Methods We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb and other covariates by means of Cox regression and random survival forests (RSF. Prediction models were validated via the bootstrap and c-index measure. Results The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70, while RSF showed a better performance (c-index≈0.73, p Conclusions GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.

Factors predicting discordant virological and immunological responses to antiretroviral therapy in HIV-1 clade C infected Zulu/Xhosa in South Africa.

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Boris Julg

Full Text Available Factors predicting suboptimal CD4 cell recovery have been studied in HIV clade-B infected US and European populations. It is, however, uncertain to what extent these results are applicable to HIV clade-C infected African populations. Multivariate analysis using logistic regression and longitudinal analyses using mixed models were employed to assess the impact of age, gender, baseline CD4 cell count, hemoglobin, body mass index (BMI, tuberculosis and other opportunistic co-infections, and frequencies of regimen change on CD4 cell recovery at 12 and 30 months and on overtime change in CD4 cells among 442 virologically suppressed South Africans. Despite adequate virological response 37% (95% CI:32%-42% and 83% (95% CI:79%-86% of patients on antiretroviral therapy failed to restore CD4 cell counts ≥ 200 cells/mm(3 after 12 and ≥ 500 cells/mm(3 after 30 months, respectively, in this South African cohort. Critical risk factors for inadequate recovery were older age (p = 0.001 and nadir CD4 cell count at ART initiation (p<0.0001, while concurrent TB co-infection, BMI, baseline hemoglobin, gender and antiretroviral regimen were not significant risk factors. These data suggest that greater efforts are needed to identify and treat HAART-eligible patients prior to severe CD4 cell decline or achievement of advanced age.

Factors predicting discordant virological and immunological responses to antiretroviral therapy in HIV-1 clade C infected Zulu/Xhosa in South Africa.

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Julg, Boris; Poole, Danielle; Ghebremichael, Musie; Castilla, Carmen; Altfeld, Marcus; Sunpath, Henry; Murphy, Richard A; Walker, Bruce D

2012-01-01

Factors predicting suboptimal CD4 cell recovery have been studied in HIV clade-B infected US and European populations. It is, however, uncertain to what extent these results are applicable to HIV clade-C infected African populations. Multivariate analysis using logistic regression and longitudinal analyses using mixed models were employed to assess the impact of age, gender, baseline CD4 cell count, hemoglobin, body mass index (BMI), tuberculosis and other opportunistic co-infections, and frequencies of regimen change on CD4 cell recovery at 12 and 30 months and on overtime change in CD4 cells among 442 virologically suppressed South Africans. Despite adequate virological response 37% (95% CI:32%-42%) and 83% (95% CI:79%-86%) of patients on antiretroviral therapy failed to restore CD4 cell counts ≥ 200 cells/mm(3) after 12 and ≥ 500 cells/mm(3) after 30 months, respectively, in this South African cohort. Critical risk factors for inadequate recovery were older age (p = 0.001) and nadir CD4 cell count at ART initiation (p<0.0001), while concurrent TB co-infection, BMI, baseline hemoglobin, gender and antiretroviral regimen were not significant risk factors. These data suggest that greater efforts are needed to identify and treat HAART-eligible patients prior to severe CD4 cell decline or achievement of advanced age.

Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness two years after treatment with Ombitasvir/Paritaprevir/Ritonavir ±Dasabuvir ±Ribavirin in the AMBER, real-world experience study.

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Flisiak, Robert; Janczewska, Ewa; Łucejko, Mariusz; Karpińska, Ewa; Zarębska-Michaluk, Dorota; Nazzal, Khalil; Bolewska, Beata; Białkowska, Jolanta; Berak, Hanna; Fleischer-Stępniewska, Katarzyna; Tomasiewicz, Krzysztof; Karwowska, Kornelia; Simon, Krzysztof; Piekarska, Anna; Tronina, Olga; Tuchendler, Ewelina; Garlicki, Aleksander

2018-06-11

We followed for 2 years patients treated with Direct Acting Agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction of liver stiffness (LS), and risk of hepatocellular carcinoma (HCC).The study included patients from 16 hepatologic centers involved in the AMBER, investigators initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of Ombitasvir/Paritaprevir/ritonavir±Dasabuvir±Ribavirin. A total of 204 patients among 209 from the primary study were enrolled; 200 with available testing at 2 years follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 non-responders retreated). During 2yFU 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses was lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, two-years follow-up confirmed durability of virologic response after treatment of HCV infection with Ombitasvir/Paritaprevir/ritonavir±Dasabuvir±Ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics, that support the need for longer than 2-year monitoring for possible disease progression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children - a EuroCoord-CHAIN-EPPICC joint project

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Ngo-Giang-Huong, Nicole; Wittkop, Linda; Judd, Ali

2016-01-01

BACKGROUND: Few studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association...... algorithm to infer resistance to prescribed drugs. Time to virological failure (VF) was defined as the first of two consecutive HIV-RNA > 500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology.......7-5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5-10.6) harboring a virus with ≥1 PDR mutations, 30 children had a virus resistant to ≥1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 %CI, 16.4-23.9). Cumulative risk for VF tended...

Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension.

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Mandorfer, Mattias; Kozbial, Karin; Schwabl, Philipp; Freissmuth, Clarissa; Schwarzer, Rémy; Stern, Rafael; Chromy, David; Stättermayer, Albert Friedrich; Reiberger, Thomas; Beinhardt, Sandra; Sieghart, Wolfgang; Trauner, Michael; Hofer, Harald; Ferlitsch, Arnulf; Ferenci, Peter; Peck-Radosavljevic, Markus

2016-10-01

We aimed to investigate the impact of sustained virologic response (SVR) to interferon (IFN)-free therapies on portal hypertension in patients with paired hepatic venous pressure gradient (HVPG) measurements. One hundred and four patients with portal hypertension (HVPG ⩾6mmHg) who underwent HVPG and liver stiffness measurement before IFN-free therapy (baseline [BL]) were retrospectively studied. Among 100 patients who achieved SVR, 60 patients underwent HVPG and transient elastography (TE) after antiviral therapy (follow-up [FU]). SVR to IFN-free therapies significantly decreased HVPG across all BL HVPG strata: 6-9mmHg (BL: 7.37±0.28 vs. FU: 5.11±0.38mmHg; -2.26±0.42mmHg; pportal hypertension across all BL HVPG strata. However, changes in HVPG seemed to be more heterogeneous among patients with BL HVPG of ⩾16mmHg and a HVPG decrease was less likely in patients with more advanced liver dysfunction. TE might be useful for the non-invasive evaluation of portal hypertension after SVR. We investigated the impact of curing hepatitis C using novel interferon-free treatments on portal hypertension, which drives the development of liver-related complications and mortality. Cure of hepatitis C decreased portal pressure, but a decrease was less likely among patients with more pronounced hepatic dysfunction. Transient elastography, which is commonly used for the non-invasive staging of liver disease, might identify patients without clinically significant portal hypertension after successful treatment. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Pharmacy refill adherence compared with CD4 count changes for monitoring HIV-infected adults on antiretroviral therapy.

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Gregory P Bisson

2008-05-01

Full Text Available World Health Organization (WHO guidelines for monitoring HIV-infected individuals taking combination antiretroviral therapy (cART in resource-limited settings recommend using CD4(+ T cell (CD4 count changes to monitor treatment effectiveness. In practice, however, falling CD4 counts are a consequence, rather than a cause, of virologic failure. Adherence lapses precede virologic failure and, unlike CD4 counts, data on adherence are immediately available to all clinics dispensing cART. However, the accuracy of adherence assessments for predicting future or detecting current virologic failure has not been determined. The goal of this study therefore was to determine the accuracy of adherence assessments for predicting and detecting virologic failure and to compare the accuracy of adherence-based monitoring approaches with approaches monitoring CD4 count changes.We conducted an observational cohort study among 1,982 of 4,984 (40% HIV-infected adults initiating non-nucleoside reverse transcriptase inhibitor-based cART in the Aid for AIDS Disease Management Program, which serves nine countries in southern Africa. Pharmacy refill adherence was calculated as the number of months of cART claims submitted divided by the number of complete months between cART initiation and the last refill prior to the endpoint of interest, expressed as a percentage. The main outcome measure was virologic failure defined as a viral load > 1,000 copies/ml (1 at an initial assessment either 6 or 12 mo after cART initiation and (2 after a previous undetectable (i.e., 0.5. In addition, adherence levels assessed 3 mo prior to viral load assessments were as accurate for virologic failure occurring approximately 3 mo later as were CD4 count changes calculated from cART initiation to the actual time of the viral load assessments, indicating the potential utility of adherence assessments for predicting future, rather than simply detecting current, virologic failure. Moreover

Pretreatment HIV drug resistance results in virological failure and accumulation of additional resistance mutations in Ugandan children

NARCIS (Netherlands)

Kityo, Cissy; Boerma, Ragna S.; Sigaloff, Kim C. E.; Kaudha, Elizabeth; Calis, Job C. J.; Musiime, Victor; Balinda, Sheila; Nakanjako, Rita; Boender, T. Sonia; Mugyenyi, Peter N.; Rinke de Wit, Tobias F.

2017-01-01

Background: Pretreatment HIV drug resistance (PDR) can impair virological response to ART, jeopardizing effective treatment for children. Methods: Children aged <12 years initiated first-line ART in Uganda during 2010-11. Baseline and 6 monthly viral load (VL) and genotypic resistance testing if VL.

Low Virologic Failure and Drug Resistance among HIV-Infected Patients Receiving Hospital-Based ART While Care and Outreach through Community in Guangxi, China.

Science.gov (United States)

Liang, Shujia; Shen, Zhiyong; Yan, Jing; Liang, Fuxiong; Tang, Zhenzhu; Liu, Wei; Kan, Wei; Liao, Lingjie; Leng, Xuebing; Ruan, Yuhua; Xing, Hui; Shao, Yiming

2015-01-01

To investigate human immunodeficiency virus (HIV) virologic suppression and drug resistance among HIV-infected patients receiving first-line antiretroviral treatment (ART) in hospitals while community care and outreach through local health workers in Guangxi, China. This was a series of cross-sectional surveys from 2004 to 2012 in Guangxi, supported by the Chinese National HIVDR Surveillance and Monitoring Network Working Group. Guangxi, China. Demographic, ART, and laboratory data (CD4(+) cell count, viral load, and drug resistance) were analyzed. Factors associated with virologic suppression were identified by logistic regression analysis. A total of 780 patients were included in this study. The median treatment duration was 20.6 months (IQR 6.6-35.9). Of 780 study participants, 95.4% of patients (744/780) had HIV virologic suppression. Among these, of the 143 patients who were infected through drug injection, only 10 (7.0%) experienced virologic failure, and the overall prevalence of HIV drug resistance was 2.8% (22/789). Factors associated with virologic suppression in the final multivariate models included self-reported missing doses in the past month (compared to not missing doses in the past month, AOR = 0.2, 95% CI: 0.1-0.6) and initial ART regimen without 3TC (compared to initial ART regimen with 3TC, AOR = 0.2, 95% CI: 0.1-0.4). Moreover, the trend chi-square test showed that the proportion of virologic suppression increased over time from 2004 to 2012 (P = 0.002). This study first demonstrated that HIV patients infected through various transmission routes can achieve an excellent treatment outcome in hospitals at or above the county level for free first-line ART in Guangxi. It is an important of ART education and adherence to intervention for achieving better treatment outcomes.

Prediction value of serum HBV large surface protein in different phases of HBV infection and virological response of chronic hepatitis B patients.

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Liu, Can; Wu, Wennan; Shang, Hongyan; Lin, Sheng; Xun, Zhen; Huang, Er; Lin, Jinpiao; Yang, Bin; Ou, Qishui

2018-06-01

Serum HBV large surface protein (HBV-LP) is an envelope protein that has a close relationship with HBV DNA level. This study is to explore the prediction value of HBV-LP in different phase of HBV infection and during antiviral therapy in chronic hepatitis B (CHB) patients. A retrospective study was conducted in 2033 individuals, which included 1677 HBV infected patients in different phases and 356 healthy controls. HBV-LP, HBV serum markers and HBV DNA were detected by ELISA, CMIA and qRT-PCR, respectively. 85 CHB patients receiving PegIFNα or ETV were divided into virological response (VR) and partial virological response (PVR). The dynamic changes of HBV DNA and HBV-LP were observed. The level of HBV-LP in 2033 individuals was shown as: HBeAg-positive hepatitis > HBeAg-positive infection > HBeAg-negative hepatitis > HBeAg-negative infection > healthy controls. HBV-LP was positive in all patients whose HBV DNA > 1.0E + 06 IU/ml. When HBsAg was 1000 IU/ml, HBV DNAs were all negative if HBV-LP HBV-LP with HBV DNA was 100% in case of HBV-LP > 4.0 S/CO in HBeAg-positive patients and HBV-LP > 2.0 S/CO in HBeAg-negative ones. During antiviral therapy, baseline HBV-LP was lower in VR patients than that in PVR patients. The optimal cut-off points to predict VR by baseline HBV-LP were 32.4 and 28.6 S/CO for HBeAg-positive and HBeAg-negative hepatitis patients, respectively. HBV-LP may be a useful marker for distinguishing the different phases of HBV infection. Moreover, baseline HBV-LP level can be used for predicting VR of CHB patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Antiretroviral therapy initiation before, during, or after pregnancy in HIV-1-infected women: maternal virologic, immunologic, and clinical response.

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Vlada V Melekhin

2009-09-01

Full Text Available Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.We conducted a retrospective cohort study from 1997-2005 among 112 pregnant HIV-infected women who started HAART before (N = 12, during (N = 70 or after pregnancy (N = 30.Women initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (-0.35 vs. 0.10 log(10 copies/mL, P = 0.03 and 183.8 vs. -70.8 cells/mm(3, P = 0.03, respectively but similar to those initiating HAART before pregnancy (-0.32 log(10 copies/mL, P = 0.96 and 155.8 cells/mm(3, P = 0.81, respectively. There were 3 (25% AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4% in those initiating HAART during pregnancy, and 5 (17% in those initiating after pregnancy (P = 0.01. There were no statistical differences in rates of HIV disease progression between groups.HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.

Are three generations of quantitative molecular methods sufficient in medical virology? Brief review.

Science.gov (United States)

Clementi, Massimo; Bagnarelli, Patrizia

2015-10-01

In the last two decades, development of quantitative molecular methods has characterized the evolution of clinical virology more than any other methodological advancement. Using these methods, a great deal of studies has addressed efficiently in vivo the role of viral load, viral replication activity, and viral transcriptional profiles as correlates of disease outcome and progression, and has highlighted the physio-pathology of important virus diseases of humans. Furthermore, these studies have contributed to a better understanding of virus-host interactions and have sharply revolutionized the research strategies in basic and medical virology. In addition and importantly from a medical point of view, quantitative methods have provided a rationale for the therapeutic intervention and therapy monitoring in medically important viral diseases. Despite the advances in technology and the development of three generations of molecular methods within the last two decades (competitive PCR, real-time PCR, and digital PCR), great challenges still remain for viral testing related not only to standardization, accuracy, and precision, but also to selection of the best molecular targets for clinical use and to the identification of thresholds for risk stratification and therapeutic decisions. Future research directions, novel methods and technical improvements could be important to address these challenges.

Applications of Next-Generation Sequencing Technologies to Diagnostic Virology

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Giorgio Palù

2011-11-01

Full Text Available Novel DNA sequencing techniques, referred to as “next-generation” sequencing (NGS, provide high speed and throughput that can produce an enormous volume of sequences with many possible applications in research and diagnostic settings. In this article, we provide an overview of the many applications of NGS in diagnostic virology. NGS techniques have been used for high-throughput whole viral genome sequencing, such as sequencing of new influenza viruses, for detection of viral genome variability and evolution within the host, such as investigation of human immunodeficiency virus and human hepatitis C virus quasispecies, and monitoring of low-abundance antiviral drug-resistance mutations. NGS techniques have been applied to metagenomics-based strategies for the detection of unexpected disease-associated viruses and for the discovery of novel human viruses, including cancer-related viruses. Finally, the human virome in healthy and disease conditions has been described by NGS-based metagenomics.

Four weeks of paritaprevir/ritonavir/ombitasvir plus dasabuvir encountering dengue fever resulted in sustained virological response in an HCV patient: A case report.

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Huang, Chung-Feng; Jang, Tyng-Yuan; Lu, Po-Liang; Yu, Ming-Lung

2016-11-01

Direct antiviral agent (DAA) has been the standard of care for patients with hepatitis C virus (HCV) infection. Twelve weeks of paritaprevir/ritonavir/ombitasvir plus dasabuvir (PROD) with or without ribavirin has shown to have a sustained virological response at post-treatment 12 weeks (SVR12) rate of >90% in HCV genotype 1 (HCV-1) patients. We report a HCV-1b patient who received only 25 days of PROD treatment. The patient early terminated treatment due to dengue fever but eventually achieved SVR12. It may attribute to low baseline viral loads and extraordinarily rapid suppression of HCV after treatment day1. The finding may shed light for possible response-guided-therapy for so-called ultra-super-responders in the DAA era. Whether the dengue virus, the Flaviviridae family as with HCV, enhanced the HCV clearance remains unclear and needs further exploration.

Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression

DEFF Research Database (Denmark)

Llibre, Josep M; Cozzi-Lepri, Alessandro; Pedersen, Court

2016-01-01

Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant.We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (p......VL), performing a time to loss of virological response (TLOVR analysis at 48, 96, and 144 weeks. Virological failure (VF) was defined as confirmed pVL >50 copies/mL.We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50 copies/mL. The third......%/67%/59% (snapshot analysis), respectively. The rates of VF were 8%/8%/6%. Rates of adverse events leading to study discontinuation were 0.4%/1%/2%. The multivariable adjusted analysis showed an association between VF and nadir CD4+ (hazard ratio [HR] 0.63 [95% confidence interval [CI]: 0.42-0.93] per 100 cells...

Mucosal immunology and virology

National Research Council Canada - National Science Library

Tyring, Stephen

2006-01-01

.... A third chapter focuses on the proximal end of the gastrointestinal tract (i.e. the oral cavity). The mucosal immunology and virology of the distal end of the gastrointestinal tract is covered in the chapter on the anogenital mucosa. Mucosa-associated lymphoid tissue (MALT) plays a role in protection against all viral (and other) infections except those that enter the body via a bite (e.g. yellow fever or dengue from a mosquito or rabies from a dog) or an injection or transfusion (e.g. HIV, Hepatitis B). ...

Factors Influencing Antiretroviral Adherence and Virological Outcomes in People Living with HIV in the Highlands of Papua New Guinea.

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Janet Gare

Full Text Available Adherence to antiretroviral therapy (ART is paramount for virological suppression and positive treatment outcomes. ART has been rapidly scaled up in Papua New Guinea (PNG in recent years, however clinical monitoring of HIV+ individuals on ART is limited. A cross-sectional study was conducted at two major sexual health clinics in high HIV prevalence provinces in the Highlands Region of PNG to assess ART adherence, factors affecting adherence and the relationship between ART adherence and virological outcomes. Ninety-five HIV+ individuals were recruited and administered a questionnaire to gather demographic and ART adherence information whilst clinical data and pill counts were extracted from patient charts and blood was collected for viral load testing. Bivariate analysis was performed to identify independent predictors of ART adherence. Fourteen percent (n = 12 of participants showed evidence of virological failure. Although the majority of participants self-reported excellent ART adherence in the last seven days (78.9%, 75/91, pill count measurements indicated only 40% (34/84 with >95% adherence in the last month. Taking other medications while on ART (p = 0.01 and taking ART for ≥1 year (p = 0.037 were positively associated with adherence by self-report and pill count, respectively. Participants who had never heard of drug resistance were more likely to show virological failure (p = 0.033. Misconception on routes of HIV transmission still persists in the studied population. These findings indicate that non-adherence to ART is high in this region of PNG and continued education and strategies to improve adherence are required to ensure the efficacy of ART and prevent HIV drug resistance.

Slower Fibrosis Progression Among Liver Transplant Recipients With Sustained Virological Response After Hepatitis C Treatment

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Habib, Shahid; Meister, Edward; Habib, Sana; Murakami, Traci; Walker, Courtney; Rana, Abbas; Shaikh, Obaid S.

2015-01-01

Background The natural course of hepatic fibrosis in HCV allograft recipients with sustained virological response (SVR) after anti-HCV therapy remains debatable. The aim of this study was to examine the progression of fibrosis in a cohort of patients who achieved SVR compared with those without treatment. Methods The 167 patients who met the inclusion and exclusion criteria were chosen from a transplant database. All patients were required to have histological evidence of recurrent HCV infection post-liver transplantation and a follow-up biopsy. The 140 of these patients had received anti-viral therapy. Twenty-seven patients were identified as controls and were matched with the treatment group in all respects. The patients were categorized into four groups based on treatment response: 1) no treatment (control) (n = 27); 2) non-responders (n = 81); 3) relapsers (n = 32); and 4) SVR (n = 27). The endpoint was the stage of fibrosis on the follow-up liver biopsy. Results The treated and untreated groups were similar in clinical characteristics at the time of transplantation and prior to the initiation of treatment. The 72% of the cohort showed a fibrosis progression of ≥ 1 stage; this change did not significantly differ between the patient groups. Nonetheless, the fibrosis progression rate was the highest in the untreated group and lowest in the patients who achieved SVR. A coefficient of determination was used. Improvements in fibrosis scores were found with greater treatment duration. These improvements were most evident with the achievement of SVR. Conclusions In conclusion, SVR after anti-viral therapy for recurrent hepatitis C infection post-transplantation was associated with slower fibrosis progression and significantly improved graft survival. PMID:27785303

Weight loss, leukopenia and thrombocytopenia associated with sustained virologic response to Hepatitis C treatment

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Suwantarat, Nuntra; Tice, Alan D.; Khawcharoenporn, Thana; Chow, Dominic C.

2010-01-01

OBJECTIVE: To identify apparent adverse effects of treatment of chronic hepatitis C and their relationship to sustained virologic response (SVR). METHODS: A retrospective study was conducted of all Hepatitis C virus (HCV)-infected patients treated with pegylated interferon and ribavirin in an academic ambulatory infectious disease practice. Clinical and laboratory characteristics were compared between patients with SVR and without SVR. RESULTS: Fifty-four patients completed therapy with the overall SVR rate of 76%. SVR was associated with genotype non-1 (P=0.01), weight loss more than 5 kilograms (P=0.04), end of treatment leukopenia (P=0.02) and thrombocytopenia (P=0.05). In multivariate analysis, SVR was significant associated with HCV genotype non-1 (Adjusted Odd Ratio [AOR] 15.22; CI 1.55 to 149.72; P=0.02), weight loss more than 5 kilograms, (AOR 5.74; CI 1.24 to 26.32; P=0.04), and end of treatment white blood cell count level less than 3 X 103 cells/µl (AOR 9.09; CI 1.59 to 52.63; P=0.02). Thrombocytopenia was not significant after adjustment. Other factors including age, gender, ethnicity, injection drug use, viral load, anemia, alanine transaminase level, and liver histology did not reach statistical significance. CONCLUSION: Besides non-1 genotype, SVR was found to be independently associated with weight loss during therapy, and leukopenia at the end of HCV treatment. These correlations suggest continuation of therapy despite adverse effects, may be of benefit. PMID:20107528

Next-Generation Sequencing and Genome Editing in Plant Virology

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Ahmed Hadidi

2016-08-01

Full Text Available Next-generation sequencing (NGS has been applied to plant virology since 2009. NGS provides highly efficient, rapid, low cost DNA or RNA high-throughput sequencing of the genomes of plant viruses and viroids and of the specific small RNAs generated during the infection process. These small RNAs, which cover frequently the whole genome of the infectious agent, are 21-24 nt long and are known as vsRNAs for viruses and vd-sRNAs for viroids. NGS has been used in a number of studies in plant virology including, but not limited to, discovery of novel viruses and viroids as well as detection and identification of those pathogens already known, analysis of genome diversity and evolution, and study of pathogen epidemiology. The genome engineering editing method, clustered regularly interspaced short palindromic repeats (CRISPR-Cas9 system has been successfully used recently to engineer resistance to DNA geminiviruses (family, Geminiviridae by targeting different viral genome sequences in infected Nicotiana benthamiana or Arabidopsis plants. The DNA viruses targeted include tomato yellow leaf curl virus and merremia mosaic virus (begomovirus; beet curly top virus and beet severe curly top virus (curtovirus; and bean yellow dwarf virus (mastrevirus. The technique has also been used against the RNA viruses zucchini yellow mosaic virus, papaya ringspot virus and turnip mosaic virus (potyvirus and cucumber vein yellowing virus (ipomovirus, family, Potyviridae by targeting the translation initiation genes eIF4E in cucumber or Arabidopsis plants. From these recent advances of major importance, it is expected that NGS and CRISPR-Cas technologies will play a significant role in the very near future in advancing the field of plant virology and connecting it with other related fields of biology.Keywords: Next-generation sequencing, NGS, plant virology, plant viruses, viroids, resistance to plant viruses by CRISPR-Cas9

A cross-sectional study to evaluate second line virological failure and elevated bilirubin as a surrogate for adherence to atazanavir/ritonavir in two urban HIV clinics in Lilongwe, Malawi.

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Ongubo, Dennis Miyoge; Lim, Robertino; Tweya, Hannock; Stanley, Christopher Chikhosi; Tembo, Petros; Broadhurst, Richard; Gugsa, Salem; Ngongondo, McNeil; Speight, Colin; Heller, Tom; Phiri, Sam; Hosseinipour, Mina C

2017-07-03

Malawi's national antiretroviral therapy program provides atazanavir/ritonavir-based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi. We conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi. Antiretroviral therapy history and adherence data were extracted from the electronic medical records and blood was drawn for viral load, complete blood count, total bilirubin, and CD4 cell count at a clinic visit. Factors associated with virological failure were assessed using multivariate logistic regression model. Out of 376 patients on second line antiretroviral therapy evaluated, 372 (98.9%) were on atazanavir/ritonavir-based therapy and 142 (37.8%) were male. Mean age was 40.9 years (SD ± 10.1), mean duration on second line antiretroviral therapy was 41.9 months (SD ± 27.6) and 256 patients (68.1%) had elevated bilirubin >1.3 mg/dL. Overall, 35 (9.3%) patients had viral load >1000 copies/ml (virological failure). Among the virologically failing vs. non-failing patients, bilirubin was elevated in 34.3% vs. 72.0% respectively (p bilirubin levels (aOR 5.4, p bilirubin levels better predicted virological failure than pill count adherence. Therefore, strategic use of bilirubin and viral load testing to target adherence counseling and support may be cost-effective in monitoring second line antiretroviral therapy adherence and virological failure. Drug resistance testing targeted for patients with virological failure despite elevated bilirubin levels would facilitate timely switch to third line antiretroviral regimens whenever available.

Artificial Intelligence and Virology - quo vadis.

Science.gov (United States)

Shapshak, Paul; Somboonwit, Charurut; Sinnott, John T

2017-01-01

Artificial Intelligence (AI), robotics, co-robotics (cobots), quantum computers (QC), include surges of scientific endeavor to produce machines (mechanical and software) among numerous types and constructions that are accelerating progress to defeat infectious diseases. There is a plethora of additional applications and uses of these methodologies and technologies for the understanding of biomedicine through bioinformation discovery. Therefore, we briefly outline the use of such techniques in virology.

Unmanned Mobile Monitoring for Nuclear Emergency Response

Energy Technology Data Exchange (ETDEWEB)

Choi, YoungSoo; Park, JongWon; Kim, TaeWon; Jeong, KyungMin [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

Severe accidents at nuclear power plant have led to significant consequences to the people, the environment or the facility. Therefore, the appropriate response is required for the mitigation of the accidents. In the past, most of responses were performed by human beings, but it was dangerous and risky. In this paper, we proposed unmanned mobile system for the monitoring of nuclear accident in order to response effectively. For the integrity of reactor cooling and containment building, reactor cooling pipe and hydrogen distribution monitoring with unmanned ground vehicle was designed. And, for the safety of workers, radiation distribution monitoring with unmanned aerial vehicle was designed. Unmanned mobile monitoring system was proposed to respond nuclear accidents effectively. Concept of reinforcing the integrity of RCS and containment building, and radiation distribution monitoring were described. RCS flow measuring, hydrogen distribution measuring and radiation monitoring deployed at unmanned vehicle were proposed. These systems could be a method for the preparedness of effective response of nuclear accidents.

Modelled in vivo HIV fitness under drug selective pressure and estimated genetic barrier towards resistance are predictive for virological response

DEFF Research Database (Denmark)

Deforche, Koen; Cozzi-Lepri, Alessandro; Theys, Kristof

2008-01-01

landscapes (nelfinavir [NFV] and zidovudine [AZT] plus lamivudine [3TC]) to predict week 12 viral load (VL) change for 176 treatment change episodes (TCEs) and probability of week 48 virological failure for 90 TCEs, in treatment experienced patients starting these drugs in combination. RESULTS: A higher...

Immunological and virological response to antiretroviral treatment in migrant and native men and women in Western Europe; is benefit equal for all?

Science.gov (United States)

2018-01-01

The aim of the study was to evaluate differences in immunovirological response to combination antiretroviral therapy (cART) in migrant and native men and women within a European collaboration of HIV cohorts Collaboration of Observational HIV Epidemiological Research in Europ (COHERE) in EuroCoord, 2004-2013. Migrants were defined as those with geographical origin (GO) different from the reporting country and were grouped as originating from Western Europe and Western Countries (WEWC), Eastern Europe (EE), North Africa and the Middle East (NAME), sub-Saharan Africa (SSA), Latin America (LA), Caribbean (CRB) and Asia/Oceania (ASIA/OCE). Native (NAT) individuals were defined as those originating from the reporting country. CD4 cell counts were modelled using piecewise linear mixed-effects models with two slopes, whereas models to estimate subdistribution hazard ratios (sHRs) were used for time to virological response (VR) (i.e. time from cART initiation to the first of two successive HIV RNA measurements response to cART in Western Europe varies by GO and sex of patients. ART benefits are not equal for all, underlining the point that efforts need to prioritize those most in need. © 2017 British HIV Association.

Risk of triple-class virological failure in children with HIV: a retrospective cohort study

DEFF Research Database (Denmark)

Castro, Hannah; Judd, Ali; Gibb, Diana M

2011-01-01

In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological...... failure to the three original drugs classes in children....

Virologic Monitoring of Poliovirus Type 2 after Oral Poliovirus Vaccine Type 2 Withdrawal in April 2016 - Worldwide, 2016-2017.

Science.gov (United States)

Diop, Ousmane M; Asghar, Humayun; Gavrilin, Evgeniy; Moeletsi, Nicksy Gumede; Benito, Gloria Rey; Paladin, Fem; Pattamadilok, Sirima; Zhang, Yan; Goel, Ajay; Quddus, Arshad

2017-05-26

The Global Polio Eradication Initiative (GPEI) has made substantial progress since its launch in 1988; only 37 wild poliovirus type 1 (WPV1) cases were detected in 2016, the lowest annual count ever. Wild poliovirus type 3 has not been detected since November 2012, and wild poliovirus type 2 was officially declared eradicated in September 2015. This success is attributable to the wide use of live oral poliovirus vaccines (OPVs). Since 2001, numerous outbreaks were caused by the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (1). In 2015, circulating VDPV type 2 (cVDPV2) outbreaks were detected in five countries worldwide (Nigeria, Pakistan, Guinea, Burma, and South Sudan), and VDPV2 single events were reported in 22 countries. These events prompted the GPEI to withdraw the type 2 component (Sabin2) of trivalent OPV (tOPV) in a globally coordinated, synchronized manner in April 2016 (2,3), at which time all OPV-using countries switched to using bivalent OPV (bOPV), containing Sabin types 1 and 3. This report details for the first time the virologic tracking of elimination of a live vaccine that has been withdrawn from routine and mass immunization systems worldwide (3). To secure elimination, further monitoring is warranted to detect any use of tOPV or monovalent OPV type 2 (mOPV2).

Molecular virology of feline calicivirus.

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Pesavento, Patricia A; Chang, Kyeong-Ok; Parker, John S L

2008-07-01

Caliciviridae are small, nonenveloped, positive-stranded RNA viruses. Much of our understanding of the molecular biology of the caliciviruses has come from the study of the naturally occurring animal caliciviruses. In particular, many studies have focused on the molecular virology of feline calicivirus (FCV), which reflects its importance as a natural pathogen of cats. FCVs demonstrate a remarkable capacity for high genetic, antigenic, and clinical diversity; "outbreak" vaccine resistant strains occur frequently. This article updates the reader on the current status of clinical behavior and pathogenesis of FCV.

Predicting HIV RNA virologic outcome at 52-weeks follow-up in antiretroviral clinical trials. The INCAS and AVANTI Study Groups.

Science.gov (United States)

Raboud, J M; Rae, S; Montaner, J S

2000-08-15

To determine the ability of intermediate plasma viral load (pVL) measurements to predict virologic outcome at 52 weeks of follow-up in clinical trials of antiretroviral therapy. Individual patient data from three clinical trials (INCAS, AVANTI-2 and AVANTI-3) were combined into a single database. Virologic success was defined to be plasma viral load (pVL) <500 copies/ml at week 52. The sensitivity and specificity of intermediate pVL measurements below the limit of detection, 100, 500, 1000, and 5000 copies/ml to predict virologic success were calculated. The sensitivity, specificity, and positive and negative predictive values of a pVL measurement <1000 copies/ml at week 16 to predict virologic outcome at week 52 were 74%, 74%, 48%, and 90%, respectively, for patients on double therapy. For patients on triple therapy, the sensitivity, specificity, and positive and negative predictive values of a pVL measurement <50 copies/ml at week 16 to predict virologic outcome were 68%, 68%, 80%, and 47%, respectively. For patients receiving double therapy, a poor virologic result at an intermediate week of follow-up is a strong indicator of virologic failure at 52 weeks whereas intermediate virologic success is no guarantee of success at 1 year. For patients on triple therapy, disappointing intermediate results do not preclude virologic success at 1 year and intermediate successes are more likely to be sustained.

Response-guided telaprevir combination treatment for hepatitis C virus infection

NARCIS (Netherlands)

Sherman, Kenneth E.; Flamm, Steven L.; Afdhal, Nezam H.; Nelson, David R.; Sulkowski, Mark S.; Everson, Gregory T.; Fried, Michael W.; Adler, Michael; Reesink, Hendrik W.; Martin, Marie; Sankoh, Abdul J.; Adda, Nathalie; Kauffman, Robert S.; George, Shelley; Wright, Christopher I.; Poordad, Fred; Adler, M.; Delwaide, Jean; Horsmans, Y.; van Vlierberghe, H.; Richter, C.; Afdhal, N.; Araya, V.; Arora, S.; Balart, L.; Bennett, M.; Berk, B.; Bernstein, D.; Bloomer, J.; Brown, R.; Bzowej, N.; Chasen, R.; Cochran, J.; Crippin, J.; Davis, G.; Davis, M.; Dejesus, E.; Di Bisceglie, A.; Dieterich, D.; Esposito, S.; Everson, G.; Flamm, S. L.; Franco, J.; Freilich, B.; Fried, M. W.; Ghalib, R.; Godofsky, E.; Gordon, S.; Howell, C.; Hutson, W.

2011-01-01

Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon-ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, -10.5%) to compare rates of sustained virologic response among patients

Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study

Directory of Open Access Journals (Sweden)

Ying Zhou

2016-01-01

Full Text Available Antiretroviral therapy (ART has been shown to improve survival of patients with Human Immunodeficiency Virus (HIV infection and to reduce HIV-1 transmission. Therefore, the Chinese central government initiated a national program to provide ART free of charge to HIV-1 patients. We conducted a cross-sectional survey in Jiangsu province to determine the level of drug resistance (DR in HIV-1 infected patients and the correlates of DR in virological failures in 2012. Approximately 10.4% of the HIV-1 patients in the study experienced virological failure after one year of ART and were divided into drug sensitive and drug resistant groups based on genotype determination. The viral loads (VLs in the drug resistant group were significantly lower than the drug sensitive group. There were two independent predictors of virological failure: male gender and increasing duration of treatment. The primary mutations observed in the study were against nucleoside reverse transcriptase inhibitors (NRTIs which were M184V (79.45% and K103N (33.70% in nonnucleoside reverse transcriptase inhibitors (NNRTIs. The overall rate of DR in Jiangsu province is still relatively low among treated patients. However, close monitoring of drug resistance in male patients in the early stages of treatment is vital to maintaining and increasing the benefits of HIV ART achieved to date.

Response to combination antiretroviral therapy: variation by age

DEFF Research Database (Denmark)

Lundgren, Jens

2008-01-01

-naive individuals starting combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed...... response. The probability of virological response was lower in those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults...... and reduced in those 60 years or older. Those aged 55-59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. CONCLUSION: Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy...

Virological Mechanisms in the Coinfection between HIV and HCV

Directory of Open Access Journals (Sweden)

Maria Carla Liberto

2015-01-01

Full Text Available Due to shared transmission routes, coinfection with Hepatitis C Virus (HCV is common in patients infected by Human Immunodeficiency Virus (HIV. The immune-pathogenesis of liver disease in HIV/HCV coinfected patients is a multifactorial process. Several studies demonstrated that HIV worsens the course of HCV infection, increasing the risk of cirrhosis and hepatocellular carcinoma. Also, HCV might increase immunological defects due to HIV and risk of comorbidities. A specific cross-talk among HIV and HCV proteins in coinfected patients modulates the natural history, the immune responses, and the life cycle of both viruses. These effects are mediated by immune mechanisms and by a cross-talk between the two viruses which could interfere with host defense mechanisms. In this review, we focus on some virological/immunological mechanisms of the pathogenetic interactions between HIV and HCV in the human host.

High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil

Directory of Open Access Journals (Sweden)

José Ernesto Vidal

Full Text Available OBJECTIVES: To assess the virologic and immunological response of darunavir/ritonavir plus optimized background therapy in highly antiretroviral-experienced HIV-infected patients in Brazil. METHODS: Prospective cohort study carried out in a tertiary center in Sao Paulo, Brazil. Three-class antiretroviral-experienced patients with confirmed virologic failure began darunavir/ritonavir plus optimized background therapy (nucleoside/tide reverse transcriptase inhibitors ± raltegravir ± enfuvirtide ± maraviroc after performing a genotypic resistance assay. Clinical evaluation and laboratory tests were collected at baseline and at weeks 12, 24, and 48. Multivariate analysis was performed to identify predictors of virologic response at 48 weeks. RESULTS: Ninety-two patients were included. The median of darunavir resistant mutation was 1 (range 0-6. The median genotypic sensitivity score in the optimized background therapy was 2 (interquartile range 1-2. At week 48, 83% (95% CI: 75-90% had an HIV RNA level 100 000 copies/mL was inversely associated with virologic success at week 48 (HR: 0.22, 95% CI: 0.06-0.85, p = 0.028. CONCLUSIONS: Darunavir/ritonavir plus optimized background therapy was a highly effective salvage regimen under clinical routine conditions in a referral center in Brazil, which is similar to the reported in high-income countries.

High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil

Directory of Open Access Journals (Sweden)

José Ernesto Vidal

2013-02-01

Full Text Available OBJECTIVES: To assess the virologic and immunological response of darunavir/ritonavir plus optimized background therapy in highly antiretroviral-experienced HIV-infected patients in Brazil. METHODS: Prospective cohort study carried out in a tertiary center in Sao Paulo, Brazil. Three-class antiretroviral-experienced patients with confirmed virologic failure began darunavir/ritonavir plus optimized background therapy (nucleoside/tide reverse transcriptase inhibitors ± raltegravir ± enfuvirtide ± maraviroc after performing a genotypic resistance assay. Clinical evaluation and laboratory tests were collected at baseline and at weeks 12, 24, and 48. Multivariate analysis was performed to identify predictors of virologic response at 48 weeks. RESULTS: Ninety-two patients were included. The median of darunavir resistant mutation was 1 (range 0-6. The median genotypic sensitivity score in the optimized background therapy was 2 (interquartile range 1-2. At week 48, 83% (95% CI: 75-90% had an HIV RNA level 100 000 copies/mL was inversely associated with virologic success at week 48 (HR: 0.22, 95% CI: 0.06-0.85, p = 0.028. CONCLUSIONS: Darunavir/ritonavir plus optimized background therapy was a highly effective salvage regimen under clinical routine conditions in a referral center in Brazil, which is similar to the reported in high-income countries.

Long term effectiveness of once-daily unboosted atazanavir plus abacavir/lamivudine as a switch strategy in subjects with virological suppression

DEFF Research Database (Denmark)

Llibre, Josep M; Cozzi-Lepri, Alessandro; La Rosa, Jorge Antonio Valencia

2014-01-01

routine however are scant. METHODS: We evaluated treatment outcomes of ATV400+ABC/3TC in pre-treated subjects in the EuroSIDA cohort with undetectable HIV-1 RNA, and previous ABC experience or assumed previous HLA B57*01 testing. We performed a time to loss of virologic response (TLOVR below 50 c...

The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda

NARCIS (Netherlands)

Bartelink, Imke H.; Savic, Rada M.; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J.; Capparelli, Edmund; Jullien, Vincent; Young, Sera L.; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

2015-01-01

Malnutrition may impact the pharmacokinetics (PKs) of antiretroviral medications and virologic responses in HIV-infected children. The authors therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected

Gender-specific risk factors for virologic failure in KwaZulu-Natal: automobile ownership and financial insecurity.

Science.gov (United States)

Hare, Anna Q; Ordóñez, Claudia E; Johnson, Brent A; Del Rio, Carlos; Kearns, Rachel A; Wu, Baohua; Hampton, Jane; Wu, Peng; Sunpath, Henry; Marconi, Vincent C

2014-11-01

We sought to examine which socioeconomic indicators are risk factors for virologic failure among HIV-1 infected patients receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa. A case-control study of virologic failure was conducted among patients recruited from the outpatient clinic at McCord Hospital in Durban, South Africa between October 1, 2010 and June 30, 2012. Cases were those failing first-line ART, defined as viral load >1,000 copies/mL. Univariate logistic regression was performed on sociodemographic data for the outcome of virologic failure. Variables found significant (p ownership was a risk factor among males, while variables of financial insecurity (unemployment, non-spouse family paying for care, staying with family) were risk factors for women. In this cohort, financial insecurity among women and automobile ownership among men were risk factors for virologic failure. Risk factor differences between genders demonstrate limitations of generalized risk factor analysis.

Paediatric Virology in the Hippocratic Corpus

Science.gov (United States)

Mammas, Ioannis N.; Spandidos, Demetrios A.

2016-01-01

Hippocrates (Island of Kos, 460 B.C.-Larissa, 370 B.C.) is the founder of the most famous Medical School of the classical antiquity. In acknowledgement of his pioneering contribution to the new scientific field of Paediatric Virology, this article provides a systematic analysis of the Hippocratic Corpus, with particular focus on viral infections predominating in neonates and children. A mumps epidemic, affecting the island of Thasos in the 5th century B.C., is described in detail. ‘Herpes’, a medical term derived from the ancient Greek word ‘ἕρπειν’, meaning ‘to creep’ or ‘crawl’, is used to describe the spreading of cutaneous lesions in both childhood and adulthood. Cases of children with exanthema ‘resembling mosquito bites’ are presented in reference to varicella or smallpox infection. A variety of upper and lower respiratory tract viral infections are described with impressive accuracy, including rhinitis, pharyngitis, tonsillitis, laryngitis, bronchiolitis and bronchitis. The ‘cough of Perinthos’ epidemic, an influenza-like outbreak in the 5th century B.C., is also recorded and several cases complicated with pneumonia or fatal outcomes are discussed. Hippocrates, moreover, describes conjunctivitis, otitis, lymphadenitis, meningoencephalitis, febrile convulsions, gastroenteritis, hepatitis, poliomyelitis and skin warts, along with proposed treatment directions. Almost 2,400 years later, Hippocrates' systematic approach and methodical innovations can inspire paediatric trainees and future Paediatric Virology subspecialists. PMID:27446241

Diagnostic virology laboratory within a microbiology setting.

OpenAIRE

Rubin, S. J.

1984-01-01

The virology section at St. Francis Hospital and Medical Center, Connecticut, is not a separate laboratory division but is a part of the microbiology division and is supervised by the same personnel who supervise bacteriology, mycology, mycobacteriology, and serology. Current volume is over 1,000 cultures yearly with 12 to 24 percent positive. Isolates are confirmed and typed by the Connecticut State Health Department Laboratory. Specimen distribution, percentage positive specimens, and distr...

Automatic duress alarms through physiological response monitoring

International Nuclear Information System (INIS)

Roehrig, S.C.

1977-07-01

Physiological response monitoring under controlled conditions can provide an effective means for passively determining if the wearer is under moderate to severe stresses. By monitoring the heart rate (HR) and galvanic skin response (GSR) of an individual, it is possible to detect in real time the increase in heart rate and GSR levels due to physiological reactions to mental duress. With existing physiological monitoring equipment, however, the work load of the wearer must be well defined since it is impossible, without additional data, to distinguish mental duress responses from those resulting from moderate physical exertion. Similarly, environmental conditions should be constrained within set limits to avoid masking increases in GSR levels due to metntal stress from those associated with increased perspiration. These constraints should not prove overly restrictive and would allow an integrated security system utilizing physiological monitoring equipment to provide an effective real time, automated early warning system for detection of mental duress or death of the wearer

Association of sustained virologic response with reduced progression to liver cirrhosis in elderly patients with chronic hepatitis C

Directory of Open Access Journals (Sweden)

Tseng CW

2016-03-01

Full Text Available Chih-Wei Tseng,1,2 Ting-Tsung Chang,3,4 Shinn-Jia Tzeng,5 Yu-Hsi Hsieh,1,2 Tsung-Hsing Hung,1,2 Hsiang-Ting Huang,6 Shu-Fen Wu,7 Kuo-Chih Tseng1,2 1Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, 2School of Medicine, Tzuchi University, Hualien, 3Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, 4Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, 5Department of Agronomy, National Chiayi University, 6Department of Nursing, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 7Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan Objective: We studied the effect of sustained virologic response (SVR after treatment with pegylated-interferon (PEG-IFN plus ribavirin on the development of liver cirrhosis in elderly patients with chronic hepatitis C (CHC. Patients and methods: This retrospective study enrolled 145 elderly CHC patients (aged ≥65 years who were treatment-naïve and were treated with PEG-IFN plus ribavirin for 6 months between January 2005 and December 2011. Abdominal sonography was performed and liver biochemistry was studied at baseline, at the end of treatment, and every 3–6 months thereafter. The development of liver cirrhosis and related complications was evaluated at the follow-ups. The aspartate aminotransferase-to-platelet ratio index was used as a noninvasive maker for fibrosis. Results: The mean patient age was 69.1±3.3 years, and the average follow-up time was 5.5 years (standard deviation: 2.5 years, range: 1.1–12.3 years. Ninety-five patients (65.5% achieved SVR, and 26 (17.9% discontinued treatment. Twenty-seven patients (18.6% developed liver cirrhosis after treatment. Patients without SVR had significantly greater risk of liver cirrhosis than those with SVR (hazard ratio [HR]: 3.39, 95% confidence interval [CI]: 1.312–8.761, P=0.012. The

Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma

DEFF Research Database (Denmark)

Shepherd, Leah; Ryom, Lene; Law, Matthew

2018-01-01

Background: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk. Methods: Data from...... the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different...

Persistent disparities in antiretroviral treatment (ART) coverage and virological suppression across Europe, 2004 to 2015

DEFF Research Database (Denmark)

Laut, Kamilla; Shepherd, Leah; Radoi, Roxana

2018-01-01

BACKGROUND: Direct comparisons between countries in core HIV care parameters are often hampered by differences in data collection. AIM: Within the EuroSIDA study, we compared levels of antiretroviral treatment (ART) coverage and virological suppression (HIV RNA ...-specific estimates of ART coverage and virological suppression. Underlying reasons for this variation warrant further analysis to identify a best practice and benchmark HIV care across EuroSIDA....

Keeping kids in care: virological failure in a paediatric antiretroviral ...

African Journals Online (AJOL)

A retrospective file audit determined the cumulative virological failure rate, that is, the sum of all ... Interviews were conducted with a purposive sample of 12 staff members and a random sample of 21 caregivers and 4 children attending care.

A Biosafety Level 2 Virology Lab for Biotechnology Undergraduates

Science.gov (United States)

Matza-Porges, Sigal; Nathan, Dafna

2017-01-01

Medical, industrial, and basic research relies heavily on the use of viruses and vectors. Therefore, it is important that bioscience undergraduates learn the practicalities of handling viruses. Teaching practical virology in a student laboratory setup presents safety challenges, however. The aim of this article is to describe the design and…

Serological and Virological Study of Newcastle Disease and Avian ...

African Journals Online (AJOL)

Serological survey on the prevalence of Newcastle disease (NCD) virus antibodies using haemagglutination inhibition test (HI) and virological detection by RT-PCR of highly pathogenic avian influenza (HPAI) H5N1, were carried out in 6 regions of Senegal from June to November 2008. Rural chickens were raised in free ...

Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease.

Science.gov (United States)

Kattakuzhy, Sarah; Wilson, Eleanor; Sidharthan, Sreetha; Sims, Zayani; McLaughlin, Mary; Price, Angie; Silk, Rachel; Gross, Chloe; Akoth, Elizabeth; McManus, Maryellen; Emmanuel, Benjamin; Shrivastava, Shikha; Tang, Lydia; Nelson, Amy; Teferi, Gebeyehu; Chavez, Jose; Lam, Brian; Mo, Hongmei; Osinusi, Anuoluwapo; Polis, Michael A; Masur, Henry; Kohli, Anita; Kottilil, Shyamasundaran

2016-02-15

Treatment of genotype 1 hepatitis C virus (HCV) infection with combination directly acting antivirals (DAA) for 8-24 weeks is associated with high rates of sustained virologic response (SVR). We previously demonstrated that adding a third DAA to ledipasvir and sofosbuvir (LDV/SOF) can result in high SVR rates in patients without cirrhosis. In this study, we investigated whether a similar regimen would yield equivalent rates of cure in patients with advanced liver fibrosis. Fifty patients were enrolled at the Clinical Research Center of the National Institutes of Health and associated healthcare centers. Enrollment and follow-up data from April 2014 to June 2015 are reported here. Eligible participants were aged ≥18 years, had chronic HCV genotype 1 infection (serum HCV RNA ≥2000 IU/mL), and stage 3-4 liver fibrosis. HCV RNA was measured using a reverse-transcription polymerase chain reaction assay. Of patients treated with LDV, SOF, and the NS3/4A protease inhibitor GS-9451 for 6 weeks, 76% (38 of 50; 95% confidence interval, 60%-85%) had SVR achieved 12 weeks after the end of treatment. There was no statistically significant difference in treatment efficacy between treatment-naive patients (72%, 18 of 25) and those with treatment experience (80%; 20 of 25) (P = .51). Overall, 11 patients (22%) experienced virologic relapse, and 1 (2%) was lost to follow-up at 4 weeks after treatment. No serious adverse events, discontinuations, or deaths were associated with this regimen. Adding a third DAA to LDV/SOF may result in a moderate SVR rate, lower than that observed in patients without cirrhosis. Significant liver fibrosis remains an impediment to achieving SVR with short-duration DAA therapy. CT01805882. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Reliability updating based on monitoring of structural response parameters

International Nuclear Information System (INIS)

Leira, B.J.

2016-01-01

Short- and long-term aspects of measuring structural response parameters are addressed. Two specific examples of such measurements are considered for the purpose of illustration and in order to focus the discussion. These examples are taken from the petroleum industry (monitoring of riser response) and from the shipping industry (monitoring of ice-induced strains in a ship hull). Similarities and differences between the two cases are elaborated with respect to which are the most relevant mechanical limit states. Furthermore, main concerns related to reliability levels within a short-term versus long-term time horizon are highlighted. Quantifying the economic benefits of applying monitoring systems is also addressed. - Highlights: • Two examples of structural response monitoring are described. • Application of measurements is discussed in relation to updating of load and structural parameters. • Quantification of the value of response monitoring is made for both of the examples.

Improving ecological response monitoring of environmental flows.

Science.gov (United States)

King, Alison J; Gawne, Ben; Beesley, Leah; Koehn, John D; Nielsen, Daryl L; Price, Amina

2015-05-01

Environmental flows are now an important restoration technique in flow-degraded rivers, and with the increasing public scrutiny of their effectiveness and value, the importance of undertaking scientifically robust monitoring is now even more critical. Many existing environmental flow monitoring programs have poorly defined objectives, nonjustified indicator choices, weak experimental designs, poor statistical strength, and often focus on outcomes from a single event. These negative attributes make them difficult to learn from. We provide practical recommendations that aim to improve the performance, scientific robustness, and defensibility of environmental flow monitoring programs. We draw on the literature and knowledge gained from working with stakeholders and managers to design, implement, and monitor a range of environmental flow types. We recommend that (1) environmental flow monitoring programs should be implemented within an adaptive management framework; (2) objectives of environmental flow programs should be well defined, attainable, and based on an agreed conceptual understanding of the system; (3) program and intervention targets should be attainable, measurable, and inform program objectives; (4) intervention monitoring programs should improve our understanding of flow-ecological responses and related conceptual models; (5) indicator selection should be based on conceptual models, objectives, and prioritization approaches; (6) appropriate monitoring designs and statistical tools should be used to measure and determine ecological response; (7) responses should be measured within timeframes that are relevant to the indicator(s); (8) watering events should be treated as replicates of a larger experiment; (9) environmental flow outcomes should be reported using a standard suite of metadata. Incorporating these attributes into future monitoring programs should ensure their outcomes are transferable and measured with high scientific credibility.

Improving Ecological Response Monitoring of Environmental Flows

Science.gov (United States)

King, Alison J.; Gawne, Ben; Beesley, Leah; Koehn, John D.; Nielsen, Daryl L.; Price, Amina

2015-05-01

Environmental flows are now an important restoration technique in flow-degraded rivers, and with the increasing public scrutiny of their effectiveness and value, the importance of undertaking scientifically robust monitoring is now even more critical. Many existing environmental flow monitoring programs have poorly defined objectives, nonjustified indicator choices, weak experimental designs, poor statistical strength, and often focus on outcomes from a single event. These negative attributes make them difficult to learn from. We provide practical recommendations that aim to improve the performance, scientific robustness, and defensibility of environmental flow monitoring programs. We draw on the literature and knowledge gained from working with stakeholders and managers to design, implement, and monitor a range of environmental flow types. We recommend that (1) environmental flow monitoring programs should be implemented within an adaptive management framework; (2) objectives of environmental flow programs should be well defined, attainable, and based on an agreed conceptual understanding of the system; (3) program and intervention targets should be attainable, measurable, and inform program objectives; (4) intervention monitoring programs should improve our understanding of flow-ecological responses and related conceptual models; (5) indicator selection should be based on conceptual models, objectives, and prioritization approaches; (6) appropriate monitoring designs and statistical tools should be used to measure and determine ecological response; (7) responses should be measured within timeframes that are relevant to the indicator(s); (8) watering events should be treated as replicates of a larger experiment; (9) environmental flow outcomes should be reported using a standard suite of metadata. Incorporating these attributes into future monitoring programs should ensure their outcomes are transferable and measured with high scientific credibility.

The role of biochemical variations and genotype testing in determining the virological response of patients infected with hepatitis C virus

Directory of Open Access Journals (Sweden)

Abid Shoukat

2018-01-01

Full Text Available Background: In hepatitis C virus (HCV, infection viral and IL28B genotype along with many clinical and biochemical factors can influence response rates to pegylated interferon plus ribavirin (Peg-IFN-a/R therapy and progression to chronic hepatitis C (CHC. Aims: The present study was conducted to determine the effect of biochemical and risk factors on treatment outcome in CHC patients in relation to their viral and host genotype. Settings and Design: The present study was a prospective Pe- IFN efficacy study consisting of Peg-IFN-a/R therapy for 24–48 weeks including 250 HCV infected patients. Materials and Methods: Biochemical parameters were determined by Beckman Coulter AU680 automated analyzer. HCV and Interleukin 28B (IL28B genotyping were carried out by polymerase chain reaction-restriction fragment length polymorphism and viral load was determined by quantitative real-time PCR. Results: Wild outnumbered the variant genotypes in rs 12979860, rs 12980275, and rs 8099917 SNP of IL28B gene. Sustained virological response (SVR SVR and viral genotype were significantly associated with age, hepatic steatosis, low-grade varices, and serum aspartate transaminase levels (at the end of treatment (P < 0.05. In addition, SVR was significantly influenced by body mass index (BMI, insulin resistance, serum low-density lipoprotein , and ferritin levels (P < 0.05. Viral genotype 1 infected patients had higher serum cholesterol and triglyceride levels (P < 0.05. Conclusions: Although the IL28B sequence variation is the major factor that can influence response rates to antiviral therapy, viral and biochemical factors also have a definite role to play in the diagnosis, etiology, and treatment outcome in HCV-infected patients.

Costs of telaprevir-based triple therapy for hepatitis C: $189,000 per sustained virological response.

Science.gov (United States)

Bichoupan, Kian; Martel-Laferriere, Valerie; Sachs, David; Ng, Michel; Schonfeld, Emily A; Pappas, Alexis; Crismale, James; Stivala, Alicia; Khaitova, Viktoriya; Gardenier, Donald; Linderman, Michael; Perumalswami, Ponni V; Schiano, Thomas D; Odin, Joseph A; Liu, Lawrence; Moskowitz, Alan J; Dieterich, Douglas T; Branch, Andrea D

2014-10-01

In registration trials, triple therapy with telaprevir (TVR), pegylated interferon (Peg-IFN), and ribavirin (RBV) achieved sustained virological response (SVR) rates between 64% and 75%, but the clinical effectiveness and economic burdens of this treatment in real-world practice remain to be determined. Records of 147 patients who initiated TVR-based triple therapy at the Mount Sinai Medical Center (May-December 2011) were reviewed. Direct medical costs for pretreatment, on-treatment, and posttreatment care were calculated using data from Medicare reimbursement databases, RED Book, and the Healthcare Cost and Utilization Project database. Costs are presented in 2012 U.S. dollars. SVR (undetectable hepatitis C virus [HCV] RNA 24 weeks after the end of treatment) was determined on an intention-to-treat basis. Cost per SVR was calculated by dividing the median cost by the SVR rate. Median age of the 147 patients was 56 years (interquartile range [IQR] = 51-61), 68% were male, 19% were black, 11% had human immunodeficiency virus/HCV coinfection, 36% had advanced fibrosis/cirrhosis (FIB-4 scores ≥3.25), and 44% achieved an SVR. The total cost of care was $11.56 million. Median cost of care was $83,721 per patient (IQR = $66,652-$98,102). The median cost per SVR was $189,338 (IQR = $150,735-$221,860). Total costs were TVR (61%), IFN (24%), RBV (4%), adverse event management (8%), professional fees (2%), and laboratory tests (1%). TVR and Peg-IFN accounted for 85% of costs. Pharmaceutical prices and the low (44%) SVR rate, in this real-world study, were major contributors to the high cost per SVR. © 2014 by the American Association for the Study of Liver Diseases.

Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepatitis C: systematic review of randomized trials

DEFF Research Database (Denmark)

Awad, Tahany; Thorlund, Kristian; Hauser, Goran

2010-01-01

) is most effective. We performed a systematic review of head-to-head randomized trials to assess the benefits and harms of the two treatments. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS through July 2009. Using standardized forms, two reviewers independently...... extracted data from each eligible trial report. We statistically combined data using a random effects meta-analysis according to the intention-to-treat principle. We identified 12 randomized clinical trials, including 5,008 patients, that compared peginterferon alpha-2a plus ribavirin versus peginterferon...... alfa-2b plus ribavirin. Overall, peginterferon alpha-2a significantly increased the number of patients who achieved a sustained virological response (SVR) versus peginterferon alfa-2b (47% versus 41%; risk ratio 1.11, 95% confidence interval 1.04-1.19; P = 0.004 [eight trials]). Subgroup analyses...

Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment-naïve HIV-1-infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort.

Science.gov (United States)

Rokx, C; Gras, L; van de Vijver, Damc; Verbon, A; Rijnders, Bja

2016-09-01

Lamivudine (3TC) and emtricitabine (FTC) are considered interchangeable in recommended tenofovir disoproxil-fumarate (TDF)-containing combination antiretroviral therapies (cARTs). This statement of equivalence has not been systematically studied. We compared the treatment responses to 3TC and FTC combined with TDF in boosted protease inhibitor (PI)-based cART for HIV-1-infected patients. An observational study in the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort was carried out between 2002 and 2013. Virological failure rates, time to HIV RNA suppression treatment failure were analysed using multivariable logistic regression and Cox proportional hazard models. Sensitivity analyses included propensity score-adjusted models. A total of 1582 ART-naïve HIV-1-infected patients initiated 3TC or FTC with TDF and ritonavir-boosted darunavir (29.6%), atazanavir (41.5%), lopinavir (27.1%) or another PI (1.8%). Week 48 virological failure rates on 3TC and FTC were comparable (8.9% and 5.6%, respectively; P = 0.208). The multivariable adjusted odds ratio of virological failure when using 3TC instead of FTC with TDF in PI-based cART was 0.75 [95% confidence interval (CI) 0.32-1.79; P = 0.51]. Propensity score-adjusted models showed comparable results. The adjusted hazard ratio (HR) for treatment failure of 3TC compared with FTC was 1.15 (95% CI 0.58-2.27) within 240 weeks after cART initiation. The time to two consecutive HIV RNA measurements treatment failure after suppression treatment-naïve HIV-1-infected patients starting either 3TC/TDF or FTC/TDF and a ritonavir-boosted PI. © 2016 British HIV Association.

Response of a neutron monitor area with TLDs pairs

Energy Technology Data Exchange (ETDEWEB)

Guzman G, K. A.; Borja H, C. G.; Valero L, C.; Hernandez D, V. M.; Vega C, H. R. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Calle Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico); Gallego, E.; Lorente, A., E-mail: ing_karen_guzman@yahoo.com.mx [Universidad Politecnica de Madrid, Departamento de Ingenieria Nuclear, Jose Gutierrez Abascal 2, E-28006 Madrid (Spain)

2011-10-15

The response of a passive neutron monitor area has been calculated using the Monte Carlo code MCNP5. The response was the amount of n({sup 6}Li, T){alpha} reactions occurring in a TLD-600 located at the center of a cylindrical polyethylene moderator. Fluence, (n, a) and H*(10) responses were calculated for 47 monoenergetic neutron sources. The H*(10) relative response was compared with responses of commercially available neutron monitors being alike. Due to {sup 6}Li cross section (n, {alpha}) reactions are mainly produced by thermal neutrons, however TLD-600 is sensitive to gamma-rays; to eliminate the signal due to photons monitor area was built to hold 2 pairs of TLD-600 and 2 pairs of TLD-700, thus from the difference between TLD-600 and TLD-700 readouts the net signal due to neutrons is obtained. The monitor area was calibrated at the Universidad Politecnica de Madrid using a {sup 241}AmBe neutron source; net TLD readout was compared with the H*(10) measured with a Bert hold Lb-6411. Performance of the neutron monitor area was determined through two independent experiments, in both cases the H*(10) was statistically equal to H*(10) measured with a Bert hold Lb-6411. Neutron monitor area with TLDs pairs can be used in working areas with intense, mixed and pulsed radiation fields. (Author)

Effect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of first-line antiretroviral treatment in sub-Saharan Africa: a multicentre cohort study

NARCIS (Netherlands)

Hamers, Raph L.; Schuurman, Rob; Sigaloff, Kim C. E.; Wallis, Carole L.; Kityo, Cissy; Siwale, Margaret; Mandaliya, Kishor; Ive, Prudence; Botes, Mariette E.; Wellington, Maureen; Osibogun, Akin; Wit, Ferdinand W.; van Vugt, Michèle; Stevens, Wendy S.; de Wit, Tobias F. Rinke

2012-01-01

Background The effect of pretreatment HIV-1 drug resistance on the response to first-line combination antiretroviral therapy (ART) in sub-Saharan Africa has not been assessed. We studied pretreatment drug resistance and virological, immunological, and drug-resistance treatment outcomes in a large

An audit on virological efficacy of anti-retroviral therapy in a specialist infectious disease clinic.

LENUS (Irish Health Repository)

Reyad, A

2009-06-01

We have assessed the efficacy of anti retroviral therapy (ART) using undetectable viral load (VL) (<50 RNA copies\\/ml) as a marker of virological success, in patients who have Human Immunodeficiency Virus (HIV) attending the Department of Infectious Disease. A cross-sectional review of patients\\' case notes was used to obtain their demographics and treatment details. 79% (253) of the hospital case notes of clinic population was available for analysis, which represents 90% of those receiving ART in the clinic. 166\\/253 of the cohort were receiving treatment at the time of this study and 95% (157\\/166) of these were on treatment for greater than 6 months. The total virological success rate is 93%, which is comparable to other centres and are as good as those from published clinical trials. 56% of those on therapy who have virological failure were Intravenous Drug Users (IVDUs). Case by case investigation for those with treatment failure is warranted.

Characterization of HIV-1 from patients with virological failure to a boosted protease inhibitor regimen

DEFF Research Database (Denmark)

Lillemark, Marie Rathcke; Gerstoft, Jan; Obel, Niels

2011-01-01

The use of highly active antiretroviral treatment (HAART) regimens with unboosted protease inhibitors (PIs) has resulted in a high level of virological failure primarily due to the development of resistant virus. Current boosted PI regimens combine successfully low-dose ritonavir (r) with a second.......3%) experienced virological failure, of whom 19 (83%) started PI/r treatment before 2001. Patients from Copenhagen (n=19) were selected to study the development of protease (PR) and gag cleavage site (CS) mutations during PI/r treatment and PI plasma levels at the time of virological failure. Three patients (16......%) developed major PI resistance mutations. Mutations in the p7/p1 and p1/p6 gag CS only developed in patients with major or minor mutations in PR. Drug concentrations were low or undetectable in 10 out of the 19 patients. In total PR resistance mutations and low drug levels could account for 12 (63...

The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda.

Science.gov (United States)

Bartelink, Imke H; Savic, Rada M; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J; Capparelli, Edmund; Jullien, Vincent; Young, Sera L; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

2015-03-01

Malnutrition may impact the pharmacokinetics (PKs) of antiretroviral medications and virologic responses in HIV-infected children. The authors therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Sparse dried blood spot samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from 3 resource-rich countries (RRC) were utilized to develop the PK models. Concentrations in 330 dried blood spot from 163 Ugandan children aged 0.7-7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5-12 years. Among Ugandan children, 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008), respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (PChildren receiving LPV, EFV or NVP had comparable risk of virologic failure. Among children on NVP, low height and weight for age Z scores were associated with reduced risk of virologic failure (P=0.034, P=0.068, respectively). Ugandan children demonstrated lower EFV and LPV and higher NVP exposure compared to children in RRC, perhaps reflecting the consequence of malnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessments, to further assess causes of virologic failure in Ugandan children.

Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201.

Directory of Open Access Journals (Sweden)

John E McKinnon

Full Text Available Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI for future use and decreased toxicity. We hypothesized that the level of immune activation (IA and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification.Thirty-four participants with virologic suppression ≥ 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8, natural killer (NK (CD3+CD56+CD16+ cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279.Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL >50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL >50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023, with an odds ratio of 10.3 (95% CI: 1.92-55.3. Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels.Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring.ClinicalTrials.gov NCT00084019.

Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

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Philip J Palumbo

Full Text Available Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART. We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM assay was used to analyze baseline (pre-treatment HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008. The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

Science.gov (United States)

Palumbo, Philip J; Wilson, Ethan A; Piwowar-Manning, Estelle; McCauley, Marybeth; Gamble, Theresa; Kumwenda, Newton; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James G; Hosseinipour, Mina C; Melo, Marineide G; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H; Fogel, Jessica M

2017-01-01

Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

The value of Institute of Human Virology meeting abstracts and beyond

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Jeang Kuan-Teh

2005-12-01

Full Text Available Abstract This month Retrovirology publishes the meeting abstracts from the 10th annual Institute of Human Virology conference held August 29th to September 2nd, 2005 in Baltimore, Maryland, USA. In this editorial, the rationale for publishing meeting abstracts is discussed.

Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study.

Science.gov (United States)

Porter, Danielle P; Toma, Jonathan; Tan, Yuping; Solberg, Owen; Cai, Suqin; Kulkarni, Rima; Andreatta, Kristen; Lie, Yolanda; Chuck, Susan K; Palella, Frank; Miller, Michael D; White, Kirsten L

2016-02-01

Antiretroviral regimen switching may be considered for HIV-1-infected, virologically-suppressed patients to enable treatment simplification or improve tolerability, but should be guided by knowledge of pre-existing drug resistance. The current study examined the impact of pre-existing drug resistance mutations on virologic outcomes among virologically-suppressed patients switching to Rilpivirine (RPV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). SPIRIT was a phase 3b study evaluating the safety and efficacy of switching to RPV/FTC/TDF in virologically-suppressed HIV-1-infected patients. Pre-existing drug resistance at baseline was determined by proviral DNA genotyping for 51 RPV/FTC/TDF-treated patients with known mutations by historical RNA genotype and matched controls and compared with clinical outcome at Week 48. Drug resistance mutations in protease or reverse transcriptase were detected in 62.7% of patients by historical RNA genotype and in 68.6% by proviral DNA genotyping at baseline. Proviral DNA sequencing detected 89% of occurrences of NRTI and NNRTI resistance-associated mutations reported by historical genotype. Mutations potentially affecting RPV activity, including E138A/G/K/Q, Y181C, and H221Y, were detected in isolates from 11 patients by one or both assays. None of the patients with single mutants had virologic failure through Week 48. One patient with pre-existing Y181Y/C and M184I by proviral DNA genotyping experienced virologic failure. Nineteen patients with K103N present by historical genotype were confirmed by proviral DNA sequencing and 18/19 remained virologically-suppressed. Virologic success rates were high among virologically-suppressed patients with pre-existing NRTI and NNRTI resistance-associated mutations who switched to RPV/FTC/TDF in the SPIRIT study. While plasma RNA genotyping remains preferred, proviral DNA genotyping may provide additional value in virologically-suppressed patients for whom historical resistance

Response comparative study of Rn-222 alpha particles track monitors

International Nuclear Information System (INIS)

Pereira, Osvaldo Luiz dos Santos

2010-01-01

This work was a comparative study between the responses of three monitors, the NRPB, an acrylic monitor (in thin film geometry) and the aluminum monitor (also thin film geometry) in controlled and mixed environment. The experiments consisted on placing the monitors in a plastic tube, with a radio-226 source internal. Only internal CR-39 plastic detectors were analyzed in this work. It was found that the monitors in thin film geometry had activities response of approximately 15% less than the NRPB monitors. All monitors responded the same way when in controlled environment. Related to the type of material, conductive plastic or dielectric (insulator) plastic, the NRPB, in environments without ventilation, responded in the same way. (author)

Post decommissioning monitoring of uranium mines; a watershed monitoring program based on biological response

International Nuclear Information System (INIS)

Russel, C.; Coggan, A.; Ludgate, I.

2006-01-01

Rio Algom Limited and Denison Mines own and operated uranium mines in the Elliot Lake area. The mines operated from the late 1950's to the mid 1960's and again for the early 1970's to the 1990's when the mines ceased operations. There are eleven decommissioned mines in the Serpent River watershed. At the time of decommissioning each mine had it's own monitoring program, which had evolved over the operating life of the mine and did not necessarily reflect the objectives associated with the monitoring of decommissioned sites. In order to assess the effectiveness of the decommissioning plans and monitoring the cumulative effects within the watershed, a single watershed monitoring program was developed in 1999: the Serpent River Watershed Monitoring Program which focused on water and sediment quality within the watershed and response of the biological community over time. In order to address other 'source area' monitoring, three complimentary objective-focused programs were developed 1) the In- Basin Monitoring Program, 2) the Source Area Monitoring Program and 3) the TMA Operational Monitoring Program. Through development this program framework and monitoring programs that were objective- focused, more meaningful data has been provided while providing a significant reduction in the cost of monitoring. These programs allow for the reduction in scope over time in response to improvement in the watershed. This talk will describe the development of these programs, their implementation and effectiveness. (author)

Integrating Social Media Monitoring Into Public Health Emergency Response Operations.

Science.gov (United States)

Hadi, Tamer A; Fleshler, Keren

2016-10-01

Social media monitoring for public health emergency response and recovery is an essential response capability for any health department. The value of social media for emergency response lies not only in the capacity to rapidly communicate official and critical incident information, but as a rich source of incoming data that can be gathered to inform leadership decision-making. Social media monitoring is a function that can be formally integrated into the Incident Command System of any response agency. The approach to planning and required resources, such as staffing, logistics, and technology, is flexible and adaptable based on the needs of the agency and size and scope of the emergency. The New York City Department of Health and Mental Hygiene has successfully used its Social Media Monitoring Team during public health emergency responses and planned events including major Ebola and Legionnaires' disease responses. The concepts and implementations described can be applied by any agency, large or small, interested in building a social media monitoring capacity. (Disaster Med Public Health Preparedness. 2016;page 1 of 6).

Immuno-Virological Discordance and the Risk of NonAIDS and AIDS Events in a Large Observational Cohort of HIV-Patients in Europe

DEFF Research Database (Denmark)

Zoufaly, Alexander; Cozzi-Lepri, Alessandro; Reekie, Joanne

2014-01-01

The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated....

Illness Representations of HIV Positive Patients Are Associated with Virologic Success.

Science.gov (United States)

Leone, Daniela; Borghi, Lidia; Lamiani, Giulia; Barlascini, Luca; Bini, Teresa; d'Arminio Monforte, Antonella; Vegni, Elena

2016-01-01

Introduction: It is important for HIV positive patients to be engaged in their care and be adherent to treatment in order to reduce disease progression and mortality. Studies found that illness representations influence adherence through the mediating role of coping behaviors. However, no study has ever tested if patient engagement to the visits mediate the relationship between illness perceptions and adherence. This study aimed to explore illness representations of HIV positive patients and test the hypothesis that illness representations predict adherence through the mediating role of a component of behavioral engagement. Methods: HIV-positive patients treated with highly active antiretroviral therapy (HAART) for at least one year and presenting to a check-up visit were eligible to participate in the study. Patients completed the Illness Perception Questionnaire-Revised. Behavioral engagement was measured based on the patients' clinical attendance to the check-up visits; adherence to HAART was measured by viral load. Undetectable viral load or HIV-RNA perception that the disease does not have serious consequences on patient's life and the prevalence of negative emotions toward HIV were associated with virologic success. On the contrary, the patient's perception that the disease has serious consequences on his/her life and the prevalence of positive emotions were associated with virologic failure. This model showed good fit indexes (CFI = 1; TLI = 1; RMSEA = 0.00; and WRMSR = 0.309). Discussion: Results do not support the mediating role of behavioral engagement in the relationship between illness representations and adherence. As perception of serious consequences coupled with positive emotions are directly associated with virologic failure, clinicians should take them into account to promote treatment adherence.

Federal Radiological Monitoring and Assessment Center Phased Response Operations

International Nuclear Information System (INIS)

Riland, C.A.; Bowman, D.R.

1999-01-01

A Federal Radiological Monitoring and Assessment Center (FRMAC) is established in response to the Lead Federal Agency (LFA) or state request when a major radiological emergency is anticipated of has occurred. The FRMAC becomes a coalition of federal off-site monitoring and assessment activities to assist the LFA, state(s), local, and tribal authorities. State, local, and tribal authorities are invited to co-locate and prioritize monitoring and assessment efforts in the FRMAC. The Department of Energy is tasked by the Federal Radiological Emergency Response Plan to coordinate the FRMAC

Factors predictive of sustained virological response following 72 weeks of combination therapy for genotype 1b hepatitis C.

Science.gov (United States)

Chayama, Kazuaki; Hayes, C Nelson; Yoshioka, Kentaro; Moriwaki, Hisataka; Okanoue, Takashi; Sakisaka, Shotaro; Takehara, Tetsuo; Oketani, Makoto; Toyota, Joji; Izumi, Namiki; Hiasa, Yoichi; Matsumoto, Akihiro; Nomura, Hideyuki; Seike, Masataka; Ueno, Yoshiyuki; Yotsuyanagi, Hiroshi; Kumada, Hiromitsu

2011-04-01

Treatment of genotype 1b chronic hepatitis C virus (HCV) infection has been improved by extending peg-interferon plus ribavirin combination therapy to 72 weeks, but predictive factors are needed to identify those patients who are likely to respond to long-term therapy. We analyzed amino acid (aa) substitutions in the core protein and the interferon sensitivity determining region (ISDR) of nonstructural protein (NS) 5A in 840 genotype 1b chronic hepatitis C patients with high viral load. We used logistic regression and classification and regression tree (CART) analysis to identify predictive factors for sustained virological response (SVR) for patients undergoing 72 weeks of treatment. When patients were separately analyzed by treatment duration using multivariate logistic regression, several factors, including sex, age, viral load, and core aa70 and ISDR substitutions (P = 0.0003, P = 0.02, P = 0.01, P = 0.0001, and P = 0.0004, respectively) were significant predictive factors for SVR with 48 weeks of treatment, whereas age, previous interferon treatment history, and ISDR substitutions (P = 0.03, P = 0.01, and P = 0.02, respectively) were the only significant predictive factors with 72 weeks of treatment. Using CART analysis, a decision tree was generated that identified age, cholesterol, sex, treatment length, and aa70 and ISDR substitutions as the most important predictive factors. The CART model had a sensitivity of 69.2% and specificity of 60%, with a positive predictive value of 68.4%. Complementary statistical and data mining approaches were used to identify a subgroup of patients likely to benefit from 72 weeks of therapy.

Potential Impact of a Free Online HIV Treatment Response Prediction System for Reducing Virological Failures and Drug Costs after Antiretroviral Therapy Failure in a Resource-Limited Setting

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Andrew D. Revell

2013-01-01

Full Text Available Objective. Antiretroviral drug selection in resource-limited settings is often dictated by strict protocols as part of a public health strategy. The objective of this retrospective study was to examine if the HIV-TRePS online treatment prediction tool could help reduce treatment failure and drug costs in such settings. Methods. The HIV-TRePS computational models were used to predict the probability of response to therapy for 206 cases of treatment change following failure in India. The models were used to identify alternative locally available 3-drug regimens, which were predicted to be effective. The costs of these regimens were compared to those actually used in the clinic. Results. The models predicted the responses to treatment of the cases with an accuracy of 0.64. The models identified alternative drug regimens that were predicted to result in improved virological response and lower costs than those used in the clinic in 85% of the cases. The average annual cost saving was $364 USD per year (41%. Conclusions. Computational models that do not require a genotype can predict and potentially avoid treatment failure and may reduce therapy costs. The use of such a system to guide therapeutic decision-making could confer health economic benefits in resource-limited settings.

Antiretroviral treatment interruptions induced by the Kenyan postelection crisis are associated with virological failure.

Science.gov (United States)

Mann, Marita; Diero, Lameck; Kemboi, Emmanuel; Mambo, Fidelis; Rono, Mary; Injera, Wilfred; Delong, Allison; Schreier, Leeann; Kaloustian, Kara W; Sidle, John; Buziba, Nathan; Kantor, Rami

2013-10-01

Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. We determined effects of unplanned TIs after the 2007-2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. Unplanned conflict-related TIs are associated with increased likelihood of virological failure.

Federal Radiological Monitoring and Assessment Center: Phase I Response

International Nuclear Information System (INIS)

Riland, C.; Bowman, D.R.; Lambert, R.; Tighe, R.

1999-01-01

A Federal Radiological Monitoring and Assessment Center (FRMAC) is established in response to a Lead Federal Agency (LFA) or State request when a radiological emergency is anticipated or has occurred. The FRMAC coordinates the off-site monitoring, assessment, and analysis activities during such an emergency. The FRMAC response is divided into three phases. FRMAC Phase 1 is a rapid, initial-response capability that can interface with Federal or State officials and is designed for a quick response time and rapid radiological data collection and assessment. FRMAC Phase 1 products provide an initial characterization of the radiological situation and information on early health effects to officials responsible for making and implementing protective action decisions

Monitoring of wind load and response for cable-supported bridges in Hong Kong

Science.gov (United States)

Wong, Kai-yuen; Chan, Wai-Yee K.; Man, King-Leung

2001-08-01

Structural health monitoring for the three cable-supported bridges located in the West of Hong Kong or the Tsing Ma Control Area has been carried out since the opening of these bridges to public traffic. The three cable-supported bridges are referred to as the Tsing Ma (suspension) Bridge, the Kap Shui Mun (cable-stayed) Bridge and the Ting Kau (cable-stayed) Bridge. The structural health monitoring works involved are classified as six monitoring categories, namely, wind load and response, temperature load and response, traffic load and response, geometrical configuration monitoring, strains and stresses/forces monitoring and global dynamic characteristics monitoring. As wind loads and responses had been a major concern in the design and construction stages, this paper therefore outlines the work of wind load and response monitoring on Tsing Ma, Kap Shui Mun and Ting Kau Bridges. The paper starts with a brief description of the sensory systems. The description includes the layout and performance requirements of sensory systems for wind load and responses monitoring. Typical results of wind load and response monitoring in graphical forms are then presented. These graphical forms include the plots of wind rose diagrams, wind incidences vs wind speeds, wind turbulence intensities, wind power spectra, gust wind factors, coefficient of terrain roughness, extreme wind analyses, deck deflections/rotations vs wind speeds, acceleration spectra, acceleration/displacement contours, and stress demand ratios. Finally conclusions on wind load and response monitoring on the three cable-supported bridges are drawn.

HIV-1 subtypes and response to combination antiretroviral therapy in Europe

DEFF Research Database (Denmark)

Bannister, WP; Ruiz, L; Loveday, C

2006-01-01

Europe/North America on the basis of the most prevalent subtype, B. However, non-B subtypes are increasingly spreading worldwide. OBJECTIVE: To compare virological and immunological response to cART between patients infected with B and non-B subtypes across Europe. DESIGN: EuroSIDA prospective....../ml and immunological response as a CD4+ T-cell count increase of ³100 cells/mm^3. RESULTS: Forty-five percent of patients were antiretroviral naive at initiation of cART. Virological suppression was achieved by 58% of 689 subtype-B-infected patients and 66% of 102 non-B-infected patients (P=0.159). After adjustment...... for potential confounders, there was no significant difference in odds of achieving virological suppression (non-B compared with B; odds ratio [OR]: 1.05, 95% confidence interval [CI]: 0.58-1.93, P=0.866). An immunological response was achieved by 43% of 753 B-infected patients and 48% of 114 non...

Social media monitoring: Responsive governance in the shadow of surveillance?

NARCIS (Netherlands)

V.J.J.M. Bekkers (Victor); A.R. Edwards (Arthur); D. de Kool (Dennis)

2013-01-01

markdownabstract__Abstract__ Social media monitoring is gradually becoming a common practice in public organizations in the Netherlands. The main purposes of social media monitoring are strategic control and responsiveness. Social media monitoring poses normative questions in terms of

Calendar time trends in the incidence and prevalence of triple-class virologic failure in antiretroviral drug-experienced people with HIV in Europe

DEFF Research Database (Denmark)

Nakagawa, Fumiyo; Lodwick, Rebecca; Costagliola, Dominique

2012-01-01

Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF...

Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study.

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Helen Kovari

Full Text Available Ribavirin (RBV is an essential component of most current hepatitis C (HCV treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN to treat chronic HCV in resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR.We included 262 HCV treatment naïve HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with HCV genotype (GT 1/4, and 128 with GT 2/3 infections. RBV levels were measured retrospectively in stored plasma samples obtained between HCV treatment week 4 and end of therapy. Uni- and multivariable logistic regression analyses were used to evaluate the association between RBV concentration and SVR in GT 1/4 and GT 2/3 infections. The analyses were repeated stratified by treatment phase (week 4-12, 13-24, >24 and IL28B genotype (CC versus CT/TT.SVR rates were 35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly across treatment phases. Patients with SVR had similar RBV concentrations compared to patients without SVR in both HCV genotype groups. SVR was not associated with RBV levels ≥2.0 mg/L (GT 1/4, OR 1.19 [0.5-2.86]; GT 2/3, 1.94 [0.78-4.80] and ≥2.5 mg/L (GT 1/4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73], regardless of treatment phase, and IL28B genotype.In HIV/HCV-coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV concentrations does not enhance the chance of HCV cure, regardless of HCV genotype, treatment phase and IL28B genotype.

Socioeconomic position and ten-year survival and virologic outcomes in a Ugandan HIV cohort receiving antiretroviral therapy.

Directory of Open Access Journals (Sweden)

Andrew G Flynn

Full Text Available Lifelong ART is essential to reducing HIV mortality and ending the epidemic, however the interplay between socioeconomic position and long-term outcomes of HIV-infected persons receiving antiretroviral therapy (ART in sub-Saharan Africa is unknown. Furthering the understanding of factors related to long-term ART outcomes in this important region will aid the successful scale-up of ART programs. We enrolled 559 HIV-infected Ugandan adults starting ART in 2004-2005 at the Infectious Diseases Institute in Kampala, Uganda and followed them for 10 years. We documented baseline employment status, regular household income, education level, housing description, physical ability, and CD4 count. Viral load was measured every six months. Proportional hazard regression tested for associations between baseline characteristics and 1 mortality, 2 virologic failure, and 3 mortality or virologic failure as a composite outcome. Over ten years 23% (n = 127 of participants died, 6% (n = 31 were lost-to-follow-up and 23% (107/472 experienced virologic treatment failure. In Kaplan-Meier analysis we observed an association between employment and mortality, with the highest cumulative probability of death occurring in unemployed individuals. In univariate analysis unemployment and disease severity were associated with mortality, but in multivariable analysis the only association with mortality was disease severity. We observed an association between higher household income and an increased incidence of both virologic failure and the combined outcome, and an association between self-employment and lower incidence of virologic failure and the combined outcome when compared to unemployment. Formal education level and housing status were unrelated to outcomes. It is feasible to achieve good ten-year survival, retention-in-care, and viral suppression in a socioeconomically diverse population in a resource-limited setting. Unemployment appears to be related to adverse 10

The Virological and Immunological Characteristics of the HIV-1-Infected Population in Brazil: From Initial Diagnosis to Impact of Antiretroviral Use.

Directory of Open Access Journals (Sweden)

Ricardo Sobhie Diaz

Full Text Available Immunological and virological status of HIV-infected individuals entering the Brazilian public system over time was analyzed. We evaluated the impact of ART on virological, immunological and antiretroviral resistance over time.CD4+ T cell counts, viral loads and genotypes from patients over 13 years old from 2001-2011 were analyzed according to demographic data. We compared groups using parametric t-tests and linear regression analysis in the R statistical software language.Mean baseline CD4+ T cell counts varied from 348 (2003 to 389 (2009 and was higher among women (p = 1.1 x 10(-8, lower in older patients (p< 1 x 10(-8 and lower in less developed regions (p = 1.864 x 10(-5. Percentage of treated patients with undetectable viral loads increased linearly from 46% (2001 to 77% (2011, was lower among women (p = 2.851 x 10(-6, younger ages (p = 1 x 10(-3, and in less developed regions (p = 1.782 x 10(-4. NRTI acquired resistance was 86% in 2001-3 and decreased over time. NNRTI resistance increased from 2001-3(50% to 2006-9 (60%, PI resistance decreased from 2001-3 (60% to 2009 (40%, and 3-class resistance was stable over time around 25%. Subtype prevalence comprised B (75.3%, B/F recombinants (12.2%, C (5.7%, F (5.3% and B/C recombinants (1.5%, with regional variations. Three-class resistance was 26.5% among Bs, 22.4% among Fs and 17.2% among Cs.HIV diagnosis occurs late, especially among elderly Brazilians. Younger individuals need special attention due to poor virological response to treatment. Antiretroviral Resistance profile is subtype related.

Energy response of neutron area monitor with silicon semiconductor detector

International Nuclear Information System (INIS)

Kitaguchi, Hiroshi; Izumi, Sigeru; Kobayashi, Kaoru; Kaihara, Akihisa; Nakamura, Takashi.

1993-01-01

A prototype neutron area monitor with a silicon semiconductor detector has been developed which has the energy response of 1 cm dose equivalent recommended by the ICRP-26. Boron and proton radiators are coated on the surface of the silicon semiconductor detector. The detector is set at the center of a cylindrical polyethylene moderator. This moderator is covered by a porous cadmium board which serves as the thermal neutron absorber. Neutrons are detected as α-particles generated by the nuclear reaction 10 B(n,α) 7 Li and as recoil protons generated by the interaction of fast neutrons with hydrogen. The neutron energy response of the monitor was measured using thermal neutrons and monoenergetic fast neutrons generated by an accelerator. The response was consistent with the 1 cm dose equivalent response required for the monitor within ±34% in the range of 0.025 - 15 Mev. (author)

Response of radiation monitors for ambient dose equivalent, H*(10)

International Nuclear Information System (INIS)

Grecco, Claudio Henrique dos Santos

2001-01-01

Radiation monitors are used all over the world to evaluate if places with presence of ionising radiation present safe conditions for people. Radiation monitors should be tested according to international or national standards in order to be qualified for use. This work describes a methodology and procedures to evaluate the energy and angular responses of any radiation monitor for ambient dose equivalent, H*(10), according to the recommendations of ISO and IEC standards. The methodology and the procedures were applied to the Monitor Inteligente de Radiacao MIR 7026, developed by the Instituto em Engenharia Nuclear (IEN), to evaluate and to adjust its response for H*(10), characterizing it as an ambient dose equivalent meter. The tests were performed at the Laboratorio Nacional de Metrologia das Radiacoes Ionizantes (LNMRI), at Instituto de Radioprotecao e Dosimetria (IRD), and results showed that the Monitor Inteligente de Radiacao MIR 7026 can be used as an EI*(10) meter, in accordance to the IEC 60846 standard requirements. The overall estimated uncertainty for the determination of the MIR 7026 response, in all radiation qualities used in this work, was 4,5 % to a 95 % confidence limit. (author)

Nevirapine Concentration in Hair Samples Is a Strong Predictor of Virologic Suppression in a Prospective Cohort of HIV-Infected Patients.

Directory of Open Access Journals (Sweden)

Sanjiv M Baxi

Full Text Available Effective antiretroviral (ARV therapy depends on adequate drug exposure, yet methods to assess ARV exposure are limited. Concentrations of ARV in hair are the product of steady-state pharmacokinetics factors and longitudinal adherence. We investigated nevirapine (NVP concentrations in hair as a predictor of treatment response in women receiving ARVs. In participants of the Women's Interagency HIV Study, who reported NVP use for >1 month from 2003-2008, NVP concentrations in hair were measured via liquid-chromatography-tandem mass-spectrometry. The outcome was virologic suppression (plasma HIV RNA below assay threshold at the time of hair sampling and the primary predictor was nevirapine concentration categorized into quartiles. We controlled for age, race/ethnicity, pre-treatment HIV RNA, CD4 cell count, and self-reported adherence over the 6-month visit interval (categorized ≤ 74%, 75%-94% or ≥ 95%. We also assessed the relation of NVP concentration with changes in hepatic transaminase levels via multivariate random intercept logistic regression and linear regression analyses. 271 women contributed 1089 person-visits to the analysis (median 3 of semi-annual visits. Viral suppression was least frequent in concentration quartile 1 (86/178 (48.3% and increased in higher quartiles (to 158/204 (77.5% for quartile 4. The odds of viral suppression in the highest concentration quartile were 9.17 times (95% CI 3.2-26, P < 0.0001 those in the lowest. African-American race was associated with lower rates of virologic suppression independent of NVP hair concentration. NVP concentration was not significantly associated with patterns of serum transaminases. Concentration of NVP in hair was a strong independent predictor of virologic suppression in women taking NVP, stronger than self-reported adherence, but did not appear to be strongly predictive of hepatotoxicity.

Early adherence to antiretroviral medication as a predictor of long-term HIV virological suppression: five-year follow up of an observational cohort.

Directory of Open Access Journals (Sweden)

Nathan Ford

Full Text Available OBJECTIVE: Previous studies have demonstrated a cross-sectional relationship between antiretroviral adherence and HIV virological suppression. We assessed the predictive value of baseline adherence in determining long-term virological failure. DESIGN: We assessed baseline adherence via an adherence questionnaire between administered to all consenting patients attending antiretroviral clinics in Khayelitsha township, South Africa, between May 2002 and March 2004. Virological status was ascertained after five years of follow up and multivariate analysis used to model associations of baseline variables and medication adherence with time to viral suppression or failure. RESULTS: Our adherence cohort comprised 207 patients, among whom 72% were female. Median age was 30 years and median CD4 count at initiation was 55 cells/mm(3. We found no statistically significant differences between baseline characteristics and early adherence groups. Multivariate analysis adjusting for baseline CD4 and age found that patients with suboptimal baseline adherence had a hazard ratio of 2.82 (95% CI 1.19-6.66, p = 0.018 for progression to virological failure compared to those whose baseline adherence was considered optimal. CONCLUSIONS: Our longitudinal study provides further confirmation of adherence as a primary determinant of subsequent confirmed virological failure, and serves as a reminder of the importance of initial early investments in adherence counseling and support as an effective way to maximize long-term treatment success.

Hepatitis C Prevalence and Responses to Pegylated Interferon + Ribavirin Treatment Among Prisoners

Directory of Open Access Journals (Sweden)

Hasan Selçuk ÖZGER

2017-12-01

Full Text Available Objective: The aim of our study was to identify the hepatitis C prevalence in prisoners and to share experiences of pegylated interferon (peg-IFN + ribavirin (RBV treatment. Materials and Methods: The study was conducted by assessing the records of prisoners between January 2014 and 2016, retrospectively. Patients in whom planned treatments were applied in a given time were determined and, virologic responses at the end of treatment and 6 months after treatment were evaluated. Chi-square test was used and a p value of less than 0.05 was considered statistically significant. Results: Among prisoners, the anti-hepatitis C virus (HCV positivity rate was 7.82% and HCV-RNA positivity rate was 5.72%. The most common genotype was genotype 3a (66 of 99 patients. End-of-treatment and 6th month sustained virologic response rates were 84.6% and 80.5%, respectively. In genotype 3a group, end-of-treatment and 6th month sustained virologic response rates were found to be higher than other genotypes but not statistically significant. Conclusion: In our study, which assessed prisoners, the rate of HCV positivity was higher than hepatitis C in the general population in Turkey. In accordance with the literature, genotype 3 was the most common genotype among prisoners. Sustained virologic response rates obtained with peg-IFN+RBV treatment suggested that peg-IFN treatment should be used with current treatment combinations in prisoners infected with HCV genotype 3.

Measuring Emotional Responses to TV Commercials: The Warmth Monitor Modernized

Directory of Open Access Journals (Sweden)

Marc Roy

2014-12-01

Full Text Available Recently there has been a lot of interest in measuring emotional responses to advertising. This study focuses on the measurement of a specific emotional response to television advertising; warmth. Nearly thirty years ago, (Aaker, Stayman and Hagerty, 1986 developed a procedure they called the Warmth Monitor; “paper and pencil” self-report process recording method. The Warmth Monitor has been used in a large number of empirical studies in marketing since, but the most recent versions of the procedure are computerized. The two methods of administering the Warmth Monitor are compared in this research.

Establishing a mobile automatic monitoring station for emergency response

International Nuclear Information System (INIS)

Fang, Hsin-Fa

2008-01-01

Full text: A radiological/nuclear emergency event may cause environmental contamination. The emergency response works always need to plan an environmental survey programme incorporating the assessment results to see what is happening. The places where are assessed to have the highest radioactive contamination/radiation dose will catch more concern and need continuous monitoring. It will cause unnecessary dangers and dose to command that personnel conduct surveying in such places when the radiological/nuclear accident become more severe. A mobile automatic monitoring station has been established for emergency response by INER (Institute of Nuclear Energy Research) to solve the problem practically. The monitoring station involves a HPIC to monitor radiation dose, an anemometer to monitor wind speed and direction, a GPS to get position data, a GPRS/3G communication module to send monitoring and positioning data to the monitoring centre where can show the monitoring result directly on a map shown on the computer. These instruments are integrated in a trailer easy to be towed to the place need to be monitored. The electric power of the station is supplied by s a solar power energy system. It can supply the station working at least 10 days without extra electric power supply designed based on the expected time length of a nuclear power plant event. The HPIC is very sensitive and stable that can discriminate a 10 nSv/hr increasing of dose rate with the monitoring time period every ten seconds. Where the radiological dispersion device events happened is not predictable, it is difficult to get suitable wind monitoring data to assess the result of radiological dispersion device events. The anemometer added on the station can provide the real time wind monitoring data to help assessment works. (author)

Rift Valley fever outbreak, Mauritania, 1998: seroepidemiologic, virologic, entomologic, and zoologic investigations.

Science.gov (United States)

Nabeth, P; Kane, Y; Abdalahi, M O; Diallo, M; Ndiaye, K; Ba, K; Schneegans, F; Sall, A A; Mathiot, C

2001-01-01

A Rift Valley fever outbreak occurred in Mauritania in 1998. Seroepidemiologic and virologic investigation showed active circulation of the Rift Valley fever virus, with 13 strains isolated, and 16% (range 1.5%-38%) immunoglobulin (Ig) M-positivity in sera from 90 humans and 343 animals (sheep, goats, camels, cattle, and donkeys). One human case was fatal.

Emergency response and radiation monitoring systems in Russian regions

International Nuclear Information System (INIS)

Arutyunyan, R.; Osipiyants, I.; Kiselev, V.; Ogar, K; Gavrilov, S.

2008-01-01

Full text: Preparedness of the emergency response system to elimination of radiation incidents and accidents is one of the most important elements of ensuring safe operation of nuclear power facilities. Routine activities on prevention of emergency situations along with adequate, efficient and opportune response actions are the key factors reducing the risks of adverse effects on population and environment. Both high engineering level and multiformity of the nuclear branch facilities make special demands on establishment of response system activities to eventual emergency situations. First and foremost, while resolving sophisticated engineering and scientific problems emerging during the emergency response process, one needs a powerful scientific and technical support system.The emergency response system established in the past decade in Russian nuclear branch provides a high efficiency of response activities due to the use of scientific and engineering potential and experience of the involved institutions. In Russia the responsibility for population protection is imposed on regional authority. So regional emergence response system should include up-to-date tools of radiation monitoring and infrastructure. That's why new activities on development of radiation monitoring and emergency response system were started in the regions of Russia. The main directions of these activities are: 1) Modernization of the existing and setting-up new facility and territorial automatic radiation monitoring systems, including mobile radiation surveillance kits; 2) Establishment of the Regional Crisis Centres and Crisis Centres of nuclear and radiation hazardous facilities; 3) Setting up communication systems for transfer, acquisition, processing, storage and presentation of data for participants of emergency response at the facility, regional and federal levels; 4) Development of software and hardware systems for expert support of decision-making on protection of personnel, population

Federal Radiological Monitoring and Assessment Center Analytical Response

International Nuclear Information System (INIS)

Nielsen, E.C.

2003-01-01

The Federal Radiological Monitoring and Assessment Center (FR-MAC) is authorized by the Federal Radiological Emergency Response Plan to coordinate all off-site radiological response assistance to state and local government s, in the event of a major radiological emergency in the United States. The FR-MAC is established by the U.S. Department of Energy, National Nuclear Security Administration, to coordinate all Federal assets involved in conducting a comprehensive program of radiological environmental monitoring, sampling, radioanalysis, quality assurance, and dose assessment. During an emergency response, the initial analytical data is provided by portable field instrumentation. As incident responders scale up their response based on the seriousness of the incident, local analytical assets and mobile laboratories add additional capability and capacity. During the intermediate phase of the response, data quality objectives and measurement quality objectives are more rigorous. These higher objectives will require the use of larger laboratories, with greater capacity and enhanced capabilities. These labs may be geographically distant FR-om the incident, which will increase sample management challenges. This paper addresses emergency radioanalytical capability and capacity and its utilization during FR-MAC operations

A comparison of computational models with and without genotyping for prediction of response to second-line HIV therapy

NARCIS (Netherlands)

Revell, A. D.; Boyd, M. A.; Wang, D.; Emery, S.; Gazzard, B.; Reiss, P.; van Sighem, A. I.; Montaner, J. S.; Lane, H. C.; Larder, B. A.

2014-01-01

We compared the use of computational models developed with and without HIV genotype vs. genotyping itself to predict effective regimens for patients experiencing first-line virological failure. Two sets of models predicted virological response for 99 three-drug regimens for patients on a failing

Determinants of virological response to antiretroviral therapy: socio-economic status still plays a role in the era of cART. Results from the ANRS-VESPA 2 study, France.

Science.gov (United States)

D'Almeida, Kayigan W; Lert, France; Spire, Bruno; Dray-Spira, Rosemary

2016-01-01

Disparities in combined antiretroviral therapy (cART) outcomes have been consistently reported among people living with HIV (PLWHIV). The present study aims at investigating the mechanisms underlying those disparities among PLWHIV in France. We used data from the Vespa2 survey, a large national cross-sectional survey, representative of HIV-infected people followed at hospitals in 2011. Among participants diagnosed ≥1996, HIV treatment-naive at the time of cART initiation and on cART for at least 12 months, the frequency of sustained virological suppression (SVS; undetectable viral load [accounting for clinical and biological determinants of response to cART. Among 1,246 participants, 77.7% had achieved SVS. SVS was less frequent among those unemployed (0.6 [range 0.3-1.0]) and those with the lowest level of education (0.4 [range 0.2-0.9]). The late presenters, diagnosed at a CD4 + T-cell count 200 but initiating cART at CD4 + T-cell count issues should also be investigated.

Time from HIV infection to virological suppression: dramatic fall from 2007 to 2016.

Science.gov (United States)

Medland, Nicholas A; Nicholson, Suellen; Chow, Eric P F; Read, Timothy R H; Bradshaw, Catriona S; Denham, Ian; Fairley, Christopher K

2017-11-13

Time from HIV infection to virological suppression: dramatic fall from 2007 to 2016. We examined the time from HIV infection to virological suppression in MSM who were first diagnosed at Melbourne Sexual Health Centre between 2007 and 2016. Retrospective cohort. Date of infection was imputed from the testing history or serological evidence of recent infection (negative or indeterminate western blot) or baseline CD4 cell count. Date of virological suppression was determined using clinical viral load data. We analysed predictors of diagnosis with serological evidence of recent infection (logistic regression) and time from diagnosis to suppression and from infection to suppression (Cox regression) using demographic, clinical, and behavioral covariates. Between 2007 and 2016, the median time from HIV infection to diagnosis fell from 6.8 to 4.3 months (P = 0.001), from diagnosis to suppression fell from 22.7 to 3.2 months (P < 0.0001), and from infection to suppression fell from 49.0 to 9.6 months (P < 0.0001). Serological evidence of recent infection increased from 15.6 to 34.3% (P < 0.0001) of diagnoses. In the multivariate analyses, age, being recently arrived from a non-English speaking country, history of IDU, other sexually transmitted infections, and sexual risk were not associated with any of these measures. The duration of infectiousness in MSM diagnosed with HIV infection at Melbourne Sexual Health Centre in Victoria has fallen dramatically between 2007 and 2016 and the proportion diagnosed with serological evidence of recent infection has increased. This effect is observed across all population subgroups and marks a positive milestone for the treatment as prevention paradigm.

Neutronic analysis of JET external neutron monitor response

Energy Technology Data Exchange (ETDEWEB)

Snoj, Luka, E-mail: luka.snoj@ijs.si [Reactor Physics Division, Jožef Stefan Institute, Jamova cesta 39, SI-1000 Ljubljana (Slovenia); Lengar, Igor; Čufar, Aljaž [Reactor Physics Division, Jožef Stefan Institute, Jamova cesta 39, SI-1000 Ljubljana (Slovenia); Syme, Brian; Popovichev, Sergey [Culham Centre for Fusion Energy, Culham Science Centre, Abingdon, OX14 3DB, United Kingdom (United Kingdom); Batistoni, Paola [ENEA C. R. Frascati, via E. Fermi 45, 00044 Frascati, Roma (Italy); Conroy, Sean [VR Association, Uppsala University, Department of Physics and Astronomy, PO Box 516, SE-75120 Uppsala (Sweden)

2016-11-01

Highlights: • We model JET tokamak containing JET remote handling system. • We investigate effect of remote handling system on external neutron monitor response. • Remote handling system correction factors are calculated. • Integral correction factors are relatively small, i.e up to 8%. - Abstract: The power output of fusion devices is measured in terms of the neutron yield which relates directly to the fusion yield. JET made a transition from Carbon wall to ITER-Like Wall (Beryllium/Tungsten/Carbon) during 2010–11. Absolutely calibrated measurement of the neutron yield by JET neutron monitors was ensured by direct measurements using a calibrated {sup 252}Cf neutron source (NS) deployed by the in-vessel remote handling system (RHS) inside the JET vacuum vessel. Neutronic calculations were required in order to understand the neutron transport from the source in the vacuum vessel to the fission chamber detectors mounted outside the vessel on the transformer limbs of the tokamak. We developed a simplified computational model of JET and the JET RHS in Monte Carlo neutron transport code MCNP and analyzed the paths and structures through which neutrons reach the detectors and the effect of the JET RHS on the neutron monitor response. In addition we performed several sensitivity studies of the effect of substantial massive structures blocking the ports on the external neutron monitor response. As the simplified model provided a qualitative picture of the process only, some calculations were repeated using a more detailed full 3D model of the JET tokamak.

Triple Bioluminescence Imaging for In Vivo Monitoring of Cellular Processes

Directory of Open Access Journals (Sweden)

Casey A Maguire

2013-01-01

Full Text Available Bioluminescence imaging (BLI has shown to be crucial for monitoring in vivo biological processes. So far, only dual bioluminescence imaging using firefly (Fluc and Renilla or Gaussia (Gluc luciferase has been achieved due to the lack of availability of other efficiently expressed luciferases using different substrates. Here, we characterized a codon-optimized luciferase from Vargula hilgendorfii (Vluc as a reporter for mammalian gene expression. We showed that Vluc can be multiplexed with Gluc and Fluc for sequential imaging of three distinct cellular phenomena in the same biological system using vargulin, coelenterazine, and D-luciferin substrates, respectively. We applied this triple imaging system to monitor the effect of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL delivered using an adeno-associated viral vector (AAV on brain tumors in mice. Vluc imaging showed efficient sTRAIL gene delivery to the brain, while Fluc imaging revealed a robust antiglioma therapy. Further, nuclear factor-κB (NF-κB activation in response to sTRAIL binding to glioma cells death receptors was monitored by Gluc imaging. This work is the first demonstration of trimodal in vivo bioluminescence imaging and will have a broad applicability in many different fields including immunology, oncology, virology, and neuroscience.

Disaster Monitoring and Emergency Response Services in China

Science.gov (United States)

Wu, J.; Han, X.; Zhou, Y.; Yue, P.; Wang, X.; Lu, J.; Jiang, W.; Li, J.; Tang, H.; Wang, F.; Li, X.; Fan, J.

2018-04-01

The Disaster Monitoring and Emergency Response Service(DIMERS) project was kicked off in 2017 in China, with the purpose to improve timely responsive service of the institutions involved in the management of natural disasters and man-made emergency situations with the timely and high-quality products derived from Space-based, Air-based and the in-situ Earth observation. The project team brought together a group of top universities and research institutions in the field of Earth observations as well as the operational institute in typical disaster services at national level. The project will bridge the scientific research and the response services of massive catastrophe in order to improve the emergency response capability of China and provide scientific and technological support for the implementation of the national emergency response strategy. In response to the call for proposal of "Earth Observation and Navigation" of 2017 National Key R&D Program of China, Professor Wu Jianjun, the deputy chairman of Faculty of Geographical Science of Beijing Normal University, submitted the Disaster Monitoring and Emergency Response Service (DIMERS) project, jointly with the experts and scholars from Institute of Remote Sensing and Digital Earth, Chinese Academy of Sciences, Wuhan University, China Institute of Earthquake Forecasting of China Earthquake Administration and China Institute of Water Resources and Hydropower Science. After two round evaluations, the proposal was funded by Ministry of Science and Technology of China.

Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals

Directory of Open Access Journals (Sweden)

Kazunori Yoh

2017-10-01

Full Text Available Aims: We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC patients undergoing interferon (IFN-free direct acting antivirals (DAAs therapy who achieved sustained virological response (SVR. Patients and methods: A total of 69 CHC patients treated with DAAs were analyzed. We compared the changes in skeletal muscle index (SMI using bio-impedance analysis at baseline and SMI at SVR. SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm2/m2. Further, we identified pretreatment parameters contributing to the increased SMI at SVR. Results: SMI in males at baseline ranged from 6.73 to 9.08 cm2/m2 (median, 7.65 cm2/m2, while that in females ranged from 4.45 to 7.27 cm2/m2 (median, 5.81 cm2/m2. At SVR, 36 patients (52.2% had increased SMI as compared with baseline. In the univariate analysis, age (p = 0.0392, hyaluronic acid (p = 0.0143, and branched-chain amino acid to tyrosine ratio (BTR (p = 0.0024 were significant pretreatment factors linked to increased SMI at SVR. In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488. Conclusion: Pretreatment BTR level can be helpful for predicting increased SMI after SVR in CHC patients undergoing IFN-free DAAs therapy.

Virological success after 12 and 24 months of antiretroviral therapy in sub-Saharan Africa: Comparing results of trials, cohorts and cross-sectional studies using a systematic review and meta-analysis.

Science.gov (United States)

Taieb, Fabien; Madec, Yoann; Cournil, Amandine; Delaporte, Eric

2017-01-01

UNAIDS recently defined the 90-90-90 target as a way to end the HIV epidemic. However, the proportion of virological success following antiretroviral therapy (ART) may not be as high as the anticipated 90%, and may in fact be highly heterogeneous. We aimed to describe the proportion of virological success in sub-Saharan Africa and to identify factors associated with the proportion of virological success. We performed a systematic review and meta-analysis focusing on the proportion of patients in sub-Saharan Africa who demonstrate virological success at 12 and 24 months since ART initiation, as well as at 6 and 36 months, where possible. Programme factors associated with the proportion of virological success were identified using meta-regression. Analyses were conducted using both on-treatment (OT) and intention-to-treat (ITT) approaches. Eighty-five articles were included in the meta-analysis, corresponding to 125 independent study populations. Using an on-treatment approach, the proportions (95% confidence interval (CI)) of virological success at 12 (n = 64) and at 24 (n = 32) months since ART initiation were 87.7% (81.3-91.0) and 83.7% (79.8-87.6), respectively. Univariate analysis indicated that the proportion of virological success was not different by study design. Multivariate analysis at 24 months showed that the proportion of virological success was significantly larger in studies conducted in public sector sites than in other sites (p = 0.045). Using an ITT approach, the proportions (95% CI) of virological success at 12 (n = 50) and at 24 (n = 20) months were 65.4% (61.8-69.1) and 56.8% (51.3-62.4), respectively. At 12 months, multivariate analysis showed that the proportion of success was significantly lower in cohort studies than in trials (63.0% vs. 71.1%; p = 0.017). At 24 months, univariate analysis demonstrated that the proportion of success was also lower in cohorts. Regardless of the time following ART initiation, and of the threshold, proportions

Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

NARCIS (Netherlands)

Caniglia, Ellen C.; Cain, Lauren E.; Sabin, Caroline A.; Robins, James M.; Logan, Roger; Abgrall, Sophie; Mugavero, Michael J.; Hernández-Díaz, Sonia; Meyer, Laurence; Seng, Remonie; Drozd, Daniel R.; Seage, George R.; Bonnet, Fabrice; Dabis, Francois; Moore, Richard D.; Reiss, Peter; van Sighem, Ard; Mathews, William C.; del Amo, Julia; Moreno, Santiago; Deeks, Steven G.; Muga, Roberto; Boswell, Stephen L.; Ferrer, Elena; Eron, Joseph J.; Napravnik, Sonia; Jose, Sophie; Phillips, Andrew; Justice, Amy C.; Tate, Janet P.; Gill, John; Pacheco, Antonio; Veloso, Valdilea G.; Bucher, Heiner C.; Egger, Matthias; Furrer, Hansjakob; Porter, Kholoud; Touloumi, Giota; Crane, Heidi; Miro, Jose M.; Sterne, Jonathan A.; Costagliola, Dominique; Saag, Michael; Hernán, Miguel A.

2017-01-01

Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. In this observational study, we used data from prospective

Stable Caloric Intake and Continued Virologic Suppression for HIV-Positive Antiretroviral Treatment-Experienced Women After Switching to a Single-Tablet Regimen of Emtricitabine, Rilpivirine, and Tenofovir Disoproxil Fumarate.

Science.gov (United States)

Menezes, Prema; Mollan, Katie; Hoffman, Erin; Xie, Zimeng; Wills, Jennifer; Marcus, Cheryl; Rublein, John; Hudgens, Michael; Eron, Joseph J

2018-05-02

Benefits of switching to a single-tablet regimen (STR) of emtricitabine/rilpivirine/tenofovir (FTC/RPV/TDF) in virologically suppressed antiretroviral treatment (ART) experienced HIV-positive women include pregnancy category B rating and lack of clinically significant drug interactions between RPV and oral contraceptives. Unfortunately, studies involving switching to FTC/RPV/TDF enrolled fewer than 25% women. We undertook this 48-week study to assess the ability of virologically suppressed HIV-positive women switching to RPV STR to remain virologically suppressed and comply with the caloric intake requirement. HIV-positive women on ART with viral load phone calls on randomly chosen dates. For each 3-day food diary, the daily median caloric intake and median value for each macronutrient consumed concurrent with FTC/RPV/TDF were computed. Medication adherence was measured using a visual analog scale. We enrolled 33 women, 73% of whom were African American. At week 48, virologic suppression (HIV RNA phone call. Median kcal intake (food diary) did not change significantly from baseline (684 kcal) to week 48 (820 kcal); median change 102 kcal, p = .15. Women who reported noncompliance with a ≥400 kcal meal did not experience virologic failure. Significant concordance between caloric adherence and virologic suppression was not detected. Our study demonstrated that HIV-positive women who switched to STR FTC/RPV/TDF continued to experience virologic suppression and were readily able to comply with the recommended caloric intake requirement.

Hepatocellular Carcinoma after Sustained Viral Response to Interferon and Ribavirin Therapy in Cirrhosis Secondary to Chronic Hepatitis C

International Nuclear Information System (INIS)

Khokhar, N.; Qureshi, M.U.; Niazi, T.K.

2013-01-01

Objective: To determine the frequency of development of hepatocellular carcinoma in patients with chronic liver disease secondary to hepatitis C who had achieved sustained virological response with Interferon and Ribavirin therapy. Study Design: Retrospective descriptive study. Place and Duration of Study: Shifa International Hospital, Islamabad, Pakistan, from January 2007 to January 2012. Methodology: Hepatitis C related chronic liver disease patients who were treated with interferon and ribavirin, after they achieved sustained virological response, they were followed for a mean of 42 A+- 17 months. During this time, development of hepatocellular carcinoma was ascertained. All underwent surveillance with alpha-feto-protein and ultrasonography every 6 months. Results: Out of the 58 patients who had achieved sustained virological response, 3 developed hepatocellular carcinoma after a mean follow-up of 38 A+- 14 months. It was multifocal in 2 cases and was single lesion in the 3rd. Two patients ultimately died, one with upper GI bleeding and the other with hepatic encephalopathy, while 3rd patient with single lesion is still surviving. Conclusion: Three out of 58 patients of hepatitis C related chronic liver disease developed hepatocellular carcinoma during follow-up in patients who had achieved sustained virological response. These patients need closer follow-up, for development of complications, even if they have achieved sustained viral response. (author)

EMIR: a configurable hierarchical system for event monitoring and incident response

Science.gov (United States)

Deich, William T. S.

2014-07-01

The Event Monitor and Incident Response system (emir) is a flexible, general-purpose system for monitoring and responding to all aspects of instrument, telescope, and general facility operations, and has been in use at the Automated Planet Finder telescope for two years. Responses to problems can include both passive actions (e.g. generating alerts) and active actions (e.g. modifying system settings). Emir includes a monitor-and-response daemon, plus graphical user interfaces and text-based clients that automatically configure themselves from data supplied at runtime by the daemon. The daemon is driven by a configuration file that describes each condition to be monitored, the actions to take when the condition is triggered, and how the conditions are aggregated into hierarchical groups of conditions. Emir has been implemented for the Keck Task Library (KTL) keyword-based systems used at Keck and Lick Observatories, but can be readily adapted to many event-driven architectures. This paper discusses the design and implementation of Emir , and the challenges in balancing the competing demands for simplicity, flexibility, power, and extensibility. Emir 's design lends itself well to multiple purposes, and in addition to its core monitor and response functions, it provides an effective framework for computing running statistics, aggregate values, and summary state values from the primitive state data generated by other subsystems, and even for creating quick-and-dirty control loops for simple systems.

A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

DEFF Research Database (Denmark)

Paredes, Roger; Puertas, Maria Carmen; Bannister, Wendy

2011-01-01

Background. The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. Methods. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated...... in NNRTI-naive patients who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI...... = .013). A376S conferred selective low-level nevirapine resistance in vitro, and led to greater affinity for double-stranded DNA. Conclusions. The A376S substitution in the connection subdomain of HIV-1 RT causes selective nevirapine resistance and confers an increased risk of virological failure...

Federal Radiological Monitoring and Assessment Center. The analytical response

International Nuclear Information System (INIS)

Nielsen, E.C.

2005-01-01

The Federal Radiological Monitoring and Assessment Center (FRMAC) is authorized by the Federal Radiological Emergency Response Plan to coordinate all off-site radiological response assistance to state and local governments, in the event of a major radiological emergency in the United States. The FRMAC is established by the U.S. Department of Energy, National Nuclear Security Administration, to coordinate all Federal assets involved in conducting a comprehensive program of radiological environmental monitoring, sampling, radioanalysis, quality assurance, and dose assessment. During an emergency response, the initial analytical data is provided by portable field instrumentation. As incident responders scale up their response based on the seriousness of the incident, local analytical assets and mobile laboratories add additional capability and capacity. During the intermediate phase of the response, data quality objectives and measurement quality objectives are more rigorous. These higher objectives will require the use of larger laboratories, with greater capacity and enhanced capabilities. These labs may be geographically distant from the incident, which will increase sample management challenges. Emergency radioanalytical capability and capacity and its utilization during FRMAC operations are discussed. (author)

Monitoring Immune Responses in Organ Recipients by Flow Cytometry

Directory of Open Access Journals (Sweden)

Al-Mukhalafi Zuha

2001-01-01

Full Text Available Allograft rejection remains a major barrier to successful organ transplan-tation. Cellular and humoral immune responses play a critical role in mediating graft rejection. During the last few years, monoclonal antibodies have been used as a new specific therapeutic approach in the prevention of allograft rejection. Recently, the technology of flow cytometry has become a useful tool for monitoring immunological responses in transplant recipients. The application of this valuable tool in clinical transplantation at the present time is aimed at, i determining the extent of immuno-suppressive therapy through T-cell receptor analysis of cellular components, ii monitoring levels of alloreactive antibodies to identify high-risk recipients (sensitized patients in the pre-operative period and iii to predict rejection by monitoring their development post-operatively. In future, further development of this technology may demonstrate greater benefit to the field of organ transplantation.

Federal Radiological Monitoring and Assessment Center advanced part phase response actions

International Nuclear Information System (INIS)

Hurley, B.

1997-01-01

Federal Radiological Monitoring and Assessment Center (FRMAC) response actions are carried out in Advance Party and Main Party phases of deployment. Response activities are initiated by a FRMAC Home Team prior to and during Advance Party deployment, with Home Team support continuing until the FRMAC Main Party is fully deployed. Upon arrival at the incident scene, the Advance Party establishes communications with other federal, state, and local response organizations, Following an Advance Party Meeting with these response organizations, FRMAC begins formulation of an initial monitoring and sampling plan, in coordination with the jurisdictional state and the Lead Federal Agency, and initiates detailed logistical arrangements for Main Party deployment and operations

Effectiveness and Risk Factors for Virological Outcome of Raltegravir-Based Therapy for Treatment-Experienced HIV-Infected Patients.

Science.gov (United States)

Mata-Marín, José Antonio; Smeke, Ariane Estrella Weiser; Rodriguez, Mariana Rotzinger; Chávez-García, Marcelino; Banda-Lara, Marco Isaac; Rios, Alma Minerva Pérez; Nuñez-Rodríguez, Nohemí; Domínguez-Hermosillo, Juan Carlos; Sánchez, Alberto Chaparro; Juarez-Kasusky, Irene; Herrera, Javier Enrique Cruz; Ramírez, Jorge Luis Sandoval; Gaytán-Martínez, Jesús

2017-03-01

We evaluated the effectiveness of a raltegravir (RAL)-containing regimen plus an optimized background regimen in HIV-1 highly treatment-experienced patients. A retrospective cohort, multicentre study was conducted. Adult (>16 years old) HIV treatment-experience patients starting therapy with a RAL-containing regimen were included. Effectiveness was evaluated as the percentage of patients with an undetectable HIV-1 RNA viral load (treatment failure. Of the 107 patients in the cohort, 86% were men, the median age was 45 years [interquartile range (IQR) 40-52] and the median number of previous regimens was six (IQR 4-7). After 48 weeks of treatment, 73% (IQR 63-80%) of patients (n = 78) had a viral load of HIV-1 RNA of 40 years [odds ratio (OR) 5.61; 95% confidence interval (CI) 1.61-18.84; P = 0.006] and use of tenofovir in the regimen (OR 0.16; 95% CI 0.03-0.80; P = 0.026). In this Mexican cohort, RAL achieved high rates of virological suppression and an increase in CD4+ cell count in highly treatment-experienced patients infected with HIV-1. Age >40 years was associated with a good virological outcome, contrary to tenofovir use, which was associated with a poor virological outcome.

Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection.

Science.gov (United States)

Real, Fernando; Sennepin, Alexis; Ganor, Yonatan; Schmitt, Alain; Bomsel, Morgane

2018-05-08

During sexual intercourse, HIV-1 crosses epithelial barriers composing the genital mucosa, a poorly understood feature that requires an HIV-1-infected cell vectoring efficient mucosal HIV-1 entry. Therefore, urethral mucosa comprising a polarized epithelium and a stroma composed of fibroblasts and macrophages were reconstructed in vitro. Using this system, we demonstrate by live imaging that efficient HIV-1 transmission to stromal macrophages depends on cell-mediated transfer of the virus through virological synapses formed between HIV-1-infected CD4 + T cells and the epithelial cell mucosal surface. We visualized HIV-1 translocation through mucosal epithelial cells via transcytosis in regions where virological synapses occurred. In turn, interleukin-13 is secreted and HIV-1 targets macrophages, which develop a latent state of infection reversed by lipopolysaccharide (LPS) activation. The live observation of virological synapse formation reported herein is key in the design of vaccines and antiretroviral therapies aimed at blocking HIV-1 access to cellular reservoirs in genital mucosa. Copyright © 2018. Published by Elsevier Inc.

Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection

Czech Academy of Sciences Publication Activity Database

Selinger, Martin; Wilkie, G. S.; Tong, L.; Gu, Q.; Schnettler, E.; Grubhoffer, Libor; Kohl, A.

2017-01-01

Roč. 98, č. 8 (2017), s. 2043-2060 ISSN 0022-1317 R&D Projects: GA ČR GA15-03044S Institutional support: RVO:60077344 Keywords : blood- brain -barrier * long noncoding RNAs * double-stranded-RNA * interferon * immune-response * gene-expression * stimulated genes * human astrocytes * viral-infection * protein * tick-borne encephalitis virus * neuronal cells * transcriptome analysis * host response * interferon Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 2.838, year: 2016

Impact of previous virological treatment failures and adherence on the outcome of antiretroviral therapy in 2007.

Directory of Open Access Journals (Sweden)

Marie Ballif

Full Text Available BACKGROUND: Combination antiretroviral treatment (cART has been very successful, especially among selected patients in clinical trials. The aim of this study was to describe outcomes of cART on the population level in a large national cohort. METHODS: Characteristics of participants of the Swiss HIV Cohort Study on stable cART at two semiannual visits in 2007 were analyzed with respect to era of treatment initiation, number of previous virologically failed regimens and self reported adherence. Starting ART in the mono/dual era before HIV-1 RNA assays became available was counted as one failed regimen. Logistic regression was used to identify risk factors for virological failure between the two consecutive visits. RESULTS: Of 4541 patients 31.2% and 68.8% had initiated therapy in the mono/dual and cART era, respectively, and been on treatment for a median of 11.7 vs. 5.7 years. At visit 1 in 2007, the mean number of previous failed regimens was 3.2 vs. 0.5 and the viral load was undetectable (4 previous failures compared to 1 were 0.9 (95% CI 0.4-1.7, 0.8 (0.4-1.6, 1.6 (0.8-3.2, 3.3 (1.7-6.6 respectively, and 2.3 (1.1-4.8 for >2 missed cART doses during the last month, compared to perfect adherence. From the cART era, odds ratios with a history of 1, 2 and >2 previous failures compared to none were 1.8 (95% CI 1.3-2.5, 2.8 (1.7-4.5 and 7.8 (4.5-13.5, respectively, and 2.8 (1.6-4.8 for >2 missed cART doses during the last month, compared to perfect adherence. CONCLUSIONS: A higher number of previous virologically failed regimens, and imperfect adherence to therapy were independent predictors of imminent virological failure.

Comparison of HIV-1 genotypic resistance test interpretation systems in predicting virological outcomes over time

NARCIS (Netherlands)

D. Frentz (Dineke); C.A.B. Boucher (Charles); M. Assel (Matthias); A. de Luca (Andrea); M. Fabbiani (Massimiliano); F. Incardona (Francesca); P. Libin (Pieter); N. Manca (Nino); V. Müller (Viktor); B.O. Nualláin (Breanndán); R. Paredes (Roger); M. Prosperi (Mattia); E. Quiros-Roldan (Eugenia); L. Ruiz (Lidia); P.M.A. Sloot (Peter); C. Torti (Carlo); A.M. Vandamme (Anne Mieke); K. Laethem (Kristel); M. Zazzi (Maurizio); D.A.M.C. van de Vijver (David)

2010-01-01

textabstractBackground: Several decision support systems have been developed to interpret HIV-1 drug resistance genotyping results. This study compares the ability of the most commonly used systems (ANRS, Rega, and Stanford's HIVdb) to predict virological outcome at 12, 24, and 48 weeks.

Monitoring of microbial indicator groups in caves through the use of RIDA ® COUNT kits

Czech Academy of Sciences Publication Activity Database

Mulec, J.; Krištůfek, Václav; Chroňáková, Alica

2012-01-01

Roč. 41, 2/3 (2012), s. 287-296 ISSN 0583-6050 R&D Projects: GA MŠk LC06066 Grant - others:SSJ(SK) ITMS 24150120041-OPZP-P05-09-01 Institutional support: RVO:60077344 Keywords : caves * microorganisms * monitoring * human impact * water quality Subject RIV: EE - Microbiology, Virology Impact factor: 0.542, year: 2012

Characteristics associated with virologic failure in high-risk HIV-positive participants with prior failure: a post hoc analysis of ACTG 5251.

Science.gov (United States)

Robbins, Gregory K; Cohn, Susan E; Harrison, Linda J; Smeaton, Laura; Moran, Laura; Rusin, David; Dehlinger, Marjorie; Flynn, Theresa; Lammert, Sara; Wu, Albert W; Safren, Steven A; Reynolds, Nancy R

2016-07-01

Patients with prior virologic failure (VF) are at an increased risk of subsequent failure, emergence of resistance, and death. This analysis identifies outcomes and correlates of VF in a high-risk population. A5251 was designed to evaluate an enhanced adherence counseling intervention delivered by nurses from a central call site on virologic suppression. Due to slow enrollment, the study was closed prematurely and revised study endpoints were evaluated (week 24 VF (HIV-1 RNA ≥200 copies/ml) and non-perfect adherence (antiretroviral regimen changes were three and the co-morbidity in this population was higher than typical for HIV clinical trials. At week 24 (n = 41), 24 (59%) failed to reach virologic suppression (HIV-1 RNA perceptions (IPQ-B) were associated with week 24 non-adherence. Early clinical assessments (week 12 HIV-RNA ≥200 copies/mL and non-perfect adherence) as well as higher depression and adverse illness perceptions were associated with week 24 VF. In this high-risk population, the proportion of participants with suboptimal adherence and VF was unacceptably high. Interventions to address this treatment gap are clearly needed. Depression and a higher illness perception score, failure to achieve virologic suppression by week 12, and less than perfect adherence could be used to target individuals for early interventions in treatment-experienced, high-risk individuals at high risk for VF.

Estimating the clinical and economic benefit associated with incremental improvements in sustained virologic response in chronic hepatitis C.

Science.gov (United States)

McEwan, Phil; Ward, Thomas; Bennett, Hayley; Kalsekar, Anupama; Webster, Samantha; Brenner, Michael; Yuan, Yong

2015-01-01

Hepatitis C virus (HCV) infection is one of the principle causes of chronic liver disease. Successful treatment significantly decreases the risk of hepatic morbidity and mortality. Current standard of care achieves sustained virologic response (SVR) rates of 40-80%; however, the HCV therapy landscape is rapidly evolving. The objective of this study was to quantify the clinical and economic benefit associated with increasing levels of SVR. A published Markov model (MONARCH) that simulates the natural history of hepatitis C over a lifetime horizon was used. Discounted and non-discounted life-years (LYs), quality-adjusted life-years (QALYs) and cost of complication management were estimated for various plausible SVR rates. To demonstrate the robustness of projections obtained, the model was validated to ten UK-specific HCV studies. QALY estimates ranged from 18.0 years for those treated successfully in fibrosis stage F0 to 7.5 years (discounted) for patients in fibrosis stage F4 who remain untreated. Predicted QALY gains per 10% improvement in SVR ranged from 0.23 (F0) to 0.64 (F4) and 0.58 (F0) to 1.35 (F4) in 40 year old patients (discounted and non-discounted results respectively). In those aged 40, projected discounted HCV-related costs are minimised with successful treatment in F0/F1 (at approximately £ 300), increasing to £ 49,300 in F4 patients who remain untreated. Validation of the model to published UK cost-effectiveness studies produce R2 goodness of fit statistics of 0.988, 0.978 and of 0.973 for total costs, QALYs and incremental cost effectiveness ratios, respectively. Projecting the long-term clinical and economic consequences associated with chronic hepatitis C is a necessary requirement for the evaluation of new treatments. The principle analysis demonstrates the significant impact on expected costs, LYs and QALYs associated with increasing SVR. A validation analysis demonstrated the robustness of the results reported.

FibroTest is an independent predictor of virologic response in chronic hepatitis C patients retreated with pegylated interferon alfa-2b and ribavirin in the EPIC³ program.

Science.gov (United States)

Poynard, Thierry; Munteanu, Mona; Colombo, Massimo; Bruix, Jordi; Schiff, Eugene; Terg, Ruben; Flamm, Steven; Moreno-Otero, Ricardo; Carrilho, Flair; Schmidt, Warren; Berg, Thomas; McGarrity, Thomas; Heathcote, E Jenny; Gonçales, Fernando; Diago, Moises; Craxi, Antonio; Silva, Marcelo; Boparai, Navdeep; Griffel, Louis; Burroughs, Margaret; Brass, Clifford; Albrecht, Janice

2011-02-01

EPIC-3 is a prospective, international study that has demonstrated the efficacy of PEG-IFN alfa-2b plus weight-based ribavirin in patients with chronic hepatitis C and significant fibrosis who previously failed any interferon-alfa/ribavirin therapy. The aim of the present study was to assess FibroTest (FT), a validated non-invasive marker of fibrosis in treatment-naive patients, as a possible alternative to biopsy as the baseline predictor of subsequent early virologic (EVR) and sustained virologic response (SVR) in previously treated patients. Of 2312 patients enrolled, 1459 had an available baseline FT, biopsy, and complete data. Uni- (UV) and multi-variable (MV) analyses were performed using FT and biopsy. Baseline characteristics were similar as in the overall population; METAVIR stage: 28% F2, 29% F3, and 43% F4, previous relapsers 29%, previous PEG-IFN regimen 41%, high baseline viral load (BVL) 64%. 506 patients (35%) had undetectable HCV-RNA at TW12 (TW12neg), with 58% achieving SVR. The accuracy of FT was similar to that in naive patients: AUROC curve for the diagnosis of F4 vs F2=0.80 (p<0.00001). Five baseline factors were associated (p<0.001) with SVR in UV and MV analyses (odds ratio: UV/MV): fibrosis stage estimated using FT (4.5/5.9) or biopsy (1.5/1.6), genotype 2/3 (4.5/5.1), BVL (1.5/1.3), prior relapse (1.6/1.6), previous treatment with non-PEG-IFN (2.6/2.0). These same factors were associated (p ≤ 0.001) with EVR. Among patients TW12neg, two independent factors remained highly predictive of SVR by MV analysis (p ≤ 0.001): genotype 2/3 (odds ratio=2.9), fibrosis estimated with FT (4.3) or by biopsy (1.5). FibroTest at baseline is a possible non-invasive alternative to biopsy for the prediction of EVR at 12 weeks and SVR, in patients with previous failures and advanced fibrosis, retreated with PEG-IFN alfa-2b and ribavirin. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PROFILE: Integrating Stressor and Response Monitoring into a Resource-Based Water-Quality Assessment Framework.

Science.gov (United States)

ROUX; KEMPSTER; KLEYNHANS; VAN; DU

1999-01-01

/ South African water law as well as the country's water resource management policies are currently under review. The Water Law Principles, which were established as part of this review process, indicate a commitment to sustainable development of water resources and the protection of an ecological "reserve." Such policy goals highlight the limitations of traditional and current water-quality management strategies, which rely on stressor monitoring and associated regulation of pollution. The concept of an assimilative capacity is central to the implementation of the current water-quality management approach. Weaknesses inherent in basing water management on the concept of assimilative capacity are discussed. Response monitoring is proposed as a way of addressing some of the weaknesses. Following a global trend, the new policy goals emphasize the need to protect rather than to use the ability of ecosystems to recover from disturbances. This necessitates the adoption of response measurements to quantify ecological condition and monitor ecological change. Response monitoring focuses on properties that are essential to the sustainability of the ecosystem. These monitoring tools can be used to establish natural ranges of ecological change within ecosystems, as well as to quantify conceptually acceptable and unacceptable ranges of change. Through a framework of biological criteria and biological impairment standards, the results of response monitoring can become an integral part of future water resource management strategies in South Africa. KEY WORDS: Stressor monitoring; Response monitoring; Assimilative capacity; Ecosystem stability; Resilience; Biocriteria

Optimization of in-vivo monitoring program for radiation emergency response

Energy Technology Data Exchange (ETDEWEB)

Ha, Wi Ho; Kim, Jong Kyung [Dept. of Nuclear Engineering, Hanyang University, Seoul (Korea, Republic of)

2016-12-15

In case of radiation emergencies, internal exposure monitoring for the members of public will be required to confirm internal contamination of each individual. In-vivo monitoring technique using portable gamma spectrometer can be easily applied for internal exposure monitoring in the vicinity of the on-site area. In this study, minimum detectable doses (MDDs) for '1'3'4Cs, {sup 137}Cs, and {sup 131}I were calculated adjusting minimum detectable activities (MDAs) from 50 to 1,000 Bq to find out the optimal in-vivo counting condition. DCAL software was used to derive retention fraction of Cs and I isotopes in the whole body and thyroid, respectively. A minimum detectable level was determined to set committed effective dose of 0.1 mSv for emergency response. We found that MDDs at each MDA increased along with the elapsed time. 1,000 Bq for {sup 134}Cs and {sup 137}Cs, and 100 Bq for {sup 131}I were suggested as optimal MDAs to provide in-vivo monitoring service in case of radiation emergencies. In-vivo monitoring program for emergency response should be designed to achieve the optimal MDA suggested from the present work. We expect that a reduction of counting time compared with routine monitoring program can achieve the high throughput system in case of radiation emergencies.

Evaluation of energy response of neutron rem monitor applied to high-energy accelerator facilities

Energy Technology Data Exchange (ETDEWEB)

Nakane, Yoshihiro; Harada, Yasunori; Sakamoto, Yukio [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment] [and others

2003-03-01

A neutron rem monitor was newly developed for applying to the high-intensity proton accelerator facility (J-PARC) that is under construction as a joint project between the Japan Atomic Energy Research Institute and the High Energy Accelerator Research Organization. To measure the dose rate accurately for wide energy range of neutrons from thermal to high-energy region, the neutron rem monitor was fabricated by adding a lead breeder layer to a conventional neutron rem monitor. The energy response of the monitor was evaluated by using neutron transport calculations for the energy range from thermal to 150 MeV. For verifying the results, the response was measured at neutron fields for the energy range from thermal to 65 MeV. The comparisons between the energy response and dose conversion coefficients show that the newly developed neutron rem monitor has a good performance in energy response up to 150 MeV, suggesting that the present study offered prospects of a practical fabrication of the rem monitor applicable to the high intensity proton accelerator facility. (author)

Virological failure of staggered and simultaneous treatment interruption in HIV patients who began Efavirenz-based regimens after allergic reactions to nevirapine

Directory of Open Access Journals (Sweden)

Siripassorn Krittaecho

2013-01-01

Full Text Available Abstract Objective The objective of this work was to study the virological outcomes associated with two different types of treatment interruption strategies in patients with allergic reactions to nevirapine (NVP. We compared the virological outcomes of (1 HIV-1-infected patients who discontinued an initial NVP-based regimen because of cutaneous allergic reactions to NVP; different types of interruption strategies were used, and second-line regimen was based on efavirenz (EFV; and (2 HIV-1-infected patients who began an EFV-based regimen as a first-line therapy (controls. Methods This retrospective cohort included patients who began an EFV-based regimen, between January 2002 and December 2008, as either an initial regimen or as a subsequent regimen after resolving a cutaneous allergic reaction against an initial NVP-based regimen. The study ended in March 2010. The primary outcome was virological failure, which was defined as either (a two consecutive plasma HIV-1 RNA levels >400 copies/mL or (b a plasma HIV-1 RNA level >1,000 copies/mL plus any genotypic resistance mutation. Results A total of 559 patients were stratified into three groups: (a Simultaneous Interruption, in which the subjects simultaneously discontinued all the drugs in an NVP-based regimen following an allergic reaction (n=161; (b Staggered Interruption, in which the subjects discontinued NVP treatment while continuing nucleoside reverse transcriptase inhibitor (NRTI backbone therapy for a median of 7 days (n=82; and (c Control, in which the subjects were naïve to antiretroviral therapy (n=316. The overall median follow-up time was 43 months. Incidence of virological failure in Simultaneous Interruption was 12.9 cases per 1,000 person-years, which trended toward being higher than the incidences in Staggered Interruption (5.4 and Control (6.6. However, differences were not statistically significant. Conclusions Among the patients who had an acute allergic reaction to first

Entomologic and virologic investigation of Chikungunya, Singapore.

Science.gov (United States)

Ng, Lee-Ching; Tan, Li-Kiang; Tan, Cheong-Huat; Tan, Sharon S Y; Hapuarachchi, Hapuarachchige C; Pok, Kwoon-Yong; Lai, Yee-Ling; Lam-Phua, Sai-Gek; Bucht, Göran; Lin, Raymond T P; Leo, Yee-Sin; Tan, Boon-Hian; Han, Hwi-Kwang; Ooi, Peng-Lim S; James, Lyn; Khoo, Seow-Poh

2009-08-01

Local transmission of chikungunya, a debilitating mosquito-borne viral disease, was first reported in Singapore in January 2008. After 3 months of absence, locally acquired Chikungunya cases resurfaced in May 2008, causing an outbreak that resulted in a total of 231 cases by September 2008. The circulating viruses were related to East, Central, and South African genotypes that emerged in the Indian Ocean region in 2005. The first local outbreak was due to a wild-type virus (alanine at codon 226 of the envelope 1 gene) and occurred in an area where Aedes aegypti mosquitoes were the primary vector. Strains isolated during subsequent outbreaks showed alanine to valine substitution (A226V) and largely spread in areas predominated by Ae. albopictus mosquitoes. These findings led to a revision of the current vector control strategy in Singapore. This report highlights the use of entomologic and virologic data to assist in the control of chikungunya in disease-endemic areas.

Gender parity trends for invited speakers at four prominent virology conference series.

Science.gov (United States)

Kalejta, Robert F; Palmenberg, Ann C

2017-06-07

Scientific conferences are most beneficial to participants when they showcase significant new experimental developments, accurately summarize the current state of the field, and provide strong opportunities for collaborative networking. A top-notch slate of invited speakers, assembled by conference organizers or committees, is key to achieving these goals. The perceived underrepresentation of female speakers at prominent scientific meetings is currently a popular topic for discussion, but one that often lacks supportive data. We compiled the full rosters of invited speakers over the last 35 years for four prominent international virology conferences, the American Society for Virology Annual Meeting (ASV), the International Herpesvirus Workshop (IHW), the Positive-Strand RNA Virus Symposium (PSR), and the Gordon Research Conference on Viruses & Cells (GRC). The rosters were cross-indexed by unique names, gender, year, and repeat invitations. When plotted as gender-dependent trends over time, all four conferences showed a clear proclivity for male-dominated invited speaker lists. Encouragingly, shifts toward parity are emerging within all units, but at different rates. Not surprisingly, both selection of a larger percentage of first time participants and the presence of a woman on the speaker selection committee correlated with improved parity. Session chair information was also collected for the IHW and GRC. These visible positions also displayed a strong male dominance over time that is eroding slowly. We offer our personal interpretation of these data to aid future organizers achieve improved equity among the limited number of available positions for session moderators and invited speakers. IMPORTANCE Politicians and media members have a tendency to cite anecdotes as conclusions without any supporting data. This happens so frequently now, that a name for it has emerged: fake news. Good science proceeds otherwise. The under representation of women as invited

A Randomized Controlled Trial of a Text Messaging Intervention to Promote Virologic Suppression and Retention in Care in an Urban Safety-Net HIV Clinic: The Connect4Care (C4C) Trial.

Science.gov (United States)

Christopoulos, Katerina A; Riley, Elise D; Carrico, Adam W; Tulsky, Jacqueline; Moskowitz, Judith T; Dilworth, Samantha; Coffin, Lara S; Wilson, Leslie; Peretz, Jason Johnson; Hilton, Joan F

2018-02-21

Text messaging is a promising strategy to support HIV care engagement, but little is known about its efficacy in urban safety-net HIV clinic populations. We conducted a randomized controlled trial of a supportive and motivational text messaging intervention, Connect4Care (C4C), among viremic patients who had a history of poor retention or were new to clinic. Participants were randomized (stratified by new HIV diagnosis status) to receive one of the following for 12 months: 1) thrice-weekly intervention messages, plus texted primary care appointment reminders and a monthly text message requesting confirmation of study participation, or; 2) texted reminders and monthly messages alone. Viral load was assessed at 6 and 12 months. The primary outcome was virologic suppression (<200 copies/mL) at 12 months, estimated via repeated measures log-binomial regression, adjusted for new diagnosis status. The secondary outcome was retention in clinic care. Between August 2013-November 2015, 230 participants were randomized. Virologic suppression at 12 months was similar between intervention and control participants (48.8% vs. 45.8%), with negligible change from 6-month estimates, yielding RR 1.07 (95% CI: 0.82, 1.39). Suppression was higher in the newly diagnosed (78.3% vs. 45.3%). There were no intervention effects on the secondary outcome. Exploratory analyses suggested that patients with more responses to study text messages had better outcomes, regardless of arm. The C4C text messaging intervention did not significantly increase virologic suppression or retention in care. Response to text messages may be a useful way for providers to gauge risk for poor HIV outcomes. NCT01917994.

The Role of Civil Society Organizations in Monitoring the Global AIDS Response.

Science.gov (United States)

Smith, Julia; Mallouris, Christoforos; Lee, Kelley; Alfvén, Tobias

2017-07-01

Civil society organizations (CSOs) are recognized as playing an exceptional role in the global AIDS response. However, there is little detailed research to date on how they contribute to specific governance functions. This article uses Haas' framework on global governance functions to map CSO's participation in the monitoring of global commitments to the AIDS response by institutions and states. Drawing on key informant interviews and primary documents, it focuses specifically on CSO participation in Global AIDS Response Progress Reporting and in Global Fund to Fight AIDS, Tuberculosis and Malaria processes. It argues that the AIDS response is unique within global health governance, in that CSOs fulfill both formal and informal monitoring functions, and considers the strengths and weaknesses of these contributions. It concludes that future global health governance arrangements should include provisions and resources for monitoring by CSOs because their participation creates more inclusive global health governance and contributes to strengthening commitments to human rights.

Improvement of liver stiffness in patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response.

Science.gov (United States)

Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Mizuno, Kazuyuki; Sone, Yasuhiro; Kataoka, Saki; Hashinokuchi, Shinichi

2017-12-01

There is insufficient research on whether direct-acting antiviral (DAA) therapy can improve liver fibrosis in patients with chronic hepatitis C virus (HCV). We evaluated sequential changes in liver stiffness using shear wave elastography in patients with HCV who received DAA therapy. A total of 210 patients with HCV who received daclatasvir and asunaprevir therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness, as evaluated by shear wave elastography, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), and at 24 weeks after EOT (SVR24). Alanine aminotransferase levels (ALT) decreased over time, and there were significant differences between baseline and EOT and between EOT and SVR24. Although platelet counts did not significantly differ between baseline and EOT, they increased significantly from EOT to SVR24. The median (interquartile range) liver stiffness values at baseline, EOT, and SVR24 were 10.2 (7.7-14.7), 8.8 (7.1-12.1), and 7.6 (6.3-10.3) kPa, respectively (P liver) and Fibrosis-4 index > 2.0 (n = 75), the liver stiffness values at baseline, EOT, and SVR24 were 9.6 (7.7-15.2), 9.2 (7.3-12.1), and 7.7 (6.3-10.1) kPa, respectively (P liver stiffness starts during the administration of DAAs in patients who achieve SVR, and this effect is particularly pronounced in patients with progressive liver fibrosis. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Any impact of blips and low-level viraemia episodes among HIV-infected patients with sustained virological suppression on ART?

Science.gov (United States)

Pernas, Berta; Grandal, Marta; Pertega, Sonia; Cañizares, Angelina; Castro-Iglesias, Ángeles; Mena, Álvaro; Rodriguez-Osorio, Iria; Tabernilla, Andrés; Pedreira, José D; Poveda, Eva

2016-04-01

The objective of this study was to evaluate the prevalence of blips and risk of virological failure (VF) among HIV-infected patients with sustained virological suppression (HIV-RNA ART. Newly diagnosed (2004-13) HIV-infected patients with sustained virological suppression on ART (minimum follow-up of 3 months) were identified. Risk of VF was evaluated according to different plasma HIV-RNA quantification values based on the limits of quantification/detection of current commercial assays (20 copies/mL). Kaplan-Meier and Cox proportional hazards models were used to compare the cumulative incidence of VF. A total of 565 newly diagnosed HIV-infected patients were identified: 453 started ART and 354 achieved virological suppression. Prevalence of blips (isolated HIV-RNA ranging from 50 to 200 copies/mL) and VF (HIV-RNA ≥50 copies/mL) was 22.7% and 8.8%, respectively (mean follow-up of 42 months). Multivariate analysis identified differences between HIV-RNA values as an independent predictor of VF (P = 0.008); risk of VF was higher for patients with blips [HR 2.500 (95% CI 0.524-11.926)] and for those with at least three consecutive detected, but not quantified, HIV-RNA determinations (HIV-RNA 200 copies/mL [33.7% at 24 and 60 months versus ART. HIV patients with blips and at least three consecutive detected, but not quantified, HIV-RNA determinations (<20 copies/mL) had a higher risk of VF. These findings highlight the relevance of maintaining HIV-RNA levels below the limits of quantification of current assays (<20 copies/mL). © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Using Item Response Theory to Develop Measures of Acquisitive and Protective Self-Monitoring From the Original Self-Monitoring Scale.

Science.gov (United States)

Wilmot, Michael P; Kostal, Jack W; Stillwell, David; Kosinski, Michal

2017-07-01

For the past 40 years, the conventional univariate model of self-monitoring has reigned as the dominant interpretative paradigm in the literature. However, recent findings associated with an alternative bivariate model challenge the conventional paradigm. In this study, item response theory is used to develop measures of the bivariate model of acquisitive and protective self-monitoring using original Self-Monitoring Scale (SMS) items, and data from two large, nonstudent samples ( Ns = 13,563 and 709). Results indicate that the new acquisitive (six-item) and protective (seven-item) self-monitoring scales are reliable, unbiased in terms of gender and age, and demonstrate theoretically consistent relations to measures of personality traits and cognitive ability. Additionally, by virtue of using original SMS items, previously collected responses can be reanalyzed in accordance with the alternative bivariate model. Recommendations for the reanalysis of archival SMS data, as well as directions for future research, are provided.

Association of Suboptimal Antiretroviral Therapy Adherence With Inflammation in Virologically Suppressed Individuals Enrolled in the SMART Study

DEFF Research Database (Denmark)

Castillo-Mancilla, Jose R; Phillips, Andrew N; Neaton, James D

2018-01-01

Suboptimal (ie, <100%) antiretroviral therapy (ART) adherence has been associated with heightened inflammation in cohort studies, even among people with virologic suppression. We aimed to evaluate this association among participants in the Strategies for Management of Antiretroviral Therapy (SMAR...

The educational challenge of Paediatric Virology: An interview with Professor of Neonatology Anne Greenough.

Science.gov (United States)

Mammas, Ioannis N; Spandidos, Demetrios A

2017-10-01

According to Professor Anne Greenough, Professor of Neonatology and Clinical Respiratory Physiology at the King's College London (London, UK), Paediatric Virology is indeed a rapidly increasing educational challenge. Professor Greenough, who in 1992 wrote her book on congenital, perinatal and neonatal infections, believes that during the past 3 decades, paediatric health professionals are becoming increasingly involved in specialised care and follow-up of paediatric patients with viral diseases, who require advanced medical care and innovative technological services. Moreover, she highlights the expected role of new vaccines and antiviral agents that are currently under investigation, as well as the impact of emerging viral diseases that require novel prevention strategies and therapeutic protocols. However, she notes that the number of Paediatric Virologists in any one country is likely to be small; hence, a separate paediatric subspecialty needs to be considered carefully. In the context of the 3rd Workshop on Paediatric Virology, which will be held in Athens, Greece, on October 7th, 2017, Professor Greenough will give her plenary lecture on the impact of viral infections on the long term outcomes of prematurely born infants.

The Effect of Malnutrition on the Pharmacokinetics and Virologic Outcomes of Lopinavir, Efavirenz and Nevirapine in Food Insecure HIV-Infected Children in Tororo, Uganda

Science.gov (United States)

Bartelink, Imke H.; Savic, Rada M.; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J.; Capparelli, Edmund; Jullien, Vincent; Young, Sera L.; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

2014-01-01

Background Malnutrition may impact the pharmacokinetics (PK) of antiretroviral medications and virologic responses in HIV-infected children. We therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Methods Sparse dried blood spot (DBS) samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from three resource-rich countries (RRC) were utilized to develop the PK models. Results Concentrations in 330 DBS from 163 Ugandan children aged 0.7–7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5–12 years. Among Ugandan children 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008) respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (Pmalnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessements, to further assess causes of virologic failure in Ugandan children. PMID:25742090

Treatment of chronic myeloid leukemia: assessing risk, monitoring response, and optimizing outcome.

Science.gov (United States)

Shanmuganathan, Naranie; Hiwase, Devendra Keshaorao; Ross, David Morrall

2017-12-01

Over the past two decades, tyrosine kinase inhibitors have become the foundation of chronic myeloid leukemia (CML) treatment. The choice between imatinib and newer tyrosine kinase inhibitors (TKIs) needs to be balanced against the known toxicity and efficacy data for each drug, the therapeutic goal being to maximize molecular response assessed by BCR-ABL RQ-PCR assay. There is accumulating evidence that the early achievement of molecular targets is a strong predictor of superior long-term outcomes. Early response assessment provides the opportunity to intervene early with the aim of ensuring an optimal response. Failure to achieve milestones or loss of response can have diverse causes. We describe how clinical and laboratory monitoring can be used to ensure that each patient is achieving an optimal response and, in patients who do not reach optimal response milestones, how the monitoring results can be used to detect resistance and understand its origins.

Evolution of drug resistance in HIV infected patients remaining on a virologically failing cART regimen

DEFF Research Database (Denmark)

Cozzi-Lepri, A; Phillips, AN; Ruiz, L

2007-01-01

OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...

Socioeconomic status and response to antiretroviral therapy in high-income countries: a literature review.

Science.gov (United States)

Burch, Lisa S; Smith, Colette J; Phillips, Andrew N; Johnson, Margaret A; Lampe, Fiona C

2016-05-15

It has been shown that socioeconomic factors are associated with the prognosis of several chronic diseases; however, there is no recent systematic review of their effect on HIV treatment outcomes. We aimed to review the evidence regarding the existence of an association of socioeconomic status with virological and immunological response to antiretroviral therapy (ART). We systematically searched the current literature using the database PubMed. We identified and summarized original research studies in high-income countries that assessed the association between socioeconomic factors (education, employment, income/financial status, housing, health insurance, and neighbourhood-level socioeconomic factors) and virological response, immunological response, and ART nonadherence among people with HIV-prescribed ART. A total of 48 studies met the inclusion criteria (26 from the United States, six Canadian, 13 European, and one Australian), of which 14, six, and 35 analysed virological, immunological, and ART nonadherence outcomes, respectively. Ten (71%), four (67%), and 23 (66%) of these studies found a significant association between lower socioeconomic status and poorer response, and none found a significant association with improved response. Several studies showed that adjustment for nonadherence attenuated the association between socioeconomic status and ART response. Our review provides strong support that socioeconomic disadvantage is associated with poorer response to ART. However, most studies have been conducted in settings such as the United States without universal free healthcare access. Further study in settings with free access to ART could help assess the impact of socioeconomic status on ART outcomes and the mechanisms by which it operates.

Genetic variants in the apoptosis gene BCL2L1 improve response to interferon-based treatment of hepatitis C virus genotype 3 infection

DEFF Research Database (Denmark)

Clausen, Louise Nygaard; Weis, Nina; Ladelund, Steen

2015-01-01

Genetic variation upstream of the apoptosis pathway has been associated with outcome of hepatitis C virus (HCV) infection. We investigated genetic polymorphisms in the intrinsic apoptosis pathway to assess their influence on sustained virological response (SVR) to pegylated interferon-α and ribav......Genetic variation upstream of the apoptosis pathway has been associated with outcome of hepatitis C virus (HCV) infection. We investigated genetic polymorphisms in the intrinsic apoptosis pathway to assess their influence on sustained virological response (SVR) to pegylated interferon...

Modernisation of Radiation Monitoring Room as a Part of Slovenian Emergency Response Centre

International Nuclear Information System (INIS)

Sarvari, A.; Mitic, D.

2003-01-01

In the year 2002 the Slovenian Nuclear Safety Administration (SNSA) moved to the new premises therefore it had to rearrange some of its rooms for the emergency situation. SNSA does not operate with a dedicated Emergency Response Centre (ERC), instead of it the SNSA has to rearrange the existing rooms in case of an emergency. Modernisation of the equipment, with the help of government of the United Kingdom of Great Britain and Northern Ireland, for the emergency situation was carried out, especially in the monitoring room. The radiation monitoring system, which is placed in the monitoring room, continuously collects, processes and archives the incoming data of exposure to radiation and meteorological parameters on the Slovenian territory (A model national emergency response plan for radiological accidents, IAEA, Vienna, 1993. IAEA-TECDOC-718). In the emergency situation the monitoring room transforms into the room for the Dose Assessment Group (DAG), which is part of ERC (IAEA emergency response network, IAEA, Vienna, 2000, EPR-ERNET (2000)). The modernisation of monitoring room and within the DAG room with new equipment and its purpose is described in this article. Modernisation of the monitoring room and the room for DAG showed to be inevitably needed. Modernisation of the monitoring room has brought the SNSA a sophisticated and reliable system of controlling the external exposure to radiation on the Slovenian territory. The equipment, especially the equipment for the use in the emergency situation, brought novelties for the Dose Assessment Group. The group has now better and easier control of radiation situation in case of an accident. In overall this modernisation has put the Slovenian Nuclear Safety Administration a step forward in having a dedicated Emergency Response Centre, since it does not need to rearrange the room for the Dose Assessment Group. (author)

Gallium 67 imaging in monitoring lymphoma response to treatment

International Nuclear Information System (INIS)

Israel, O.; Front, D.; Lam, M.; Ben-Haim, S.; Kleinhaus, U.; Ben-Shachar, M.; Robinson, E.; Kolodny, G.M.

1988-01-01

The value of gallium 67 (Ga) imaging in monitoring lymphoma response to treatment was assessed in 25 patients with Ga-avid tumors and compared to body computed tomography (CT), chest radiographs, and palpation of tumor infiltrated peripheral lymph nodes. Ga imaging was negative in 95% (20/21) of the patients who were clinically considered to be in remission and in whom treatment was stopped. The disease did not recur during a follow-up of 12 to 26 months in 15 patients. Six patients developed recurrence of the disease 3 to 12 months after treatment was stopped. In all six patients Ga imaging became positive again at the time of the appearance of active disease. In the group of patients in remission, CT was negative in 57% (11/19), chest x-rays in 55% (6/11) and peripheral lymph nodes were palpated in none of the patients (13/13). In four patients that did not achieve remission after treatment, Ga scans were positive. Ga imaging appears useful in monitoring lymphoma response to treatment. This is probably because Ga imaging monitors tumor cell viability, whereas body CT and chest radiographs show the tumor mass, which may consist of fibrotic or necrotic tissue

Determinants of virological outcome and adverse events in African children treated with paediatric nevirapine fixed-dose-combination tablets

NARCIS (Netherlands)

Bienczak, A.; Denti, P.; Cook, A.; Wiesner, L.; Mulenga, V.; Kityo, C.; Kekitiinwa, A.; Gibb, D.M.; Burger, D.M.; Walker, A.S.; McIlleron, H.

2017-01-01

BACKGROUND: Nevirapine is the only nonnucleoside reverse transcriptase inhibitor currently available as a paediatric fixed-dose-combination tablet and is widely used in African children. Nonetheless, the number of investigations into pharmacokinetic determinants of virological suppression in African

Sensor response monitoring in pressurized water reactors using time series modeling

International Nuclear Information System (INIS)

Upadhyaya, B.R.; Kerlin, T.W.

1978-01-01

Random data analysis in nuclear power reactors for purposes of process surveillance, pattern recognition and monitoring of temperature, pressure, flow and neutron sensors has gained increasing attention in view of their potential for helping to ensure safe plant operation. In this study, application of autoregressive moving-average (ARMA) time series modeling for monitoring temperature sensor response characteristrics is presented. The ARMA model is used to estimate the step and ramp response of the sensors and the related time constant and ramp delay time. The ARMA parameters are estimated by a two-stage algorithm in the spectral domain. Results of sensor testing for an operating pressurized water reactor are presented. 16 refs

An error-related negativity potential investigation of response monitoring function in individuals with Internet addiction disorder

Directory of Open Access Journals (Sweden)

Zhenhe eZhou

2013-09-01

Full Text Available Internet addiction disorder (IAD is an impulse disorder or at least related to impulse control disorder. Deficits in executive functioning, including response monitoring, have been proposed as a hallmark feature of impulse control disorders. The error-related negativity (ERN reflects individual’s ability to monitor behavior. Since IAD belongs to a compulsive-impulsive spectrum disorder, theoretically, it should present response monitoring functional deficit characteristics of some disorders, such as substance dependence, ADHD or alcohol abuse, testing with an Erikson flanker task. Up to now, no studies on response monitoring functional deficit in IAD were reported. The purpose of the present study was to examine whether IAD displays response monitoring functional deficit characteristics in a modified Erikson flanker task.23 subjects were recruited as IAD group. 23 matched age, gender and education healthy persons were recruited as control group. All participants completed the modified Erikson flanker task while measured with event-related potentials (ERPs. IAD group made more total error rates than did controls (P < 0.01; Reactive times for total error responses in IAD group were shorter than did controls (P < 0.01. The mean ERN amplitudes of total error response conditions at frontal electrode sites and at central electrode sites of IAD group were reduced compared with control group (all P < 0.01. These results revealed that IAD displays response monitoring functional deficit characteristics and shares ERN characteristics of compulsive-impulsive spectrum disorder.

Monitoring and Correcting for Response Changes in the CMS Lead-tungstate Electromagnetic Calorimeter

International Nuclear Information System (INIS)

Ferri, Federico

2012-01-01

The CMS Electromagnetic Calorimeter (ECAL) comprises 75848 lead-tungstate scintillating crystals. Changes in the ECAL response, due to crystal radiation damage or changes in photo-detector output, are monitored in real time with a sophisticated system of lasers to allow corrections to the energy measurements to be calculated and used. The excellent intrinsic resolution of the CMS ECAL requires the monitoring system itself to be calibrated to a high precision and its stability to be controlled and understood. The components of the CMS ECAL monitoring system, and how it has evolved to include modern solid-state lasers, are described. Several physics channels are exploited to normalise the ECAL response to the changes measured by the monitoring system. These include low energy diphoton resonances, electrons from W and Z decays (using shower energy versus track momentum measurements), and the azimuthal symmetry of low energy deposits in minimum bias events. This paper describes how the monitoring system is operated, how the corrections are obtained, and the resulting ECAL performance.

Antiviral Resistance and Correlates of Virologic Failure in the first Cohort of HIV-Infected Children Gaining Access to Structured Antiretroviral Therapy in Lima, Peru: A Cross-Sectional Analysis

Directory of Open Access Journals (Sweden)

Rath Barbara A

2013-01-01

Full Text Available Abstract Background The impact of extended use of ART in developing countries has been enormous. A thorough understanding of all factors contributing to the success of antiretroviral therapy is required. The current study aims to investigate the value of cross-sectional drug resistance monitoring using DNA and RNA oligonucleotide ligation assays (OLA in treatment cohorts in low-resource settings. The study was conducted in the first cohort of children gaining access to structured ART in Peru. Methods Between 2002–5, 46 eligible children started the standard regimen of AZT, 3TC and NFV Patients had a median age of 5.6 years (range: 0.7-14y, a median viral load of 1.7·105 RNA/ml (range: 2.1·103 – 1.2·106, and a median CD4-count of 232 cells/μL (range: 1–1591. Of these, 20 patients were classified as CDC clinical category C and 31/46 as CDC immune category 3. At the time of cross-sectional analysis in 2005, adherence questionnaires were administered. DNA OLAs and RNA OLAs were performed from frozen PBMC and plasma, RNA genotyping from dried blood spots. Results During the first year of ART, 44% of children experienced virologic failure, with an additional 9% failing by the end of the second year. Virologic failure was significantly associated with the number of resistance mutations detected by DNA-OLA (p Conclusions Advanced immunosuppression at baseline and previous exposures to unsupervised brief cycles of ART significantly impaired treatment outcomes at a time when structured ART was finally introduced in his cohort. Brief maternal exposures to with AZT +/− NVP for the prevention of mother-to-child transmission did not affect treatment outcomes in this group of children. DNA-OLA from frozen PBMC provided a highly specific tool to detect archived drug resistance. RNA consensus genotyping from dried blood spots and RNA-OLA from plasma consistently detected drug resistance mutations, but merely in association with virologic failure.

Nonlinearities in the response of beam position monitors

International Nuclear Information System (INIS)

Assmann, R.; Dehning, B.; Matheson, J.; Prochnow, J.

2000-01-01

At the LEP e + /e - collider at CERN, Geneva, a Spectrometer is used to determine the beam energy with a relative accuracy of 10 -4 .The Spectrometer measures the change in bending angle in a dipole magnet, the beam trajectory being obtained using beam position monitors (BPMs), which must have an accuracy close to 1 μm in order to achieve the desired precision. The BPMs used feature an aluminum block with an elliptical aperture and capacitive pickup electrodes. The response depends on the electrode geometry and also on the shape of the monitor aperture. In addition, the size of the beam itself contributes if the beam is off-center. The beam size varies according to the beta and dispersion functions at the Spectrometer, so that each BPM may exhibit a systematic shift of the measured beam position. We have investigated the implications of such shifts on the performance of the Spectrometer. We present analytical results, a computer model of the BPM response, and comparison with measurements. The model suggests strategies such as beam-based alignment to minimize the systematic effects arising from the BPMs

Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B.

Science.gov (United States)

Angelo, Ana Luiza Dias; Cavalcante, Lourianne Nascimento; Abe-Sandes, Kiyoko; Machado, Taísa Bonfim; Lemaire, Denise Carneiro; Malta, Fernanda; Pinho, João Renato; Lyra, Luiz Guilherme Costa; Lyra, Andre Castro

2013-10-01

Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin. Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers. We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (pC/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population. Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 genes. The combined

Cytokine response to Escherichia coli in gnotobiotic pigs

Czech Academy of Sciences Publication Activity Database

Šplíchal, Igor; Šplíchalová, Alla; Trebichavský, Ilja

2008-01-01

Roč. 53, č. 2 (2008), s. 161-164 ISSN 0015-5632 R&D Projects: GA ČR GA523/05/0249 Institutional research plan: CEZ:AV0Z50200510 Keywords : germ-free pigs * escherichia coli * cytokine response Subject RIV: EE - Microbiology, Virology Impact factor: 1.172, year: 2008

Regulating task-monitoring systems in response to variable reward contingencies and outcomes in cocaine addicts.

Science.gov (United States)

Morie, Kristen P; De Sanctis, Pierfilippo; Garavan, Hugh; Foxe, John J

2016-03-01

We investigated anticipatory and consummatory reward processing in cocaine addiction. In addition, we set out to assess whether task-monitoring systems were appropriately recalibrated in light of variable reward schedules. We also examined neural measures of task-monitoring and reward processing as a function of hedonic tone, since anhedonia is a vulnerability marker for addiction that is obviously germane in the context of reward processing. High-density event-related potentials were recorded while participants performed a speeded response task that systematically varied anticipated probabilities of reward receipt. The paradigm dissociated feedback regarding task success (or failure) from feedback regarding the value of reward (or loss), so that task-monitoring and reward processing could be examined in partial isolation. Twenty-three active cocaine abusers and 23 age-matched healthy controls participated. Cocaine abusers showed amplified anticipatory responses to reward predictive cues, but crucially, these responses were not as strongly modulated by reward probability as in controls. Cocaine users also showed blunted responses to feedback about task success or failure and did not use this information to update predictions about reward. In turn, they showed clearly blunted responses to reward feedback. In controls and users, measures of anhedonia were associated with reward motivation. In cocaine users, anhedonia was also associated with diminished monitoring and reward feedback responses. Findings imply that reward anticipation and monitoring deficiencies in addiction are associated with increased responsiveness to reward cues but impaired ability to predict reward in light of task contingencies, compounded by deficits in responding to actual reward outcomes.

High Virologic Failure Rates with Maraviroc-Based Salvage Regimens Among Indian Patients: A Preliminary Analysis-Maraviroc Effectiveness in HIV-1 Subtype C.

Science.gov (United States)

Pujari, Sanjay; Gaikwad, Sunil; Bele, Vivek; Joshi, Kedar; Dabhade, Digamber

2018-01-01

There is no information on the clinical effectiveness of Maraviroc (MVC) amongst People Living with HIV (PLHIV) in India infected with HIV-1 Subtype C viruses. We conducted a retrospective chart review of adult PLHIV on MVC based Antiretroviral (ARV) regimens for at least 6 months. Maraviroc was initiated amongst PLHIV with documented R5 tropic viruses (determined by in-house population sequencing of the V3 loop in triplicate and interpreted using the Geno2Pheno algorithm) in combination with an Optimized Background regimen (designed using genotypic resistance testing and past ARV history). Plasma viral loads (PVL) are performed 6 months post-initiation and annually thereafter. Primary outcome d. Median duration on MVC treatment was 1.8 years (range 1-2.9 years) while median duration of ART prior to switching to MVC was 13 years. Maraviroc was combined with Darunavir/ritonavir (DRV/r) (n=10), Atazanavir/r (ATV/r) (n=2) and Lopinavir/r (LPV/r) (n=1). All PLHIV were infected with HIV-1 Subtype C. Only 23.3% PLHIV achieved virologic suppression at 6 months and sustained it for 2.3 years. Median CD4 count change from baseline was +117 (n=13), +228 (n=10), +253 (n=9), and +331 (n=4) at 6, 12, 18 and 24 months respectively. Repeat tropism among patients with virologic failure demonstrated R5 virus. High rates of virologic failure was seen when MVC was used amongst treatment experienced PLHIV infected with HIV-1 Subtype C in India. was the proportion of PLHIV with virologic success (PVL<50 copies/ml) at last follow up visit. Data on 13 PLHIV were analyze.

Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment.

Directory of Open Access Journals (Sweden)

Olof Elvstam

Full Text Available Although most HIV-infected individuals achieve undetectable viremia during antiretroviral therapy (ART, a subset have low-level viremia (LLV of varying duration and magnitude. The impact of LLV on treatment outcomes is unclear. We investigated the association between LLV and virological failure and/or all-cause mortality among Swedish patients receiving ART.HIV-infected patients from two Swedish HIV centers were identified from the nationwide register InfCare HIV. Subjects aged ≥15 years with triple agent ART were included at 12 months after treatment initiation if ≥2 following viral load measurements were available. Patients with 2 consecutive HIV RNA values ≥1000 copies/mL at this time point were excluded. Participants were stratified into four categories depending on viremia profiles: permanently suppressed viremia (<50 copies/mL, LLV 50-199 copies/mL, LLV 200-999 copies/mL and viremia ≥1000 copies/mL. Association between all four viremia categories and all-cause death was calculated using survival analysis with viremia as a time-varying covariate, so that patients could change viremia category during follow-up. Association between the three lower categories and virological failure (≥2 consecutive measurements ≥1000 copies/mL was calculated in a similar manner.LLV 50-199 copies/mL was recorded in 70/1015 patients (6.9% and LLV 200-999 copies/mL in 89 (8.8% during 7812 person-years of follow-up (median 6.5 years. LLV 200-999 copies/mL was associated with virological failure (adjusted hazard ratio 3.14 [95% confidence interval 1.41-7.03, p<0.01], whereas LLV 50-199 copies/mL was not (1.01 [0.34-4.31, p = 0.99]; median follow-up 4.5 years. LLV 200-999 copies/mL had an adjusted mortality hazard ratio of 2.29 (0.98-5.32, p = 0.05 and LLV 50-199 copies/mL of 2.19 (0.90-5.37, p = 0.09.In this Swedish cohort followed during ART for a median of 4.5 years, LLV 200-999 copies/mL was independently associated with virological failure. Patients

Laboratory tools for diagnosis and monitoring response in patients with chronic myeloid leukemia.

Science.gov (United States)

Tohami, Tali; Nagler, Arnon; Amariglio, Ninette

2012-08-01

Chronic myeloid leukemia (CML) is a clonal hematological disease that represents 15-20% of all adult leukemia cases. The study and treatment of CML has contributed pivotal advances to translational medicine and cancer therapy. The discovery that a single chromosomal abnormality, the Philadelphia (Ph) chromosome, is responsible for the etiology of this disease was a milestone for treating and understanding CML. Subsequently, CML became the first disease for which allogeneic bone marrow transplantation is the treatment of choice. Currently, CML is one of the few diseases where treatment targeted against the chromosomal abnormality is the sole frontline therapy for newly diagnosed patients. The use of directed therapy for CML challenged disease monitoring during treatment and led to the development of definitions that document response and predict relapse sooner than the former routine methods. These methods relied on classical cytogenetics through molecular cytogenetics (FISH) and, finally, on molecular monitoring assays. This review discusses the laboratory tools used for diagnosing CML, for monitoring during treatment, and for assessing remission or relapse. The advantages and disadvantages of each test, the common definition of response levels, and the efforts to standardize molecular monitoring for CML patient management are discussed.

The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study

NARCIS (Netherlands)

Collaboration, H.-C.; Koopmans †, P.P.; Brouwer, A.M.; Dofferhoff, A.S.M.; Flier, M. van der; Groot, R. de; Hofstede, H.J.M. ter; Keuter, M.; Ven, A.J.A.M. van der; et al.,

2012-01-01

OBJECTIVE: To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. DESIGN: Prospective

The World of Microbes 2002: scientific advances and challenges--impressions and highlights from the 12th Congress of Virology.

Science.gov (United States)

Becker, Yechiel

2002-12-01

Thousands of scientists participated in the World of Microbes Congress, which was organized by the International Union of the Microbiological Societies (IUMS) and took place in the Palais de Congres in Paris, France from 27 July to 1 August 2002. The attendees were members of the IUMS divisions of Bacteriology and Applied Microbiology, Mycology, and Virology. In addition to the symposia that were organized by each division, joined plenary symposia were held, which encompassed subjects of common interest to all microbiologists. The activities at the 12th Congress of Virology's plenary lectures, symposia, and poster sessions were organized to accommodate the presentation of over 1500 presentations. These brief comments are aimed to provide a sample of only a few presentations that dealt with subjects of emerging and re-emerging virus diseases, which are of general interest.

Real-time monitoring/emergency response modeling workstation for a tritium facility

International Nuclear Information System (INIS)

Lawver, B.S.; Sims, J.M.; Baskett, R.L.

1993-01-01

At Lawrence Livermore National Laboratory (LLNL) we have developed a real-time system to monitor two stacks on our tritium handling facility. The monitors transmit the stack data to a workstation, which computes a three-dimensional numerical model of atmospheric dispersion. The workstation also collects surface and upper air data from meteorological towers and a sodar. The complex meteorological and terrain setting in the Livermore Valley demands more sophisticated resolution of the three-dimensional structure of the atmosphere to reliably calculate plume dispersion than afforded by Gaussian models. We experience both mountain valley and sea breeze flows. To address these complexities, we have implemented the three-dimensional diagnostic MATHEW mass-adjusted wind field and ADPIC particle-in-cell dispersion models on the workstation for use in real-time emergency response modeling. Both MATHEW and ADPIC have shown their utility in a variety of complex settings over the last 15 yr within the U.S. Department of Energy's Atmospheric Release Advisory Capability (ARAC) project. Faster workstations and real-time instruments allow utilization of more complex three-dimensional models, which provides a foundation for building a real-time monitoring and emergency response workstation for a tritium facility. The stack monitors are two ion chambers per stack

Conflict-triggered goal shielding: response conflicts attenuate background monitoring for prospective memory cues.

Science.gov (United States)

Goschke, Thomas; Dreisbach, Gesine

2008-01-01

Action control in a changing environment requires that one shield current goals from distracting information (goal shielding) and at the same time monitor the environment for potentially significant stimuli that may afford a goal switch (background monitoring). Response conflicts modulate the balance between goal shielding and background monitoring, as indicated by reduced susceptibility to interference after response conflicts. Such conflict-adaptation effects have been attributed to enhanced recruitment of cognitive control on trials following conflicts. Here we show that conflict triggers increased goal shielding on the conflict trial itself. Subjects performed a spatial compatibility task during which they had to notice rare prospective memory cues. Such cues were overlooked more often on conflict trials than on nonconflict trials, a result indicating that shielding of the current goal and inhibition of distractors were increased on the current trial when it involved a response conflict. Thus, evidence for enhanced recruitment of control following conflict may partly reflect aftereffects of goal shielding on the conflict trial itself.

Failure to achieve immunological recovery in HIV-infected patients with clinical and virological success after 10 years of combined ART: role of treatment course.

Science.gov (United States)

Raffi, François; Le Moing, Vincent; Assuied, Alex; Habak, Sofiane; Spire, Bruno; Cazanave, Charles; Billaud, Eric; Dellamonica, Pierre; Ferry, Tristan; Fagard, Catherine; Leport, Catherine

2017-01-01

We assessed factors, including treatment course, associated with failure to obtain a 10 year immunological response after starting first-generation PI-containing combined ART (cART). In the prospective COPILOTE cohort of HIV-infected patients started on a first-generation PI-containing regimen in 1997-99, the impact of cART history on the failure to achieve immunological response measured at 10 years was assessed by multivariate logistic regression models in the 399 patients with clinical and virological success of cART. Failure of CD4 response (CD4 >500/mm 3 ) was associated with age ≥40 years at baseline (P failure to achieve complete immunological response (CD4 >500/mm 3 and CD4:CD8 ratio >1) were CD4:CD8 ratio ≤0.8 at month 8 (P success. Lack of treatment interruption may improve long-term immunological outcome in HIV infection. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Monitors display of radiological images: quality control and response of the observer; Monitores de visualizacion de imagenes radiologicas: control de calidad y respuesta del observador

Energy Technology Data Exchange (ETDEWEB)

Cesares Magaz, O.; Catalan Acosta, A.; Hernandez Armas, O. C.; Gonzalez Martin, A. E.; Hernandez Armas, J.

2011-07-01

This thesis is aimed to determine the possible change experienced by a human reader response to the qualification of a test image on a monitor diagnostic radiographic image when observed before and after calibration of the monitor following the provisions of the AAPM TG18 protocol. It also quantified the change experienced by the monitor as a result of the calibration, by measuring the luminance response as set out in the protocol.

Effectiveness of Ritonavir-Boosted Protease Inhibitor Monotherapy in Clinical Practice Even with Previous Virological Failures to Protease Inhibitor-Based Regimens.

Directory of Open Access Journals (Sweden)

Luis F López-Cortés

Full Text Available Significant controversy still exists about ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv as a simplification strategy that is used up to now to treat patients that have not experienced previous virological failure (VF while on protease inhibitor (PI -based regimens. We have evaluated the effectiveness of two mtPI/rtv regimens in an actual clinical practice setting, including patients that had experienced previous VF with PI-based regimens.This retrospective study analyzed 1060 HIV-infected patients with undetectable viremia that were switched to lopinavir/ritonavir or darunavir/ritonavir monotherapy. In cases in which the patient had previously experienced VF while on a PI-based regimen, the lack of major HIV protease resistance mutations to lopinavir or darunavir, respectively, was mandatory. The primary endpoint of this study was the percentage of participants with virological suppression after 96 weeks according to intention-to-treat analysis (non-complete/missing = failure.A total of 1060 patients were analyzed, including 205 with previous VF while on PI-based regimens, 90 of whom were on complex therapies due to extensive resistance. The rates of treatment effectiveness (intention-to-treat analysis and virological efficacy (on-treatment analysis at week 96 were 79.3% (CI95, 76.8-81.8 and 91.5% (CI95, 89.6-93.4, respectively. No relationships were found between VF and earlier VF while on PI-based regimens, the presence of major or minor protease resistance mutations, the previous time on viral suppression, CD4+ T-cell nadir, and HCV-coinfection. Genotypic resistance tests were available in 49 out of the 74 patients with VFs and only four patients presented new major protease resistance mutations.Switching to mtPI/rtv achieves sustained virological control in most patients, even in those with previous VF on PI-based regimens as long as no major resistance mutations are present for the administered drug.

The dogma of bacteriology and other events as spearheads of virology Dogma de la bacteriología y otros eventos como puntas de lanza de la virología

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Charles Volcy

2009-11-01

Full Text Available

This review analyzes some of the main events during the twentieth century that led to the birth of virology. In the literature of the time, a relationship of causality was established between virus and disease, and within this pathological context, the notions of fixed virus, volatile virus, contagium vivum fluidum and contagium fixum were formed. The transformation of the virus concept as a technoscientific object took place based on the criterion of filterability and on the methodology devised for the bacteriology dogma. Studies on tobacco mosaic virus are highlighted, as well as those on viral diseases of human beings and animals, which led to the discovery of these submicroscopic agents through the appropriation of technologies and the impulse triggered by political and economic factors.

Esta investigación analiza algunos de los eventos principales del siglo XIX que condujeron hacia la cristalización de la virología. En los documentos de esta investigación analiza algunos de los eventos principales del siglo XIX que condujeron hacia la cristalización de la virología. En los documentos de aquella época, se plasmó una relación de causalidad entre virus y enfermedad o contagio, y en este contexto patológico, se elaboraron las nociones de virus fijo, virus volátil, contagium vivum fluidum y contagium fixum. De otro lado, la transformación conceptual hacia el virus como objeto tecnocientífico tuvo lugar con base en el criterio de filtrabilidad y en la metodología trazada por la bacteriología convertida en dogma. Asimismo, se

The results of virological surveillance for intrauterine infections in Saint-Petersburg

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E. A. Murina

2014-01-01

Full Text Available The purpose of researchis the determiningthe etiological structure ofintrauterine infections in Saint-Petersburg pediatric patients, pregnant women andinfants born to them using a variety of virological methods.Methods: serum from 164 children aged from 1 month to 14 years with diagnosis of «intrauterine infection». Serum from 80 pregnant women, collected in each trimester (total – 240 samples, their 42 children (at the age of 1–2 and 4–6  months of life, total – 82 samples. Immunoglobulin Mand G (IgM and IgGto herpes virus type 1, cytomegalovirus (CMV, Toxoplasma gondii, mycoplasma and chlamydia, rubella, Epstein-Barr virus (EBV and parvovirus B19, as well as IgG avidity,were determined by ELISA in all these samples. Theimmunoblot (Western blot, using the «Immunoblot2000» with test kits from «Euroimmun AG» (Germany, was applied to confirm cases. Statistical analysis wasperformed with theprograms Microsoft Excel, Statistica6.Results: cytomegalovirus, herpes virus 1st type and Epstein-Barr virus infections are dominate in the structure of intrauterine ones (45%, 23% and 14%, respectively. Laboratory evidence ofreactivationof cytomegalovirus (35% ofpregnant womenin the 2nd and/or 3rd trimesters and acuteparvovirus infection (15% of cases were found. Specific IgM to cytomegalovirus were detected in 6,2% ofchildren in the firstsix months of life.Conclusions: with the aim of early detection of cytomegalovirus reactivation and acute parvovirus infection it isnecessary to monitor pregnant women with the definition of specific IgM, IgG and avidity IgG. The procedure to using immunoblotting in the diagnosis of intrauterine infectionsneeds to be further study.

Response Monitoring and Adjustment: Differential Relations with Psychopathic Traits

Science.gov (United States)

Bresin, Konrad; Finy, M. Sima; Sprague, Jenessa; Verona, Edelyn

2014-01-01

Studies on the relation between psychopathy and cognitive functioning often show mixed results, partially because different factors of psychopathy have not been considered fully. Based on previous research, we predicted divergent results based on a two-factor model of psychopathy (interpersonal-affective traits and impulsive-antisocial traits). Specifically, we predicted that the unique variance of interpersonal-affective traits would be related to increased monitoring (i.e., error-related negativity) and adjusting to errors (i.e., post-error slowing), whereas impulsive-antisocial traits would be related to reductions in these processes. Three studies using a diverse selection of assessment tools, samples, and methods are presented to identify response monitoring correlates of the two main factors of psychopathy. In Studies 1 (undergraduates), 2 (adolescents), and 3 (offenders), interpersonal-affective traits were related to increased adjustment following errors and, in Study 3, to enhanced monitoring of errors. Impulsive-antisocial traits were not consistently related to error adjustment across the studies, although these traits were related to a deficient monitoring of errors in Study 3. The results may help explain previous mixed findings and advance implications for etiological models of psychopathy. PMID:24933282

Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy.

Science.gov (United States)

Tenney, Daniel J; Rose, Ronald E; Baldick, Carl J; Pokornowski, Kevin A; Eggers, Betsy J; Fang, Jie; Wichroski, Michael J; Xu, Dong; Yang, Joanna; Wilber, Richard B; Colonno, Richard J

2009-05-01

Patients with chronic hepatitis B virus (HBV) infection who develop antiviral resistance lose benefits of therapy and may be predisposed to further resistance. Entecavir (ETV) resistance (ETVr) results from HBV reverse transcriptase substitutions at positions T184, S202, or M250, which emerge in the presence of lamivudine (LVD) resistance substitutions M204I/V +/- L180M. Here, we summarize results from comprehensive resistance monitoring of patients with HBV who were continuously treated with ETV for up to 5 years. Monitoring included genotypic analysis of isolates from all patients at baseline and when HBV DNA was detectable by polymerase chain reaction (> or = 300 copies/mL) from Years 1 through 5. In addition, genotyping was performed on isolates from patients experiencing virologic breakthrough (> or = 1 log(10) rise in HBV DNA). In vitro phenotypic ETV susceptibility was determined for virologic breakthrough isolates, and for HBV containing novel substitutions emerging during treatment. The results over 5 years of therapy showed that in nucleoside-naïve patients, the cumulative probability of genotypic ETVr and genotypic ETVr associated with virologic breakthrough was 1.2% and 0.8%, respectively. In contrast, a reduced barrier to resistance was observed in LVD-refractory patients, as the LVD resistance substitutions, a partial requirement for ETVr, preexist, resulting in a 5-year cumulative probability of genotypic ETVr and genotypic ETVr associated with breakthrough of 51% and 43%, respectively. Importantly, only four patients who achieved < 300 copies/mL HBV DNA subsequently developed ETVr. Long-term monitoring showed low rates of resistance in nucleoside-naïve patients during 5 years of ETV therapy, corresponding with potent viral suppression and a high genetic barrier to resistance. These findings support ETV as a primary therapy that enables prolonged treatment with potent viral suppression and minimal resistance.

Brief Report: CYP2B6 516G>T Minor Allele Protective of Late Virologic Failure in Efavirenz-Treated HIV-Infected Patients in Botswana.

Science.gov (United States)

Vujkovic, Marijana; Bellamy, Scarlett L; Zuppa, Athena F; Gastonguay, Marc; Moorthy, Ganesh S; Ratshaa, Bakgaki R; Han, Xiaoyan; Steenhoff, Andrew P; Mosepele, Mosepele; Strom, Brian L; Aplenc, Richard; Bisson, Gregory P; Gross, Robert

2017-08-01

CYP2B6 polymorphisms that affect efavirenz (EFV) concentrations are common, but the effect of this polymorphism on HIV virologic failure in clinical practice settings has not fully been elucidated. Our objective was to investigate the relationship between the CYP2B6 516G>T genotype and late virologic failure in patients treated with EFV in Gaborone, Botswana. We performed a case-control study that included 1338 HIV-infected black Batswana on EFV-based antiretroviral therapy (ART). Patients were approached for enrollment during regular visits at one of the outpatient HIV clinics between July 2013 and April 2014. Cases experienced late HIV failure, defined as plasma HIV RNA >1000 copies/mL after maintaining viral suppression (ART for at least 6 months. Logistic regression was used to determine the adjusted odds of late HIV failure by 516G>T genotype. After adjustment for the confounding variables age and CD4 count, the CYP2B6 516 T-allele was protective against late HIV virologic breakthrough, adjusted OR 0.70; 95% CI: 0.50 to 0.97. The CYP2B6 516 T-allele was protective against late virologic breakthrough in patients with initial (6 month) HIV RNA suppression on EFV-based ART. Future studies are needed to assess long-term viral benefits of identifying and offering EFV containing ART to black African HIV-infected patients with CYP2B6 T-alleles, especially given the wider availability of a single pill EFV in this setting.

Omitting cytogenetic assessment from routine treatment response monitoring in chronic myeloid leukemia is safe.

Science.gov (United States)

Geelen, Inge G P; Thielen, Noortje; Janssen, Jeroen J W M; Hoogendoorn, Mels; Roosma, Tanja J A; Valk, Peter J M; Visser, Otto; Cornelissen, Jan J; Westerweel, Peter E

2018-04-01

The monitoring of response in chronic myeloid leukemia (CML) is of great importance to identify patients failing their treatment in order to adjust TKI choice and thereby prevent progression to advanced stage disease. Cytogenetic monitoring has a lower sensitivity, is expensive, and requires invasive bone marrow sampling. Nevertheless, chronic myeloid leukemia guidelines continue to recommend performing routine cytogenetic response assessments, even when adequate molecular diagnostics are available. In a population-based registry of newly diagnosed CML patients in the Netherlands, all simultaneous cytogenetic and molecular assessments performed at 3, 6, and 12 months were identified and response of these matched assessments was classified according to European Leukemia Net (ELN) recommendations. The impact of discrepant cytogenetic and molecular response classifications and course of patients with additional chromosomal abnormalities were evaluated. The overall agreement of 200 matched assessments was 78%. In case of discordant responses, response at 24 months was consistently better predicted by the molecular outcome. Cytogenetic response assessments provided relevant additional clinical information only in some cases of molecular "warning." The development of additional cytogenetic abnormalities was always accompanied with molecular failure. We conclude that it is safe to omit routine cytogenetics for response assessment during treatment and to only use molecular monitoring, in order to prevent ambiguous classifications, reduce costs, and reduce the need for invasive bone marrow sampling. Cytogenetic re-assessment should still be performed when molecular response is suboptimal. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

DEFF Research Database (Denmark)

Chereau, Fanny; Madec, Yoann; Sabin, Caroline

2017-01-01

OBJECTIVE: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. MET...

Dynamics of response-conflict monitoring and individual differences in response control and behavioral control: an electrophysiological investigation using a stop-signal task.

Science.gov (United States)

Stahl, Jutta; Gibbons, Henning

2007-03-01

The aim of the present study was to investigate the functional significance of error (related) negativity Ne/ERN and individual differences in human action monitoring. A response-conflict model of Ne/ERN should be tested applying a stop-signal paradigm. After a few modifications of Ne/ERN response-conflict theory (Yeung N, Botvinick MM, Cohen JD. The neural basis of error detection: conflict monitoring and the error-related negativity. Psychological Review 2004:111(4);931-959), strength and time course of response conflict could be modeled as a function of stop-signal delay. In Experiment 1, 35 participants performed a visual two-choice response-time task but tried to withhold the response if an auditory stop signal was presented. Probability of stopping errors was held at 50% using variable delays between visual and auditory stimuli. Experiment 2 (n=10) employed both auditory go and stop signals and confirmed that Ne/ERN effects are due to conflict induced by the auditory stop signal, and not the mere presence or absence of an additional stimulus. As predicted, amplitudes of both the stimulus-locked and response-locked Ne/ERN were largest for non-stopped responses, followed by successfully stopped and go responses. However, independently of response type Ne/ERN also increased with increasing stop-signal delay. Since longer delay invokes stronger response conflict, results specifically support the notion of Ne/ERN reflecting response-conflict monitoring. Furthermore, individual differences related to measures of response control and behavioral control were observed. Both low response control estimated from stop-task performance and high psychometric impulsivity were accompanied by smaller Ne/ERN amplitude on stop trials, suggesting reduced response-conflict monitoring. The present study supported the response-conflict view of Ne/ERN. Furthermore, the observed relationship between impulsivity and Ne/ERN amplitude suggested that individuals with low behavioral

Clinical and virological efficacy of etravirine plus two active Nucleos(tide analogs in an heterogeneous HIV-infected population.

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Luis F López-Cortés

Full Text Available Etravirine (ETV is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(tide reverse-transcriptase inhibitors (NRTIs. This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs switched due to adverse events and group B subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to 200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1% and 77.4% (CI95, 65.0-89.7%, respectively; the rates reached 97.2% (CI95, 95.1-99.3% and 90.5% (CI95, 81.7-99.3, by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity.ClinicalTrials.gov NCT01437241.

Optimal antiretroviral therapy adherence as evaluated by CASE index score tool is associated with virological suppression in HIV-infected adults in Dakar, Senegal.

Science.gov (United States)

Byabene, A K; Fortes-Déguénonvo, L; Niang, K; Manga, M N; Bulabula, A N H; Nachega, J B; Seydi, M

2017-06-01

To determine the prevalence and factors associated with optimal antiretroviral therapy (ART) adherence and virological failure (VLF) among HIV-infected adults enrolled in the national ART programme at the teaching hospital of Fann, Dakar, Senegal. Cross-sectional study from 1 September 2013 to 30 January 2014. (1) optimal ART adherence by the Center for Adherence Support Evaluation (CASE) Index Score (>10) and (2) VLF (HIV RNA > 1000 copies/ml). Diagnostic accuracy of CASE Index Score assessed using sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and corresponding 95% confidence intervals (CIs). Multivariate logistic regression analysis was performed to identify independent factors associated with optimal adherence and VLF. Of 98 HIV-infected patients on ART, 68% were female. The median (IQR) age was 42 (20-50) years. A total of 57 of 98 (60%) were on ART more than 3 years, and majority (88%) were on NNRTI-based first-line ART regimen. A total of 79 of 98 (80%) patients reported optimal ART adherence, and only five of 84 (5.9%) had documented VLF. Patients with VLF were significantly more likely to have suboptimal ART adherence (17.7% vs. 2.9%; P = 0.02). CASE Index Score showed the best trade-off in Se (78.9%, 95% CI: 54.4-93.9%), Sp (20.0%, 95% CI: 11.1-31.7), PPV (22.4, 95% CI: 13.1-34.2%) and NPV (76.5%, 95% CI: 50.1-93.2), when used VLF threshold of HIV RNA >50 copies/ml. Factors independently associated with VLF were CASE Index Score CASE Index Score was independently associated with virological outcomes, supporting usefulness of this low-cost ART adherence monitoring tool in this setting. © 2017 John Wiley & Sons Ltd.

Protein pathway activation associated with sustained virologic response in patients with chronic hepatitis C treated with pegylated interferon (PEG-IFN) and ribavirin (RBV).

Science.gov (United States)

Younossi, Zobair M; Limongi, Dolores; Stepanova, Maria; Pierobon, Mariaelena; Afendy, Arian; Mehta, Rohini; Baranova, Ancha; Liotta, Lance; Petricoin, Emanuel

2011-02-04

Only half of chronic hepatitis C (CH-C) patients treated with pegylated interferon and ribavirin (PEG-IFN+RBV) achieve sustained virologic response) SVR. In addition to known factors, we postulated that activation of key protein signaling networks in the peripheral blood mononuclear cells (PBMCs) may contribute to SVR due to inherent patient-specific basal immune cell signaling architecture. In this study, we included 92 patients with CH-C. PBMCs were collected while patients were not receiving treatment and used for phosphoprotein-based network profiling. Patients received a full course of PEG-IFN+RBV with overall SVR of 55%. From PBMC, protein lysates were extracted and then used for Reverse Phase Protein Microarray (RPMA) analysis, which quantitatively measured the levels of cytokines and activation levels of 25 key protein signaling molecules involved in immune cell regulation and interferon alpha signaling. Regression models for predicting SVR were generated by stepwise bidirectional selection. Both clinical-laboratory and RPMA parameters were used as predictor variables. Model accuracies were estimated using 10-fold cross-validation. Our results show that by comparing patients who achieved SVR to those who did not, phosphorylation levels of 6 proteins [AKT(T308), JAK1(Y1022/1023), p70 S6 Kinase (S371), PKC zeta/lambda(T410/403), TYK2(Y1054/1055), ZAP-70(Y319)/Syk(Y352)] and overall levels of 6 unmodified proteins [IL2, IL10, IL4, IL5, TNF-alpha, CD5L] were significantly different (P < 0.05). For SVR, the model based on a combination of clinical and proteome parameters was developed, with an AUC = 0.914, sensitivity of 92.16%, and specificity of 85.0%. This model included the following parameters: viral genotype, previous treatment status, BMI, phosphorylated states of STAT2, AKT, LCK, and TYK2 kinases as well as steady state levels of IL4, IL5, and TNF-alpha. In conclusion, SVR could be predicted by a combination of clinical, cytokine, and protein signaling

Computational models can predict response to HIV therapy without a genotype and may reduce treatment failure in different resource-limited settings.

Science.gov (United States)

Revell, A D; Wang, D; Wood, R; Morrow, C; Tempelman, H; Hamers, R L; Alvarez-Uria, G; Streinu-Cercel, A; Ene, L; Wensing, A M J; DeWolf, F; Nelson, M; Montaner, J S; Lane, H C; Larder, B A

2013-06-01

Genotypic HIV drug-resistance testing is typically 60%-65% predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART without a genotype and evaluated their potential as a treatment support tool in RLSs. Random forest models were trained to predict the probability of response to ART (≤400 copies HIV RNA/mL) using the following data from 14 891 treatment change episodes (TCEs) after virological failure, from well-resourced countries: viral load and CD4 count prior to treatment change, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. Models were assessed by cross-validation during development, with an independent set of 800 cases from well-resourced countries, plus 231 cases from Southern Africa, 206 from India and 375 from Romania. The area under the receiver operating characteristic curve (AUC) was the main outcome measure. The models achieved an AUC of 0.74-0.81 during cross-validation and 0.76-0.77 with the 800 test TCEs. They achieved AUCs of 0.58-0.65 (Southern Africa), 0.63 (India) and 0.70 (Romania). Models were more accurate for data from the well-resourced countries than for cases from Southern Africa and India (P < 0.001), but not Romania. The models identified alternative, available drug regimens predicted to result in virological response for 94% of virological failures in Southern Africa, 99% of those in India and 93% of those in Romania. We developed computational models that predict virological response to ART without a genotype with comparable accuracy to genotyping with rule-based interpretation. These models have the potential to help optimize antiretroviral therapy for patients in RLSs where genotyping is not generally available.

Five-year follow-up of patients with chronic C hepatitis and sustained virological response Seguimiento a 5 años de pacientes con hepatitis crónica C y respuesta viral sostenida

Directory of Open Access Journals (Sweden)

I. Puig-del-Castillo

2011-02-01

Full Text Available Objective: to assess persistence of sustained viral response at 5 years of follow-up in patients with chronic viral hepatitis C treated with pegylated interferon and ribavirin. Design: a descriptive study. Patients: from August 2001 to May 2004, all patients treated at our center with pegylated interferon and ribavirin who achieved a sustained viral response were consecutively enrolled (93 patients. Demographic, histological, biochemical, and virological data were collected during treatment and 5 years after achievement of the sustained viral response. Eighty-six percent of patients enrolled (n = 80 attended the control visit at 5 years. Results: mean age of enrolled patients was 41 years (standard deviation = 10 years, and 30.1% (n = 28 were women. Liver biopsy had been performed before treatment in 68.8% of patients (n = 64, showing no or mild fibrosis in 62.3% (F0 and F1 and significant fibrosis and cirrhosis in 37.7% (F ≥ 3. Genotype distribution was: 58.1% genotype 1 (n = 54; 8.6% genotype 2 (n = 8; 24.7% genotype 3 (n = 23; 7.5% genotype 4 (n = 7, and indeterminate in one patient. Only one patient experienced virological recurrence. All other patients had negative HCV RNA levels and, in the absence of other liver diseases, normal ALT levels. Conclusion: in patients treated with pegylated interferon and ribavirin with sustained viral response, long-term recurrence rate was very low.Objetivo: evaluar la persistencia de respuesta viral sostenida a los 5 años de seguimiento en pacientes con hepatitis crónica por virus C tratados con interferón pegilado y ribavirina. Diseño: estudio descriptivo. Pacientes: desde agosto de 2001 hasta mayo de 2004, se incluyeron de forma consecutiva todos los pacientes de nuestro centro tratados con interferón pegilado y ribavirina que alcanzaron respuesta viral sostenida (93 pacientes. Se recogieron datos demográficos, histológicos, bioquímicos y virológicos durante el tratamiento y a los 5 años de

A radioactive waste transportation package monitoring system for normal transport and accident emergency response conditions

International Nuclear Information System (INIS)

Brown, G.S.; Cashwell, J.W.; Apple, M.L.

1993-01-01

This paper addresses spent fuel and high level waste transportation history and prospects, discusses accident histories of radioactive material transport, discusses emergency responder needs and provides a general description of the Transportation Intelligent Monitoring System (TRANSIMS) design. The key objectives of the monitoring system are twofold: (1) to facilitate effective emergency response to accidents involving a radioactive waste transportation package, while minimizing risk to the public and emergency first-response personnel, and (2) to allow remote monitoring of transportation vehicle and payload conditions to enable research into radioactive material transportation for normal and accident conditions. (J.P.N.)

Factors associated with HIV-1 virological failure in an outpatient clinic for HIV-infected people in Haiphong, Vietnam

DEFF Research Database (Denmark)

Huong, D T M; Bannister, W; Phong, P T

2011-01-01

starting ART, 23% had detectable HIV-1 viral load (= 400 copies/mL). Patients who had developed a World Health Organization (WHO) clinical stage 4 condition at the time of initiation of ART were more likely to experience virological failure than those in stages 1-3, odds ratio (OR): 5.20 (95% confidence...

Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study

Science.gov (United States)

Cesar, Carina; Jenkins, Cathy A.; Shepherd, Bryan E.; Padgett, Denis; Mejía, Fernando; Ribeiro, Sayonara Rocha; Cortes, Claudia P.; Pape, Jean W.; Madero, Juan Sierra; Fink, Valeria; Sued, Omar; McGowan, Catherine; Cahn, Pedro

2015-01-01

Background Access to combination antiretroviral therapy (cART) is expanding in Latin America and the Caribbean (LAC). There is little information in this region regarding incidence of and factors associated with regimen failure and regimen change. Methods Antiretroviral-naïve adults starting cART from 2000-2014 at sites in seven countries throughout LAC were included. Cumulative incidence of virologic failure and major regimen change were estimated with death considered a competing event. Findings 14,027 cART initiators (60% male, median age 37 years, median CD4 156 cells/mm3, median HIV-RNA 5·0 log10 copies/mL, and 28% with clinical AIDS) were followed for a median of 3·9 years. 1,719 patients presented virologic failure and 1,955 had a major regimen change. Excluding GHESKIO-Haiti (which did not regularly measure HIV-RNA), cumulative incidence of virologic failure was 7·8%, 19·2%, and 25·8% at one, three, and five years after cART initiation, respectively; cumulative incidence of major regimen change was 5·9%, 12·7%, and 18·2%. Incidence of major regimen change at GHESKIO-Haiti at five years was 10·7%. Virologic failure was associated with younger age (adjusted hazard ratio[aHR]=2·03 for 20 vs. 40 years; 95% confidence interval[CI] 1·68-2·44), infection through injection-drug use (IDU) (aHR=1·60; 95%CI 1·02-2·52), initiation in earlier calendar years (aHR=1·28 for 2002 vs. 2006; 95%CI 1·13-1·46), and starting with a boosted protease inhibitor (aHR=1·17 vs. non-nucleoside reverse transcriptase inhibitor; 95%CI 1·00-1·64). Interpretation Incidence of virologic failure was generally lower than in North America/Europe. Our results suggest the need to design strategies to reduce failure and major regimen change among younger patients and those with a history of IDU. Funding US National Institutes of Health: U01 AI069923. PMID:26520929

Clinical, Virologic, Immunologic Outcomes and Emerging HIV Drug Resistance Patterns in Children and Adolescents in Public ART Care in Zimbabwe.

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A T Makadzange

Full Text Available To determine immunologic, virologic outcomes and drug resistance among children and adolescents receiving care during routine programmatic implementation in a low-income country.A cross-sectional evaluation with collection of clinical and laboratory data for children (0-<10 years and adolescents (10-19 years attending a public ART program in Harare providing care for pediatric patients since 2004, was conducted. Longitudinal data for each participant was obtained from the clinic based medical record.Data from 599 children and adolescents was evaluated. The participants presented to care with low CD4 cell count and CD4%, median baseline CD4% was lower in adolescents compared with children (11.0% vs. 15.0%, p<0.0001. The median age at ART initiation was 8.0 years (IQR 3.0, 12.0; median time on ART was 2.9 years (IQR 1.7, 4.5. On ART, median CD4% improved for all age groups but remained below 25%. Older age (≥ 5 years at ART initiation was associated with severe stunting (HAZ <-2: 53.3% vs. 28.4%, p<0.0001. Virologic failure rate was 30.6% and associated with age at ART initiation. In children, nevirapine based ART regimen was associated with a 3-fold increased risk of failure (AOR: 3.5; 95% CI: 1.3, 9.1, p = 0.0180. Children (<10 y on ART for ≥4 years had higher failure rates than those on ART for <4 years (39.6% vs. 23.9%, p = 0.0239. In those initiating ART as adolescents, each additional year in age above 10 years at the time of ART initiation (AOR 0.4 95%CI: 0.1, 0.9, p = 0.0324, and each additional year on ART (AOR 0.4, 95%CI 0.2, 0.9, p = 0.0379 were associated with decreased risk of virologic failure. Drug resistance was evident in 67.6% of sequenced virus isolates.During routine programmatic implementation of HIV care for children and adolescents, delayed age at ART initiation has long-term implications on immunologic recovery, growth and virologic outcomes.

Predictors of having a resistance test following confirmed virological failure of combination antiretroviral therapy: data from EuroSIDA

DEFF Research Database (Denmark)

Fox, Zoe V; Cozzi-Lepri, Alessandro; D'Arminio Monforte, Antonella

2011-01-01

these recommendations. Methods: In EuroSIDA, virological failure (VF) was defined as confirmed VL>1,000 copies/ml after =4 months continuous use of any antiretroviral in a =3-drug regimen started during or after 2002. We assessed whether a resistance test was performed around VF (from 4 months before to 1 year after VF...

Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

Science.gov (United States)

Chen Yi Mei, Swee Lin G; Thompson, Alexander J; Christensen, Britt; Cunningham, Georgina; McDonald, Lucy; Bell, Sally; Iser, David; Nguyen, Tin; Desmond, Paul V

2017-01-01

Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR) in people with chronic hepatitis C (CHC) infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart. CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM) using transient elastography [FibroScan]) were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa) or advanced (METAVIR F3-4/ LSM >9.5 kPa). The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2) to advanced fibrosis at follow-up liver fibrosis assessment. 131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62) years with median estimated duration of infection 33-years (IQR 29-38). At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17). 109 (83%) participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002). The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343). However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F/U (p

Brief Report: Efficacy and Safety of Switching to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide (E/C/F/TAF) in Virologically Suppressed Women.

Science.gov (United States)

Hodder, Sally; Squires, Kathleen; Kityo, Cissy; Hagins, Debbie; Avihingsanon, Anchalee; Kido, Anna; Jiang, Shuping; Kulkarni, Rima; Cheng, Andrew; Cao, Huyen

2018-06-01

The integrase inhibitor regimen [elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (TDF)] demonstrated superior efficacy when compared with a protease inhibitor regimen [ritonavir-boosted atazanavir (ATV + RTV) and FTC/TDF] in 575 treatment-naive women at week 48. We investigated the efficacy, safety, and tolerability of switching to a TAF-based, single-tablet regimen containing elvitegravir, cobicistat, FTC, and tenofovir alafenamide (E/C/F/TAF) versus remaining on ATV + RTV plus FTC/TDF. After completing the initial randomized, blinded phase, virologically suppressed (HIV-1 RNA TAF versus remaining on their current regimen. The primary end point was proportion of participants with plasma HIV-1 RNA TAF and 53 to remain on ATV + RTV plus FTC/TDF. At week 48, virologic suppression was maintained in 150 (94%) of women on E/C/F/TAF and 46 (87%) on ATV + RTV plus FTC/TDF [difference 7.5% (95% confidence interval -1.2% to 19.4%)], demonstrating noninferiority of E/C/F/TAF to ATV + RTV and FTC/TDF. Incidence of AEs was similar between groups; study drug-related AEs were more common with E/C/F/TAF (11% versus 4%). Switching to E/C/F/TAF was noninferior to continuing ATV + RTV plus FTC/TDF in maintaining virologic suppression and was well tolerated at 48 weeks.

Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy

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Rupak Shivakoti

2014-11-01

Full Text Available A case-cohort study, within a multi-country trial of antiretroviral therapy (ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS, was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO stage 3, 4 or death by 96 weeks or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR: 57.28–99.89 and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 μg/L of serum selenium, we observed increased hazards (adjusted hazards ratio (HR: 3.50; 95% confidence intervals (CI: 1.30–9.42 of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium.

Pathogenesis and host response in Syrian hamsters following intranasal infection with Andes virus.

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David Safronetz

2011-12-01

Full Text Available Hantavirus pulmonary syndrome (HPS, also referred to as hantavirus cardiopulmonary syndrome (HCPS, is a rare but frequently fatal disease caused by New World hantaviruses. In humans HPS is associated with severe pulmonary edema and cardiogenic shock; however, the pathogenesis of this disease remains unclear largely due to a lack of suitable animal models for the study of disease progression. In this study we monitored clinical, virological, pathophysiological parameters and host immunological responses to decipher pathological factors and events in the lethal Syrian hamster model of HPS following intranasal inoculation of Andes virus. Transcriptional profiling of the host gene responses demonstrated a suppression of innate immune responses in most organs analyzed during the early stage of infection, except for in the lung which had low level activation of several pro-inflammatory genes. During this phase Andes virus established a systemic infection in hamsters, with viral antigen readily detectable in the endothelium of the majority of tissues analyzed by 7-8 days post-inoculation. Despite wide-spread infection, histological analysis confirmed pathological abnormalities were almost exclusively found in the lungs. Immediately preceding clinical signs of disease, intense activation of pro-inflammatory and Th1/Th2 responses were observed in the lungs as well as the heart, but not in peripheral organs, suggesting that localized immune-modulations by infection is paramount to pathogenesis. Throughout the course of infection a strong suppression of regulatory T-cell responses was noted and is hypothesized to be the basis of the aberrant immune activations. The unique and comprehensive monitoring of host immune responses to hantavirus infection increases our understanding of the immuno-pathogenesis of HPS and will facilitate the development of treatment strategies targeting deleterious host immunological responses.

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

DEFF Research Database (Denmark)

NN, NN; Mugavero, Michael J; May, Margaret

2008-01-01

, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. MAIN OUTCOME MEASURES: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation.......58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1......OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between...

SU-F-J-147: Magnetic Field Dose Response Considerations for a Linac Monitor Chamber

Energy Technology Data Exchange (ETDEWEB)

Reynolds, M; Fallone, B [Cross Cancer Institute, Edmonton, AB (Canada)

2016-06-15

Purpose: The impact of magnetic fields on the readings of a linac monitor chamber have not yet been investigated. Herein we examine the total dose response as well as any deviations in the beam parameters of flatness and symmetry when a Varian monitor chamber is irradiated within an applied magnetic field. This work has direct application to the development of Linac-MR systems worldwide. Methods: A Varian monitor chamber was modeled in the Monte Carlo code PENELOPE and irradiated in the presence of a magnetic field with a phase space generated from a model of a Linac-MR prototype system. The magnetic field strength was stepped from 0 to 3.0T in both parallel and perpendicular directions with respect to the normal surface of the phase space. Dose to each of the four regions in the monitor chamber were scored separately for every magnetic field adaptation to evaluate the effect of the magnetic field on flatness and symmetry. Results: When the magnetic field is perpendicular to the phase space normal we see a change in dose response with a maximal deviation (10–25% depending on the chamber region) near 0.75T. In the direction of electron deflection we expectedly see opposite responses in chamber regions leading to a measured asymmetry. With a magnetic field parallel to the phase space normal we see no measured asymmetries, however there is a monotonic rise in dose response leveling off at about +12% near 2.5T. Conclusion: Attention must be given to correct for the strength and direction of the magnetic field at the location of the linac monitor chamber in hybrid Linac-MR devices. Elsewise the dose sampled by these chambers may not represent the actual dose expected at isocentre; additionally there may be a need to correct for the symmetry of the beam recorded by the monitor chamber. Fallone is a co-founder and CEO of MagnetTx Oncology Solutions (under discussions to license Alberta bi-planar linac MR for commercialization).

Response monitoring in de novo patients with Parkinson's disease.

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Rita Willemssen

Full Text Available BACKGROUND: Parkinson's disease (PD is accompanied by dysfunctions in a variety of cognitive processes. One of these is error processing, which depends upon phasic decreases of medial prefrontal dopaminergic activity. Until now, there is no study evaluating these processes in newly diagnosed, untreated patients with PD ("de novo PD". METHODOLOGY/PRINCIPAL FINDINGS: Here we report large changes in performance monitoring processes using event-related potentials (ERPs in de novo PD-patients. The results suggest that increases in medial frontal dopaminergic activity after an error (Ne are decreased, relative to age-matched controls. In contrast, neurophysiological processes reflecting general motor response monitoring (Nc are enhanced in de novo patients. CONCLUSIONS/SIGNIFICANCE: It may be hypothesized that the Nc-increase is at costs of dopaminergic activity after an error; on a functional level errors may not always be detected and correct responses sometimes be misinterpreted as errors. This pattern differs from studies examining patients with a longer history of PD and may reflect compensatory processes, frequently occurring in pre-manifest stages of PD. From a clinical point of view the clearly attenuated Ne in the de novo PD patients may prove a useful additional tool for the early diagnosis of basal ganglia dysfunction in PD.

A search for solar neutron response in neutron monitor data

International Nuclear Information System (INIS)

Kudela, K.

1990-01-01

The search for an impulsive increase corresponding to a solar neutron response on high-mountain neutron monitors requires control of the stability of the measurement and elimination of other sources of short-time increases of different kinds which are involved in fluctuations of cosmic-ray intensity. For the solar flare of June 3, 1982 the excess of counting rate on the Lomnicky stit neutron monitor is, within a factor or 1.8, equal to that expected from solar neutrons. Superposed epoch analysis of 17 flares with gamma-ray or hard X-ray production gives a slight tendency of an occurring signal in cases of high heliocentric angles, indicating anisotropic production of neutrons on the sun. The low statistical significance of the result indicates that higher temporal resolution, better evaluation of multiplicity, better knowledge of the power spectra of short-term intensity fluctuations on neutron monitors, as well as coordinated measurements of solar gamma-rays and neutrons on satellites, are required. 21 refs

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

NARCIS (Netherlands)

Mugavero, Michael J; May, Margaret; Harris, Ross; Saag, Michael S; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F; Dabis, Francois; Hogg, Robert; de Wolf, Frank; Fatkenheuer, Gerd; Gill, M John; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M; Staszewski, Schlomo; Sterne, Jonathan A C; Niesters, Bert

2008-01-01

OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between

Faunal and vegetation monitoring in response to harbor dredging in the Port of Miami

Science.gov (United States)

Daniels, Andre; Stevenson, Rachael; Smith, Erin; Robblee, Michael

2018-04-11

Seagrasses are highly productive ecosystems. A before-after-control-impact (BACI) design was used to examine effects of dredging on seagrasses and the animals that inhabit them. The control site North Biscayne Bay and the affected site Port of Miami had seagrass densities decrease during both the before, Fish and Invertebrate Assessment Network 2006-2011, and after, Faunal Monitoring in Response to Harbor Dredging 2014-2016, studies. Turbidity levels increased at North Biscayne Bay and Port of Miami basins during the Faunal Monitoring in Response to Harbor Dredging study, especially in 2016. Animal populations decreased significantly in North Biscayne Bay and Port of Miami in the Faunal Monitoring in Response to Harbor Dredging study compared to the Fish and Invertebrate Assessment Network study. Predictive modeling shows that numbers of animal populations will likely continue to decrease if the negative trends in seagrass densities continue unabated. There could be effects on several fisheries vital to the south Florida economy. Additional research could determine if animal populations and seagrass densities have rebounded or continued to decrease.

Growth, immune and viral responses in HIV infected African children receiving highly active antiretroviral therapy: a prospective cohort study

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Bagenda Danstan

2010-08-01

Full Text Available Abstract Background Scale up of paediatric antiretroviral therapy in resource limited settings continues despite limited access to routine laboratory monitoring. We documented the weight and height responses in HIV infected Ugandan children on highly active antiretroviral therapy and determined clinical factors associated with successful treatment outcomes. Methods A prospective cohort of HIV infected children were initiated on HAART and followed for 48 weeks. Body mass index for age z scores(BAZ, weight and height-for-age z scores (WAZ & HAZ were calculated: CD4 cell % and HIV-1 RNA were measured at baseline and every 12 weeks. Treatment outcomes were classified according to; both virological and immunological success (VS/IS, virological failure and immunological success (VF/IS. virological success and immunological failure (VS/IF and both virological and immunological failure (VF/IF. Results From March 2004 until May 2006, 124 HIV infected children were initiated on HAART. The median age (IQR was 5.0 years (2.1 - 7.0 and 49% (61/124 were female. The median [95% confidence interval (CI] BAZ, WAZ and HAZ at baseline were 0.29 (-2.9, -1.2, -1.2 (-2.1, -0.5 and -2.06 (-2.9, -1.2 respectively. Baseline median CD4 cell % and log10 HIV-1 RNA were; 11.8% (7.5-18.0 and 5.6 (5.2-5.8 copies/ml. By 48 weeks, mean WAZ and HAZ in the VF/IS group, which was younger, increased from - 0.98 (SD 1.7 to + 1.22 (SD 1.2 and from -1.99 (1.7 to + 0.76 (2.4 respectively. Mean increase in WAZ and HAZ in the VS/IF group, an older group was modest, from -1.84 (1.3 to - 0.41 (1.2 and -2.25 (1.2 to -1.16 (1.3 respectively. Baseline CD4 cell % [OR 6.97 95% CI (2.6 -18.6], age [OR 4.6 95% CI (1.14 -19.1] and WHO clinical stage [OR 3.5 95%CI (1.05 -12.7] were associated with successful treatment outcome. Conclusions HIV infected Ugandan children demonstrated a robust increase in height and weight z scores during the first 48 weeks of HAART, including those who failed to

Monitoring T-Cell Responses in Translational Studies: Optimization of Dye-Based Proliferation Assay for Evaluation of Antigen-Specific Responses

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Anja Ten Brinke

2017-12-01

Full Text Available Adoptive therapy with regulatory T cells or tolerance-inducing antigen (Ag-presenting cells is innovative and promising therapeutic approach to control undesired and harmful activation of the immune system, as observed in autoimmune diseases, solid organ and bone marrow transplantation. One of the critical issues to elucidate the mechanisms responsible for success or failure of these therapies and define the specificity of the therapy is the evaluation of the Ag-specific T-cell responses. Several efforts have been made to develop suitable and reproducible assays. Here, we focus on dye-based proliferation assays. We highlight with practical examples the fundamental issues to take into consideration for implementation of an effective and sensitive dye-based proliferation assay to monitor Ag-specific responses in patients. The most critical points were used to design a road map to set up and analyze the optimal assay to assess Ag-specific T-cell responses in patients undergoing different treatments. This is the first step to optimize monitoring of tolerance induction, allowing comparison of outcomes of different clinical studies. The road map can also be applied to other therapeutic interventions, not limited to tolerance induction therapies, in which Ag-specific T-cell responses are relevant such as vaccination approaches and cancer immunotherapy.

Influence of IL28B polymorphisms on response to a lower-than-standard dose peg-IFN-α 2a for genotype 3 chronic hepatitis C in HIV-coinfected patients.

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Luis F López-Cortés

Full Text Available Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients.Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed. Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR, SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype.Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses.ClinicalTrials.gov NCT00553930.

Bioinformatics Meets Virology: The European Virus Bioinformatics Center's Second Annual Meeting.

Science.gov (United States)

Ibrahim, Bashar; Arkhipova, Ksenia; Andeweg, Arno C; Posada-Céspedes, Susana; Enault, François; Gruber, Arthur; Koonin, Eugene V; Kupczok, Anne; Lemey, Philippe; McHardy, Alice C; McMahon, Dino P; Pickett, Brett E; Robertson, David L; Scheuermann, Richard H; Zhernakova, Alexandra; Zwart, Mark P; Schönhuth, Alexander; Dutilh, Bas E; Marz, Manja

2018-05-14

The Second Annual Meeting of the European Virus Bioinformatics Center (EVBC), held in Utrecht, Netherlands, focused on computational approaches in virology, with topics including (but not limited to) virus discovery, diagnostics, (meta-)genomics, modeling, epidemiology, molecular structure, evolution, and viral ecology. The goals of the Second Annual Meeting were threefold: (i) to bring together virologists and bioinformaticians from across the academic, industrial, professional, and training sectors to share best practice; (ii) to provide a meaningful and interactive scientific environment to promote discussion and collaboration between students, postdoctoral fellows, and both new and established investigators; (iii) to inspire and suggest new research directions and questions. Approximately 120 researchers from around the world attended the Second Annual Meeting of the EVBC this year, including 15 renowned international speakers. This report presents an overview of new developments and novel research findings that emerged during the meeting.

A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

NARCIS (Netherlands)

Paredes, Roger; Puertas, Maria Carmen; Bannister, Wendy; Kisic, Mónica; Cozzi-Lepri, Alessandro; Pou, Christian; Bellido, Rocío; Betancor, Gilberto; Bogner, Johannes; Gargalianos, Panagiotis; Bánhegyi, Dénes; Clotet, Bonaventura; Lundgren, Jens; Menéndez-Arias, Luis; Martinez-Picado, Javier; Losso, M.; Elias, C.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Suetnov, O.; Clumeck, N.; de Wit, S.; Poll, B.; Colebunders, R.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Rozsypal, H.; Sedlacek, D.; Nielsen, J.; Kronborg, G.; Benfield, T.; Larsen, M.; Gerstoft, J.; Katzenstein, T.; Hansen, A.-B. E.; Skinhøj, P.; Pedersen, C.; Oestergaard, L.; Zilmer, K.; Ristola, M.; Katlama, C.; Viard, J.-P.; Girard, P.-M.; Livrozet, J. M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Rockstroh, J.; Schmidt, R.; van Lunzen, J.; Degen, O.; Stellbrink, H. J.; Staszewski, S.; Fätkenheuer, G.; Kosmidis, J.; Gargalianos, P.; Xylomenos, G.; Perdios, J.; Panos, G.; Filandras, A.; Karabatsaki, E.; Sambatakou, H.; Banhegyi, D.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Pollack, S.; Hassoun, G.; Maayan, S.; Vella, S.; Esposito, R.; Mazeu, I.; Mussini, C.; Arici, C.; Pristera, R.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Chirianni, A.; Montesarchio, E.; Gargiulo, M.; Antonucci, G.; Iacomi, F.; Narciso, P.; Vlassi, C.; Zaccarelli, M.; Lazzarin, A.; Finazzi, R.; Galli, M.; Ridolfo, A.; d'Arminio, A.; Rozentale, B.; Aldins, P.; Chaplinskas, S.; Hemmer, R.; Staub, T.; Reiss, P.; Ormaasen, V.; Maeland, A.; Brunn, J.; Knysz, B.; Gasiorowski, J.; Horban, A.; Bakowska, E.; Prokopowicz, D.; Flisiak, R.; Boron-Kaczmarska, A.; Pynka, M.; Beniowski, M.; Mularska, E.; Trocha, H.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Antunes, F.; Valadas, E.; Mansinho, K.; Maltez, F.; Duiculescu, D.; Rakhmanova, A.; Vinogradova, E.; Buzunova, S.; Jevtovic, D.; Mokrás, M.; Staneková, D.; Tomazic, J.; González-Lahoz, J.; Soriano, V.; Martin-Carbonero, L.; Labarga, P.; Moreno, S.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gatell, J. M.; Miró, J. M.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Karlsson, A.; Persson, P. O.; Ledergerber, B.; Weber, R.; Francioli, P.; Cavassini, M.; Hirschel, B.; Boffi, E.; Furrer, H.; Battegay, M.; Elzi, L.; Kravchenko, E.; Chentsova, N.; Kutsyna, G.; Servitskiy, S.; Krasnov, M.; Barton, S.; Johnson, A. M.; Mercey, D.; Phillips, A.; Johnson, M. A.; Murphy, M.; Weber, J.; Scullard, G.; Fisher, M.; Leen, C.; Gatell, J.; Gazzard, B.; Lundgren, J.; d'Arminio Monforte, A.; Kirk, O.; Mocroft, A.; Cozzi-Lepri, A.; Grint, D.; Ellefson, M.; Podlekareva, D.; Kjaer, J.; Peters, L.; Reekie, J.; Kowalska, J.; Tverland, J.; Fischer, A. H.

2011-01-01

The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated in NNRTI-naive patients who

Hepatitis C virus coinfection does not influence the CD4 cell recovery in HIV-1-infected patients with maximum virologic suppression

DEFF Research Database (Denmark)

Peters, Lars; Mocroft, Amanda; Soriano, Vincent

2009-01-01

BACKGROUND: Conflicting data exist whether hepatitis C virus (HCV) affects the CD4 cell recovery in patients with HIV starting antiretroviral treatment. OBJECTIVE: To investigate the influence of HCV coinfection on the CD4 recovery in patients with maximum virologic suppression within the EuroSIDA...

Analysis of virological efficacy in trials of antiretroviral regimens: drawbacks of not including viral load measurements after premature discontinuation of therapy

DEFF Research Database (Denmark)

Kirk, Ole; Pedersen, Court; Law, Matthew

2002-01-01

OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (EuroSIDA...

Clinical, virologic, and immunologic outcomes in lymphoma survivors and in cancer-free, HIV-1-infected patients: a matched cohort study.

Science.gov (United States)

Spagnuolo, Vincenzo; Travi, Giovanna; Galli, Laura; Cossarini, Francesca; Guffanti, Monica; Gianotti, Nicola; Salpietro, Stefania; Lazzarin, Adriano; Castagna, Antonella

2013-08-01

The objective of this study was to compare immunologic, virologic, and clinical outcomes between living human immunodeficiency virus (HIV)-infected individuals who had a diagnosis of lymphoma versus outcomes in a control group of cancer-free, HIV-infected patients. In this matched cohort study, patients in the case group were survivors of incident lymphomas that occurred between 1997 and June 2010. Controls were living, cancer-free, HIV-infected patients who were matched to cases at a 4:1 ratio by age, sex, nadir CD4 cell count, and year of HIV diagnosis. The date of lymphoma diagnosis served as the baseline in cases and in the corresponding controls. In total, 62 patients (cases) who had lymphoma (20 with Hodgkin disease [HD] and 42 with non-Hodgkin lymphoma [NHL]) were compared with 211 controls. The overall median follow-up was 4.8 years (interquartile range, 2.0-7.9 years). The CD4 cell count at baseline was 278 cells/mm³ (interquartile range, 122-419 cells/mm³) in cases versus 421 cells/mm³ (interquartile range, 222-574 cells/mm³) in controls (P = .003). At the last available visit, the CD4 cell count was 412 cells/mm³ (range, 269-694 cells/mm³) in cases versus 518 cells/mm³ (interquartile range, 350-661 cells/mm³) in controls (P = .087). The proportion of patients who achieved virologic success increased from 30% at baseline to 74% at the last available visit in cases (P = .008) and from 51% to 81% in controls (P = .0286). Patients with HD reached higher CD4 cell counts at their last visit than patients with NHL (589 cells/mm³ [range, 400-841 cells/mm³] vs 332 cells/mm³ [interquartile range, 220-530 cells/mm³], respectively; P = .003). Virologic success was similar between patients with HD and patients with NHL at the last visit. Forty cases (65%) and 76 controls (36%) experienced at least 1 clinical event after baseline (P < .0001); cases were associated with a shorter time to occurrence of the first clinical event compared with controls (P

The proposal of Paediatric Virology and its perspectives: An interview with Professor of Paediatrics Maria Theodoridou.

Science.gov (United States)

Mammas, Ioannis N; Spandidos, Demetrios A

2017-10-01

Professor Maria Theodoridou, Emeritus Professor of Paediatrics at the University of Athens, is one of the few paediatricians in Greece, who have experienced almost all the infectious diseases of the second half of the 20th century and their severe consequences, prior to the widespread adoption of immunisations. A milestone during her career was the establishment of a specialised National Reference Unit for the care of paediatric patients with acquired immune deficiency syndrome (AIDS) at the 'Aghia Sophia' Children's Hospital in Athens, Greece. According to Professor Theodoridou, training on the prevention, management and treatment of neonatal and paediatric viral infections represents a new educational challenge for both community as well as hospital-based paediatric health professionals. The debate of the potential strategically principal role of Paediatric Virology subspecialists in the primary, secondary and tertiary clinical practice is definitely necessary and needs further discussion and evaluation, she adds. She describes the difficulties that Greece, a country under a long-standing financial crisis, faces for the hospital-based management of paediatric viral infections and refers to the future advances, which are expected in the field of diagnosis and treatment of viral infections in neonates and children. In the context of the 3rd Workshop on Paediatric Virology, which will be held in Athens on October 7th, 2017, Professor Theodoridou will focus on the immigration crisis and vaccination policy.

[Seventy years of research in experimental mycology at the Institute of Microbiology and Virology of the National Academy of Sciences of Ukraine].

Science.gov (United States)

Zhdanova, N M

2003-01-01

The history of development of mycology at the D.K. Zabolotny Institute of Microbiology and Virology of the NAS of Ukraine and main achievements of the Department of Physiology and Taxonomy of Micromycetes during 1933-2003 were described in this publication.

Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

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Swee Lin G Chen Yi Mei

Full Text Available Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR in people with chronic hepatitis C (CHC infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart.CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM using transient elastography [FibroScan] were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa or advanced (METAVIR F3-4/ LSM >9.5 kPa. The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2 to advanced fibrosis at follow-up liver fibrosis assessment.131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62 years with median estimated duration of infection 33-years (IQR 29-38. At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17. 109 (83% participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002. The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343. However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F

Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir

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Suzuki F

2014-06-01

Full Text Available Fumitaka Suzuki,1,2 Hitomi Sezaki,1 Norio Akuta,1 Yoshiyuki Suzuki,1 Yusuke Kawamura,1 Tetsuya Hosaka,1 Masahiro Kobayashi,1 Satoshi Saitoh,1 Yasuji Arase,1 Kenji Ikeda,1 Mariko Kobayashi,3 Sachiyo Watahiki,3 Rie Mineta,3 Yukiko Suzuki,3 Hiromitsu Kumada1 1Department of Hepatology, Toranomon Hospital, Tokyo, Japan; 2Okinaka Memorial Institute for Medical Research, Tokyo, Japan; 3Research Institute for Hepatology, Toranomon Branch Hospital, Kawasaki, Japan Abstract: Tenofovir disoproxil fumarate (TDF is widely used to treat hepatitis B virus (HBV patients in the USA and Europe. No confirmed report of resistance selection during treatment with TDF in treatment-naïve and nucleoside/nucleotide analog-treated chronic hepatitis B patients has yet been reported. Here, we report for the first time a patient with chronic hepatitis B and cirrhosis who emerged with virologic breakthrough during combination therapy with TDF and entecavir (ETV, against ETV-resistant virus. A 51-year-old Japanese woman with hepatitis B e-antigen (HBeAg, whose genotype was C, received ETV monotherapy continuously followed by TDF and ETV combination therapy, because her HBV DNA levels had been >3.5 log copies/mL. At the start of combination therapy, amino acid substitutions of the reverse transcriptase (rt gene, rtL180M, rtT184I/M, and rtM204V, were detected. After this, serum HBV DNA decreased to less than 2.1 log copies/mL and remained at this level until 31 months of combination therapy, when it again began to increase. Amino acid substitutions of rtL180M, rtS202G, and rtM204V emerged and were associated with an increase in serum HBV DNA at virologic breakthrough. Long-term therapy with TDF against the ETV-resistant virus has the potential to induce virologic breakthrough and resistance, and careful follow-up should be carried out. Keywords: hepatitis B virus, resistant

Virological confirmation of suspected dengue in a Phase 2 Latin American vaccine trial: Implications for vaccine efficacy evaluation

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Mark Boaz

2014-01-01

Full Text Available The CYD tetravalent dengue vaccine candidate is being evaluated for protective efficacy against symptomatic dengue in Phase 3 efficacy trials. The laboratory test algorithm to confirm dengue cases was evaluated prior to Phase 3 trials. During a Phase 2 trial in Latin America a dengue epidemic occurred in the study countries. A total of 72 suspected dengue cases were reported and assessed: virological confirmation comprised qRT-PCR methods and a commercial ELISA kit for NS1 protein (Bio-Rad. The qRT-PCR included a screening assay targeting a conserved dengue region of the 3′-UTR (dengue screen assay followed by 4 individual serotype assays targeting the conserved dengue NS5 genomic region (WT dengue qRT-PCR assays. The NS1 and WT dengue qRT-PCR were endpoint assays for protocol virological confirmation (PVC. Of the 72 suspected cases, 14 were PVC. However, a unique pattern of dengue qRT-PCR results were observed in 5 suspected cases from Honduras: the dengue screen qRT-PCR assay was positive but WT dengue qRT-PCR and NS1 Ag ELISA were negative. To investigate these observations, additional molecular methods were applied: a SYBR® Green-based RT-PCR assay, sequencing assays directed at the genome regions covered by the WT dengue qRT-PCR, and a modified commercial dengue RT-PCR test (Simplexa™ Dengue, Focus Diagnostics. The exploratory data confirmed these additional cases as dengue and indicated the serotype 2 WT dengue qRT-PCR assay was unable to detect a circulating Latin American strain (DENV-2/NI/BID-V608/2006 due to a sequence variation in the isolate. The Simplexa Dengue RT-PCR test was able to detect and serotype dengue. Based on these findings an updated molecular test algorithm for the virological confirmation of dengue cases was developed and implemented in the Phase 3 efficacy trials.

Microbiological and serological monitoring in hooded crow (Corvus corone cornix in the Region Lombardia, Italy

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Guido Grilli

2010-01-01

Full Text Available The health status of 276 hooded crows (Corvus corone cornix from various provinces of Lombardy was monitored for three years. Bacteriological examination detected E. coli (76%, Campylobacter jejuni (17%, Salmonella typhimurium (11.6%, Yersinia spp. (6.5%, Clamydophila abortus and C. psittaci (2.6%; from six birds showing severe prostration Pasteurella multocida was isolated. Virological and serological tests were negative for Avian Influenza virus (AIV, West Nile virus (WNV and only three samples were positive for Newcastle disease virus (NDV but only at serology (titre 1:16.

Arabidopsis RETINOBLASTOMA RELATED directly regulates DNA damage responses through functions beyond cell cycle control

Czech Academy of Sciences Publication Activity Database

Horvath, B.M.; Kourová, Hana; Nagy, S.; Nemeth, E.; Magyar, Z.; Papdi, C.; Ahmad, Z.; Sanchez-Perez, G.F.; Perilli, S.; Blilou, I.; Pettko-Szandtner, A.; Darula, Z.; Meszaros, T.; Binarová, Pavla; Bogre, L.; Scheres, B.

2017-01-01

Roč. 36, č. 9 (2017), s. 1261-1278 ISSN 0261-4189 R&D Projects: GA ČR GA15-11657S Institutional support: RVO:61388971 Keywords : Arabidopsis * BRCA1 * DNA damage response Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 9.792, year: 2016

Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIV-1 subtype B and non-subtype B receiving a salvage regimen

DEFF Research Database (Denmark)

De Luca, Andrea; Flandre, Philippe; Dunn, David

2016-01-01

OBJECTIVES: The objective of this study was to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. METHODS: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from...... was derived based on best subset least squares estimation with mutational weights corresponding to regression coefficients. Virological outcome prediction accuracy was compared with that from existing genotypic resistance interpretation systems (GISs) (ANRS 2013, Rega 9.1.0 and HIVdb 7.0). RESULTS: TCEs were...

Monitoring and accountability for the Pacific response to the non-communicable diseases crisis

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Hilary Tolley

2016-09-01

Full Text Available Abstract Background Non-communicable diseases (NCD are the leading cause of premature death and disability in the Pacific. In 2011, Pacific Forum Leaders declared “a human, social and economic crisis” due to the significant and growing burden of NCDs in the region. In 2013, Pacific Health Ministers’ commitment to ‘whole of government’ strategy prompted calls for the development of a robust, sustainable, collaborative NCD monitoring and accountability system to track, review and propose remedial action to ensure progress towards the NCD goals and targets. The purpose of this paper is to describe a regional, collaborative framework for coordination, innovation and application of NCD monitoring activities at scale, and to show how they can strengthen accountability for action on NCDs in the Pacific. A key component is the Dashboard for NCD Action which aims to strengthen mutual accountability by demonstrating national and regional progress towards agreed NCD policies and actions. Discussion The framework for the Pacific Monitoring Alliance for NCD Action (MANA draws together core country-level components of NCD monitoring data (mortality, morbidity, risk factors, health system responses, environments, and policies and identifies key cross-cutting issues for strengthening national and regional monitoring systems. These include: capacity building; a regional knowledge exchange hub; innovations (monitoring childhood obesity and food environments; and a robust regional accountability system. The MANA framework is governed by the Heads of Health and operationalised by a multi-agency technical Coordination Team. Alliance membership is voluntary and non-conditional, and aims to support the 22 Pacific Island countries and territories to improve the quality of NCD monitoring data across the region. In establishing a common vision for NCD monitoring, the framework combines data collected under the WHO Global Framework for NCDs with a set of action

Monitoring and accountability for the Pacific response to the non-communicable diseases crisis.

Science.gov (United States)

Tolley, Hilary; Snowdon, Wendy; Wate, Jillian; Durand, A Mark; Vivili, Paula; McCool, Judith; Novotny, Rachel; Dewes, Ofa; Hoy, Damian; Bell, Colin; Richards, Nicola; Swinburn, Boyd

2016-09-10

Non-communicable diseases (NCD) are the leading cause of premature death and disability in the Pacific. In 2011, Pacific Forum Leaders declared "a human, social and economic crisis" due to the significant and growing burden of NCDs in the region. In 2013, Pacific Health Ministers' commitment to 'whole of government' strategy prompted calls for the development of a robust, sustainable, collaborative NCD monitoring and accountability system to track, review and propose remedial action to ensure progress towards the NCD goals and targets. The purpose of this paper is to describe a regional, collaborative framework for coordination, innovation and application of NCD monitoring activities at scale, and to show how they can strengthen accountability for action on NCDs in the Pacific. A key component is the Dashboard for NCD Action which aims to strengthen mutual accountability by demonstrating national and regional progress towards agreed NCD policies and actions. The framework for the Pacific Monitoring Alliance for NCD Action (MANA) draws together core country-level components of NCD monitoring data (mortality, morbidity, risk factors, health system responses, environments, and policies) and identifies key cross-cutting issues for strengthening national and regional monitoring systems. These include: capacity building; a regional knowledge exchange hub; innovations (monitoring childhood obesity and food environments); and a robust regional accountability system. The MANA framework is governed by the Heads of Health and operationalised by a multi-agency technical Coordination Team. Alliance membership is voluntary and non-conditional, and aims to support the 22 Pacific Island countries and territories to improve the quality of NCD monitoring data across the region. In establishing a common vision for NCD monitoring, the framework combines data collected under the WHO Global Framework for NCDs with a set of action-orientated indicators captured in a NCD Dashboard for

Rapid reduction of hepatitis C virus-Core protein in the peripheral blood improve the immunological response in chronic hepatitis C patients.

Science.gov (United States)

Kondo, Yasuteru; Ueno, Yoshiyuki; Wakui, Yuta; Ninomiya, Masashi; Kakazu, Eiji; Inoue, Jun; Kobayashi, Koju; Obara, Noriyuki; Shimosegawa, Tooru

2011-12-01

  The extracellular hepatitis C virus (HCV)-antigen, including HCV-Core protein, can suppress immune cells. Recently, the efficacy of double filtration plasmapheresis (DFPP) for chronic hepatitis C (CHC) was reported. However, the mechanism of efficacy of DFPP might not be only the reduction of HCV but also the effect of immune cells via direct and/or indirect mechanisms. The aim of this study is to analyze the virological and immunological parameters of difficult-to-treat HCV patients treated with DFPP combined with Peg-interferon and RBV (DFPP/Peg-IFN/RBV) therapy.   Twelve CHC patients were enrolled and treated with DFPP/Peg-IFN/RBV therapy. The immunological, virological and genetic parameters were studied.   All patients (4/4) treated with the major IL28B allele (T/T) could achieve complete early virological response (EVR). The amounts of HCV-Core antigen in the peripheral blood of EVR patients treated with DFPP/Peg-IFN/RBV rapidly declined in comparison to those of late virological response (LVR) patients treated with DFPP/Peg-IFN/RBV and EVR patients treated with Peg-IFN and RBV (Peg-IFN/RBV). The amount of IFN-γ produced from peripheral blood gradually increased. On the other hand, the amount of IL10 gradually decreased in the EVR patients. The frequencies of HCV-Core binding on CD3+ T cells rapidly declined in EVR patients treated with DFPP/Peg-IFN/RBV therapy. Moreover, the distributions of activated CD4(+) and CD8(+) T cells and CD16-CD56 high natural killer cells were significantly changed between before and after DFPP.   The rapid reduction of HCV-Core antigens and changes in the distribution of lymphoid cells could contribute to the favorable immunological response during DFPP/Peg-IFN/RBV therapy. © 2011 The Japan Society of Hepatology.

A Unique ISR Program Determines Cellular Responses to Chronic Stress

Czech Academy of Sciences Publication Activity Database

Guan, B.J.; van Hoef, V.; Jobava, R.; Elroy-Stein, O.; Valášek, Leoš Shivaya; Cargnello, M.; Gao, X.H.; Krokowski, D.; Merrick, W.C.; Kimball, S.R.; Komar, A.A.; Koromilas, A.E.; Wynshaw-Boris, A.; Topisirovic, I.; Larsson, O.; Hatzoglou, M.

2017-01-01

Roč. 68, č. 5 (2017), s. 885-900 ISSN 1097-2765 R&D Projects: GA ČR(CZ) GA17-06238S EU Projects: Wellcome Trust(GB) 090812/B/09/A Institutional support: RVO:61388971 Keywords : UNFOLDED PROTEIN RESPONSE * EUKARYOTIC TRANSLATION INITIATION * ENDOPLASMIC-RETICULUM STRESS Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 14.714, year: 2016

Viral Response to Specifically Targeted Antiviral Therapy for Hepatitis C and the Implications for Treatment Success

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Curtis L Cooper

2010-01-01

Full Text Available Currently, hepatitis C virus (HCV antiviral therapy is characterized by long duration, a multitude of side effects, difficult administration and suboptimal success; clearly, alternatives are needed. Collectively, specifically targeted antiviral therapy for HCV (STAT-C molecules achieve rapid viral suppression and very high rapid virological response rates, and improve sustained virological response rates. The attrition rate of agents within this class has been high due to various toxicities. Regardless, several STAT-C molecules are poised to become the standard of care for HCV treatment in the foreseeable future. Optimism must be tempered with concerns related to the rapid development of drug resistance with resulting HCV rebound. Strategies including induction dosing with interferon and ribavirin, use of combination high-potency STAT-C molecules and an intensive emphasis on adherence to HCV antiviral therapy will be critical to the success of this promising advance in HCV therapy.

Resistance profiles and adherence at primary virological failure in three different highly active antiretroviral therapy regimens: analysis of failure rates in a randomized study

DEFF Research Database (Denmark)

Røge, B T; Barfod, T S; Kirk, O

2004-01-01

OBJECTIVES: To investigate the interplay between resistance and adherence in the virological failure of three fundamentally different highly active antiretroviral therapy (HAART) regimens. METHODS: We retrospectively identified 56 verified primary virological failures (viral load >400 HIV-1 RNA...... copies/mL) among 293 patients randomized to two nucleoside reverse transcriptase inhibitors (NRTIs)+ritonavir+saquinavir (RS-arm) (n=115), two NRTIs+nevirapine+nelfinavir (NN-arm) (n=118), or abacavir+stavudine+didanosine (ASD-arm) (n=60) followed up for a median of 90 weeks. Data on adherence were...... collected from patient files, and genotyping was performed on plasma samples collected at time of failure. RESULTS: Treatment interruption or poor adherence was mainly caused by side effects and accounted for 74% of failures, and was associated with absence of resistance mutations. In the 30 failing...

Virological and bacteriological quality of drinking water in Ethiopia

Science.gov (United States)

Bedada, Tesfaye Legesse; Mezemir, Walelign Dessie; Dera, Firehiwot Abera; Sima, Waktole Gobena; Gebre, Samson Girma; Edicho, Redwan Muzeyin; Biegna, Almaz Gonfa; Teklu, Dejenie Shiferaw; Tullu, Kassu Desta

2018-05-01

Since unsafe water is responsible for many illness, deaths, and economic failure, water quality monitoring is essential. A cross-sectional study was conducted on 218 drinking waters samples collected between February and June 2016 to assess water quality using phages by the help of CB390 E. coli host, plaque assay; multiple tube fermentation for coliforms and pour plate for heterotrophic bacteria at Ethiopian Public Health Institute. Heterotrophic plate count greater than 100 cfu/ml was noted in 41 samples and detections of total and thermotolerant coliforms and E. coli in 38, 24, and 10 samples, respectively, and no phages detection in chlorinated waters. While heterotrophic plate count greater than 100 cfu/ml was observed in 100 samples and detections of total and thermotolerant coliforms, E. coli, and phages in 75, 60, 42, and 5 samples, respectively, for untreated waters. The majority of the waters contained indicators above standard limits. This indicates that the sources are contaminated and they are potential threats for health. Hence, regular water monitoring should be a priority agenda.

Tracking the harmonic response of magnetically-soft sensors for wireless temperature, stress, and corrosive monitoring

Science.gov (United States)

Ong, Keat G.; Grimes, Craig A.

2002-01-01

This paper describes the application of magnetically-soft ribbon-like sensors for measurement of temperature and stress, as well as corrosive monitoring, based upon changes in the amplitudes of the higher-order harmonics generated by the sensors in response to a magnetic interrogation signal. The sensors operate independently of mass loading, and so can be placed or rigidly embedded inside nonmetallic, opaque structures such as concrete or plastic. The passive harmonic-based sensor is remotely monitored through a single coplanar interrogation and detection coil. Effects due to the relative location of the sensor are eliminated by tracking harmonic amplitude ratios, thereby, enabling wide area monitoring. The wireless, passive, mass loading independent nature of the described sensor platform makes it ideally suited for long-term structural monitoring applications, such as measurement of temperature and stress inside concrete structures. A theoretical model is presented to explain the origin and behavior of the higher-order harmonics in response to temperature and stress. c2002 Elsevier Science B.V. All rights reserved.

On-line acquisition of plant related and environmental parameters (plant monitoring) in gerbera: determining plant responses

NARCIS (Netherlands)

Baas, R.; Slootweg, G.

2004-01-01

For on-line plant monitoring equipment to be functional in commercial glasshouse horticulture, relations between sensor readings and plant responses on both the short (days) and long term (weeks) are required. For this reason, systems were installed to monitor rockwool grown gerbera plants on a

Task-dependent response conflict monitoring and cognitive control in anterior cingulate and dorsolateral prefrontal cortices.

Science.gov (United States)

Kim, Chobok; Chung, Chongwook; Kim, Jeounghoon

2013-11-06

Previous experience affects our behavior in terms of adjustments. It has been suggested that the conflict monitor-controller system implemented in the prefrontal cortex plays a critical role in such adjustments. Previous studies suggested that there exists multiple conflict monitor-controller systems associated with the level of information (i.e., stimulus and response levels). In this study, we sought to test whether different types of conflicts occur at the same information processing level (i.e., response level) are independently processed. For this purpose, we designed a task paradigm to measure two different types of response conflicts using color-based and location-based conflict stimuli and measured the conflict adaptation effects associated with the two types of conflicts either independently (i.e., single conflict conditions) or simultaneously (i.e., a double-conflict condition). The behavioral results demonstrated that performance on current incongruent trials was faster only when the preceding trial was the same type of response conflict regardless of whether they included a single- or double-conflict. Imaging data also showed that anterior cingulate and dorsolateral prefrontal cortices operate in a task-specific manner. These findings suggest that there may be multiple monitor-controller loops for color-based and location-based conflicts even at the same response level. Importantly, our results suggest that double-conflict processing is qualitatively different from single-conflict processing although double-conflict shares the same sources of conflict with two single-conflict conditions. © 2013 Published by Elsevier B.V.

Una Perspectiva sobre la Situación Actual de la Virología

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Domingo Solans, Esteban

2001-02-01

Full Text Available Not available

La Virología se ha desarrollado durante la última parte del siglo XX en paralelo con las nuevas técnicas de análisis y manipulación genética y con el auxilio de técnicas físicas e informáticas. En España se han formado núcleos activos tanto en genética viral como en virus patógenos de animales y plantas. Contrariamente a predicciones de hace tan solo tres décadas, las enfermedades víricas siguen siendo un importante problema en medicina, veterinaria y agricultura. Un gran número de enfermedades víricas emergentes constituyen un importante desafío para el siglo XXI.

HIV-1 DNA predicts disease progression and post-treatment virological control

Science.gov (United States)

Williams, James P; Hurst, Jacob; Stöhr, Wolfgang; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Cooper, David; Schechter, Mauro; Tambussi, Giuseppe; Fidler, Sarah; Carrington, Mary; Babiker, Abdel; Weber, Jonathan

2014-01-01

In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials. Clinical trial registration: ISRCTN76742797 and EudraCT2004-000446-20 DOI: http://dx.doi.org/10.7554/eLife.03821.001 PMID:25217531

Porting of Bio-Informatics Tools for Plant Virology on a Computational Grid

International Nuclear Information System (INIS)

Lanzalone, G.; Lombardo, A.; Muoio, A.; Iacono-Manno, M.

2007-01-01

The goal of Tri Grid Project and PI2S2 is the creation of the first Sicilian regional computational Grid. In particular, it aims to build various software-hardware interfaces between the infrastructure and some scientific and industrial applications. In this context, we have integrated some among the most innovative computing applications in virology research inside these Grid infrastructure. Particularly, we have implemented in a complete work flow, various tools for pairwise or multiple sequence alignment and phylogeny tree construction (ClustalW-MPI), phylogenetic networks (Splits Tree), detection of recombination by phylogenetic methods (TOPALi) and prediction of DNA or RNA secondary consensus structures (KnetFold). This work will show how the ported applications decrease the execution time of the analysis programs, improve the accessibility to the data storage system and allow the use of metadata for data processing. (Author)

GeneXpert HIV-1 quant assay, a new tool for scale up of viral load monitoring in the success of ART programme in India.

Science.gov (United States)

Kulkarni, Smita; Jadhav, Sushama; Khopkar, Priyanka; Sane, Suvarna; Londhe, Rajkumar; Chimanpure, Vaishali; Dhilpe, Veronica; Ghate, Manisha; Yelagate, Rajendra; Panchal, Narayan; Rahane, Girish; Kadam, Dilip; Gaikwad, Nitin; Rewari, Bharat; Gangakhedkar, Raman

2017-07-21

Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings. A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure. The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r = 0.886) was statistically significant (p performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.

Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes

DEFF Research Database (Denmark)

Costagliola, Dominique; Ledergerber, Bruno; Torti, Carlo

2013-01-01

Low CD4(+) T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4(+) T-cell counts after triple-class virological failure....

Study of response of radiation monitors for environmental dose equivalent measurements

International Nuclear Information System (INIS)

Souza, Macilene N.; Khoury, H.J.

2005-01-01

The environmental dose equivalent H * (10), is the magnitude recommended by ICRU 39 for environmental monitoring in fields of radiation of photons. Most of the equipment used for area monitoring, only quantifies the magnitudes exposure or dose not being designed to this new magnitude. In Brazil, particularly, is not yet regulated the use of H * (10). However, with the revision of the standard 3.01 it will necessary the use of monitors that allow the achievement of measures according to H * (10). The transition for using new magnitudes will be a slow process and the contribution that the laboratories of metrology of ionizing radiation in the country can give is, at first, promote and create the habit of using the unit Sievert (Sv) in the calibration of the instruments, and that is the unit recommended for H * (10). In a second step, the tests for determining the response of the instruments for H * (10) should be made and this is the harder step, taking into account the large number of area monitors around the country. These tests will provide information about the limitations of the instrument to the new magnitude, that is, the range where the instrument will have the best performance in quantification of new magnitude. This paper evaluates the performance for H * (10), with the variation of energy and angle of incidence of radiation, of three of the most used monitors in the country

Innate immune responses of calves during transient infection with a noncytopathic strain of bovine viral diarrhea virus

DEFF Research Database (Denmark)

Muller-Doblies, D.; Arquint, A.; Schaller, P.

2004-01-01

In this study, six immunocompetent calves were experimentally infected with a noncytopathic strain of bovine viral diarrhea virus (BVDV), and the effects of the viral infection on parameters of the innate immune response of the host were analyzed. Clinical and virological data were compared...

A detection method in living plant cells for rapidly monitoring the response of plants to exogenous lanthanum.

Science.gov (United States)

Cheng, Mengzhu; Wang, Lihong; Yang, Qing; Huang, Xiaohua

2018-08-30

The pollution of rare earth elements (REEs) in ecosystem is becoming more and more serious, so it is urgent to establish methods for monitoring the pollution of REEs. Monitoring environmental pollution via the response of plants to pollutants has become the most stable and accurate method compared with traditional methods, but scientists still need to find the primary response of plants to pollutants to improve the sensitivity and speed of this method. Based on the facts that the initiation of endocytosis is the primary cellular response of the plant leaf cells to REEs and the detection of endocytosis is complex and expensive, we constructed a detection method in living plant cells for rapidly monitoring the response of plants to exogenous lanthanum [La(III), a representative of REEs] by designing a new immuno-electrochemical method for detecting the content change in extracellular vitronectin-like protein (VN) that are closely related to endocytosis. Results showed that when 30 μM La(III) initiated a small amount of endocytosis, the content of extracellular VN increased by 5.46 times, but the structure and function of plasma membrane were not interfered by La(III); when 80 μM La(III) strongly initiated a large amount of endocytosis, the content of extracellular VN increased by 119 times, meanwhile, the structure and function of plasma membrane were damaged. In summary, the detection method can reflect the response of plants to La(III) via detecting the content change in extracellular VN, which provides an effective and convenient way to monitor the response of plants to exogenous REEs. Copyright © 2018. Published by Elsevier Inc.

Effect of Pregnancy on Response to Antiretroviral Therapy in HIV-Infected African Women.

Science.gov (United States)

Kourtis, Athena P; Wiener, Jeffrey; King, Caroline C; Heffron, Renee; Mugo, Nelly R; Nanda, Kavita; Pyra, Maria; Donnell, Deborah; Celum, Connie; Lingappa, Jairam R; Baeten, Jared M

2017-01-01

While most recent evidence does not support a role for pregnancy in accelerating HIV disease progression, very little information is available on the effects of incident pregnancy in response to antiretroviral therapy (ART). Hormonal, immune, and behavioral changes during pregnancy may influence response to ART. We sought to explore the effects of incident pregnancy (after ART initiation) on virologic, immunologic, and clinical response to ART. Data were collected from HIV-infected women participating in 3 prospective studies (Partners in Prevention Herpes simplex virus/HIV Transmission Study, Couples Observational Study, and Partners Preexposure Prophylaxis Study) from 7 countries in Africa from 2004 to 2012. Women were included in this analysis if they were ≤45 years of age, were started on ART during the study and were not pregnant at ART initiation. Pregnancy was treated as a time-dependent exposure variable covering the duration of pregnancy, including all pregnancies occurring after ART initiation. Virologic failure was defined as a viral load (VL) greater than 400 copies per milliliter ≥6 months after ART initiation and viral suppression was defined as VL ≤400 copies per milliliter. Multivariable Cox proportional hazards models were used to assess the association between pregnancy and time to viral suppression, virologic failure, World Health Organization clinical stage III/IV, and death. Linear mixed-effects models were used to assess the association between pregnancy and CD4 count and VL. All analyses were adjusted for confounders, including pre-ART CD4 count and plasma VL. A total of 1041 women were followed, contributing 1196.1 person-years of follow-up. Median CD4 count before ART initiation was 276 cells per cubic millimeter (interquartile range, 209-375); median pre-ART VL was 17,511 copies per milliliter (interquartile range, 2480-69,286). One hundred ten women became pregnant after ART initiation. Pregnancy was not associated with time to

Virological and clinical characteristics of hepatitis delta virus in South Asia

Directory of Open Access Journals (Sweden)

Moatter Tariq

2011-06-01

Full Text Available Abstract Background & Aims There is a paucity of data on the impact of hepatitis D virus (HDV in patients with hepatitis B virus (HBV infection from South Asia. We studied the impact of HDV co-infection on virological and clinical characteristics. Methods We collected data of 480 patients with HBsAg positive and a detectable HBV DNA PCR, who presented to the Aga Khan University, Karachi and Isra University in Hyderabad, Pakistan in the last 5 years. HDV co-infection was diagnosed on the basis of anti-HDV. ALT, HBeAg, HBeAb and HBV DNA PCR quantitative levels were checked in all patients. We divided all patients into two groups based on anti-HDV, and compared their biochemical, serological & virological labs and clinical spectrum. Clinical spectrum of disease included asymptomatic carrier (AC, chronic active hepatitis (CAH, immuno-tolerant phase (IP, and compensated cirrhosis (CC. Results HDV co-infection was found in 169 (35.2%. There were 164 (34.6% HBeAg positive and 316 (65.4% HBeAg negative patients. Mean ALT level was 66 ± 73 IU. 233 (48.5% had raised ALT. HBV DNA level was ≥ 10e5 in 103(21.5% patients. Overall, among HBV/HDV co-infection, 146/169 (86.4% had suppressed HBV DNA PCR as compared to 231/311 (74.3% patients with HBV mono-infection; p-value = 0.002. Among HBeAg negative patients 71/128(55.5% had raised ALT levels among HBV/HDV co-infection as compared to 71/188 (37.8% with HBV mono-infection (p-value = 0.002; levels of HBV DNA were equal in two groups; there were 27/128 (21% patients with CC among HBV/HDV co-infection as compared to 23 (12% in HBV mono-infection (p-value = 0.009; there were less AC (p-value = 0.009 and more CAH (p-value = 0.009 among HBV/HDV co-infection patients. Among HBeAg positive patients, serum ALT, HBV DNA levels and the spectrum of HBV were similar in the two groups. Conclusions HBV/HDV co-infection results in the suppression of HBV DNA. A fair proportion of HBV/HDV co-infected patients with HBe

Evolution of HVR-1 quasispecies after 1-year treatment in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy.

Science.gov (United States)

Solmone, Mariacarmela; Girardi, Enrico; Lalle, Eleonora; Abbate, Isabella; D'Arminio Monforte, Antonella; Cozzi-Lepri, Alessandro; Alessandrini, Anna; Piscopo, Rita; Ebo, Francesca; Cosco, Lucio; Antonucci, Giorgio; Ippolito, Giuseppe; Capobianchi, Maria R

2006-01-01

Hepatitis C virus (HCV) variability is mainly attributed to the ability of the virus to respond to host immune pressure, acting as a driving force for the evolution of quasispecies. This study was aimed at studying the changes in HVR-1 heterogeneity and the evolution of HCV quasispecies in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy (HAART). Sixteen HIV/HCV-coinfected patients harbouring HCV genotype 1 and who had been on HAART for at least 1 year, 8 showing increasing CD4+ T-cell counts (immunological responders) and 8 showing a stable or decreasing CD4+ T-cell counts (immunological nonresponders), were selected from a prospective cohort study. After 1 year of HAART, 11 patients showed HIV viral load HVR-1 region of HCV. Nonsynonymous/synonymous substitutions ratio (Ka/Ks), aminoacidic complexity (normalized Shannon entropy) and diversity (p-distance), were considered as parameters of quasispecies heterogeneity. After 1 year of HAART, heterogeneity of HVR-1 quasispecies significantly decreased in virological non-responders, whereas the heterogeneity tended to increase in virological responders. The differences in the evolution were less stringent, when considering immunological response. On the other hand, profound qualitative modifications of HVR-1 quasispecies were observed only in patients with both immunological and virological HAART response. On the whole, these findings suggest that, in patients undergoing HAART, the extent of HCV variability and the evolution of HVR-1 quasispecies is influenced by the pattern of response to antiretroviral therapy.

Gallium-67 scintigraphy for monitoring therapy response and follow-up of paracoccidioidomycosis

International Nuclear Information System (INIS)

Yamaga, L.Y.; Watanabe, T.; Hironaka, F.; Buchpiguel, C.; Cerri, G.; Benard, G.; Shikanai-Yasuda, M.A.

2002-01-01

Objectives: The current tools to evaluate patients' therapy response in paracoccidioidomycosis (PCM) are based on clinical, immunological and radiological data. However, these criteria may be of limited value in the follow-up of asymptomatic lesions, negative pre-treatment serological tests and in severe pulmonary involvement whose chest radiography usually doesn't differentiate active from fibrotic lesions. The purpose of this study was to determine the value of Ga imaging for monitoring therapy response and follow-up of PCM patients. Methods: We studied 45 patients with confirmed PCM. Each patient underwent 2 to 7 Ga scintigraphies (total:147 scans) during a follow-up period of 4 months to 8,5 years. The Ga findings were compared to the clinical outcome and serum specific antibody levels. Results: Most patients showed improvement in the sequential Ga scans during the treatment with progressive decrease in number and intensity of sites with active infectious process. Ga scan was performed in nine patients with clinical cure and negative or persistently low levels of serum antibody following prolonged treatment. The scintigraphy confirmed the absence of inflammatory disease in all of these cases. Three patients with clinically suspected recurrence after irregular treatment showed positive Ga scans, confirming disease reactivation. Conclusion: Ga imaging is helpful in monitoring therapy response of PCM patients. Moreover, this method may be used to evaluate disease activity by confirming apparent cure and clinical recurrence

Meteorological monitoring for dose assessment and emergency response modeling - how much is enough?

International Nuclear Information System (INIS)

Glantz, C.S.

1990-01-01

Individuals responsible for emergency response or environmental/dose assessment routinely ask if there are enough meteorological data to adequately support their objectives. The answer requires detailed consideration of the intended applications, capabilities of the atmospheric dispersion model data, pollutant release characteristics, terrain in the modeling region, and size and distribution of the human population in the modeling domain. The meteorologist's detailed knowledge of, and experience in, studying atmospheric transport and diffusion can assist in determining the appropriate level of meteorological monitoring

A Production-Rule Analysis System for Nuclear Plant monitoring and emergency response applications

International Nuclear Information System (INIS)

Ragheb, M.; Tsoukalas, L.; McDonough, T.; Parker, M.

1987-01-01

A Production-Rule Analysis System for Nuclear Power Plant Monitoring is presented. The signals generated by the Zion-1 Plant are considered for emergency Response applications. The integrity of the Plant Radiation, the Reactor Coolant, the Fuel Clad, and the Containment Systems, is monitored. Representation of the system is in the form of a goal-tree generating a Knowledge-Base searched by an Inference Engine functioning in the forward-chaining mode. The Gaol-tree is built from Fault-Trees based on plant operational information. The system is implemented on a VAX-8500 and is programmed in OPS-5

Optical satellite data volcano monitoring: a multi-sensor rapid response system

Science.gov (United States)

Duda, Kenneth A.; Ramsey, Michael; Wessels, Rick L.; Dehn, Jonathan

2009-01-01

In this chapter, the use of satellite remote sensing to monitor active geological processes is described. Specifically, threats posed by volcanic eruptions are briefly outlined, and essential monitoring requirements are discussed. As an application example, a collaborative, multi-agency operational volcano monitoring system in the north Pacific is highlighted with a focus on the 2007 eruption of Kliuchevskoi volcano, Russia. The data from this system have been used since 2004 to detect the onset of volcanic activity, support the emergency response to large eruptions, and assess the volcanic products produced following the eruption. The overall utility of such integrative assessments is also summarized. The work described in this chapter was originally funded through two National Aeronautics and Space Administration (NASA) Earth System Science research grants that focused on the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) instrument. A skilled team of volcanologists, geologists, satellite tasking experts, satellite ground system experts, system engineers and software developers collaborated to accomplish the objectives. The first project, Automation of the ASTER Emergency Data Acquisition Protocol for Scientific Analysis, Disaster Monitoring, and Preparedness, established the original collaborative research and monitoring program between the University of Pittsburgh (UP), the Alaska Volcano Observatory (AVO), the NASA Land Processes Distributed Active Archive Center (LP DAAC) at the U.S. Geological Survey (USGS) Earth Resources Observation and Science (EROS) Center, and affiliates on the ASTER Science Team at the Jet Propulsion Laboratory (JPL) as well as associates at the Earth Remote Sensing Data Analysis Center (ERSDAC) in Japan. This grant, completed in 2008, also allowed for detailed volcanic analyses and data validation during three separate summer field campaigns to Kamchatka Russia. The second project, Expansion and synergistic use

Responses of intestinal virome to silver nanoparticles: safety assessment by classical virology, whole-genome sequencing and bioinformatics approaches

Directory of Open Access Journals (Sweden)

Gokulan K

2018-05-01

Full Text Available Kuppan Gokulan,1,* Aschalew Z Bekele,1,* Kenneth L Drake,2 Sangeeta Khare1 1Division of Microbiology, US Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR, USA; 2Seralogix, Inc., Austin, TX, USA *These authors contributed equally to this work Background: Effects of silver nanoparticles (AgNP on the intestinal virome/phage community are mostly unknown. The working hypothesis of this study was that the exposure of pharmaceutical/nanomedicine and other consumer-use material containing silver ions and nanoparticles to the gastrointestinal tract may result in disturbance of the beneficial gut viruses/phages. Methods: This study assesses the impact of AgNP on the survival of individual bacteriophages using classical virology cultivation and electron microscopic techniques. Moreover, how the ingested AgNP may affect the intestinal virus/phages was investigated by conducting whole-genome sequencing (WGS. Results: The viral cultivation methods showed minimal effect on selected viruses during short-term exposure (24 h to 10 nm AgNP. However, long-term exposure (7 days resulted in significant reduction in the viral/phage population. Data obtained from WGS were filtered and compared with a nonredundant viral database composed of the complete viral genomes from NCBI using KRAKEN (confidence scoring threshold of 0.5. To compare the relative differential changes, the sequence counts in each treatment group were normalized to account for differences in DNA sequencing library sizes. Bioinformatics techniques were developed to visualize the virome comparative changes in a phylogenic tree graph. The computed data revealed that AgNP had an impact on several intestinal bacteriophages that prey on bacterial genus Enterobacteria, Yersinia and Staphylococcus as host species. Moreover, there was an independent effect of nanoparticles and released ions. Conclusion: Overall, this study reveals that the small-size AgNP could lead to

Evaluation of the genotypic prediction of HIV-1 coreceptor use versus a phenotypic assay and correlation with the virological response to maraviroc: the ANRS GenoTropism study.

Science.gov (United States)

Recordon-Pinson, Patricia; Soulié, Cathia; Flandre, Philippe; Descamps, Diane; Lazrek, Mouna; Charpentier, Charlotte; Montes, Brigitte; Trabaud, Mary-Anne; Cottalorda, Jacqueline; Schneider, Véronique; Morand-Joubert, Laurence; Tamalet, Catherine; Desbois, Delphine; Macé, Muriel; Ferré, Virginie; Vabret, Astrid; Ruffault, Annick; Pallier, Coralie; Raymond, Stéphanie; Izopet, Jacques; Reynes, Jacques; Marcelin, Anne-Geneviève; Masquelier, Bernard

2010-08-01

Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of <50 copies/ml was obtained in 68% of cases at month 6. In multivariate analysis, the prediction of the X4 genotype at baseline with the Geno2pheno10 algorithm including baseline viral load and CD4 nadir was independently associated with a worse VR at months 1 and 3. The baseline weighted genotypic sensitivity score was associated with VR at month 6. There were strong arguments in favor of using genotypic coreceptor use assays for determining which patients would respond to CCR5 antagonist.

Federal Radiological Monitoring and Assessment Center Monitoring Manual Volume 2, Radiation Monitoring and Sampling

Energy Technology Data Exchange (ETDEWEB)

NSTec Aerial Measurement Systems

2012-07-31

The FRMAC Monitoring and Sampling Manual, Volume 2 provides standard operating procedures (SOPs) for field radiation monitoring and sample collection activities that are performed by the Monitoring group during a FRMAC response to a radiological emergency.

Antiretroviral therapeutic drug monitoring

African Journals Online (AJOL)

Winnie

hepatotoxicity, particularly among women with a lower body mass index, reported in ... limitations of TDM. Lastly, the potential role of TDM in southern Africa will be discussed. ... higher rates of virological suppression in the TDM arms. However ...

Instrument Response Modeling and Simulation for the GLAST Burst Monitor

International Nuclear Information System (INIS)

Kippen, R. M.; Hoover, A. S.; Wallace, M. S.; Pendleton, G. N.; Meegan, C. A.; Fishman, G. J.; Wilson-Hodge, C. A.; Kouveliotou, C.; Lichti, G. G.; Kienlin, A. von; Steinle, H.; Diehl, R.; Greiner, J.; Preece, R. D.; Connaughton, V.; Briggs, M. S.; Paciesas, W. S.; Bhat, P. N.

2007-01-01

The GLAST Burst Monitor (GBM) is designed to provide wide field of view observations of gamma-ray bursts and other fast transient sources in the energy range 10 keV to 30 MeV. The GBM is composed of several unshielded and uncollimated scintillation detectors (twelve NaI and two BGO) that are widely dispersed about the GLAST spacecraft. As a result, reconstructing source locations, energy spectra, and temporal properties from GBM data requires detailed knowledge of the detectors' response to both direct radiation as well as that scattered from the spacecraft and Earth's atmosphere. This full GBM instrument response will be captured in the form of a response function database that is derived from computer modeling and simulation. The simulation system is based on the GEANT4 Monte Carlo radiation transport simulation toolset, and is being extensively validated against calibrated experimental GBM data. We discuss the architecture of the GBM simulation and modeling system and describe how its products will be used for analysis of observed GBM data. Companion papers describe the status of validating the system

Real-Time Molecular Monitoring of Chemical Environment in ObligateAnaerobes during Oxygen Adaptive Response

Energy Technology Data Exchange (ETDEWEB)

Holman, Hoi-Ying N.; Wozei, Eleanor; Lin, Zhang; Comolli, Luis R.; Ball, David. A.; Borglin, Sharon; Fields, Matthew W.; Hazen, Terry C.; Downing, Kenneth H.

2009-02-25

Determining the transient chemical properties of the intracellular environment canelucidate the paths through which a biological system adapts to changes in its environment, for example, the mechanisms which enable some obligate anaerobic bacteria to survive a sudden exposure to oxygen. Here we used high-resolution Fourier Transform Infrared (FTIR) spectromicroscopy to continuously follow cellular chemistry within living obligate anaerobes by monitoring hydrogen bonding in their cellular water. We observed a sequence of wellorchestrated molecular events that correspond to changes in cellular processes in those cells that survive, but only accumulation of radicals in those that do not. We thereby can interpret the adaptive response in terms of transient intracellular chemistry and link it to oxygen stress and survival. This ability to monitor chemical changes at the molecular level can yield important insights into a wide range of adaptive responses.

Impact of donor and recipient single nucleotide polymorphisms of IL28B rs8099917 in living donor liver transplantation for hepatitis C.

Directory of Open Access Journals (Sweden)

Nobuhiro Harada

Full Text Available Single nucleotide polymorphisms of interleukin-28B (IL28B rs8099917 are reported to be associated with virologic clearance in interferon-and ribavirin -based treatment for hepatitis C virus (HCV-infected patients. We examined virologic response in accordance with IL28B polymorphisms in our living donor liver transplantation series under a preemptive interferon and RBV treatment approach. Adequate DNA samples from both the recipient and donor for the study of single nucleotide polymorphisms of IL28B were available from 96 cases and were the subjects of the present study. Various clinical factors related with virologic response including early virologic response (EVR and sustained virologic response (SVR were examined. Totally 51% presented with EVR and 44% achieved SVR. Presence of the major allele (TT in either the recipient or the donor corresponded to SVR of 53% and 48%. Presence of the minor allele (TG or GG corresponded to SVR of 26% and 32%. Multivariate analysis revealed that genotype of HCV or EVR, but not IL28B polymorphisms in either the recipient or donor, was an independent factor for achieving SVR. When virologic response to treatment was incorporated into analysis, the impact of IL28B polymorphism on virological clearance remained relative to other factors and was not significantly independent.

Cotton Fabric Coated with Conducting Polymers and its Application in Monitoring of Carnivorous Plant Response

Directory of Open Access Journals (Sweden)

Václav Bajgar

2016-04-01

Full Text Available The paper describes the electrical plant response to mechanical stimulation monitored with the help of conducting polymers deposited on cotton fabric. Cotton fabric was coated with conducting polymers, polyaniline or polypyrrole, in situ during the oxidation of respective monomers in aqueous medium. Thus, modified fabrics were again coated with polypyrrole or polyaniline, respectively, in order to investigate any synergetic effect between both polymers with respect to conductivity and its stability during repeated dry cleaning. The coating was confirmed by infrared spectroscopy. The resulting fabrics have been used as electrodes to collect the electrical response to the stimulation of a Venus flytrap plant. This is a paradigm of the use of conducting polymers in monitoring of plant neurobiology.

Evaluating immunologic response and clinical deterioration in treatment-naïve patients initiating first-line therapies infected with HIV-1 CRF01_AE and subtype B

Science.gov (United States)

Oyomopito, Rebecca A.; Li, Patrick CK.; Sungkanuparph, Somnuek; Phanuphak, Praphan; Tee, Kok Keng; Sirisanthana, Thira; Kantipong, Pacharee; Oka, Shinichi; Lee, Chris KC.; Kamarulzaman, Adeeba; Choi, Jun Yong; Sohn, Annette H.; Law, Matthew; Chen, Yi-Ming A.

2012-01-01

Background HIV-1 group M viruses diverge 25%–35% in envelope, important for viral attachment during infection, and 10–15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunologic or virologic treatment responses differed by genotype in treatment-naïve patients initiating first-line therapy. Methods Prospectively collected, longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of CDC category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post-therapy, evaluated by linear and logistic regression, respectively. Results Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median:413 days, IQR:169–672 days). Patients >40 years demonstrated smaller immunological increases (p=0.002) and higher risk of clinical deterioration (HR=2.17; p=0.008). Patients with baseline CD4 cell counts >200 cells/μL had lower risk of clinical deterioration (HR=0.373; p=0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post-therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (p=0.024). A total of 530 patients (48.0% of eligible) were included in virologic analyses with no differences in response found between genotypes. Conclusions Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared to

Replication capacity in relation to immunologic and virologic outcomes in HIV-1-infected treatment-naive subjects.

Science.gov (United States)

Skowron, Gail; Spritzler, John G; Weidler, Jodi; Robbins, Gregory K; Johnson, Victoria A; Chan, Ellen S; Asmuth, David M; Gandhi, Rajesh T; Lie, Yolanda; Bates, Michael; Pollard, Richard B

2009-03-01

To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy. RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = -0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = -0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (DeltaCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and DeltaCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL. At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.

Monitoring treatment response and metastatic relapse in advanced bladder cancer by liquid biopsy analysis

DEFF Research Database (Denmark)

Birkenkamp-Demtröder, Karin; Christensen, Emil; Nordentoft, Iver Kristiansen

2017-01-01

of circulating tumour DNA (ctDNA) in plasma and urine to detect metastatic relapse after cystectomy and measure treatment efficacy. We exome sequenced tumour and germline DNA from patients with muscle-invasive bladder cancer and monitored ctDNA in 370 liquid biopsies throughout the disease courses by 84......DNA detection in plasma and diagnosis of relapse was 101 d after cystectomy (range 0-932 d). Early detection of metastatic relapse and treatment response using liquid biopsies represents a novel, highly sensitive tool for monitoring patients, supporting clinicians, and guiding treatment decisions. PATIENT...

The clinical impact of continuing to prescribe antiretroviral therapy in patients with advanced AIDS who manifest no virologic or immunologic benefit.

Directory of Open Access Journals (Sweden)

David A Wohl

Full Text Available Despite the efficacy and tolerability of modern antiretroviral therapy (ART, many patients with advanced AIDS prescribed these regimens do not achieve viral suppression or immune reconstitution as a result of poor adherence, drug resistance, or both. The clinical outcomes of continued ART prescription for such patients have not been well characterized.We examined the causes and predictors of all-cause mortality, AIDS-defining conditions, and serious non-AIDS-defining events among a cohort of participants in a clinical trial of pre-emptive therapy for CMV disease. We focused on participants who, despite ART had failed to achieve virologic suppression and substantive immune reconstitution.233 ART-receiving participants entered with a median baseline CD4+ T cell count of 30/mm(3 and plasma HIV RNA of 5 log10 copies/mL. During a median 96 weeks of follow-up, 24.0% died (a mortality rate of 10.7/100 patient-years; 27.5% reported a new AIDS-defining condition, and 22.3% a new serious non-AIDS event. Of the deaths, 42.8% were due to an AIDS-defining condition, 44.6% were due to a non-AIDS-defining condition, and 12.5% were of unknown etiology. Decreased risk of mortality was associated with baseline CD4+ T cell count ≥25/mm(3 and lower baseline HIV RNA.Among patients with advanced AIDS prescribed modern ART who achieve neither virologic suppression nor immune reconstitution, crude mortality percentages appear to be lower than reported in cohorts of patients studied a decade earlier. Also, in contrast to the era before modern ART became available, nearly half of the deaths in our modern-era study were caused by serious non-AIDS-defining events. Even among the most advanced AIDS patients who were not obtaining apparent immunologic and virologic benefit from ART, continued prescription of these medications appears to alter the natural history of AIDS--improving survival and shifting the causes of death from AIDS- to non-AIDS-defining conditions.

Implementation of distributed computing system for emergency response and contaminant spill monitoring

International Nuclear Information System (INIS)

Ojo, T.O.; Sterling, M.C.Jr.; Bonner, J.S.; Fuller, C.B.; Kelly, F.; Page, C.A.

2003-01-01

The availability and use of real-time environmental data greatly enhances emergency response and spill monitoring in coastal and near shore environments. The data would include surface currents, wind speed, wind direction, and temperature. Model predictions (fate and transport) or forensics can also be included. In order to achieve an integrated system suitable for application in spill or emergency response situations, a link is required because this information exists on many different computing platforms. When real-time measurements are needed to monitor a spill, the use of a wide array of sensors and ship-based post-processing methods help reduce the latency in data transfer between field sampling stations and the Incident Command Centre. The common thread linking all these modules is the Transmission Control Protocol/Internet Protocol (TCP/IP), and the result is an integrated distributed computing system (DCS). The in-situ sensors are linked to an onboard computer through the use of a ship-based local area network (LAN) using a submersible device server. The onboard computer serves as both the data post-processor and communications server. It links the field sampling station with other modules, and is responsible for transferring data to the Incident Command Centre. This link is facilitated by a wide area network (WAN) based on wireless broadband communications facilities. This paper described the implementation of the DCS. The test results for the communications link and system readiness were also included. 6 refs., 2 tabs., 3 figs

Meteorological monitoring for environmental/dose assessment and emergency response modeling: How much is enough?

International Nuclear Information System (INIS)

Glantz, C.S.

1989-01-01

In evaluation the effectiveness and appropriateness of meteorological monitoring programs, managers responsible for planning and operating emergency response or environmental/dose assessment systems must routinely question whether enough meteorological data are being obtained to adequately support system applications. There is no simple answer or cookbook procedure that can be followed in generating an appropriate answer to this question. The answer must be developed through detailed consideration of the intended applications for the data, the capabilities of the models that would use the data, pollutant release characteristics, terrain in the modeling region, the size of the modeling domain, and the distribution of human population in the modeling domain. It is recommended that manager consult meteorologists when assessing these factors; the meteorologist's detailed knowledge of, and experience in, studying atmospheric transport and diffusion should assist the manager in determining the appropriate level of meteorological monitoring. 1 ref

Acute HIV infection (AHI) in a specialized clinical setting: case-finding, description of virological, epidemiological and clinical characteristics.

Science.gov (United States)

Ammassari, Adriana; Abbate, Isabella; Orchi, Nicoletta; Pinnetti, Carmela; Rozera, Gabriella; Libertone, Raffaella; Pierro, Paola; Martini, Federico; Puro, Vincenzo; Girardi, Enrico; Antinori, Andrea; Capobianchi, Maria Rosaria

2014-01-01

Diagnosis of HIV infection during early stages is mandatory to catch up with the challenge of limiting HIV viral replication and reservoirs formation, as well as decreasing HIV transmissions by immediate cART initiation. Aims were to describe (a) virological characteristics of AHI identified, (b) epidemiological and clinical factors associated with being diagnosed with AHI. Cross-sectional, retrospective study. All individuals diagnosed with AHI according to Fiebig's staging between Jan 2013 and Mar 2014 at the INMI "L. Spallanzani" were included. Serum samples reactive to a fourth generation HIV-1/2 assay (Architect HIV Ag/Ab Combo, Abbott) were retested with another fourth generation assay (VIDAS DUO HIV Ultra, Biomérieux) and underwent confirmation with HIV-1 WB (New Lav I Bio-Rad) and/or with Geenius confirmatory assay (Bio-Rad). WHO criteria (two env products reactivity) were used to establish positivity of confirmatory assays. In case of clinically suspected AHI, HIV-1 RNA (Real time, Abbott) and p24 assay (VIDAS HIV P24 Bio-Rad) were also performed. Avidity test was carried out, on confirmed positive samples lacking p31 reactivity, to discriminate between recent (true Fiebig V phase) and late infections; to avoid possible misclassifications, clinical data were also used. Demographic, epidemiological, clinical and laboratory data are routinely, and anonymously recorded in the SENDIH and SIREA studies. During the study period, we observed 483 newly HIV diagnosed individuals, of whom 40 were identified as AHI (8.3%). Fiebig classification showed: 7 stage II/III, 13 stage IV, 20 stage V. Demographic, epidemiological, and clinical characteristics of patients are shown in the Table. Overall, the study population had a median S/Co ratio at fourth generation EIA (Architect) of 49.50 (IQR, 23.54-98.05): values were significantly lower in Fiebig II-IV than in Fiebig V (38.68 [IQR, 20.08-54.84] vs 75.72 [IQR, 42.66-249.80], p=0.01). Overall, median HIV-1 RNA was 5

Salient features, response and operation of Lead-Free Gulmarg Neutron Monitor

International Nuclear Information System (INIS)

Mufti, S.; Chatterjee, S.; Ishtiaq, P.M.; Darzi, M.A.; Mir, T.A.; Shah, G.N.

2016-01-01

Lead-Free Gulmarg Neutron Monitor (LFGNM) provides continuous ground level intensity measurements of atmospheric secondary neutrons produced in interactions of primary cosmic rays with the Earth's constituent atmosphere. We report the LFGNM detector salient features and simulation of its energy response for 10"−"1"1 MeV to 10"4 MeV energy incident neutrons using the FLUKA Monte Carlo package. An empirical calibration of the LFGNM detector carried out with a Pu–Be neutron source for maximising its few MeV neutron counting sensitivity is also presented. As an illustration of its functionality a single representative transient solar modulation event recorded by LFGNM depicting Forbush decrease in integrated neutron data for which the geospace consequences are well known is also presented. Performance of LFGNM under actual observation conditions for effectively responding to transient solar modulation is seen to compare well with other world-wide conventional neutron monitors.

The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1-infected patients who do or do not achieve sustained virological response to therapy.

Science.gov (United States)

Backx, M; Lewszuk, A; White, J R; Cole, J; Sreedharan, A; van Sanden, S; Diels, J; Lawson, A; Neal, K R; Wiselka, M J; Ito, T; Irving, W L

2014-03-01

Chronic hepatitis C virus (HCV) infection places a considerable economic burden on health services. Cost-effectiveness analyses of antiviral treatment for patients with chronic HCV infection are dependent on assumptions about cost reductions following sustained virological response (SVR) to therapy. This study quantified the medium-term difference in health resource usage and costs depending on treatment outcome. Retrospective chart review of patients with HCV genotype 1 infection who had received at least 2 months pegylated interferon and ribavirin therapy, with known treatment outcome was conducted. Disease status was categorized as chronic hepatitis, cirrhosis or decompensated liver disease. Health resource use was documented for each patient in each disease state. Unit costs were from the NHS 'Payment by Results' database and the British National Formulary. One hundred and ninety three patients (108 SVR, 85 non-SVR) with mean follow-up of 3.5 (SVR) and 4.9 (non-SVR) years were enrolled. No SVR patient progressed to a more severe liver disease state. Annual transition rates for non-SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to decompensated liver disease). By extrapolation of modelled data over a 5-year post-treatment period, failure of patients with chronic hepatitis to achieve SVR was associated with a 13-fold increase (roughly £2300) in costs, whilst for patients who were retreated, the increase was 56-fold, equating to more than £10 000. Achievement of an SVR has significant effects on health service usage and costs. This work provides real-life data for future cost-effectiveness analyses related to the treatment for chronic HCV infection. © 2013 John Wiley & Sons Ltd.

[Caprine arthritis-encephalitis: trial of an adjuvant vaccine preparation. I. Clinical and virological study].

Science.gov (United States)

Russo, P; Vitu, C; Fontaine, J J; Vignoni, M

1993-04-01

In purpose to protect goats against caprine arthritis encephalitis virus (CAEV), the first group of kids (I) was inoculated with purified, inactivated and adjuvant-treated virions, the second group (II) with adjuvant and the third one (III) with culture medium. 2-4 months later, the three groups were challenged with virulent CAEV by intraarticular route. On the clinical level, vaccinated and challenged kids show more early and severe arthritis than other groups. On the virological level, isolation of lentivirus from white blood cells and different organs is more important in group I than groups II and III. Therefore, vaccinations with inactivated and adjuvant-treated virions do not protect against a virulent challenge; there is an enhancement of lesions. We note that the adjuvant elicits a mild non-specific protection against virulent challenge.

Auditory brainstem evoked responses and temperature monitoring during pediatric cardiopulmonary bypass.

Science.gov (United States)

Rodriguez, R A; Edmonds, H L; Auden, S M; Austin, E H

1999-09-01

To examine the effects of temperature on auditory brainstem responses (ABRs) in infants during hypothermic cardiopulmonary bypass for total circulatory arrest (TCA). The relationship between ABRs (as a surrogate measure of core-brain temperature) and body temperature as measured at several temperature monitoring sites was determined. In a prospective, observational study, ABRs were recorded non-invasively at normothermia and at every 1 or 2 degrees C change in ear-canal temperature during cooling and rewarming in 15 infants (ages: 2 days to 14 months) that required TCA. The ABR latencies and amplitudes and the lowest temperatures at which an ABR was identified (the threshold) were measured during both cooling and rewarming. Temperatures from four standard temperature monitoring sites were simultaneously recorded. The latencies of ABRs increased and amplitudes decreased with cooling (P < 0.01), but rewarming reversed these effects. The ABR threshold temperature as related to each monitoring site (ear-canal, nasopharynx, esophagus and bladder) was respectively determined as 23 +/- 2.2 degrees C, 20.8 +/- 1.7 degrees C, 14.6 +/- 3.4 degrees C, and 21.5 +/- 3.8 degrees C during cooling and 21.8 +/- 1.6 degrees C, 22.4 +/- 2.0 degrees C, 27.6 +/- 3.6 degrees C, and 23.0 +/- 2.4 degrees C during rewarming. The rewarming latencies were shorter and Q10 latencies smaller than the corresponding cooling values (P < 0.01). Esophageal and bladder sites were more susceptible to temperature variations as compared with the ear-canal and nasopharynx. No temperature site reliably predicted an electrophysiological threshold. A faster latency recovery during rewarming suggests that body temperature monitoring underestimates the effects of rewarming in the core-brain. ABRs may be helpful to monitor the effects of cooling and rewarming on the core-brain during pediatric cardiopulmonary bypass.

Study of the response of radiation protection monitors in terms of H*(10) in X radiation

International Nuclear Information System (INIS)

Nonato, Fernanda B.C.; Carvalho, Valdir S.; Vivolo, Vitor; Caldas, Linda V.E.

2009-01-01

The ambient dose equivalent, H * (10), is an operational quantity recommended by the International Commission of radiation Units and Measurements Report 39 for measurements in area monitoring. However, most of the monitoring instruments used in radiation protection in Brazil still use the old quantities exposure rate and absorbed dose rate. Therefore, it is necessary to study how to change the operational quantity to H * (10). In this work, the response of radiation protection monitoring detectors was studied in terms of H * (10) for different energies using standard X-rays (narrow beams) at the Calibration Laboratory of IPEN. (author)

Response of .i.Alteromonadaceae./i. and .i.Rhodobacteriaceae./i. to glucose and phosphorus manipulation in marine mesocosms

Czech Academy of Sciences Publication Activity Database

Allers, E.; Gómez-Consarnau, L.; Pinhassi, J.; Gasol, J.M.; Šimek, Karel; Pernthaler, J.

2007-01-01

Roč. 9, č. 10 (2007), s. 2417-2429 ISSN 1462-2912 Grant - others:EU(XE) EVK3-2001-00194 BASICS Institutional research plan: CEZ:AV0Z60170517 Keywords : bacterial community composition * Alteromonadaceae * Rhodobacteriaceae * responses to phosphorus and glucose additions * protozoan bacterivory Subject RIV: EE - Microbiology, Virology Impact factor: 4.929, year: 2007

A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.

Science.gov (United States)

Armenia, Daniele; Soulie, Cathia; Di Carlo, Domenico; Fabeni, Lavinia; Gori, Caterina; Forbici, Federica; Svicher, Valentina; Bertoli, Ada; Sarmati, Loredana; Giuliani, Massimo; Latini, Alessandra; Boumis, Evangelo; Zaccarelli, Mauro; Bellagamba, Rita; Andreoni, Massimo; Marcelin, Anne-Geneviève; Calvez, Vincent; Antinori, Andrea; Ceccherini-Silberstein, Francesca; Perno, Carlo-Federico; Santoro, Maria Mercedes

2014-01-01

We previously found that a very low geno2pheno false positive rate (FPR ≤ 2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤ 2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART. The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤ 2; 2-5; 5-10; 10-20; 20-60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥ 150 cells/mm(3)) and on the time to achieve virological success (the first HIV-RNA measurement immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤ 2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2-5; 77.5%, FPR 5-10; 71.7%, FPR 10-20; 81.8%, FPR 20-60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤ 2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20-0.71], p = 0.003) and to achieve virological success (0.50 [0.26-0.94], p = 0.031) than those with pre-HAART FPR >60%. Beyond the genotypically-inferred tropism determination, FPR ≤ 2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability.

Monitoring the response to rTMS in depression with visual analog scales.

Science.gov (United States)

Grunhaus, Leon; Dolberg, Ornah T; Polak, Dana; Dannon, Pinhas N

2002-10-01

Visual analog scales (VAS) administered on a daily basis provide a fast and reliable method for assessing clinical change during transcranial magnetic stimulation (TMS). We treated 40 patients with major depression with TMS and assessed their clinical condition with VAS. Response to TMS was defined with the Hamilton rating scale for depression and the Global assessment of function scale. Nineteen patients of 40 were responders to TMS (when the whole sample was considered) whereas 17 of 29 responded when only the non-psychotic patients were considered. Patients who eventually responded to TMS demonstrated early changes in the VAS scores. We conclude that monitoring with VAS scores can detect early response to TMS. Copyright 2002 John Wiley & Sons, Ltd.

Discordant CSF/plasma HIV-1 RNA in individuals on virologically suppressive antiretroviral therapy in Western India.

Science.gov (United States)

Dravid, Ameet N; Natrajan, Kartik; Kulkarni, Milind M; Saraf, Chinmay K; Mahajan, Uma S; Kore, Sachin D; Rathod, Niranjan M; Mahajan, Umakant S; Wadia, Rustom S

2018-02-01

Aim of this study was to estimate the prevalence of cerebrospinal fluid (CSF)/Plasma HIV-1 RNA discordance in virologically suppressed individuals presenting with incident neurologic symptoms.In this retrospective cohort study conducted between March 1, 2009, and March 1, 2017, HIV-1 infected adults exposed to atleast 12 months of antiretroviral therapy (ART) and having plasma viral load (VL) CSF/Plasma HIV-1 RNA discordance by measuring HIV-1 RNA in collected plasma and CSF samples. CSF/plasma HIV-1 RNA discordance was defined as either detectable CSF HIV-1 RNA (VL > 20 copies/mL) with an undetectable plasma RNA (complete viral suppression, VL ≤20 copies/mL) or CSF HIV-1 RNA ≥ 0.5 log10 higher than plasma RNA when plasma VL was between 20 and 1000 copies/mL (low-level viremia, LLV).Out of 1584 virologically suppressed patients, 71 (4.4%) presented with incident neurologic symptoms. Twenty out of 71 (28.2%) patients were diagnosed with CSF/Plasma HIV-1 discordance. Median plasma and CSF VL in patients with discordance was 120 [interquartile range (IQR): CSF HIV-1 genotypic resistance testing was done showed mutations that would compromise efficacy of prescribed ART regimen. Prevalence of CSF/plasma HIV-1 RNA discordance was higher among neurologically symptomatic patients with plasma LLV as compared with those with complete viral suppression (70% vs 11.8%, P CSF/plasma HIV-1 RNA discordance indicates replication of HIV-1 that has adapted to the CNS or has developed antiretroviral drug resistance. Larger studies should be performed to study incidence of discordance in India. This will help in managing patients presenting with neurologic symptoms on suppressive ART with appropriate neuroeffective therapy.

Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

DEFF Research Database (Denmark)

Ledergerber, Bruno; Lundgren, Jens D; Walker, A Sarah

2014-01-01

Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure....

Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial: raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART

NARCIS (Netherlands)

Lambert-Niclot, S.; George, E. C.; Pozniak, A.; White, E.; Schwimmer, C.; Jessen, H.; Johnson, M.; Dunn, D.; Perno, C. F.; Clotet, B.; Plettenberg, A.; Blaxhult, A.; Palmisano, L.; Wittkop, L.; Calvez, V.; Marcelin, A. G.; Raffi, F.; Dedes, Nikos; Chêne, Geneviève; Richert, Laura; Allavena, Clotilde; Raffi, François; Autran, Brigitte; Antinori, Andrea; Bucciardini, Raff Aella; Vella, Stefano; Horban, Andrzej; Arribas, Jose; Babiker, Abdel G.; Boffito, Marta; Pillay, Deenan; Pozniak, Anton; Franquet, Xavier; Schwarze, Siegfried; Grarup, Jesper; Fischer, Aurélie; Wallet, Cédrick; Diallo, Alpha; Molina, Jean-Michel; Saillard, Juliette; Moecklinghoff, Christiane; Stellbrink, Hans-Jürgen; van Leeuwen, Remko; Gatell, Jose; Sandstrom, Eric; Flepp, Markus; Ewings, Fiona; George, Elizabeth C.; Hudson, Fleur; Pearce, Gillian; Quercia, Romina; Rogatto, Felipe; Leavitt, Randi; Nguyen, Bach-Yen; Goebel, Frank; Marcotullio, Simone; Kaur, Navrup; Sasieni, Peter; Spencer-Drake, Christina; Peto, Tim; Miller, Veronica; Arnault, Fabien; Boucherie, Céline; Jean, Delphine; Paniego, Virginie; Paraina, Felasoa; Rouch, Elodie; Schwimmer, Christine; Soussi, Malika; Taieb, Audrey; Termote, Monique; Touzeau, Guillaume; Cursley, Adam; Dodds, Wendy; Hoppe, Anne; Kummeling, Ischa; Pacciarini, Filippo; Paton, Nick; Russell, Charlotte; Taylor, Kay; Ward, Denise; Aagaard, Bitten; Eid, Marius; Gey, Daniela; Jensen, Birgitte Gram; Jakobsen, Marie-Louise; Jansson, Per O.; Jensen, Karoline; Joensen, Zillah Maria; Larsen, Ellen Moseholm; Pahl, Christiane; Pearson, Mary; Nielsen, Birgit Riis; Reilev, Søren Stentoft; Christ, Ilse; Lathouwers, Desiree; Manting, Corry; Mendy, Bienvenu Yves; Metro, Annie; Couffin-Cadiergues, Sandrine; Knellwolf, Anne-Laure; Palmisiano, Lucia; Aznar, Esther; Barea, Cristina; Cotarelo, Manuel; Esteban, Herminia; Girbau, Iciar; Moyano, Beatriz; Ramirez, Miriam; Saiz, Carmen; Sanchez, Isabel; Yllescas, Maria; Binelli, Andrea; Colasanti, Valentina; Massella, Maurizio; Anagnostou, Olga; Gioukari, Vicky; Touloumi, Giota; Schmied, Brigitte; Rieger, Armin; Vetter, Norbert; de Wit, Stephane; Florence, Eric; Vandekerckhove, Linos; Gerstoft, Jan; Mathiesen, Lars; Katlama, Christine; Cabie, Andre; Cheret, Antoine; Dupon, Michel; Ghosn, Jade; Girard, Pierre-Marie; Goujard, Cécile; Lévy, Yves; Morlat, Philippe; Neau, Didier; Obadia, Martine; Perre, Philippe; Piroth, Lionel; Reynes, Jacques; Tattevin, Pierre; Ragnaud, Jean Marie; Weiss, Laurence; Yazdan, Yazdanpanah; Yeni, Patrick; Zucman, David; Behrens, Georg; Esser, Stefan; Fätkenheuer, Gerd; Hoffmann, Christian; Jessen, Heiko; Rockstroh, Jürgen; Schmidt, Reinhold; Stephan, Christoph; Unger, Stefan; Hatzakis, Angelos; Daikos, George L.; Papadopoulos, Antonios; Skoutelis, Athamasios; Banhegyi, Denes; Mallon, Paddy; Mulcahy, Fiona; Andreoni, Massimo; Bonora, Stefano; Castelli, Francesco; Monforte, Antonella D.'Arminio; Di Perri, Giovanni; Galli, Massimo; Lazzarin, Adriano; Mazzotta, Francesco; Carlo, Torti; Vullo, Vincenzo; Prins, Jan; Richter, Clemens; Verhagen, Dominique; van Eeden, Arne; Doroana, Manuela; Antunes, Francisco; Maltez, Fernando; Sarmento-Castro, Rui; Garcia, Juan Gonzalez; Aldeguer, José López; Clotet, Bonaventura; Domingo, Pere; Gatell, Jose M.; Knobel, Hernando; Marquez, Manuel; Miralles, Martin Pilar; Portilla, Joaquin; Soriano, Vicente; Tellez, Maria-Jesus; Thalme, Anders; Blaxhult, Anders; Gisslen, Magnus; Winston, Alan; Fox, Julie; Gompels, Mark; Herieka, Elbushra; Johnson, Margaret; Leen, Clifford; Teague, Alastair; Williams, Ian; Boyd, Mark Alastair; Møller, Nina Friis; Larsen, Ellen Frøsig Moseholm; Le Moing, Vincent; Wit, Ferdinand W. N. M.; Kowalska, Justyna; Berenguer, Juan; Moreno, Santiago; Müller, Nicolas J.; Török, Estée; Post, Frank; Angus, Brian; Calvez, Vincent; Boucher, Charles; Collins, Simon; Dunn, David; Lambert, Sidonie; Marcelin, Anne-Geneviève; Perno, Carlo Federico; White, Ellen; Ammassari, Adriana; Stoehr, Wolgang; Schmidt, Reinhold Ernst; Odermarsky, Michal; Smith, Colette; Thiébaut, Rodolphe; de La Serna, Jose Ignacio Bernardino; Castagna, Antonella; Furrer, Hans-Jackob; Mocroft, Amanda; Reiss, Peter; Bucciardini, Raffaella; Fragola, Vincenzo; Lauriola, Marco; Murri, Rita; Nieuwkerk, Pythia; Spire, Bruno; Volny-Anne, Alain; West, Brian; Amieva, Hélène; Llibre Codina, Josep Maria; Braggion, Marco; Focà, Emanuele

2016-01-01

To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and

On-line acquisition of plant related and environmental parameters (plant monitoring) in gerbera: determining plant responses

OpenAIRE

Baas, R.; Slootweg, G.

2004-01-01

For on-line plant monitoring equipment to be functional in commercial glasshouse horticulture, relations between sensor readings and plant responses on both the short (days) and long term (weeks) are required. For this reason, systems were installed to monitor rockwool grown gerbera plants on a minute-to-minute basis from July 2002 until April 2003. Data collected included, amongst others, crop transpiration from lysimeter data (2 m2), canopy temperature using infrared sensors, rockwool water...

The role of interferon gamma release assays in the monitoring of response to anti-tuberculosis treatment in children.

Science.gov (United States)

Shaik, Junaid; Pillay, Manormoney; Jeena, Prakash

2014-09-01

Successful control of childhood TB requires early diagnosis, effective chemotherapy and a method of evaluating the response to therapy. Identification of suitable biomarkers that predict the response to anti-TB therapy may allow the duration of treatment to be shortened. The majority of biomarker studies in paediatric TB have focused on the role of T cell-based interferon-gamma (IFN-γ) release assays (IGRAs) in the diagnosis of either latent or active disease. Little has been published on the role of IGRAs in the monitoring response to therapy in children. We reviewed the available literature to ascertain the value of IGRAs in the monitoring of response to anti-TB therapy in children. We explored the results of the few studies that have investigated the role of IGRAs as markers of response to anti-TB treatment in children. We conclude that the role of IGRAs as surrogate markers appears promising. Robust clinical trials are, however, needed to entrench the value of IGRAs as surrogate biomarkers of response to anti-TB therapy in children. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIRaben-1 subtype B and non-subtype B receiving a salvage regimen

NARCIS (Netherlands)

De Luca, Andrea; Flandre, Philippe; Dunn, David; Zazzi, Maurizio; Wensing, Annemarie; Santoro, Maria Mercedes; Günthard, Huldrych F.; Wittkop, Linda; Kordossis, Theodoros; Garcia, Federico; Castagna, Antonella; Cozzi-Lepri, Alessandro; Churchill, Duncan; De Wit, Stéphane; Brockmeyer, Norbert H.; Imaz, Arkaitz; Mussini, Cristina; Obel, Niels; Perno, Carlo Federico; Roca, Bernardino; Reiss, Peter; Schülter, Eugen; Torti, Carlo; van Sighem, Ard; Zangerle, Robert; Descamps, Diane; Mocroft, Amanda; Kirk, Ole; Sabin, Caroline; De Wit, Stéphane; Casabona, Jordi; Miró, Jose M.; Touloumi, Giota; Garrido, Myriam; Teira, Ramon; Wit, Ferdinand; Warszawski, Josiane; Meyer, Laurence; Dabis, François; Krause, Murielle Mary; Ghosn, Jade; Leport, Catherine; Prins, Maria; Bucher, Heiner; Gibb, Diana; Fätkenheuer, Gerd; del Amo, Julia; Thorne, Claire; Stephan, Christoph; Pérez-Hoyos, Santiago; Hamouda, Osamah; Bartmeyer, Barbara; Chkhartishvili, Nikoloz; Noguera-Julian, Antoni; Antinori, Andrea; d'Arminio Monforte, Antonella; Prieto, Luis; Conejo, Pablo Rojo; Soriano-Arandes, Antoni; Battegay, Manuel; Kouyos, Roger; Tookey, Pat; Konopnick, Deborah; Goetghebuer, Tessa; Sönnerborg, Anders; Haerry, David; de Wit, Stéphane; Costagliola, Dominique; Raben, Dorthe; Chêne, Geneviève; Ceccherini-Silberstein, Francesca; Günthard, Huldrych; Judd, Ali; Barger, Diana; Schwimmer, Christine; Termote, Monique; Campbell, Maria; Frederiksen, Casper M.; Friis-Møller, Nina; Kjaer, Jesper; Brandt, Rikke Salbøl; Berenguer, Juan; Bohlius, Julia; Bouteloup, Vincent; Davies, Mary Anne; Dorrucci, Maria; Egger, Matthias; Furrer, Hansjakob; Guiguet, Marguerite; Grabar, Sophie; Lambotte, Olivier; Leroy, Valériane; Lodi, Sara; Matheron, Sophie; Monge, Susana; Nakagawa, Fumiyo; Paredes, Roger; Phillips, Andrew; Puoti, Massimo; Schomaker, Michael; Smit, Colette; Sterne, Jonathan; Thiebaut, Rodolphe; van der Valk, Marc; Wyss, Natasha; Aubert, V.; Battegay, M.; Bernasconi, E.; Böni, J.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Dollenmaier, G.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Fux, C. A.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H. H.; Hoffmann, M.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kouyos, R.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Nicca, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schöni-Affolter, F.; Schmid, P.; Schüpbach, J.; Speck, R.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.

2016-01-01

Objectives: The objective of this studywas to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. Methods: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from large

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-week results of a randomized trial.

Directory of Open Access Journals (Sweden)

Barbara Rossetti

Full Text Available Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption per protocol at week 48.Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm or continue current ART (continuation arm.In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm. The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005. The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030. At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm.Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy.

Stress-response sigma factor sigH is essential for morphological differentiation of Streptomyces coelicolor A3(2)

Czech Academy of Sciences Publication Activity Database

Ševčíková, B.; Benada, Oldřich; Kofroňová, Olga; Kormanec, J.

2001-01-01

Roč. 177, - (2001), s. 98-106 ISSN 0302-8933 R&D Projects: GA ČR GA204/98/0421; GA AV ČR IAA5020903; GA AV ČR IPP1043020 Institutional research plan: CEZ:AV0Z5020903 Keywords : Streptomyces * stress response * RNA polymerase Subject RIV: EE - Microbiology, Virology Impact factor: 2.156, year: 2001

10 CFR 850.24 - Exposure monitoring.

Science.gov (United States)

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Exposure monitoring. 850.24 Section 850.24 Energy... Exposure monitoring. (a) General. The responsible employer must ensure that: (1) Exposure monitoring is... activities properly. (b) Initial monitoring. The responsible employer must perform initial monitoring in...

Low-complexity Wireless Monitoring of Respiratory Movements Using Ultra-wideband Impulse Response Estimation

KAUST Repository

Sana, Furrukh

2014-03-01

In this paper; we present a comprehensive scheme for wireless monitoring of the respiratory movements in humans. Our scheme overcomes the challenges low signal-to-noise ratio, background clutter and high sampling rates. It is based on the estimation of the ultra-wideband channel impulse response. We suggest techniques for dealing with background clutter in situations when it might be time variant. We also present a novel methodology for reducing the required sampling rate of the system significantly while achieving the accuracy offered by the Nyquist rate. Performance results from simulations conducted with pre-recorded respiratory signals demonstrate the robustness of our scheme for tackling the above challenges and providing a low-complexity solution for the monitoring of respiratory movements.

Environmental Monitoring Plan

International Nuclear Information System (INIS)

Hunter, S.W.; Gallegos, G.M.; Surano, K.A.; Lamson, K.C.; Tate, P.J.; Balke, B.K.; Biermann, A.H.; Hoppes, W.G.; Fields, B.C.; Gouveia, F.J.; Berger, R.L.; Miller, F.S.; Rueppel, D.W.; Sims, J.M.

1992-04-01

The primary tasks of the environmental monitoring section (EMS) Livermore National Laboratory (LLNL) are: effluent monitoring of air, sewer, and NPDES water. Surveillance monitoring of soil, vegetation and foodstuff, water, air particulate, and air tritium. Radiation monitoring, dose assessment, emergency response, quality assurance, and reporting. This report describes LLNL and the monitoring plan

Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

Directory of Open Access Journals (Sweden)

Soo-Yon Rhee

2017-04-01

Full Text Available Tenofovir disoproxil fumarate (TDF genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs, we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 – A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F – were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.

Performance Monitoring and Response Inhibition in a Saccadic Countermanding Task in High and Low proficient bilinguals.

Directory of Open Access Journals (Sweden)

Niharika eSingh

2015-01-01

Full Text Available We compared Hindi-English bilinguals differing in their L2 fluency on a saccadic countermanding task which taps inhibitory control as well as monitoring. We particularly explored whether response inhibition and performance monitoring within the oculomotor domain are affected by language proficiency in bilinguals. There were two different oculomotor redirect tasks: Visually Guided Redirect (VGR task (Experiment1 and Memory Guided Redirect (MGR task (Experiment 2. In this task typically a target is presented to which subject must make saccade (No step trials, unless a new target appears on the other location after some delay from the first target onset (Step trials. On such trials participants are required to inhibit and cancel the saccade to the first instead program a saccade to the new target. Using trial switch reaction time (TSRT, which is the time taken to inhibit the initiated saccade to the first target, as a measure of response inhibition, and post-stop slowing as a measure of performance monitoring, we observed two important results. It was found that high proficiency bilinguals showed more post-stop slowing on the no-step trials as compared to the low proficiency bilinguals for both VGR and MGR. Secondly, high and low proficiency bilingual exhibited comparable TSRT in both VGR and MGR, showing no altering effect of language proficiency on the response inhibition in bilinguals. These results suggest that bilingualism impacts performance monitoring which is modulated by language proficiency if not the inhibitory control system. Higher fluency may lead to superior cognitive flexibility, and ability to adjust behaviour that facilitates attainment of cognitive goal. These findings are in consonance with other current studies that suggest a top-down effect of bilingualism on action control systems.

Performance monitoring and response conflict resolution associated with choice stepping reaction tasks.

Science.gov (United States)

Watanabe, Tatsunori; Tsutou, Kotaro; Saito, Kotaro; Ishida, Kazuto; Tanabe, Shigeo; Nojima, Ippei

2016-11-01

Choice reaction requires response conflict resolution, and the resolution processes that occur during a choice stepping reaction task undertaken in a standing position, which requires maintenance of balance, may be different to those processes occurring during a choice reaction task performed in a seated position. The study purpose was to investigate the resolution processes during a choice stepping reaction task at the cortical level using electroencephalography and compare the results with a control task involving ankle dorsiflexion responses. Twelve young adults either stepped forward or dorsiflexed the ankle in response to a visual imperative stimulus presented on a computer screen. We used the Simon task and examined the error-related negativity (ERN) that follows an incorrect response and the correct-response negativity (CRN) that follows a correct response. Error was defined as an incorrect initial weight transfer for the stepping task and as an incorrect initial tibialis anterior activation for the control task. Results revealed that ERN and CRN amplitudes were similar in size for the stepping task, whereas the amplitude of ERN was larger than that of CRN for the control task. The ERN amplitude was also larger in the stepping task than the control task. These observations suggest that a choice stepping reaction task involves a strategy emphasizing post-response conflict and general performance monitoring of actual and required responses and also requires greater cognitive load than a choice dorsiflexion reaction. The response conflict resolution processes appear to be different for stepping tasks and reaction tasks performed in a seated position.

Response of interferon alone and with ribavirin inpatients of chronic hepatitis C

International Nuclear Information System (INIS)

Niaz, A.

2003-01-01

Objective: The aim of the study was to compare the response of interferon alone and interferon plus ribavirin in patients of chronic hepatitis C. Results: At completion of treatment HCV-RNA levels in serum were not detectable in 15 of 20 (75%) patients who received interferon alpha and ribavirin combination therapy as compared to 10 of 20 (50%) patients who received interferon alpha alone. Only 1 patient became HCV RNA negative in the control group. Normalization of ALT concentration and histologic response was proportionate to the virological response. Conclusion: Combination therapy of interferon and ribavirin is more effective than treatment with interferon alone for minimizing viral load, improving ALT levels and histology. (author)

Replication Capacity in Relation to Immunologic and Virologic Outcomes in HIV-1 infected, Treatment-Naïve Subjects

Science.gov (United States)

Skowron, Gail; Spritzler, John G.; Weidler, Jodi; Robbins, Gregory K.; Johnson, Victoria A.; Chan, Ellen S.; Asmuth, David M.; Gandhi, Rajesh T.; Lie, Yolanda; Bates, Michael; Pollard, Richard B.

2012-01-01

Objectives To evaluate the association between baseline (BL) replication capacity (RC) [RCBL] and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1 infected subjects initiating antiretroviral therapy. Methods RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naïve subjects from ACTG384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Results Higher RCBL was associated with lower baseline CD4 (CD4BL) (r=−0.23, p<0.0001), higher baseline HIV-1 (RNABL) (r=0.25, p<0.0001), higher CD4BL activation percent (r=0.23, p<0.0001) and lower CD4BL memory count (r=−0.21, p=0.0002). In a multivariable model, week 48 CD4 increase (ΔCD448) was associated with lower CD4BL memory count and higher CD4BL naive percent (p=0.004, p=0.015, respectively). The interaction between CD4BL and RCBL was significant (p=0.018), with a positive association between RCBL and ΔCD448 in subjects with higher CD4BL, and a negative association at lower absCD4BL. Conclusions At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different baseline CD4 counts. PMID:19194319

Rates of sustained virological response 12 weeks after the scheduled end of direct-acting antiviral (DAA)-based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

Science.gov (United States)

Bischoff, J; Mauss, S; Cordes, C; Lutz, T; Scholten, S; Moll, A; Jäger, H; Cornberg, M; Manns, M P; Baumgarten, A; Rockstroh, J K

2018-04-01

The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV-infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany. Data acquired from the Deutsches Hepatitis C-Registry were analysed. A total of 5657 HCV-monoinfected subjects and 488 HIV/HCV-coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients. HIV/HCV-coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P  350 cells/μL in 63.1% of HIV-positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV-monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV-monoinfected and HIV/HCV-coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups). We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration. © 2018 British HIV Association.

The association between cigarette smoking, virologic suppression, and CD4+ lymphocyte count in HIV-Infected Russian women.

Science.gov (United States)

Brown, Jennifer L; Winhusen, Theresa; DiClemente, Ralph J; Sales, Jessica M; Rose, Eve S; Safonova, Polina; Levina, Olga; Belyakov, Nikolay; Rassokhin, Vadim V

2017-09-01

Cigarette smoking among people living with HIV/AIDS is associated with significant morbidity and mortality, but findings regarding the association between cigarette smoking and HIV viral load and CD4+ lymphocyte counts have been inconsistent. This study characterized the prevalence of cigarette smoking among HIV-infected Russian women and examined the association between smoking frequency and quantity and HIV viral load and CD4+ lymphocyte counts. HIV-infected Russian women (N = 250; M age = 30.0) in St. Petersburg, Russia, completed an audio computer-assisted self-interview survey assessing cigarette use, antiretroviral medication adherence, and provided blood samples assayed for HIV viral load and CD4+ lymphocyte counts. The majority (60.4%) reported cigarette smoking in the past month; 49.0% of recent smokers were classified as moderate or heavy smokers, defined as smoking ≥10 cigarettes daily. Viral load status did not differ between infrequent smokers and regular smokers. However, moderate/heavy smokers (relative to light smokers) were more likely to have a detectable viral load (AOR = 2.3, 95% CI: 1.1, 5.1). There were no significant differences in CD4+ lymphocyte counts by smoking frequency or quantity of cigarettes smoked. Results highlight the need for additional research to examine the association between cigarette smoking and virologic suppression and markers of HIV disease progression. Adverse health consequences of cigarette smoking coupled with a potential link between heavy smoking and poor virologic suppression highlight the need for assessment of cigarette use and provision of evidence-based smoking-cessation interventions within HIV medical care.

Multiple proviral integration events after virological synapse-mediated HIV-1 spread

International Nuclear Information System (INIS)

Russell, Rebecca A.; Martin, Nicola; Mitar, Ivonne; Jones, Emma; Sattentau, Quentin J.

2013-01-01

HIV-1 can move directly between T cells via virological synapses (VS). Although aspects of the molecular and cellular mechanisms underlying this mode of spread have been elucidated, the outcomes for infection of the target cell remain incompletely understood. We set out to determine whether HIV-1 transfer via VS results in productive, high-multiplicity HIV-1 infection. We found that HIV-1 cell-to-cell spread resulted in nuclear import of multiple proviruses into target cells as seen by fluorescence in-situ hybridization. Proviral integration into the target cell genome was significantly higher than that seen in a cell-free infection system, and consequent de novo viral DNA and RNA production in the target cell detected by quantitative PCR increased over time. Our data show efficient proviral integration across VS, implying the probability of multiple integration events in target cells that drive productive T cell infection. - Highlights: • Cell-to-cell HIV-1 infection delivers multiple vRNA copies to the target cell. • Cell-to-cell infection results in productive infection of the target cell. • Cell-to-cell transmission is more efficient than cell-free HIV-1 infection. • Suggests a mechanism for recombination in cells infected with multiple viral genomes

Epidemiological and virological studies into the poliomyelitis in Valencia (1959-1969

Directory of Open Access Journals (Sweden)

Báguena Cervellera, María José

2009-06-01

Full Text Available Studies into the polio virus began in Valencia in 1959 with the work undertaken by the microbiologist Vicente Sanchis-Bayarri Vaillant. After his education at the Rochester University and at the Pasteur Institute, Sanchis-Bayarri Vaillant established a laboratory of cell cultures at the Faculty of Medicine in Valencia, where he developed a new diagnostic technique for the poliomyelitis virus. In addition, epidemiological studies were carried out both prior to and post the 1963 vaccination campaign, which proved that Sabin’s oral vaccine was both effective and safe for use.

Los estudios sobre el virus de la polio comenzaron en Valencia en 1959 de la mano del microbiólogo Vicente Sanchis-Bayarri Vaillant. Tras su formación en virología en la Universidad de Rochester y en el Instituto Pasteur, puso en marcha un laboratorio de cultivos celulares en la Facultad de Medicina de Valencia, en donde desarrolló una técnica diagnóstica nueva para el virus de la polio. Por otra parte, se llevaron a cabo estudios epidemiológicos antes y después de la campaña de vacunación de 1963, que demostraron la eficacia de la vacuna oral de Sabin y su inocuidad.

The response of the radionuclide monitoring programme for agricultural products in Great Britain to the accident at Chernobyl

International Nuclear Information System (INIS)

Morris, J.A.

1986-01-01

The overall objective of the radiation monitoring and control programme of the Ministry of Agriculture, Fisheries and Food in Great Britain is to ensure the safety of foodstuffs. The particular responsibility of my department within the Ministry is the analysis of agricultural products for the presence of radionuclides entering the human food chain from atmospheric releases. The Ministry also has a laboratory which monitors the marine environment. This presentation describes the surveillance programme for agricultural foodstuffs and show how it was used to monitor the deposition from the Chernobyl accident, and shows some of the monitoring data obtained and indicate how the information was used in formulating protective measures. It also mentions future plans

The response of the radionuclide monitoring programme for agricultural products in Great Britain to the accident at Chernobyl

Energy Technology Data Exchange (ETDEWEB)

Morris, J A [Central Veterinary Laboratory, Weybridge, Surrey (United Kingdom)

1986-07-01

The overall objective of the radiation monitoring and control programme of the Ministry of Agriculture, Fisheries and Food in Great Britain is to ensure the safety of foodstuffs. The particular responsibility of my department within the Ministry is the analysis of agricultural products for the presence of radionuclides entering the human food chain from atmospheric releases. The Ministry also has a laboratory which monitors the marine environment. This presentation describes the surveillance programme for agricultural foodstuffs and show how it was used to monitor the deposition from the Chernobyl accident, and shows some of the monitoring data obtained and indicate how the information was used in formulating protective measures. It also mentions future plans.

Rapid response sensor to monitor the temperature and flow of liquid metals

International Nuclear Information System (INIS)

McCann, J.D.

1980-01-01

Two forms of a sensor capable of simultaneously monitoring the temperature and flow of liquid metal coolants within a reactor are described. They operate by measuring the coupling impedances between the sensor and the surrounding electrically conductive coolant. Since the system utilises electrical rather than thermal properties, the response to perturbations is rapid, typically displaying the changed conditions within a few milliseconds. The first form of the sensor was designed to operate whilst protected by a thick walled service tube positioned in the reactor coolant. Providing bends in the tube had a radius greater than 70 cm, the sensor could be removed for inspection and maintenance if necessary. The second sensor was fitted inside a streamlined NaK proof capsule. This was inserted directly into the coolant outlet stream of a fuel pin assembly in the Dounreay Fast Reactor. In this form the sensor successfully monitored flow, entrained gas and temperature excursions during the final operating cycle of D.F.R. (author)

A real-time monitoring/emergency response modeling workstation for a tritium facility

International Nuclear Information System (INIS)

Lawver, B.S.; Sims, J.M.; Baskett, R.L.

1993-07-01

At Lawrence Livermore National Laboratory (LLNL) we developed a real-time system to monitor two stacks on our tritium handling facility. The monitors transmit the stack data to a workstation which computes a 3D numerical model of atmospheric dispersion. The workstation also collects surface and upper air data from meteorological towers and a sodar. The complex meteorological and terrain setting in the Livermore Valley demands more sophisticated resolution of the three-dimensional structure of the atmosphere to reliably calculate plume dispersion than afforded by Gaussian models. We experience both mountain valley and sea breeze flows. To address these complexities, we have implemented the three-dimensional diagnostic MATHEW mass-adjusted wind field and ADPIC particle-in-cell dispersion models on the workstation for use in real-time emergency response modeling. Both MATHEW and ADPIC have shown their utility in a variety of complex settings over the last 15 years within the Department of Energy's Atmospheric Release Advisory Capability (ARAC[1,2]) project

Diffusion-weighted magnetic resonance imaging in monitoring rectal cancer response to neoadjuvant chemoradiotherapy.

Science.gov (United States)

Barbaro, Brunella; Vitale, Renata; Valentini, Vincenzo; Illuminati, Sonia; Vecchio, Fabio M; Rizzo, Gianluca; Gambacorta, Maria Antonietta; Coco, Claudio; Crucitti, Antonio; Persiani, Roberto; Sofo, Luigi; Bonomo, Lorenzo

2012-06-01

To prospectively monitor the response in patients with locally advanced nonmucinous rectal cancer after chemoradiotherapy (CRT) using diffusion-weighted magnetic resonance imaging. The histopathologic finding was the reference standard. The institutional review board approved the present study. A total of 62 patients (43 men and 19 women; mean age, 64 years; range, 28-83) provided informed consent. T(2)- and diffusion-weighted magnetic resonance imaging scans (b value, 0 and 1,000 mm(2)/s) were acquired before, during (mean 12 days), and 6-8 weeks after CRT. We compared the median apparent diffusion coefficients (ADCs) between responders and nonresponders and examined the associations with the Mandard tumor regression grade (TRG). The postoperative nodal status (ypN) was evaluated. The Mann-Whitney/Wilcoxon two-sample test was used to evaluate the relationships among the pretherapy ADCs, extramural vascular invasion, early percentage of increases in ADCs, and preoperative ADCs. Low pretreatment ADCs (23% ADC increase had a 96.3% negative predictive value for TRG 4. In 9 of 16 complete responders, CRT-related tumor downsizing prevented ADC evaluations. The preoperative ADCs were significantly different (p = .0012) between the patients with and without downstaging (preoperative ADC ≥1.4 × 10(-3)mm(2)/s showed a positive and negative predictive value of 78.9% and 61.8%, respectively, for response assessment). The TRG 1 and TRG 2-4 groups were not significantly different. Diffusion-weighted magnetic resonance imaging seems to be a promising tool for monitoring the response to CRT. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of a Real-Time Radiological Area Monitoring Network for Emergency Response at Lawrence Livermore National Laboratory

International Nuclear Information System (INIS)

Bertoldo, N; Hunter, S; Fertig, R; Laguna, G; MacQueen, D

2004-01-01

A real-time radiological sensor network for emergency response was developed and deployed at the Lawrence Livermore National Laboratory (LLNL). The Real-Time Radiological Area Monitoring (RTRAM) network is comprised of 16 Geiger-Mueller (GM) sensors positioned on the LLNL Livermore site perimeter to continuously monitor for a radiological condition resulting from a terrorist threat to site security and the health and safety of LLNL personnel. The RTRAM network sensor locations coincide with wind sector directions to provide thorough coverage of the one square mile site. These loW--power sensors are supported by a central command center (CCC) and transmit measurement data back to the CCC computer through the LLNL telecommunications infrastructure. Alarm conditions are identified by comparing current data to predetermined threshold parameters and are validated by comparison with plausible dispersion modeling scenarios and prevailing meteorological conditions. Emergency response personnel are notified of alarm conditions by automatic radio and computer based notifications. A secure intranet provides emergency response personnel with current condition assessment data that enable them to direct field response efforts remotely. The RTRAM network has proven to be a reliable system since initial deployment in August 2001 and maintains stability during inclement weather conditions

Electronic medication monitoring-informed counseling to improve adherence to combination anti-retroviral therapy and virologic treatment outcomes: a meta-analysis

NARCIS (Netherlands)

Langebeek, Nienke; Nieuwkerk, Pythia

2015-01-01

Adherence to combination anti-retroviral therapy for HIV infection is a primary determinant of treatment success, but is often suboptimal. Previous studies have suggested that electronic medication monitoring-informed counseling is among the most effective adherence intervention components. Our

An overview of HCV molecular biology, replication and immune responses

Directory of Open Access Journals (Sweden)

Nawaz Zafar

2011-04-01

Full Text Available Abstract Hepatitis C virus (HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. In this review, we summarize molecular virology, replication and immune responses against HCV and discussed how HCV escape from adaptive and humoral immune responses. This advance knowledge will be helpful for development of vaccine against HCV and discovery of new medicines both from synthetic chemistry and natural sources.

The heuristics of nurse responsiveness to critical patient monitor and ventilator alarms in a private room neonatal intensive care unit.

Science.gov (United States)

Joshi, Rohan; Mortel, Heidi van de; Feijs, Loe; Andriessen, Peter; Pul, Carola van

2017-01-01

Alarm fatigue is a well-recognized patient safety concern in intensive care settings. Decreased nurse responsiveness and slow response times to alarms are the potentially dangerous consequences of alarm fatigue. The aim of this study was to determine the factors that modulate nurse responsiveness to critical patient monitor and ventilator alarms in the context of a private room neonatal intensive care setting. The study design comprised of both a questionnaire and video monitoring of nurse-responsiveness to critical alarms. The Likert scale questionnaire, comprising of 50 questions across thematic clusters (critical alarms, yellow alarms, perception, design, nursing action, and context) was administered to 56 nurses (90% response rate). Nearly 6000 critical alarms were recorded from 10 infants in approximately 2400 hours of video monitoring. Logistic regression was used to identify patient and alarm-level factors that modulate nurse-responsiveness to critical alarms, with a response being defined as a nurse entering the patient's room within the 90s of the alarm being generated. Based on the questionnaire, the majority of nurses found critical alarms to be clinically relevant even though the alarms did not always mandate clinical action. Based on video observations, for a median of 34% (IQR, 20-52) of critical alarms, the nurse was already present in the room. For the remaining alarms, the response rate within 90s was 26%. The median response time was 55s (IQR, 37-70s). Desaturation alarms were the most prevalent and accounted for more than 50% of all alarms. The odds of responding to bradycardia alarms, compared to desaturation alarms, were 1.47 (95% CI = 1.21-1.78; heuristics in determining whether or not to respond to the alarm. Amongst other factors, the category and duration of critical alarms along with the clinical status of the patient determine nurse-responsiveness to alarms.

Virologic response to tipranavir-ritonavir or darunavir-ritonavir based regimens in antiretroviral therapy experienced HIV-1 patients: a meta-analysis and meta-regression of randomized controlled clinical trials.

Directory of Open Access Journals (Sweden)

Asres Berhan

Full Text Available The development of tipranavir and darunavir, second generation non-peptidic HIV protease inhibitors, with marked improved resistance profiles, has opened a new perspective on the treatment of antiretroviral therapy (ART experienced HIV patients with poor viral load control. The aim of this study was to determine the virologic response in ART experienced patients to tipranavir-ritonavir and darunavir-ritonavir based regimens.A computer based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative, Medline and Cochrane library. Meta-analysis was performed by including randomized controlled studies that were conducted in ART experienced patients with plasma viral load above 1,000 copies HIV RNA/ml. The odds ratios and 95% confidence intervals (CI for viral loads of <50 copies and <400 copies HIV RNA/ml at the end of the intervention were determined by the random effects model. Meta-regression, sensitivity analysis and funnel plots were done. The number of HIV-1 patients who were on either a tipranavir-ritonavir or darunavir-ritonavir based regimen and achieved viral load less than 50 copies HIV RNA/ml was significantly higher (overall OR = 3.4; 95% CI, 2.61-4.52 than the number of HIV-1 patients who were on investigator selected boosted comparator HIV-1 protease inhibitors (CPIs-ritonavir. Similarly, the number of patients with viral load less than 400 copies HIV RNA/ml was significantly higher in either the tipranavir-ritonavir or darunavir-ritonavir based regimen treated group (overall OR = 3.0; 95% CI, 2.15-4.11. Meta-regression showed that the viral load reduction was independent of baseline viral load, baseline CD4 count and duration of tipranavir-ritonavir or darunavir-ritonavir based regimen.Tipranavir and darunavir based regimens were more effective in patients who were ART experienced and had poor viral load control. Further studies are required to determine their consistent

Detection of resistance mutations and CD4 slopes in individuals experiencing sustained virological failure

DEFF Research Database (Denmark)

Schultze, Anna; Paredes, Roger; Sabin, Caroline

2014-01-01

during the episode were included. Mutations were identified using the IAS-US (2013) list, and were presumed to be present from detection until the end of an episode. Multivariable linear mixed models with a random intercept and slope adjusted for age, baseline CD4 count, hepatitis C, drug type, RNA (log...... mutations on CD4 slopes in patients undergoing episodes of viral failure. MATERIALS AND METHODS: Patients from the EuroSIDA and UK CHIC cohorts undergoing at least one episode of virological failure (>3 consecutive RNA measurements >500 on ART) with at least three CD4 measurements and a resistance test......-scale), risk group and subtype were used to estimate CD4 slopes. Individual mutations with a population prevalence of >10% were tested for their effect on the CD4 slope. RESULTS: A total of 2731 patients experiencing a median of 1 (range 1-4) episodes were included in this analysis. The prevalence of any...

Identification of the determinants of efficient Pestivirus replication

DEFF Research Database (Denmark)

Risager, Peter Christian

, and in depth knowledge of the traits that determine the fitness of the virus in this regard are highly valuable. Recent advances in the field of molecular virology with methods to manipulate viral genomes have significantly helped to uncover these core mechanisms responsible for exploitation of the host......, BMC genomics). Manuscript II describes the generation of replicons that express two different types of luciferases (Rluc and Gluc), and their application as a tool for easy monitoring of replication competence (published paper, Journal of General Virology (94), 1739-1748). Manuscript III describes...... the properties of chimeric replicons and infectious clones that include a RNA dependent RNA polymerase (NS5B) from one of three different CSFV strains with distinct virulence properties. The entire NS5B proved to influence replication competence and key residues for replication competence was identified...

Monitoring Cancer Response to Treatment with Hyperpolarized ¹³C MRS

DEFF Research Database (Denmark)

Eldirdiri, Abubakr

, and the patient is exposed to ionizing radiation. The introduction of hyperpolarized 13C MRS has opened completely new possibilities to study the biochemical changes in disease processes. Numerous 13C-labeled compounds were proposed to interrogate various aspects of cancer cell metabolism. The aim of this study......Monitoring the cancer response to treatment, non-invasively, by medical imaging is a key element in the management of cancer. For patients undergoing treatment, it is crucial to determine responders from non-responders in order to guide treatment decisions. Currently, PET is the most widely used...

The strategic control of prospective memory monitoring in response to complex and probabilistic contextual cues.

Science.gov (United States)

Bugg, Julie M; Ball, B Hunter

2017-07-01

Participants use simple contextual cues to reduce deployment of costly monitoring processes in contexts in which prospective memory (PM) targets are not expected. This study investigated whether this strategic monitoring pattern is observed in response to complex and probabilistic contextual cues. Participants performed a lexical decision task in which words or nonwords were presented in upper or lower locations on screen. The specific condition was informed that PM targets ("tor" syllable) would occur only in words in the upper location, whereas the nonspecific condition was informed that targets could occur in any location or word type. Context was blocked such that word type and location changed every 8 trials. In Experiment 1, the specific condition used the complex contextual cue to reduce monitoring in unexpected contexts relative to the nonspecific condition. This pattern largely was not evidenced when the complex contextual cue was probabilistic (Experiment 2). Experiment 3 confirmed that strategic monitoring is observed for a complex cue that is deterministic, but not one that is probabilistic. Additionally, Experiments 1 and 3 demonstrated a disadvantage associated with strategic monitoring-namely, that the specific condition was less likely to respond to a PM target in an unexpected context. Experiment 3 provided evidence that this disadvantage is attributable to impaired noticing of the target. The novel findings suggest use of a complex contextual cue per se is not a boundary condition for the strategic, context-specific allocation of monitoring processes to support prospective remembering; however, strategic monitoring is constrained by the predictive utility of the complex contextual cue.

MR Imaging in Monitoring and Predicting Treatment Response in Multiple Sclerosis.

Science.gov (United States)

Río, Jordi; Auger, Cristina; Rovira, Àlex

2017-05-01

MR imaging is the most sensitive tool for identifying lesions in patients with multiple sclerosis (MS). MR imaging has also acquired an essential role in the detection of complications arising from these treatments and in the assessment and prediction of efficacy. In the future, other radiological measures that have shown prognostic value may be incorporated within the models for predicting treatment response. This article examines the role of MR imaging as a prognostic tool in patients with MS and the recommendations that have been proposed in recent years to monitor patients who are treated with disease-modifying drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantitative Magnetization Transfer in Monitoring Glioblastoma (GBM) Response to Therapy.

Science.gov (United States)

Mehrabian, Hatef; Myrehaug, Sten; Soliman, Hany; Sahgal, Arjun; Stanisz, Greg J

2018-02-06

Quantitative magnetization transfer (qMT) was used as a biomarker to monitor glioblastoma (GBM) response to chemo-radiation and identify the earliest time-point qMT could differentiate progressors from non-progressors. Nineteen GBM patients were recruited and MRI-scanned before (Day 0 ), two weeks (Day 14 ), and four weeks (Day 28 ) into the treatment, and one month after the end of the treatment (Day 70 ). Comprehensive qMT data was acquired, and a two-pool MT model was fit to the data. Response was determined at 3-8 months following the end of chemo-radiation. The amount of magnetization transfer ([Formula: see text]) was significantly lower in GBM compared to normal appearing white matter (p GBM are more sensitive to treatment effects compared to clinically used metrics. qMT could assess tumor aggressiveness and identify early progressors even before the treatment. Changes in qMT parameters within the first 14 days of the treatment were capable of separating early progressors from non-progressors, making qMT a promising biomarker to guide adaptive radiotherapy for GBM.

Computational Model and Numerical Simulation for Submerged Mooring Monitoring Platform’s Dynamical Response

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He Kongde

2015-01-01

Full Text Available Computational model and numerical simulation for submerged mooring monitoring platform were formulated aimed at the dynamical response by the action of flow force, which based on Hopkinson impact load theory, taken into account the catenoid effect of mooring cable and revised the difference of tension and tangential direction action force by equivalent modulus of elasticity. Solved the equation by hydraulics theory and structural mechanics theory of oceaneering, studied the response of buoy on flow force. The validity of model were checked and the results were in good agreement; the result show the buoy will engender biggish heave and swaying displacement, but the swaying displacement got stable quickly and the heaven displacement cause vibration for the vortex-induced action by the flow.

Persistence of hepatocellular carcinoma risk in hepatitis C patients with a response to IFN and cirrhosis regression.

Science.gov (United States)

D'Ambrosio, Roberta; Aghemo, Alessio; Rumi, Maria Grazia; Degasperi, Elisabetta; Sangiovanni, Angelo; Maggioni, Marco; Fraquelli, Mirella; Perbellini, Riccardo; Rosenberg, William; Bedossa, Pierre; Colombo, Massimo; Lampertico, Pietro

2018-01-27

In patients with HCV-related cirrhosis, a sustained virological response may lead to cirrhosis regression. Whether histological changes translate into prevention of long-term complications, particularly hepatocellular carcinoma is still unknown. This was investigated in a cohort of histological cirrhotics who had been prospectively followed-up for 10 years after the achievement of a sustained virological response to IFN. In all, 38 sustained virological response cirrhotics who underwent a liver biopsy 5 years post-SVR were prospectively followed to assess the impact of cirrhosis regression on clinical endpoints. During a follow-up of 86 (30-96) months from liver biopsy, no patients developed clinical decompensation, whilst 5 (13%) developed hepatocellular carcinoma after 79 (7-88) months. The 8-year cumulative probability of hepatocellular carcinoma was 17%, without differences between patients with or without cirrhosis regression (19% [95% CI 6%-50%] vs 14% [95% CI 4%-44%], P = .88). Patients who developed or did not an hepatocellular carcinoma had similar rates of residual cirrhosis (P = 1.0), collagen content (P = .48), METAVIR activity (P = .34), portal inflammation (P = .06) and steatosis (P = .17). At baseline, patients who developed an hepatocellular carcinoma had higher γGT (HR 1.03, 95% CI 1.00-1.06; P = .014) and glucose (HR 1.02, 95% CI 1.00-1.02; P = .012) values; moreover, they had increased Forns Score (HR 12.8, 95% CI 1.14-143.9; P = .039), Lok Index (HR 6.24, 95% CI 1.03-37.6; P = .046) and PLF (HR 19.3, 95% CI 1.72-217.6; P = .016) values. One regressor died of lung cancer. The 8-year cumulative survival probability was 97%, independently on cirrhosis regression (96% vs 100%, P = 1.0) or hepatocellular carcinoma (100% vs 97%, P = 1.0). Post-SVR cirrhosis regression does not prevent hepatocellular carcinoma occurrence. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

History of the department of virology and molecular and biological methods of investigation of pediatric research and clinical center for infectious diseases

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E. A. Murina

2017-01-01

Full Text Available The article deals with the history of formation of virology laboratory since 1963 after the resolution of the Academy of Medical Sciences of the USSR and the Ministry of Public Health on the expansion of virology investigation in the USSR.The results of the research work on studying various infections in children, developing new modified approaches to etiological express-diagnostics of the diseases, including those introduced into practice of the laboratory and regional medical centers are generalized. The laboratory got the name of the Department of Etiological Diagnostics Methods due to the basic direction of the research work. The primary goal of the department is to develop the methods and diagnostic algorithms for definite verification of infectious forms and the prognosis of the development of pathological process that allows determining the direction of further therapeutic approach to improve the disease outcome. In 2008 the Department of Etiological Diagnostics Methods began its «golden age» characterized by cardinal re-equipment and strengthening of the staff. There appeared the devices of expert class which completely replaced the manual testing process, the work connected with interpretation of serous meningitis outbreaks in Russia and the near abroad became more active.Now the department is a hi-technology scientific and practical center on studying viral and invasive forms of diseases with a priority direction of further innovations in laboratory diagnostics. 

Composition and fundamental requirements of nuclear emergency response monitoring equipment

International Nuclear Information System (INIS)

Lai Yongfang; Huang Weiqi; Wang Yonghong

2009-01-01

Nuclear emergency monitoring equipment is concrete foundation for accomplishing radiation monitoring in nuclear or radiation accidents. Based on technical report: Generic procedures for monitoring in a nuclear or radiological emergency published by IAEA in 1999, this paper presents the main task and composition of nuclear emergency monitoring briefly, and then the basic equipment and trends of nuclear emergency monitoring equipment is put forward in detail, which is useful to construction and reinforcement of our nuclear emergency monitoring. (authors)

Clinical, serological and virological characteristics of an outbreak of paresis and neonatal foal disease due to equine herpesvirus-1 on a stud farm.

Science.gov (United States)

McCartan, C G; Russell, M M; Wood, J L; Mumford, J A

1995-01-07

An outbreak of equine herpesvirus-1 (EHV-1) occurred on a large stud farm with 133 mares, 54 foals and four stallions, and at least 85 mares, 22 foals and three stallions were infected. Clinical disease was observed in 16 mares, two stallions and 13 foals and the predominant clinical signs were scrotal oedema, ataxia and loss of libido in the stallions, ataxia and recumbency in the mares and uveitis and nasal discharge in the foals, although pneumonia and colic with intussusception were also recorded at autopsy. Neurological disease was more common in the mares nursing foals (12 of 38 infected) than in barren mares (one of 46 infected). Three mares died during the outbreak and no mares that had been recumbent bred again. Control procedures were based on virological and serological testing and stringent management practices to limit the spread of infection between groups of mares and foals and away from the stud farm. There were marked antibody responses in the adult horses, but they were generally poor in the foals; three of the nine viraemic foals did not develop significant increases in the levels of circulating antibody. Recommendations are made for the management of future outbreaks.

Pregnancy risk assessment monitoring system in Ireland: methods and response rates

LENUS (Irish Health Repository)

O’Keeffe, Linda M.

2014-06-01

To describe response rates and characteristics associated with response to the Pregnancy Risk Assessment Monitoring System study in Ireland (PRAMS Ireland). Using hospital discharge records of live births at a large, urban, obstetric hospital, a sampling frame of approximately 2,400 mother-infant pairs were used to alternately sample 1,200 women. Mothers’ information including name, address, parity, age and infant characteristics such as sex and gestational age at delivery were extracted from records. Modes of contact included an invitation letter with option to opt out of the study, three mail surveys, a reminder letter and text message reminder for remaining non-respondents. Sixty-one per cent of women responded to the PRAMS Ireland survey over a 133 day response period. Women aged <30, single women, multiparous women and women with a preterm delivery were less likely to respond. Women participating in PRAMS Ireland were similar to the national birth profile in 2011 which had a mean age of 32, were 40 % primiparous, 33 % single or never married and had a 28 % caesarean section rate. Survey and protocol changes are required to increase response rates above recommended Centers for Disease Control and Prevention (CDC) thresholds of 65 % within the recommended 90 day data collection cycle. Additional efforts such as stratification and over-sampling are required to increase representativeness among hard to reach groups such as younger, single and multiparous women before expanding the project to an ongoing, national surveillance system in Ireland.

Integration of laser trapping for continuous and selective monitoring of photothermal response of a single microparticle.

Science.gov (United States)

Vasudevan, Srivathsan; Chen, George C K; Ahluwalia, Balpreet Singh

2008-12-01

Photothermal response (PTR) is an established pump and probe technique for real-time sensing of biological assays. Continuous and selective PTR monitoring is difficult owing to the Brownian motion changing the relative position of the target with respect to the beams. Integration of laser trapping with PTR is proposed as a solution. The proposed method is verified on red polystyrene microparticles. PTR is continuously monitored for 30 min. Results show that the mean relaxation time variation of the acquired signals is less than 5%. The proposed method is then applied to human red blood cells for continuous and selective PTR.

Monte carlo calculation of energy-dependent response of high-sensitive neutron monitor, HISENS

International Nuclear Information System (INIS)

Imanaka, Tetsuji; Ebisawa, Tohru; Kobayashi, Keiji; Koide, Hiroaki; Seo, Takeshi; Kawano, Shinji

1988-01-01

A highly sensitive neutron monitor system, HISENS, has been developed to measure leakage neutrons from nuclear facilities. The counter system of HISENS contains a detector bank which consists of ten cylindrical proportional counters filled with 10 atm 3 He gas and a paraffin moderator mounted in an aluminum case. The size of the detector bank is 56 cm high, 66 cm wide and 10 cm thick. It is revealed by a calibration experiment using an 241 Am-Be neutron source that the sensitivity of HISENS is about 2000 times as large as that of a typical commercial rem-counter. Since HISENS is designed to have a high sensitivity in a wide range of neutron energy, the shape of its energy dependent response curve cannot be matched to that of the dose equivalent conversion factor. To estimate dose equivalent values from neutron counts by HISENS, it is necessary to know the energy and angular characteristics of both HISENS and the neutron field. The area of one side of the detector bank is 3700 cm 2 and the detection efficiency in the constant region of the response curve is about 30 %. Thus, the sensitivity of HISENS for this energy range is 740 cps/(n/cm 2 /sec). This value indicates the extremely high sensitivity of HISENS as compared with exsisting highly sensitive neutron monitors. (Nogami, K.)

Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients.

Science.gov (United States)

Baril, Jean-Guy; Angel, Jonathan B; Gill, M John; Gathe, Joseph; Cahn, Pedro; van Wyk, Jean; Walmsley, Sharon

2016-01-01

We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection. A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations. Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels. The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the

Analytical investigation of response of birefringent fiber Bragg grating sensors in distributed monitoring system based on optical frequency domain reflectometry

Science.gov (United States)

Wada, D.; Murayama, H.

2014-01-01

When Fiber Bragg gratings (FBGs) are used as strain sensors, both longitudinal and lateral strain can be applied uniformly or non-uniformly over the length of the FBGs. In order for the demodulation of such FBG signal, this paper investigates the response of birefringent FBGs which are monitored by distributed measurement system based on optical frequency domain reflectometry. A numerical model of the distributed measurement system is built based on piece-wise uniform approach, which considers polarization states of propagating lights. The numerical model simulates analytical response of birefringent FBGs especially when birefringence induces power fluctuations in the distributed spectra, which can be noise or new opportunity for sensitive monitoring of birefringence. Simulation results show the relationships between the power fluctuations and the polarization states of the propagating lights. Consequently, appropriate methods of polarization control for sensitive distributed birefringent FBG monitoring are discussed.

A multi-detector neutron spectrometer with nearly isotropic response for environmental and workplace monitoring

Energy Technology Data Exchange (ETDEWEB)

Gomez-Ros, J.M., E-mail: jm.gomezros@ciemat.e [CIEMAT, Av. Complutense 22, 28040 Madrid (Spain); Bedogni, R. [INFN-LNF Frascati National Laboratory-U.F. Fisica Sanitaria, via E. Fermi n. 40, 00044 Frascati (Italy); Moraleda, M.; Delgado, A.; Romero, A. [CIEMAT, Av. Complutense 22, 28040 Madrid (Spain); Esposito, A. [INFN-LNF Frascati National Laboratory-U.F. Fisica Sanitaria, via E. Fermi n. 40, 00044 Frascati (Italy)

2010-01-21

This communication describes an improved design for a neutron spectrometer consisting of {sup 6}Li thermoluminescent dosemeters located at selected positions within a single moderating polyethylene sphere. The spatial arrangement of the dosemeters has been designed using the MCNPX Monte Carlo code to calculate the response matrix for 56 log-equidistant energies from 10{sup -9} to 100 MeV, looking for a configuration that permits to obtain a nearly isotropic response for neutrons in the energy range from thermal to 20 MeV. The feasibility of the proposed spectrometer and the isotropy of its response have been evaluated by simulating exposures to different reference and workplace neutron fields. The FRUIT code has been used for unfolding purposes. The results of the simulations as well as the experimental tests confirm the suitability of the prototype for environmental and workplace monitoring applications.

Application of laser tweezers Raman spectroscopy techniques to the monitoring of single cell response to stimuli

Science.gov (United States)

Chan, James W.; Liu, Rui; Matthews, Dennis L.

2012-06-01

Laser tweezers Raman spectroscopy (LTRS) combines optical trapping with micro-Raman spectroscopy to enable label-free biochemical analysis of individual cells and small biological particles in suspension. The integration of the two technologies greatly simplifies the sample preparation and handling of suspension cells for spectroscopic analysis in physiologically meaningful conditions. In our group, LTRS has been used to study the effects of external perturbations, both chemical and mechanical, on the biochemistry of the cell. Single cell dynamics can be studied by performing longitudinal studies to continuously monitor the response of the cell as it interacts with its environment. The ability to carry out these measurements in-vitro makes LTRS an attractive tool for many biomedical applications. Here, we discuss the use of LTRS to study the response of cancer cells to chemotherapeutics and bacteria cells to antibiotics and show that the life cycle and apoptosis of the cells can be detected. These results show the promise of LTRS for drug discovery/screening, antibiotic susceptibility testing, and chemotherapy response monitoring applications. In separate experiments, we study the response of red blood cells to the mechanical forces imposed on the cell by the optical tweezers. A laser power dependent deoxygenation of the red blood cell in the single beam trap is reported. Normal, sickle cell, and fetal red blood cells have a different behavior that enables the discrimination of the cell types based on this mechanochemical response. These results show the potential utility of LTRS for diagnosing and studying red blood cell diseases.

Hepatitis B surface antigen titer is a good indicator of durable viral response after entecavir off-treatment for chronic hepatitis B

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Han Ah Lee

2016-09-01

Full Text Available Background/Aims Clear indicators for stopping antiviral therapy in chronic hepatitis B (CHB patients are not yet available. Since the level of hepatitis B surface antigen (HBsAg is correlated with covalently closed circular DNA, the HBsAg titer might be a good indicator of the off-treatment response. This study aimed to determine the relationship between the HBsAg titer and the entecavir (ETV off-treatment response. Methods This study analyzed 44 consecutive CHB patients (age, 44.6±11.4 years, mean±SD; men, 63.6%; positive hepatitis B envelope antigen (HBeAg at baseline, 56.8%; HBV DNA level, 6.8±1.3 log10 IU/mL treated with ETV for a sufficient duration and in whom treatment was discontinued after HBsAg levels were measured. A virological relapse was defined as an increase in serum HBV DNA level of >2000 IU/mL, and a clinical relapse was defined as a virological relapse with a biochemical flare, defined as an increase in the serum alanine aminotransferase level of >2 × upper limit of normal. Results After stopping ETV, virological relapse and clinical relapse were observed in 32 and 24 patients, respectively, during 20.8±19.9 months of follow-up. The cumulative incidence rates of virological relapse were 36.2% and 66.2%, respectively, at 6 and 12 months, and those of clinical relapse were 14.3% and 42.3%. The off-treatment HBsAg level was an independent factor associated with clinical relapse (hazard ratio, 2.251; 95% confidence interval, 1.076–4.706; P=0.031. When patients were grouped according to off-treatment HBsAg levels, clinical relapse did not occur in patients with an off-treatment HBsAg level of ≤2 log10 IU/mL (n=5, while the incidence rates of clinical relapse at 12 months after off-treatment were 28.4% and 55.7% in patients with off-treatment HBsAg levels of >2 and ≤3 log10 IU/mL (n=11 and >3 log10 IU/mL (n=28, respectively. Conclusion The off-treatment HBsAg level is closely related to clinical relapse after treatment

Treatment dose-response in amblyopia therapy: the Monitored Occlusion Treatment of Amblyopia Study (MOTAS).

Science.gov (United States)

Stewart, Catherine E; Moseley, Merrick J; Stephens, David A; Fielder, Alistair R

2004-09-01

Amblyopia is the commonest visual disorder of childhood. Yet the contributions of the two principal treatments (spectacle wear and occlusion) to outcome are unknown. This study was undertaken to investigate the dose-response relationship of amblyopia therapy. The study comprised three distinct phases: baseline, in which repeat measures of visual function were undertaken to confirm the initial visual deficit; refractive adaptation: an 18-week period of spectacle wear with six weekly measurements of logarithm of the minimum angle of resolution (logMAR) visual acuity; occlusion: in which participants were prescribed 6 hours of "patching" per day. In the latter phase, occlusion was objectively monitored and logMAR visual acuity recorded at 2-week intervals until any observed gains had ceased. Data were obtained from 94 participants (mean age, 5.1 +/- 1.4 years) with amblyopia associated with strabismus (n = 34), anisometropia (n = 23), and both anisometropia and strabismus (n = 37). Eighty-six underwent refractive adaptation. Average concordance with patching was 48%. The relationship between logMAR visual acuity gain and total occlusion dose was monotonic and linear. Increasing dose rate beyond 2 h/d hastened the response but did not improve outcome. More than 80% of the improvement during occlusion occurred within 6 weeks. Treatment outcome was significantly better for children younger than 4 years (n = 17) than in those older than 6 years (n = 24; P = 0.0014). Continuous objective monitoring of the amount of patching therapy received has provided insight into the dose-response relationship of occlusion therapy for amblyopia. Patching is most effective within the first few weeks of treatment, even for those in receipt of a relatively small dose. Further studies are needed to elucidate the neural basis for the dose-response functions. Copyright Association for Research in Vision and Ophthalmology

IMPACT OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C ON CYTOKINE SYNTHESIS AND HEPATIC FIBROSING PROCESSES

Directory of Open Access Journals (Sweden)

V. V. Shchekotov

2015-01-01

Full Text Available Objective: to estimate the time course of changes in the levels of tumor necrosis factor-α (TNF-α, interleukin-4 (IL-4, IL-6, and the hepatic fibrosis indicators hyaluronic acid (HA and liver elasticity index during combined antiviral therapy (AVT with interferon alpha-2b and ribavirin in patients with chronic hepatitis C (CHC. Subjects and methods. Fifty patients with CHC were examined. Serum TNF-α, IL-6, IL-4, and HA were estimated using an enzyme immunoassay. The stage of hepatic fibrosis was determined by fibroelastography with the liver elastic index being measured; the time course of changes in the indicators was assessed in 20 patients at the end of AVT. A virological response was monitored at therapy completion and 6 months later. Results. The patients with CHC in the reactivation phase were found to have enhanced TNF-α, IL-6, and IL-4 activities in 84, 60, and 100 % of the cases, respectively (р < 0.001, р = 0.01, р < 0.001, respectively. The median serum concentration of HA in CHC was 1.8-fold higher than that in the control group (p = 0.03; the liver elastic index averaged 6.5 kPa. TNF-α and IL-6 levels correlated with viremia, transaminases, and hepatic fibrosis indicators. At combined AVT completion, the virological response rate was as high as 85 %, which was attended by a considerable reduction in cytolysis, HA concentrations, and liver density index to 5.4 kPa (3.6–6.8 kPa (p < 0.04, and in the activity of the examined cytokines. The sustained virological response rate was 80 %. Only IL-4 levels decreased and TNF-α and IL-6 concentration remained at the baseline level in patients unresponsive to AVT. Conclusion. It is expedient to monitor TNF-α, IL-4, IL-6, and HA to evaluate the severity of liver involvement in CHC and to predict the efficiency of AVT.

12 CFR 361.5 - What are the FDIC's oversight and monitoring responsibilities in administering this program?

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false What are the FDIC's oversight and monitoring responsibilities in administering this program? 361.5 Section 361.5 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY MINORITY AND WOMEN OUTREACH PROGRAM CONTRACTING § 361...

Protocol for a randomised controlled implementation trial of point-of-care viral load testing and task shifting: the Simplifying HIV TREAtment and Monitoring (STREAM) study.

Science.gov (United States)

Dorward, Jienchi; Garrett, Nigel; Quame-Amaglo, Justice; Samsunder, Natasha; Ngobese, Hope; Ngomane, Noluthando; Moodley, Pravikrishnen; Mlisana, Koleka; Schaafsma, Torin; Donnell, Deborah; Barnabas, Ruanne; Naidoo, Kogieleum; Abdool Karim, Salim; Celum, Connie; Drain, Paul K

2017-09-27

Achieving the Joint United Nations Programme on HIV and AIDS 90-90-90 targets requires models of HIV care that expand antiretroviral therapy (ART) coverage without overburdening health systems. Point-of-care (POC) viral load (VL) testing has the potential to efficiently monitor ART treatment, while enrolled nurses may be able to provide safe and cost-effective chronic care for stable patients with HIV. This study aims to demonstrate whether POC VL testing combined with task shifting to enrolled nurses is non-inferior and cost-effective compared with laboratory-based VL monitoring and standard HIV care. The STREAM (Simplifying HIV TREAtment and Monitoring) study is an open-label, non-inferiority, randomised controlled implementation trial. HIV-positive adults, clinically stable at 6 months after ART initiation, will be recruited in a large urban clinic in South Africa. Approximately 396 participants will be randomised 1:1 to receive POC HIV VL monitoring and potential task shifting to enrolled nurses, versus laboratory VL monitoring and standard South African HIV care. Initial clinic follow-up will be 2-monthly in both arms, with VL testing at enrolment, 6 months and 12 months. At 6 months (1 year after ART initiation), stable participants in both arms will qualify for a differentiated care model involving decentralised ART pickup at community-based pharmacies. The primary outcome is retention in care and virological suppression at 12 months from enrolment. Secondary outcomes include time to appropriate entry into the decentralised ART delivery programme, costs per virologically suppressed patient and cost-effectiveness of the intervention compared with standard care. Findings will inform the scale up of VL testing and differentiated care in HIV-endemic resource-limited settings. Ethical approval has been granted by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC296/16) and University of Washington Institutional Review Board (STUDY

Noradrenaline and acetylcholine responsiveness of glucose-monitoring and glucose-insensitive neurons in the mediodorsal prefrontal cortex.

Science.gov (United States)

Nagy, Bernadett; Szabó, István; Csetényi, Bettina; Hormay, Edina; Papp, Szilárd; Keresztes, Dóra; Karádi, Zoltán

2014-01-16

The mediodorsal prefrontal cortex (mdPFC), as part of the forebrain glucose-monitoring (GM) system, plays important role in several regulatory processes to control the internal state of the organism and to initiate behavioral outputs accordingly. Little is known, however, about the neurochemical sensitivity of neurons located in this area. Substantial evidence indicates that the locus ceruleus - noradrenaline (NA) projection system and the nucleus basalis magnocellularis - cholinergic projection system regulate behavioral state and state dependent processing of sensory information, various cognitive functions already associated with the mdPFC. The main goal of the present study was to examine noradrenergic and cholinergic responsiveness of glucose-monitoring and glucose-insensitive (GIS) neurons in the mediodorsal prefrontal cortex. One fifth of the neurons tested changed in firing rate to microelectrophoretically applied NA. Responsiveness of the GM cells to this catecholamine proved to be significantly higher than that of the GIS units. Microiontophoretic application of acetylcholine (Ach) resulted in activity changes (predominantly facilitation) of more than 40% of the mdPFC neurons. Proportion of Ach sensitive units among the GM and the GIS neurons was found to be similar. The glucose-monitoring neurons of the mdPFC and their distinct NA and remarkable Ach sensitivity are suggested to be of particular significance in prefrontal control of adaptive behaviors. © 2013 Published by Elsevier B.V.

HCV-specific immune responses induced by CIGB-230 in combination with IFN-α plus ribavirin

Science.gov (United States)

Amador-Cañizares, Yalena; Martínez-Donato, Gillian; Álvarez-Lajonchere, Liz; Vasallo, Claudia; Dausá, Mariacarla; Aguilar-Noriega, Daylen; Valenzuela, Carmen; Raíces, Ivette; Dubuisson, Jean; Wychowski, Czeslaw; Cinza-Estévez, Zurina; Castellanos, Marlén; Núñez, Magdalys; Armas, Anny; González, Yaimé; Revé, Ismariley; Guerra, Ivis; Pérez Aguiar, Ángel; Dueñas-Carrera, Santiago

2014-01-01

AIM: To analyze hepatitis C virus (HCV)-specific immune responses in chronically infected patients under triple therapy with interferon-α (IFN-α) plus ribavirin and CIGB-230. METHODS: CIGB-230 was administered in different schedules with respect to IFN-α plus ribavirin therapy. Paired serum and peripheral blood mononuclear cells (PBMC) samples from baseline and end of treatment were analyzed. The HCV-specific humoral response was tested by enzyme-linked immunosorbent assay, neutralizing antibodies were evaluated by cell culture HCV neutralization assays, PBMC proliferation was assayed by carboxyfluorescein succinimidyl ester staining and IFN-γ secretion was assessed by enzyme-linked immunospot. Data on virological and histological response and their association with immune variables are also provided. RESULTS: From week 12 to week 48, all groups of patients showed a significant reduction in mean leukocyte counts. Statistically significant reductions in antibody titers were frequent, but only individuals immunized with CIGB-230 as early add-on treatment sustained the core-IgG response, and the neutralizing antibody response was enhanced only in patients receiving CIGB-230. Cell-mediated immune responses also tended to decline, but significant reductions in IFN-γ secretion and total absence of core-specific lymphoproliferation were exclusive of the control group. Only CIGB-230-immunized individuals showed de novo induced lymphoproliferative responses against the structural antigens. Importantly, it was demonstrated that the quality of the CIGB-230-induced immune response depended on the number of doses and timing of administration in relation to the antiviral therapy. Specifically, the administration of 6 doses of CIGB-230 as late add-on to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γ secretion, both of which were associated with the sustained virological response. CONCLUSION: CIGB-230, combined with IFN

Development of a spherical neutron rem monitor

International Nuclear Information System (INIS)

Panchal, C.G.; Madhavi, V.; Bansode, P.Y.; Jakati, R.K.; Ghodgaonkar, M.D.; Desai, S.S.; Shaikh, A.M.; Sathian, V.

2007-01-01

A new neutron rem monitor based on spherical LINUS with the state of art electronic circuits has been designed in Electronics Division. This prototype instrument encompasses a spherical double polythene moderator to improve an isotropic response and a lead layer to extend its energy response compared to the conventional neutron rem monitors. A systematic testing and calibration of the energy and directional response of the prototype monitor have been carried out. Although the monitor is expected to perform satisfactorily upto an energy ∼ 55 MeV, at present its response has been tested upto 5 MeV. (author)

Diffusion-Weighted Magnetic Resonance Imaging in Monitoring Rectal Cancer Response to Neoadjuvant Chemoradiotherapy

International Nuclear Information System (INIS)

Barbaro, Brunella; Vitale, Renata; Valentini, Vincenzo; Illuminati, Sonia; Vecchio, Fabio M.; Rizzo, Gianluca; Gambacorta, Maria Antonietta; Coco, Claudio; Crucitti, Antonio; Persiani, Roberto; Sofo, Luigi; Bonomo, Lorenzo

2012-01-01

Purpose: To prospectively monitor the response in patients with locally advanced nonmucinous rectal cancer after chemoradiotherapy (CRT) using diffusion-weighted magnetic resonance imaging. The histopathologic finding was the reference standard. Methods and Materials: The institutional review board approved the present study. A total of 62 patients (43 men and 19 women; mean age, 64 years; range, 28–83) provided informed consent. T 2 - and diffusion-weighted magnetic resonance imaging scans (b value, 0 and 1,000 mm 2 /s) were acquired before, during (mean 12 days), and 6–8 weeks after CRT. We compared the median apparent diffusion coefficients (ADCs) between responders and nonresponders and examined the associations with the Mandard tumor regression grade (TRG). The postoperative nodal status (ypN) was evaluated. The Mann-Whitney/Wilcoxon two-sample test was used to evaluate the relationships among the pretherapy ADCs, extramural vascular invasion, early percentage of increases in ADCs, and preoperative ADCs. Results: Low pretreatment ADCs ( −3 mm 2 /s) were correlated with TRG 4 scores (p = .0011) and associated to extramural vascular invasion with ypN+ (85.7% positive predictive value for ypN+). During treatment, the mean percentage of increase in tumor ADC was significantly greater in the responders than in the nonresponders (p 23% ADC increase had a 96.3% negative predictive value for TRG 4. In 9 of 16 complete responders, CRT-related tumor downsizing prevented ADC evaluations. The preoperative ADCs were significantly different (p = .0012) between the patients with and without downstaging (preoperative ADC ≥1.4 × 10 −3 mm 2 /s showed a positive and negative predictive value of 78.9% and 61.8%, respectively, for response assessment). The TRG 1 and TRG 2–4 groups were not significantly different. Conclusion: Diffusion-weighted magnetic resonance imaging seems to be a promising tool for monitoring the response to CRT.

Reactivation of hepatitis B in patients of chronic hepatitis C with hepatitis B virus infection treated with direct acting antivirals.

Science.gov (United States)

Yeh, Ming-Lun; Huang, Chung-Feng; Hsieh, Meng-Hsuan; Ko, Yu-Min; Chen, Kuan-Yu; Liu, Ta-Wei; Lin, Yi-Hung; Liang, Po-Cheng; Hsieh, Ming-Yen; Lin, Zu-Yau; Chen, Shinn-Cherng; Huang, Ching-I; Huang, Jee-Fu; Kuo, Po-Lin; Dai, Chia-Yen; Yu, Ming-Lung; Chuang, Wan-Long

2017-10-01

Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA therapy. Chronic hepatitis C patients receiving pan-oral DAA therapy from December 2013 to August 2016 were evaluated. Fifty-seven patients that had a past HBV infection (negative hepatitis B surface antigen [HBsAg] and positive hepatitis B core antibody) and seven patients that had a current HBV infection (positive HBsAg) were enrolled. Serum HBV and hepatitis C virus (HCV) markers were regularly measured. The endpoints were the HCV sustained virological response (SVR) and the HBV virological/clinical reactivation. The overall SVR 12 rate was 96.9%, and two patients, one with positive HBsAg, had a relapse of HCV. No episodes of HBV virological reactivation were observed among the patients with a past HBV infection. For the seven patients with a current HBV infection, HBV virological reactivation was found in four (57.1%) of the seven patients. Clinical reactivation of HBV was observed in one patient with pretreatment detectable HBV DNA and recovered after entecavir administration. For the other three patients with HBV virological reactivation, the reappearance of low level HBV DNA without clinical reactivation was observed. HBsAg levels demonstrated only small fluctuations in all the patients. There was a minimal impact of hepatitis B core antibody seropositivity on HCV efficacy and safety. For CHC patients with current HBV infection, the risk of HBV reactivation was present, and monitoring the HBV DNA level during therapy is warranted. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Assays for predicting and monitoring responses to lung cancer immunotherapy

International Nuclear Information System (INIS)

Teixidó, Cristina; Karachaliou, Niki; González-Cao, Maria; Morales-Espinosa, Daniela; Rosell, Rafael

2015-01-01

Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 (PD-1) and its ligand (PD-L1), have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer (NSCLC). Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. Therefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry (IHC) with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack specificity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-1/PD-L1 pathway

Lamivudine plus adefovir combination therapy versus entecavir monotherapy for lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Hu Peng

2011-08-01

Full Text Available Abstract Background Chronic hepatitis B virus (HBV infection represents a serious global health problem and resistance to lamivudine (LAM has become a serious clinical challenge. Previous rescue therapy for the treatment of chronic LAM-resistant hepatitis B infected patients included switching to entecavir (ETV and adding adefovir (ADV or tenofovir (TFV. At present, switching to ETV is not recommended for rescue therapy for LAM-resistant chronic hepatitis B (CHB. The aim of this report was to determine whether add-on ADV was a superior rescue strategy in the treatment of CHB patients with LAM resistance. Methods We searched Medline/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library. Relative risks (RRs of virologic response, virologic breakthrough, normalization of serum alanine aminotransferase (ALT levels and HBeAg seroconversion rates were studied. Factors predicting virologic response, standardized mean differences (SMD in HBV DNA levels and safety were reviewed. Results Six eligible trials (451 patients in total were included in the analysis. The rate of virologic breakthrough in the ETV group was higher than that in the LAM plus ADV group. There were no statistical differences in virologic response, ALT normalization and HBeAg seroconversion in either group 48 weeks post treatment. LAM plus ADV combination therapy produced faster and greater HBV DNA reduction rates 24 weeks post therapy compared to ETV monotherapy. HBV DNA baseline levels and the initial virologic response (IVR were predictive of the virologic response. Additionally, combination therapy or monotherapy were both well tolerated. Conclusions LAM plus ADV combination therapy was more effective and produced longer-lasting effects than switching to ETV monotherapy in treating CHB patients with LAM resistance. However, considering the practical benefits and limitations of ADV, individualized therapy will be needed in patients with prior history of LAM resistant infections.

Camera-based microswitch technology to monitor mouth, eyebrow, and eyelid responses of children with profound multiple disabilities

NARCIS (Netherlands)

Lancioni, G.E.; Bellini, D.; Oliva, D.; Singh, N.N.; O'Reilly, M.F.; Sigafoos, J.; Lang, R.B.; Didden, H.C.M.

2011-01-01

A camera-based microswitch technology was recently used to successfully monitor small eyelid and mouth responses of two adults with profound multiple disabilities (Lancioni et al., Res Dev Disab 31:1509-1514, 2010a). This technology, in contrast with the traditional optic microswitches used for

Dried blood spots for viral load monitoring in Malawi: feasible and effective.

Directory of Open Access Journals (Sweden)

Sarah E Rutstein

Full Text Available To evaluate the feasibility and effectiveness of dried blood spots (DBS use for viral load (VL monitoring, describing patient outcomes and programmatic challenges that are relevant for DBS implementation in sub-Saharan Africa.We recruited adult antiretroviral therapy (ART patients from five district hospitals in Malawi. Eligibility reflected anticipated Ministry of Health VL monitoring criteria. Testing was conducted at a central laboratory. Virological failure was defined as >5000 copies/ml. Primary outcomes were program feasibility (timely result availability and patient receipt and effectiveness (second-line therapy initiation.We enrolled 1,498 participants; 5.9% were failing at baseline. Median time from enrollment to receipt of results was 42 days; 79.6% of participants received results within 3 months. Among participants with confirmed elevated VL, 92.6% initiated second-line therapy; 90.7% were switched within 365 days of VL testing. Nearly one-third (30.8% of participants with elevated baseline VL had suppressed (4 years were more likely to be failing than participants on therapy 1-4 years (RR 1.7, 95% CI 1.0-2.8; older participants were less likely to be failing (RR 0.95, 95% CI 0.92-0.98. There was no difference in likelihood of failure based on clinical symptoms (RR 1.17, 95% CI 0.65-2.11.DBS for VL monitoring is feasible and effective in real-world clinical settings. Centralized DBS testing may increase access to VL monitoring in remote settings. Programmatic outcomes are encouraging, especially proportion of eligible participants switched to second-line therapy.

Real-time seismic monitoring of the integrated cape girardeau bridge array and recorded earthquake response

Science.gov (United States)

Celebi, M.

2006-01-01

This paper introduces the state of the art, real-time and broad-band seismic monitoring network implemented for the 1206 m [3956 ft] long, cable-stayed Bill Emerson Memorial Bridge in Cape Girardeau (MO), a new Mississippi River crossing, approximately 80 km from the epicentral region of the 1811-1812 New Madrid earthquakes. The bridge was designed for a strong earthquake (magnitude 7.5 or greater) during the design life of the bridge. The monitoring network comprises a total of 84 channels of accelerometers deployed on the superstructure, pier foundations and at surface and downhole free-field arrays of the bridge. The paper also presents the high quality response data obtained from the network. Such data is aimed to be used by the owner, researchers and engineers to assess the performance of the bridge, to check design parameters, including the comparison of dynamic characteristics with actual response, and to better design future similar bridges. Preliminary analyses of ambient and low amplitude small earthquake data reveal specific response characteristics of the bridge and the free-field. There is evidence of coherent tower, cable, deck interaction that sometimes results in amplified ambient motions. Motions at the lowest tri-axial downhole accelerometers on both MO and IL sides are practically free from any feedback from the bridge. Motions at the mid-level and surface downhole accelerometers are influenced significantly by feedback due to amplified ambient motions of the bridge. Copyright ASCE 2006.

A solution to the varying response of the linear power monitor induced by xenon poisoning

Energy Technology Data Exchange (ETDEWEB)

Godsey, T A; Randall, J D [Texas A and M University (United States)

1974-07-01

After conversion to FLIP fuel at Texas A and M, the fuel temperatures were examined very carefully. It was observed that the fuel temperature at 1 Mw varied over a wide range during the week. This variation was shown to be due to the variation in response of the linear CIC which was used to establish reactor power level. A modification of the linear power monitor was designed and installed. The response of this system was verified by using cobalt wires, fuel temperature, and a fission chamber located at 6 feet from the reactor core. The system has proven to be operationally satisfactory. (author)

Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia.

Directory of Open Access Journals (Sweden)

Hubert Barennes

Full Text Available INTRODUCTION: In resource limited settings, patients entering an antiretroviral therapy (ART program comprise ART naive and ART pre-treated patients who may show differential virological outcomes. METHODS: This retrospective study, conducted in 2010-2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia assessed virological failure (VF rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF (>1,000 copies/ml underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms. RESULTS: On a total of 209 patients, 164 (78.4% were naive and 45 (21.5% were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30-194 and 279 cells/mm3 (IQR: 103-455 (p<0.001, respectively. Twenty seven patients (12.9% exhibited VF (95% CI: 8.6-18.2%, including 10 naive (10/164, 6.0% and 17 pre-treated (17/45, 37.8% patients (p<0.001. Among these viremic patients, twenty-two (81.4% were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3% harbored ≥1 drug resistance mutations (DRMs whereas 3 (all belonging to pre-treated patients harbored wild-types viruses. The most frequent DRMs were M184V (86.3%, K103N (45.5% and thymidine analog mutations (TAMs (40.9%. Two (13.3% pre-treated patients harbored viruses that showed a multi-nucleos(tide resistance including Q151M, K65R, E33A/D, E44A/D mutations. CONCLUSION: In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre

Factors Associated with Low-Level Viraemia and Virological Failure: Results from the Austrian HIV Cohort Study.

Directory of Open Access Journals (Sweden)

Gisela Leierer

Full Text Available In human immunodeficiency virus treatment adequate virological suppression is warranted, nevertheless for some patients it remains a challenge. We investigated factors associated with low-level viraemia (LLV and virological failure (VF under combined antiretroviral therapy (cART.We analysed patients receiving standard regimens between 1st July 2012 and 1st July 2013 with at least one viral load (VL measurement below the quantification limit (BLQ in their treatment history. After a minimum of 6 months of unmodified cART, the next single VL measurement within 6 months was analysed. VF was defined as HIV RNA levels ≥ 200 copies/mL and all other quantifiable measurements were classified as LLV. Factors associated with LLV and VF compared to BLQ were identified by logistic regression models.Of 2276 participants, 1972 (86.6% were BLQ, 222 (9.8% showed LLV and 82 (3.6% had VF. A higher risk for LLV and VF was shown in patients with cART interruptions and in patients with boosted PI therapy. The risk for LLV and VF was lower in patients from centres using the Abbott compared to the Roche assay to measure VL. A higher risk for LLV but not for VF was found in patients with a higher VL before cART [for >99.999 copies/mL: aOR (95% CI: 4.19 (2.07-8.49; for 10.000-99.999 copies/mL: aOR (95% CI: 2.52 (1.23-5.19] and shorter cART duration [for <9 months: aOR (95% CI: 2.59 (1.38-4.86]. A higher risk for VF but not for LLV was found in younger patients [for <30 years: aOR (95% CI: 2.76 (1.03-7.35; for 30-50 years: aOR (95% CI: 2.70 (1.26-5.79], people originating from high prevalence countries [aOR (95% CI: 2.20 (1.09-4.42] and in male injecting drug users [aOR (95% CI: 2.72 (1.38-5.34].For both VF and LLV, factors associated with adherence play a prominent role. Furthermore, performance characteristics of the diagnostic assay used for VL quantification should also be taken into consideration.

Clinical trials using IFN-α as a vaccine adjuvant: new strategies for the molecular monitoring of the immune response

International Nuclear Information System (INIS)

Belardelli, F.; Arico, E.; Marincola, F.; Wang, E.

2009-01-01

The main general objective of this project was to define immunotherapy protocols based on the new concept of using IFN-a as and immune adjuvant, developing innovative methodologies suitable for predicting and monitoring the immunological and clinical responses. Specific aim of developing new micro arrays technologies particularly suitable for a molecular tracking and prediction of the response to IFN of cytokine-treated patients

Federal Radiological Monitoring and Assessment Center Monitoring Manual Volume 1, Operations

Energy Technology Data Exchange (ETDEWEB)

NSTec Aerial Measurement Systems

2012-07-31

The Monitoring division is primarily responsible for the coordination and direction of: Aerial measurements to delineate the footprint of radioactive contaminants that have been released into the environment. Monitoring of radiation levels in the environment; Sampling to determine the extent of contaminant deposition in soil, water, air and on vegetation; Preliminary field analyses to quantify soil concentrations or depositions; and Environmental and personal dosimetry for FRMAC field personnel, during a Consequence Management Response Team (CMRT) and Federal Radiological Monitoring and Assessment Center (FRMAC) response. Monitoring and sampling techniques used during CM/FRMAC operations are specifically selected for use during radiological emergencies where large numbers of measurements and samples must be acquired, analyzed, and interpreted in the shortest amount of time possible. In addition, techniques and procedures are flexible so that they can be used during a variety of different scenarios; e.g., accidents involving releases from nuclear reactors, contamination by nuclear waste, nuclear weapon accidents, space vehicle reentries, or contamination from a radiological dispersal device. The Monitoring division also provides technicians to support specific Health and Safety Division activities including: The operation of the Hotline; FRMAC facility surveys; Assistance with Health and Safety at Check Points; and Assistance at population assembly areas which require support from the FRMAC. This volume covers deployment activities, initial FRMAC activities, development and implementation of the monitoring and assessment plan, the briefing of field teams, and the transfer of FRMAC to the EPA.

Reactor power monitoring device

International Nuclear Information System (INIS)

Kono, Shigehiro.

1990-01-01

Among a plurality of power monitoring programs in a reactor power monitoring device, rapid response is required for a scram judging program for the power judging processing of scram signals. Therefore, the scram judging program is stored independently from other power monitoring programs, applied with a priority order, and executed in parallel with other programs, to output scram signals when the detected data exceeds a predetermined value. As a result, the capacity required for the scram judging program is reduced and the processing can be conducted in a short period of time. In addition, since high priority is applied to the scram judging program which is divided into a small capacity, it is executed at higher frequency than other programs when they are executed in parallel. That is, since the entire processings for the power monitoring program are repeated in a short cycle, the response speed of the scram signals required for high responsivity can be increased. (N.H.)

Simplified response monitoring criteria for multiple myeloma in patients undergoing therapy with novel agents using computed tomography

Energy Technology Data Exchange (ETDEWEB)

Schabel, Christoph; Horger, Marius; Kum, Sara [Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Weisel, Katja [Department of Internal Medicine II – Hematology & Oncology, Eberhard-Karls-University Tuebingen, Otfried-Müller-Str. 5, 72076 Tuebingen (Germany); Fritz, Jan [Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 600 N Wolfe St., Baltimore, MD 21287 (United States); Ioanoviciu, Sorin D. [Department of Internal Medicine, Clinical Municipal Hospital Timisoara, Gheorghe Dima Str. 5, 300079 Timisoara (Romania); Bier, Georg, E-mail: georg.bier@med.uni-tuebingen.de [Department of Neuroradiology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)

2016-12-15

Highlights: • A simplified method for response monitoring of multiple myeloma is proposed. • Medullary bone lesions of all limbs were included and analysed. • Diameters of ≥2 medullary bone lesions are sufficient for therapy monitoring. - Abstract: Introduction: Multiple myeloma is a malignant hematological disorder of the mature B-cell lymphocytes originating in the bone marrow. While therapy monitoring is still mainly based on laboratory biomarkers, the additional use of imaging has been advocated due to inaccuracies of serological biomarkers or in a-secretory myelomas. Non-enhanced CT and MRI have similar sensitivities for lesions in yellow marrow-rich bone marrow cavities with a favourable risk and cost-effectiveness profile of CT. Nevertheless, these methods are still limited by frequently high numbers of medullary lesions and its time consumption for proper evaluation. Objective: To establish simplified response criteria by correlating size and CT attenuation changes of medullary multiple myeloma lesions in the appendicular skeleton with the course of lytic bone lesions in the entire skeleton. Furthermore to evaluate these criteria with respect to established hematological myeloma-specific parameters for the prediction of treatment response to bortezomib or lenalidomide. Materials and methods: Non-enhanced reduced-dose whole-body CT examinations of 78 consecutive patients (43 male, 35 female, mean age 63.69 ± 9.2 years) with stage III multiple myeloma were retrospectively re-evaluated. On per patient basis, size and mean CT attenuation of 2–4 representative lesions in the limbs were measured at baseline and at a follow-up after a mean of 8 months. Results were compared with the course of lytical bone lesions as well with that of specific hematological biomarkers. Myeloma response was assessed according to the International Myeloma Working Group (IMWG) uniform response criteria. Testing for correlation between response of medullary lesions (Resp

Convenient monitoring of brewery fermentation course by refractometry

Czech Academy of Sciences Publication Activity Database

Šavel, J.; Košín, P.; Brož, A.; Sigler, Karel

2009-01-01

Roč. 55, č. 4 (2009), s. 94-99 ISSN 0023-5830 R&D Projects: GA MŠk 1M0570 Institutional research plan: CEZ:AV0Z50200510 Keywords : wort * fermentation * refractometry Subject RIV: EE - Microbiology, Virology

Air monitoring activities of the U.S. Environmental Protection Agency/Environmental Response Team during the September 11, 2001 terrorist attacks

Energy Technology Data Exchange (ETDEWEB)

Turpin, R.; Mickunas, D.; Campagna, P.; Burchette, S. [U.S. Environmental Protection Agency, Environmental Response Team, Edison, NJ (United States)

2002-07-01

The Environmental Response Team (ERT) of the United States Environmental Protection Agency (USEPA) conducted air monitoring activities during the September 11, 2001 attack on the World Trade Center in New York City. This paper describes ERT's response actions and analytical support. It covers ERT activities from the morning of September 11 to October 17, 2001 when ERT was alerted of anthrax activities in Washington, DC and Boca Raton, Florida. ERT members provided technical support regarding respirator/personnel protective equipment selection, decontamination and health and safety protocols. In the first few weeks, ERT was also providing analytical laboratory support to the EPA, the Occupational Safety and Health Administration, the National Institute for Occupational Safety and Health, and the New York City Department of Health. ERT also provided on-site gas chromatography-mass spectrometry analysis via the Trace Atmospheric Gas Analyzer (TAGA) bus, providing real-time direct readings to the EPA and the New York Fire Department. Site boundary air monitoring stations were maintained until early November at which point the EPA Region 2 took over all monitoring responsibilities. Air sampling efforts were initially directed at worker health and safety and the surrounding environments. Air sampling was conducted for asbestos, acid gases, heavy metals, phosgene, mercury, dioxins/furans, volatile organic compounds, and polychlorinated biphenyls. The sampling activities were later expanded to include chlorine, hydrogen chloride, sulfur dioxide, and hydrogen cyanide. Site assessment is still ongoing. What began as a typical emergency response air sampling effort soon became a huge air monitoring effort with the original six stations expanded to more than 20. ERT made every effort to collect, analyze, quality assure and transfer data for posting on publicly accessible website within less than 24 hours. It was noted that one of the lessons learned from the disaster is

Alizarin Complexone Functionalized Mesoporous Silica Nanoparticles: A Smart System Integrating Glucose-Responsive Double-Drugs Release and Real-Time Monitoring Capabilities.

Science.gov (United States)

Zou, Zhen; He, Dinggeng; Cai, Linli; He, Xiaoxiao; Wang, Kemin; Yang, Xue; Li, Liling; Li, Siqi; Su, Xiaoya

2016-04-06

The outstanding progress of nanoparticles-based delivery systems capable of releasing hypoglycemic drugs in response to glucose has dramatically changed the outlook of diabetes management. However, the developed glucose-responsive systems have not offered real-time monitoring capabilities for accurate quantifying hypoglycemic drugs released. In this study, we present a multifunctional delivery system that integrates both delivery and monitoring issues using glucose-triggered competitive binding scheme on alizarin complexone (ALC) functionalized mesoporous silica nanoparticles (MSN). In this system, ALC is modified on the surface of MSN as the signal reporter. Gluconated insulin (G-Ins) is then introduced onto MSN-ALC via benzene-1,4-diboronic acid (BA) mediated esterification reaction, where G-Ins not only blocks drugs inside the mesopores but also works as a hypoglycemic drug. In the absence of glucose, the sandwich-type boronate ester structure formed by BA binding to the diols of ALC and G-Ins remains intact, resulting in an fluorescence emission peak at 570 nm and blockage of pores. Following a competitive binding, the presence of glucose cause the dissociation of boronate ester between ALC and BA, which lead to the pores opening and disappearance of fluorescence. As proof of concept, rosiglitazone maleate (RSM), an insulin-sensitizing agent, was doped into the MSN to form a multifunctional MSN (RSM@MSN-ALC-BA-Ins), integrating with double-drugs loading, glucose-responsive performance, and real-time monitoring capability. It has been demonstrated that the glucose-responsive release behaviors of insulin and RSM in buffer or in human serum can be quantified in real-time through evaluating the changes of fluorescence signal. We believe that this developed multifunctional system can shed light on the invention of a new generation of smart nanoformulations for optical diagnosis, individualized treatment, and noninvasive monitoring of diabetes management.

Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors.

Directory of Open Access Journals (Sweden)

Alison Castley

Full Text Available We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p0.2. Associations between higher sCD163 and protease inhibitor therapy (p = 0.05 and lower sCD14 with integrase inhibitor therapy (p = 0.02 were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI, with a favourable influence of Framingham score <10% (p = 0.04. Soluble CD14 levels were higher among smokers (p = 0.002, with no effect of other CVD risk factors, except age (p = 0.045. Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation.

Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors

Science.gov (United States)

Castley, Alison; Williams, Leah; James, Ian; Guelfi, George; Berry, Cassandra; Nolan, David

2016-01-01

We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile) and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p0.2). Associations between higher sCD163 and protease inhibitor therapy (p = 0.05) and lower sCD14 with integrase inhibitor therapy (p = 0.02) were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI), with a favourable influence of Framingham score <10% (p = 0.04). Soluble CD14 levels were higher among smokers (p = 0.002), with no effect of other CVD risk factors, except age (p = 0.045). Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation. PMID:27355513

Emergency radiological monitoring and analysis: Federal Radiological Monitoring and Assessment Center

International Nuclear Information System (INIS)

Thome, D.J.

1995-01-01

The US Federal Radiological Emergency Response Plan (FRERP) provides the framework for integrating the various Federal agencies responding to a major radiological emergency. The FRERP authorizes the creation of the Federal Radiological Monitoring and Assessment Center (FRMAC), which is established to coordinate all Federal agencies involved in the monitoring and assessment of the off-site radiological conditions in support of the impacted State(s) and the Lead Federal Agency (LFA). Within the FRMAC, the Monitoring and Analysis Division (M ampersand A) is responsible for coordinating all FRMAC assets involved in conducting a comprehensive program of environmental monitoring, sampling, radioanalysis, and quality assurance. To assure consistency, completeness, and the quality of the data produced, a methodology and procedures manual is being developed. This paper discusses the structure, assets, and operations of the FRMAC M ampersand A and the content and preparation of the manual

Functional pathway analysis of genes associated with response to treatment for chronic hepatitis C.

Science.gov (United States)

Birerdinc, A; Afendy, A; Stepanova, M; Younossi, I; Manyam, G; Baranova, A; Younossi, Z M

2010-10-01

Chronic hepatitis C (CH-C) is among the most common causes of chronic liver disease. Approximately 50% of patients with CH-C treated with pegylated interferon-α and ribavirin (PEG-IFN-α + RBV) achieve a sustained virological response (SVR). Several factors such as genotype 1, African American (AA) race, obesity and the absence of an early virological response (EVR) are associated with low SVR. This study elucidates molecular pathways deregulated in patients with CH-C with negative predictors of response to antiviral therapy. Sixty-eight patients with CH-C who underwent a full course of treatment with PEG-IFN-α + RBV were included in the study. Pretreatment blood samples were collected in PAXgene™ RNA tubes. EVR, complete EVR (cEVR), and SVR rates were 76%, 57% and 41%, respectively. Total RNA was extracted from pretreatment peripheral blood mononuclear cells, quantified and used for one-step RT-PCR to profile 154 mRNAs. The expression of mRNAs was normalized with six 'housekeeping' genes. Differentially expressed genes were separated into up and downregulated gene lists according to the presence or absence of a risk factor and subjected to KEGG Pathway Painter which allows high-throughput visualization of the pathway-specific changes in expression profiles. The genes were consolidated into the networks associated with known predictors of response. Before treatment, various genes associated with core components of the JAK/STAT pathway were activated in the cohorts least likely to achieve SVR. Genes related to focal adhesion and TGF-β pathways were activated in some patients with negative predictors of response. Pathway-centred analysis of gene expression profiles from treated patients with CH-C points to the Janus kinase-signal transducers and activators of transcription signalling cascade as the major pathogenetic component responsible for not achieving SVR. In addition, focal adhesion and TGF-β pathways are associated with some predictors of response. �

Methods for monitoring endoplasmic reticulum stress and the unfolded protein response.

LENUS (Irish Health Repository)

Samali, Afshin

2010-01-01

The endoplasmic reticulum (ER) is the site of folding of membrane and secreted proteins in the cell. Physiological or pathological processes that disturb protein folding in the endoplasmic reticulum cause ER stress and activate a set of signaling pathways termed the Unfolded Protein Response (UPR). The UPR can promote cellular repair and sustained survival by reducing the load of unfolded proteins through upregulation of chaperones and global attenuation of protein synthesis. Research into ER stress and the UPR continues to grow at a rapid rate as many new investigators are entering the field. There are also many researchers not working directly on ER stress, but who wish to determine whether this response is activated in the system they are studying: thus, it is important to list a standard set of criteria for monitoring UPR in different model systems. Here, we discuss approaches that can be used by researchers to plan and interpret experiments aimed at evaluating whether the UPR and related processes are activated. We would like to emphasize that no individual assay is guaranteed to be the most appropriate one in every situation and strongly recommend the use of multiple assays to verify UPR activation.

Methods for Monitoring Endoplasmic Reticulum Stress and the Unfolded Protein Response

Directory of Open Access Journals (Sweden)

Afshin Samali

2010-01-01

Full Text Available The endoplasmic reticulum (ER is the site of folding of membrane and secreted proteins in the cell. Physiological or pathological processes that disturb protein folding in the endoplasmic reticulum cause ER stress and activate a set of signaling pathways termed the Unfolded Protein Response (UPR. The UPR can promote cellular repair and sustained survival by reducing the load of unfolded proteins through upregulation of chaperones and global attenuation of protein synthesis. Research into ER stress and the UPR continues to grow at a rapid rate as many new investigators are entering the field. There are also many researchers not working directly on ER stress, but who wish to determine whether this response is activated in the system they are studying: thus, it is important to list a standard set of criteria for monitoring UPR in different model systems. Here, we discuss approaches that can be used by researchers to plan and interpret experiments aimed at evaluating whether the UPR and related processes are activated. We would like to emphasize that no individual assay is guaranteed to be the most appropriate one in every situation and strongly recommend the use of multiple assays to verify UPR activation.

A report on upgraded seismic monitoring stations in Myanmar: Station performance and site response

Science.gov (United States)

Thiam, Hrin Nei; Min Htwe, Yin Myo; Kyaw, Tun Lin; Tun, Pa Pa; Min, Zaw; Htwe, Sun Hninn; Aung, Tin Myo; Lin, Kyaw Kyaw; Aung, Myat Min; De Cristofaro, Jason; Franke, Mathias; Radman, Stefan; Lepiten, Elouie; Wolin, Emily; Hough, Susan E.

2017-01-01

Myanmar is in a tectonically complex region between the eastern edge of the Himalayan collision zone and the northern end of the Sunda megathrust. Until recently, earthquake monitoring and research efforts have been hampered by a lack of modern instrumentation and communication infrastructure. In January 2016, a major upgrade of the Myanmar National Seismic Network (MNSN; network code MM) was undertaken to improve earthquake monitoring capability. We installed five permanent broadband and strong‐motion seismic stations and real‐time data telemetry using newly improved cellular networks. Data are telemetered to the MNSN hub in Nay Pyi Taw and archived at the Incorporated Research Institutions for Seismology Data Management Center. We analyzed station noise characteristics and site response using noise and events recorded over the first six months of station operation. Background noise characteristics vary across the array, but indicate that the new stations are performing well. MM stations recorded more than 20 earthquakes of M≥4.5 within Myanmar and its immediate surroundings, including an M 6.8 earthquake located northwest of Mandalay on 13 April 2016 and the Mw 6.8 Chauk event on 24 August 2016. We use this new dataset to calculate horizontal‐to‐vertical spectral ratios, which provide a preliminary characterization of site response of the upgraded MM stations.

Reusable radiation monitor

International Nuclear Information System (INIS)

Fanselow, D.L.; Ersfeld, D.A.

1978-01-01

An integrating, reusable device for monitoring exposure to actinic radiation is disclosed. The device comprises a substrate having deposited thereon at least one photochromic aziridine compound which is sealed in an oxygen barrier to stabilize the color developed by the aziridine compound in response to actinic radiation. The device includes a spectral response shaping filter to transmit only actinic radiation of the type being monitored. A color standard is also provided with which to compare the color developed by the aziridine compound

Biophysical Monitoring and dose response characteristics of irradiated hemoglobin

International Nuclear Information System (INIS)

Elshemey, W.M; Selim, N.S.; Desouky, O.

2003-01-01

The present work aims to move a step forward towards a deeper understanding of the scattering of x-ray, from lyophilized biological samples. Comparative study has been performed using LAXS and UV-visible spectrophotometry for monitoring the dose response characteristics of the hemoglobin molecule of irradiated blood. Blood samples were irradiated at doses ranging from 5 up to 100 Gy. Diluted hemoglobin solution was scanned in the UV- visible range (200-700 nm), and lyophilized hemoglobin was prepared for LAXS measurement. The radiation-induced changes in the hemoglobin structure have been evaluated. The LAXS profile of hemoglobin molecule is characterized by the presence of two peaks in the forward direction of scattering. These peaks were found to be sensitive to the variations in the molecular structure of a given sample. The obtained results suggest that the 1 s t peak, recorded at 4.65 o , is sensitive to the tertiary and quaternary structure of the globin part, while the major peak, recorded at 10.5 o , appeared to be related to its primary and secondary structure

The regulated secretory pathway in CD4(+ T cells contributes to human immunodeficiency virus type-1 cell-to-cell spread at the virological synapse.

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Clare Jolly

2011-09-01

Full Text Available Direct cell-cell spread of Human Immunodeficiency Virus type-1 (HIV-1 at the virological synapse (VS is an efficient mode of dissemination between CD4(+ T cells but the mechanisms by which HIV-1 proteins are directed towards intercellular contacts is unclear. We have used confocal microscopy and electron tomography coupled with functional virology and cell biology of primary CD4(+ T cells from normal individuals and patients with Chediak-Higashi Syndrome and report that the HIV-1 VS displays a regulated secretion phenotype that shares features with polarized secretion at the T cell immunological synapse (IS. Cell-cell contact at the VS re-orientates the microtubule organizing center (MTOC and organelles within the HIV-1-infected T cell towards the engaged target T cell, concomitant with polarization of viral proteins. Directed secretion of proteins at the T cell IS requires specialized organelles termed secretory lysosomes (SL and we show that the HIV-1 envelope glycoprotein (Env localizes with CTLA-4 and FasL in SL-related compartments and at the VS. Finally, CD4(+ T cells that are disabled for regulated secretion are less able to support productive cell-to-cell HIV-1 spread. We propose that HIV-1 hijacks the regulated secretory pathway of CD4(+ T cells to enhance its dissemination.

Monitoring Activities Review action report for the Environmental Monitoring Program

International Nuclear Information System (INIS)

Wilhelmsen, R.N.; Wright, K.C.

1990-12-01

To improve program planning and to provide bases for technical improvement of the monitoring program, the EG ampersand G Environmental Monitoring (EM) organization has regularly used the Monitoring Activities Review (MAR) process since 1982. Each MAR is conducted by a committee of individuals selected for their experience in the various types of monitoring performed by the EM organization. An MAR of the Environmental Monitoring Program was conducted in 1988. This action report identifies and discusses the recommendations of this MAR committee. This action report also identifies the actions already taken by the EM Unit in response to these recommendations, as well as the actions and schedules to be taken. 10 refs

Hepatitis C treatment response kinetics and impact of baseline predictors

DEFF Research Database (Denmark)

Lindh, M; Arnholm, B; Eilard, A

2011-01-01

Summary. The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics...... above 400 000 IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected...... by the early viral kinetics as assessed by repeated HCV RNA quantifications. The kinetic patterns and the high relapse rate in genotype 2/3 patients without RVR suggest that this group might benefit from treatment durations longer than 24 weeks....

Impact of hepatitis B virus infection on HIV response to antiretroviral therapy in a Chinese antiretroviral therapy center

Directory of Open Access Journals (Sweden)

Rongrong Yang

2014-11-01

Conclusions: HBV co-infection can affect late immunological and virological responses to ART and increase the risk of hepatotoxicity. Mortality due to liver disease was high among HIV/HBV co-infected individuals in this study, despite HBV-active ART. As long as HIV/HBV co-infected persons need anti-HBV therapy, they should be recommended ART that includes agents with activity against both HIV and HBV, regardless of the CD4 cell count level.

Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients.

Directory of Open Access Journals (Sweden)

Jean-Guy Baril

Full Text Available We reviewed the current literature regarding antiretroviral (ARV-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection.A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations.Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels.The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable

Contrast-enhanced MR imaging monitoring of acute tumor response to chemotherapy

International Nuclear Information System (INIS)

Ranney, D.F.; Cohen, J.M.; Antich, P.P.; Endman, W.A.; Kulkarni, P.; Weinreb, J.C.; Giovanella, B.

1987-01-01

Treatment responses of human malignant melanomas were monitored at millimeter resolution in athymic mice by injecting a new polymeric contrast agent, Gd-DTPA-dextran (0.1 mmol Gd/kg, intravenously). Proton MR imaging (0.35 T, spin-echo, repetition time = 0.5 second, echo time = 50 msec) was performed 30 hours after administering diphtheria toxin. Pre-contrast medium images revealed only homogeneous intermediate-intensity tumor masses. Post-contrast medium images of untreated (viable) tumors demonstrated 32% enhancement throughout the entire mass. Post-contrast medium images of toxin-treated tumors revealed marked enhancement (65%) of the histologically viable outer rims, lesser enhancement (38%) of heavily damaged subregions, and no enhancement of dead tumor. These acute, contrast medium-enhanced MR images accurately identified tumor subregions that survived for longer than one week

Monitoring of vegetation dynamics and assessing vegetation response to drought in the Iberian Peninsula

Energy Technology Data Exchange (ETDEWEB)

Garcia-Haro, F. J.; Moreno, A.; Perez-Hoyos, A.; Gilabert, M. A.; Melia, J.; Belda, F.; Poquet, D.; Martinez, B.; Verger, A.

2009-07-01

Monitoring the vegetation activity over long time-scales is necessary to discern ecosystem response to climate variability. Spatial and temporally consistent estimates of the biophysical variables such as fractional vegetation cover (FVC) and leaf area index (LAI) have been obtained in the context of DULCINEA Project. We used long-term monthly climate statistics to build simple climatic indices (SPI, moisture index) at different time scales. From these indices, we estimated that the climatic disturbances affected both the growing season and the total amount of vegetation. This implies that the anomaly of vegetation cover is a good indicator of moisture condition and can be an important data source when used for detecting an monitoring drought in the Iberian Peninsula. The impact of climate variability on the vegetation dynamics has shown not to be the same for every region. We concluded that the relationships between vegetation anomaly and moisture availability are significant for the arid and semiarid areas. (Author) 6 refs.

Monitoring of vegetation dynamics and assessing vegetation response to drought in the Iberian Peninsula

International Nuclear Information System (INIS)

Garcia-Haro, F. J.; Moreno, A.; Perez-Hoyos, A.; Gilabert, M. A.; Melia, J.; Belda, F.; Poquet, D.; Martinez, B.; Verger, A.

2009-01-01

Monitoring the vegetation activity over long time-scales is necessary to discern ecosystem response to climate variability. Spatial and temporally consistent estimates of the biophysical variables such as fractional vegetation cover (FVC) and leaf area index (LAI) have been obtained in the context of DULCINEA Project. We used long-term monthly climate statistics to build simple climatic indices (SPI, moisture index) at different time scales. From these indices, we estimated that the climatic disturbances affected both the growing season and the total amount of vegetation. This implies that the anomaly of vegetation cover is a good indicator of moisture condition and can be an important data source when used for detecting an monitoring drought in the Iberian Peninsula. The impact of climate variability on the vegetation dynamics has shown not to be the same for every region. We concluded that the relationships between vegetation anomaly and moisture availability are significant for the arid and semiarid areas. (Author) 6 refs.

HVSR Response Evolution due to Seasonal Variation: Observations from 2 Years of Continuous Monitoring

Science.gov (United States)

Nurse, K. B.; Milkereit, B.

2017-12-01

The seismic Horizontal to Vertical Spectral Ratio analysis technique reliably gives overburden depth to bedrock, for an independently determined Vs, based on the frequency of the main resonance peak. Above this, smaller resonances reflect the velocity structure within the overburden itself. This range in the HVSR response shows sufficient sensitivity to be exploited as a monitoring tool, to detect change in seismic physical properties and from that, change in overburden conditions. To explore the variation of the response, several 3C geophones have been deployed in southern Ontario, Canada since December 2015 (and ongoing). The local geology is a sedimentary basin with 30m of overburden, a simple 2D environment well suited for the HVSR method. Data are collected for 15s per minute, with an effective frequency band of 2-400Hz. HVSR estimates are produced for each sampling period and archived. Over these two years, winter freeze/thaw, saturated spring and summer draught conditions were sampled. H/V daily averages are dominated by the stable 3Hz resonance due to the overall surface layer, but smaller spectral peaks up to 100Hz are clear and evolve in frequency and amplitude over the collection period. Ground freeze/thaw cycles are clearly evident by significant reduction in the horizontal field, but also the changing of the soil moisture content throughout the year causes subtle shifts in the response (correlated to rain events and water table variation). The long term sampling does show a sensitivity of the HVSR method to the overburden in proximity to the sensor, and suggests a possibility for its use in monitoring soil / water-table conditions. But it also highlights that the estimate from an isolated H/V acquisition does include this variability and needs to be adequately quantified in VS30 estimates.

Diffusion-Weighted Magnetic Resonance Imaging in Monitoring Rectal Cancer Response to Neoadjuvant Chemoradiotherapy

Energy Technology Data Exchange (ETDEWEB)

Barbaro, Brunella, E-mail: bbarbaro@rm.unicatt.it [Department of Bioimaging and Radiological Sciences, Catholic University School of Medicine, Rome (Italy); Vitale, Renata; Valentini, Vincenzo; Illuminati, Sonia [Department of Bioimaging and Radiological Sciences, Catholic University School of Medicine, Rome (Italy); Vecchio, Fabio M. [Department of Pathology, Catholic University School of Medicine, Rome (Italy); Rizzo, Gianluca [Department of Surgery, Catholic University School of Medicine, Rome (Italy); Gambacorta, Maria Antonietta [Department of Bioimaging and Radiological Sciences, Catholic University School of Medicine, Rome (Italy); Coco, Claudio; Crucitti, Antonio; Persiani, Roberto; Sofo, Luigi [Department of Surgery, Catholic University School of Medicine, Rome (Italy); Bonomo, Lorenzo [Department of Bioimaging and Radiological Sciences, Catholic University School of Medicine, Rome (Italy)

2012-06-01

Purpose: To prospectively monitor the response in patients with locally advanced nonmucinous rectal cancer after chemoradiotherapy (CRT) using diffusion-weighted magnetic resonance imaging. The histopathologic finding was the reference standard. Methods and Materials: The institutional review board approved the present study. A total of 62 patients (43 men and 19 women; mean age, 64 years; range, 28-83) provided informed consent. T{sub 2}- and diffusion-weighted magnetic resonance imaging scans (b value, 0 and 1,000 mm{sup 2}/s) were acquired before, during (mean 12 days), and 6-8 weeks after CRT. We compared the median apparent diffusion coefficients (ADCs) between responders and nonresponders and examined the associations with the Mandard tumor regression grade (TRG). The postoperative nodal status (ypN) was evaluated. The Mann-Whitney/Wilcoxon two-sample test was used to evaluate the relationships among the pretherapy ADCs, extramural vascular invasion, early percentage of increases in ADCs, and preoperative ADCs. Results: Low pretreatment ADCs (<1.0 Multiplication-Sign 10{sup -3}mm{sup 2}/s) were correlated with TRG 4 scores (p = .0011) and associated to extramural vascular invasion with ypN+ (85.7% positive predictive value for ypN+). During treatment, the mean percentage of increase in tumor ADC was significantly greater in the responders than in the nonresponders (p < .0001) and a >23% ADC increase had a 96.3% negative predictive value for TRG 4. In 9 of 16 complete responders, CRT-related tumor downsizing prevented ADC evaluations. The preoperative ADCs were significantly different (p = .0012) between the patients with and without downstaging (preoperative ADC {>=}1.4 Multiplication-Sign 10{sup -3}mm{sup 2}/s showed a positive and negative predictive value of 78.9% and 61.8%, respectively, for response assessment). The TRG 1 and TRG 2-4 groups were not significantly different. Conclusion: Diffusion-weighted magnetic resonance imaging seems to be a promising

Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa.

Directory of Open Access Journals (Sweden)

Julie H Levison

Full Text Available We investigated the prevalence of wild-type virus (no major drug resistance and drug resistance mutations at second-line antiretroviral treatment (ART failure in a large HIV treatment program in South Africa.HIV-infected patients ≥ 15 years of age who had failed protease inhibitor (PI-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%. Mean duration on ART (SD prior to initiation of second-line ART was 23 (17 months, and time from second-line ART initiation to failure was 10 (9 months. Plasma samples were obtained 7(9 months from confirmed failure. At second-line failure, 22 patients (67% had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5 months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged.Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure.

Evolution of drug resistance in HIV infected patients remaining on a virologically failing cART regimen

DEFF Research Database (Denmark)

Cozzi-Lepri, A; Phillips, AN; Ruiz, L

2007-01-01

OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...... (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1...... January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance...

Monitoring tumor response to neoadjuvant chemotherapy using MRI and 18F-FDG PET/CT in breast cancer subtypes

NARCIS (Netherlands)

Schmitz, Alexander M Th; Teixeira, Suzana C; Pengel, Kenneth E; Loo, Claudette E; Vogel, Wouter V; Wesseling, Jelle; Rutgers, Emiel J Th; Valdés Olmos, Renato A; Sonke, Gabe S; Rodenhuis, Sjoerd; Vrancken Peeters, Marie Jeanne T F D; Gilhuijs, Kenneth G A

2017-01-01

PURPOSE: To explore guidelines on the use of MRI and PET/CT monitoring primary tumor response to neoadjuvant chemotherapy (NAC), taking breast cancer subtype into account. MATERIALS AND METHODS: In this prospective cohort study, 188 women were included with stages II and III breast cancer. MRI and

Emergency radiological monitoring and analysis United States Federal Radiological Monitoring and Assessment Center

International Nuclear Information System (INIS)

Thome, D.J.

1994-01-01

The United States Federal Radiological Emergency Response Plan (FRERP) provides the framework for integrating the various Federal agencies responding to a major radiological emergency. Following a major radiological incident the FRERP authorizes the creation of the Federal Radiological Monitoring and Assessment Center (FRMAC). The FRMAC is established to coordinate all Federal agencies involved in the monitoring and assessment of the off-site radiological conditions in support of the impacted states and the Lead Federal Agency (LFA). Within the FRMAC, the Monitoring and Analysis Division is responsible for coordinating all FRMAC assets involved in conducting a comprehensive program of environmental monitoring, sampling, radioanalysis and quality assurance. This program includes: (1) Aerial Radiological Monitoring - Fixed Wing and Helicopter, (2) Field Monitoring and Sampling, (3) Radioanalysis - Mobile and Fixed Laboratories, (4) Radiation Detection Instrumentation - Calibration and Maintenance, (5) Environmental Dosimetry, and (6) An integrated program of Quality Assurance. To assure consistency, completeness and the quality of the data produced, a methodology and procedures handbook is being developed. This paper discusses the structure, assets and operations of FRMAC monitoring and analysis and the content and preparation of this handbook

Metagenomic approaches for direct and cell culture evaluation of the virological quality of wastewater

Energy Technology Data Exchange (ETDEWEB)

Aw, Tiong Gim; Howe, Adina; Rose, Joan B.

2014-12-01

Genomic-based molecular techniques are emerging as powerful tools that allow a comprehensive characterization of water and wastewater microbiomes. Most recently, next generation sequencing (NGS) technologies which produce large amounts of sequence data are beginning to impact the field of environmental virology. In this study, NGS and bioinformatics have been employed for the direct detection and characterization of viruses in wastewater and of viruses isolated after cell culture. Viral particles were concentrated and purified from sewage samples by polyethylene glycol precipitation. Viral nucleic acid was extracted and randomly amplified prior to sequencing using Illumina technology, yielding a total of 18 million sequence reads. Most of the viral sequences detected could not be characterized, indicating the great viral diversity that is yet to be discovered. This sewage virome was dominated by bacteriophages and contained sequences related to known human pathogenic viruses such as adenoviruses (species B, C and F), polyomaviruses JC and BK and enteroviruses (type B). An array of other animal viruses was also found, suggesting unknown zoonotic viruses. This study demonstrated the feasibility of metagenomic approaches to characterize viruses in complex environmental water samples.

Beta response of CaSO4:Dy based TLD badge and its angular dependence studies for personnel monitoring applications

International Nuclear Information System (INIS)

Kumar, Munish; Rakesh, R.B.; Sneha, C.; Ratna, P.; Bakshi, A.K.; Datta, D.

2016-01-01

In India, shallow/skin doses received by radiation workers from beta particles are measured using CaSO 4 :Dy based Teflon embedded TLD badge. The beta particles having maximum energy E max > 0.6 MeV - ≥ 3.54 MeV are monitored. The ratio of the response of discs under open and plastic regions (D Open/ D Perspex ) is used to estimate the energy of the beta source and to apply response correction factor. This is required as the disc dosimeters are thick and exhibit energy dependent response. Due to lack of comprehensive information regarding disc ratios and associated beta multiplication/response correction factors, present study was performed

Monitoring natural phytoplankton communities

DEFF Research Database (Denmark)

Haraguchi, L.; Jakobsen, H. H.; Lundholm, Nina

2017-01-01

The phytoplankton community can vary within hours (physiology) to years (climatic and anthropogenic responses), and monitoring at different timescales is relevant for understanding community functioning and assessing changes. However, standard techniques used in monitoring programmes are time...

Development of lichen response indexes using a regional gradient modeling approach for large-scale monitoring of forests

Science.gov (United States)

Susan Will-Wolf; Peter Neitlich

2010-01-01

Development of a regional lichen gradient model from community data is a powerful tool to derive lichen indexes of response to environmental factors for large-scale and long-term monitoring of forest ecosystems. The Forest Inventory and Analysis (FIA) Program of the U.S. Department of Agriculture Forest Service includes lichens in its national inventory of forests of...

A seismic monitoring system for response and failure of structures with intentionally reduced seismic strength

International Nuclear Information System (INIS)

Takanashi, Koichi; Ohi, Kenichi

1988-01-01

A group of steel and reinforced concrete scaled structures with intentionally reduced seismic strength to 1/3 to 1/2 were constructed in 1983 for long term observation in order to collect precise data of earthquake response and grasp failure mechanisms during earthquakes. A monitoring system was installed in the structures as well as in the surrounding soil. Some reliable data have been successfully recorded since then, which can be available for verification of analytical models. (author)

Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial.

Science.gov (United States)

Orkin, Chloe; Molina, Jean-Michel; Negredo, Eugenia; Arribas, José R; Gathe, Joseph; Eron, Joseph J; Van Landuyt, Erika; Lathouwers, Erkki; Hufkens, Veerle; Petrovic, Romana; Vanveggel, Simon; Opsomer, Magda

2018-01-01

Simplified regimens with reduced pill burden and fewer side-effects are desirable for people living with HIV. We investigated the efficacy and safety of switching to a single-tablet regimen of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide versus continuing a regimen of boosted protease inhibitor, emtricitabine, and tenofovir disoproxil fumarate. EMERALD was a phase-3, randomised, active-controlled, open-label, international, multicentre trial, done at 106 sites across nine countries in North America and Europe. HIV-1-infected adults were eligible to participate if they were treatment-experienced and virologically suppressed (viral load <50 copies per mL for ≥2 months; one viral load of 50-200 copies per mL was allowed within 12 months before screening), and patients with a history of virological failure on non-darunavir regimens were allowed. Randomisation was by computer-generated interactive web-response system and stratified by boosted protease inhibitor use at baseline. Patients were randomly assigned (2:1) to switch to the open-label study regimen or continue the control regimen. The study regimen consisted of a fixed-dose tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg, which was taken once per day for 48 weeks. The primary outcome was the proportion of participants with virological rebound (confirmed viral load ≥50 copies per mL or premature discontinuations, with last viral load ≥50 copies per mL) cumulative through week 48; we tested non-inferiority (4% margin) of the study regimen versus the control regimen in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT02269917. The study began on April 1, 2015, and the cutoff date for the week 48 primary analysis was Feb 24, 2017. Of 1141 patients (763 in the study group and 378 in the control group), 664 (58%) had previously received five or more antiretrovirals, including screening

Retreatment of Chronic Hepatitis C Infection with Telaprevir: Preliminary Results in Turkey

Directory of Open Access Journals (Sweden)

Orhan Yıldız

2015-09-01

Full Text Available Background: The use of pegylated interferon alpha and ribavirin (PegIFN/RBV for the retreatment of chronic hepatitis C virus (HCV infection without a sustained virological response (SVR prior to PegIFN/RBV treatment has resulted in low success rates. Aims: To investigate the efficacy and safety of telaprevir (TVR in combination with PegIFN/RBV in patients infected with HCV genotypes 1 and 4 who were previously treated with PegIFN/RBV and failed to achieve SVR. Study Design: Multi-center, retrospective, cross-sectional study. Methods: The study included 111 patients: 80 prior relapsers, 25 prior null responders, and six prior partial responders to PegIFN/RBV treatment. The patients were given TVR/PegIFN/RBV for 12 weeks, followed by a 12-week PegIFN/RBV treatment; virological response results were assessed at weeks 4, 12, and 24. Treatment was discontinued in patients with HCV RNA >1000 IU/mL at week 4 or with negative RNA results at week 4 but >1000 IU/mL at week 12. Rapid virological response (RVR, early virological response (EVR, extended rapid virological response (eRVR, and virological response at 24th week of treatment were evaluated. The side effects of combination therapy and the rates of treatment discontinuation were investigated. Results: The mean age of the patients was 56.02±9.96 years and 45.9% were male. Ninety-one percent of the patients were infected with viral genotype 1, 69.6% with the interleukin (IL 28B genotype CT and 20.2% were cirrhotic. The RVR rate was 86.3% in prior relapsers, 56% in prior null responders, and 50% in prior partial responders (p=0.002. EVR rates in those groups were 91.3%, 56%, and 83.3%, respectively (p<0.001. eRVR rates were 83.8% in prior relapsers, 48% in prior null responders, and 50% in prior partial responders (<0.001. The virological response at the 24th week of treatment was found to be the highest in prior relapsers (88.8%; it was 56% in prior null responders and 66.7% in prior partial

Treatment response in HCV related chronic hepatitis

International Nuclear Information System (INIS)

Hussain, A.B.; Hussain, T.; Hussain, S.; Masood, A.; Kazmi, Y.; Tariq, W.Z.; Karamat, K.A.

2004-01-01

Objective: To evaluate the virological response to treatment with interferon and ribavirin in-patients with hepatitis C related liver disease. Material and Methods: Two hundred seventy-nine patients were included in the study. These patients had taken interferon and ribavirin treatment for HCV related chronic hepatitis, and were referred to AFIP for HCV RNA testing by polymerase chain reaction (PCR) between January 2002 and September 2002. Out of 279 cases, 229 had taken the treatment for 06 or 12 months and were tested for end-of-treatment response (ETR). Fifty patients had completed there treatment regimens of 6 or 12 months treatment, at least 24 weeks before their PCR test and were having follow-up testing for sustained viral response (SVR). The sera of these patients were tested for HCV RNA by PCR, using a commercial kit of Amplicor (Roche) for qualitative detection of HCV RNA. Results: Out of 229 cases tested for end-of-treatment response, 198 (86.5%) had no detectable HCV RNA (responders) and 31 (13.50%) were PCR positive (non-responders). Thirty-eight out of 50 cases, tested for a sustained viral response, had a negative result for HCV PCR thus showing sustained response rate of 76%. Conclusion: The viral remission/response to interferon and ribavirin combination therapy in our patients was better than that quoted in other regions. (author)

Monitoring device for withdrawing control rods

International Nuclear Information System (INIS)

Higashigawa, Yuichi.

1985-01-01

Purpose: To improve the sensitivity and the responsivity to an equivalent extent to those in the case where local power range monitors are densely arranged near each of the control rods, with no actual but pseudo increase of the number of local power range monitors. Constitution: The monitor arrangement is patterned by utilizing the symmetricity of the reactor core and stored in a monitor designating device. The symmetricity of control rods to be selected and withdrawn by an operator is judged by a control rod symmetry monitoring device, while the symmetricity of the withdrawn control rods is judged by a control rod withdrawal state monitoring device. Then, only when both of the devices judge the symmetricity, the control rods are subjected to gang driving by the control rod drive mechanisms. In this way, monitoring at a high sensitivity and responsivity is enabled with no increase for the number of monitors. (Yoshino, Y.)

Monitoring tumor response to neoadjuvant chemotherapy using MRI and 18F-FDG PET/CT in breast cancer subtypes

NARCIS (Netherlands)

Schmitz, Alexander M. Th; Teixeira, Suzana C.; Pengel, Kenneth E.; Loo, Claudette E.; Vogel, Wouter V.; Wesseling, Jelle; Rutgers, Emiel J. Th; Valdés Olmos, Renato A.; Sonke, Gabe S.; Rodenhuis, Sjoerd; Vrancken Peeters, Marie Jeanne T. F. D.; Gilhuijs, Kenneth G. A.

2017-01-01

To explore guidelines on the use of MRI and PET/CT monitoring primary tumor response to neoadjuvant chemotherapy (NAC), taking breast cancer subtype into account. In this prospective cohort study, 188 women were included with stages II and III breast cancer. MRI and 18F-FDG-PET/CT were acquired

Preparedness for response to the challenges from orphan sources: nationwide environmental radiation mapping with state of the art monitoring systems

International Nuclear Information System (INIS)

Saindane, Shashank S.; Pradeepkumar, K.S.; Suri, M.M.K.; Sharma, D.N.

2008-01-01

Based on the various international reports on orphan sources, the potential for radiological emergencies in public domain is recognized as a cause of concern. To detect the presence of any such orphan sources and to strengthen the preparedness for response to any radiological emergencies in public domain, a nationwide radiation mapping programme was initiated in India. Various radiation monitoring systems, few of them integrated with Global Positioning System (GPS) installed in mobile monitoring vans were used for this purpose. This monitoring also helped in generating the base line dose rate data of the cities and also in demonstrating the methodology of environmental monitoring for locating the presence of orphan sources, if any. During the detailed monitoring of various cities of the country, different systems such as GSM based Radiation Monitoring System (GRaMS), Compact Radiation Monitoring system, Portable Mobile Gamma Spectrometry System, Gamma Tracer System etc. installed in a vehicle were made to continuously acquire the data at a varying rate from 10 sec to 1 minute acquisition time. These systems can measure dose rate in the range of 0.01 - 100 μGy h -1 and can detect 7.4 MBq (200 μCi) of 60 Co and 25 MBq (675 μCi) of 137 Cs from a distance of 5 metre. Average dose rate recorded during these environmental monitoring was 81 ± 07 nGy h -1 with a maximum of 210 ± 11 nGyh -1 at Bangalore (attributed to the presence of K-40). The digital topographic map and the data acquired from the radiation mapping are used to generate terrestrial radiation map. This radiation profile stored in the database can be used as reference while carrying out the impact assessment following any nuclear / radiological emergencies. These systems also help to tag the radiation levels along with positional coordinates online onto the GIS map of the area. GRaMS also demonstrated its capability for online transmission of the data to the centralized data acquisition Base Station

Onset of Type 1 Diabetes Mellitus During Pegylated-interferon Alfa and Ribavirin Therapy for Chronic Hepatitis C Virus Infection

Science.gov (United States)

Ranganathan, Raghini; Janarthanan, Krishnaveni; Rajasekaran, Senthilkumar

2012-01-01

A 16-year-old female was treated with pegylated-interferon (PEG-IFN) alfa (a)-2b and ribavirin combination therapy for chronic hepatitis C virus (HCV) infection. She attained rapid virological response. She presented with diabetic ketoacidosis after 41 weeks of therapy. Anti-glutamic acid decarboxylase antibodies and islet cell antibodies were negative. Her fasting serum C-peptide level was <0.1 ng/mL, and the treatment course was completed. This case underlines the importance of periodic plasma glucose monitoring in patients during and after PEG-IFN and ribavirin therapy. PMID:25755410

Monitoring Bridge Dynamic Responses Using Fiber Bragg Grating Tiltmeters.

Science.gov (United States)

Xiao, Feng; Chen, Gang S; Hulsey, J Leroy

2017-10-20

In bridge health monitoring, tiltmeters have been used for measuring rotation and curvature; however, their application in dynamic parameter identification has been lacking. This study installed fiber Bragg grating (FBG) tiltmeters on the bearings of a bridge and monitored the dynamic rotational angle. The dynamic features, including natural frequencies and mode shapes, have been identified successfully. The innovation presented in this paper is the first-time use of FBG tiltmeter readings to identify the natural frequencies of a long-span steel girder bridge. The identified results have been verified using a bridge finite element model. This paper introduces a new method for the dynamic monitoring of a bridge using FBG tiltmeters. Limitations and future research directions are also discussed in the conclusion.

Monitoring Bridge Dynamic Responses Using Fiber Bragg Grating Tiltmeters

Directory of Open Access Journals (Sweden)

Feng Xiao

2017-10-01

Full Text Available In bridge health monitoring, tiltmeters have been used for measuring rotation and curvature; however, their application in dynamic parameter identification has been lacking. This study installed fiber Bragg grating (FBG tiltmeters on the bearings of a bridge and monitored the dynamic rotational angle. The dynamic features, including natural frequencies and mode shapes, have been identified successfully. The innovation presented in this paper is the first-time use of FBG tiltmeter readings to identify the natural frequencies of a long-span steel girder bridge. The identified results have been verified using a bridge finite element model. This paper introduces a new method for the dynamic monitoring of a bridge using FBG tiltmeters. Limitations and future research directions are also discussed in the conclusion.

Response-cue interval effects in extended-runs task switching: memory, or monitoring?

Science.gov (United States)

Altmann, Erik M

2017-09-26

This study investigated effects of manipulating the response-cue interval (RCI) in the extended-runs task-switching procedure. In this procedure, a task cue is presented at the start of a run of trials and then withdrawn, such that the task has to be stored in memory to guide performance until the next task cue is presented. The effects of the RCI manipulation were not as predicted by an existing model of memory processes in task switching (Altmann and Gray, Psychol Rev 115:602-639, 2008), suggesting that either the model is incorrect or the RCI manipulation did not have the intended effect. The manipulation did produce a theoretically meaningful pattern, in the form of a main effect on response time that was not accompanied by a similar effect on the error rate. This pattern, which replicated across two experiments, is interpreted here in terms of a process that monitors for the next task cue, with a longer RCI acting as a stronger signal that a cue is about to appear. The results have implications for the human factors of dynamic task environments in which critical events occur unpredictably.

Formal hepatitis C education enhances HCV care coordination, expedites HCV treatment and improves antiviral response.

Science.gov (United States)

Lubega, Samali; Agbim, Uchenna; Surjadi, Miranda; Mahoney, Megan; Khalili, Mandana

2013-08-01

Formal Hepatitis C virus (HCV) education improves HCV knowledge but the impact on treatment uptake and outcome is not well described. We aimed to evaluate the impact of formal HCV patient education on primary provider-specialist HCV comanagement and treatment. Primary care providers within the San Francisco safety-net health care system were surveyed and the records of HCV-infected patients before and after institution of a formal HCV education class by liver specialty (2006-2011) were reviewed retrospectively. Characteristics of 118 patients who received anti-HCV therapy were: mean age 51, 73% males and ~50% White and uninsured. The time to initiation of HCV treatment was shorter among those who received formal education (median 136 vs 284 days, P non-1 genotype (OR 6.17, 95% CI 2.3-12.7, P = 0.0003) and receipt of HCV education (OR 3.0, 95% CI 1.1-7.9, P = 0.03) were associated with sustained virologic treatment response. Among 94 provider respondents (response rate = 38%), mean age was 42, 62% were White, and 63% female. Most providers agreed that the HCV education class increased patients' HCV knowledge (70%), interest in HCV treatment (52%), and provider-patient communication (56%). A positive provider attitude (Coef 1.5, 95% CI 0.1-2.9 percent, P = 0.039) was independently associated with referral rate to education class. Formal HCV education expedites HCV therapy and improves virologic response rates. As primary care provider attitude plays a significant role in referral to HCV education class, improving provider knowledge will likely enhance access to HCV specialty services in the vulnerable population. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical and Virologic Outcomes After Changes in First Antiretroviral Regimen at 7 Sites in the Caribbean, Central and South America Network.

Science.gov (United States)

Wolff, Marcelo; Shepherd, Bryan E; Cortés, Claudia; Rebeiro, Peter; Cesar, Carina; Wagner Cardoso, Sandra; Pape, Jean W; Padgett, Denis; Sierra-Madero, Juan; Echevarria, Juan; McGowan, Catherine C

2016-01-01

HIV-infected persons in resource-limited settings may experience high rates of antiretroviral therapy (ART) change, particularly because of toxicity or other nonfailure reasons. Few reports address patient outcomes after these modifications. HIV-infected adults from the 7 Caribbean, Central and South America network clinical cohorts who modified >1 drug from the first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. We assessed cumulative incidence of, and factors associated with, death, virologic failure (VF), and regimen change after starting ART-2. Five thousand five hundred sixty-five ART-naive highly active ART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 because of toxicity and 11% because of failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4%, and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio = 1.5 vs. failure, 95% confidence interval: 1.0 to 2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at the start of ART-2, and starting ART-2 because of failure (adjusted hazard ratio = 2.1 vs. toxicity, 95% confidence interval: 1.5 to 2.8). Among patients modifying the first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success.

Supplementation with Sodium Selenite and Selenium-Enriched Microalgae Biomass Show Varying Effects on Blood Enzymes Activities, Antioxidant Response, and Accumulation in Common Barbel (Barbus barbus)

Czech Academy of Sciences Publication Activity Database

Kouba, A.; Velíšek, J.; Stará, A.; Masojídek, Jiří; Kozák, P.

2014-01-01

Roč. 2014, Article ID 408270 (2014) ISSN 2314-6141 R&D Projects: GA ČR GA521/09/0656; GA MŠk ED2.1.00/03.0110; GA MŠk LO1205; GA MŠk ED2.1.00/01.0024 Grant - others:GA JU(CZ) 087/2013/Z Institutional support: RVO:61388971 Keywords : selenite * selenium * antioxidant response Subject RIV: EE - Microbiology, Virology

Monitoring human papillomavirus prevalence in urine samples: a review

Directory of Open Access Journals (Sweden)

Enerly E

2013-03-01

Full Text Available Espen Enerly, Cecilia Olofsson, Mari NygårdDepartment of Research, Cancer Registry of Norway, Oslo, NorwayAbstract: Human papillomavirus (HPV is the main cause of cervical cancer, and many countries now offer vaccination against HPV to girls by way of government-funded national immunization programs. Monitoring HPV prevalence in adolescents could offer a near-term biological measure of vaccine impact, and urine sampling may be an attractive large-scale method that could be used for this purpose. Our objective was to provide an overview of the literature on HPV DNA detection in urine samples, with an emphasis on adolescents. We searched the PubMed database using the terms “HPV” and “urine” and identified 21 female and 14 male study populations in which HPV prevalence in urine samples was reported, four of which included only asymptomatic female adolescents. We provide herein an overview of the recruitment setting, age, urine sampling procedure, lesion type, HPV assay, and HPV prevalence in urine samples and other urogenital samples for the studies included in this review. In female study populations, concordance for any HPV type and type-specific concordance in paired urine and cervical samples are provided in addition to sensitivity and specificity. We concluded that few studies on HPV prevalence in urine samples have been performed in asymptomatic female adolescent populations but that urine samples may be a useful alternative to cervical samples to monitor changes in HPV prevalence in females in the post-HPV vaccination era. However, care should be taken when extrapolating HPV findings from urine samples to the cervix. In males, urine samples do not seem to be optimal for monitoring HPV prevalence due to a low human genomic DNA content and HPV DNA detection rate compared to other urogenital sites. In each situation the costs and benefits of HPV DNA detection in urine compared to alternative monitoring options should be carefully

Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe

DEFF Research Database (Denmark)

Judd, A; Lodwick, R; Noguera-Julian, A

2017-01-01

OBJECTIVES: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. METHODS...... compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4-111) vs. 8 (IQR 2-38) weeks, respectively], and highest in perinatally infected participants aged 10-14 years [49 (IQR 9-267) weeks]. The cumulative proportion with TCVF 5 years after starting ART......: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged

Efficacy and safety of emtricitabine/tenofovir alafenamide (FTC/TAF) vs. emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as a backbone for treatment of HIV-1 infection in virologically suppressed adults: subgroup analysis by third agent of a randomized, double-blind, active-controlled phase 3 trial.

Science.gov (United States)

Post, Frank A; Yazdanpanah, Yazdan; Schembri, Gabriel; Lazzarin, Adriano; Reynes, Jacques; Maggiolo, Franco; Yan, Mingjin; Abram, Michael E; Tran-Muchowski, Cecilia; Cheng, Andrew; Rhee, Martin S

2017-05-01

FTC/TAF was shown to be noninferior to FTC/TDF with advantages in markers of renal and bone safety. To evaluate the efficacy and safety of switching to FTC/TAF from FTC/TDF by third agent (boosted protease inhibitor [PI] vs. unboosted third agent). We conducted a 48-week subgroup analysis based on third agent from a randomized, double blind study in virologically suppressed adults on a FTC/TDF-containing regimen who switched to FTC/TAF vs. continued FTC/TDF while remaining on the same third agent. We randomized (1:1) 663 participants to either switch to FTC/TAF (N = 333) or continue FTC/TDF (N = 330), each with baseline third agent stratifying by class of third agent in the prior treatment regimen (boosted PI 46%, unboosted third agent 54%). At week 48, significant differences in renal biomarkers and bone mineral density were observed favoring FTC/TAF over FTC/TDF (p TAF arm in those who received boosted PI vs. unboosted third agents. At week 48, virologic success rates were similar between treatment groups for those who received a boosted PI (FTC/TAF 92%, FTC/TDF 93%) and for those who received an unboosted third agent (97% vs. 93%). In virologically suppressed patients switching to FTC/TAF from FTC/TDF, high rates of virologic suppression were maintained, while renal and bone safety parameters improved, regardless of whether participants were receiving a boosted PI or an unboosted third agent. FTC/TAF offers safety advantages over FTC/TDF and can be an important option as an NRTI backbone given with a variety of third agents.

Track-monitoring from the dynamic response of an operational train

Science.gov (United States)

Lederman, George; Chen, Siheng; Garrett, James; Kovačević, Jelena; Noh, Hae Young; Bielak, Jacobo

2017-03-01

We explore a data-driven approach for monitoring rail infrastructure from the dynamic response of a train in revenue-service. Presently, track inspection is performed either visually or with dedicated track geometry cars. In this study, we examine a more economical approach where track inspection is performed by analyzing vibration data collected from an operational passenger train. The high frequency with which passenger trains travel each section of track means that faults can be detected sooner than with dedicated inspection vehicles, and the large number of passes over each section of track makes a data-driven approach statistically feasible. We have deployed a test-system on a light-rail vehicle and have been collecting data for the past two years. The collected data underscores two of the main challenges that arise in train-based track monitoring: the speed of the train at a given location varies from pass to pass and the position of the train is not known precisely. In this study, we explore which feature representations of the data best characterize the state of the tracks despite these sources of uncertainty (i.e., in the spatial domain or frequency domain), and we examine how consistently change detection approaches can identify track changes from the data. We show the accuracy of these different representations, or features, and different change detection approaches on two types of track changes, track replacement and tamping (a maintenance procedure to improve track geometry), and two types of data, simulated data and operational data from our test-system. The sensing, signal processing, and data analysis we propose in the study could facilitate safer trains and more cost-efficient maintenance in the future. Moreover, the proposed approach is quite general and could be extended to other parts of the infrastructure, including bridges.

1988 Monitoring Activities Review (MAR) of the environmental monitoring program

International Nuclear Information System (INIS)

1989-03-01

The EGandG Idaho Environmental Monitoring (EM) Unit is responsible for coordinating and conducting environmental measurements of radioactive and hazardous contaminants around facilities operated by EGandG Idaho. The EM Unit has several broad program objectives, which include complying with regulatory standards and developing a basis for estimating future impacts of operations at EGandG Idaho facilities. To improve program planning and to provide bases for technical improvement of the monitoring program, the EGandG Environmental Monitoring organization has regularly used the Monitoring Activities Review (MAR) process since 1982. Each MAR is conducted by a committee of individuals selected for their experience in the various types of monitoring performed by the EM organization. Previous MAR studies have focused on procedures for all currently monitored media except biota. Biotic monitoring was initiated following the last MAR. This report focuses on all currently monitored media, and includes the first review of biotic monitoring. The review of biotic monitoring has been conducted at a level of detail consistent with initial MAR reports for other parts of the Waste Management Program Facilities Environmental Monitoring Program. The review of the biotic monitoring activities is presented in Section 5.5 of this report. 21 refs., 7 figs., 4 tabs

24 CFR 108.20 - Monitoring office responsibility for monitoring plans and reports.

Science.gov (United States)

2010-04-01

... documenting the implementation of the AFHM plan, including sales or rental reports, as required by the.... When sales or rental reports show that 20% of the units covered by the AFHM plan have been sold or... for monitoring plans and reports. 108.20 Section 108.20 Housing and Urban Development Regulations...

Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

DEFF Research Database (Denmark)

Cozzi-Lepri, Alessandro; Phillips, Andrew N; Ruiz, Lidia

2007-01-01

OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...... (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1...... January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance...

Serologic and virologic investigations into pestivirus infection in wild and domestic ruminants in the Pyrenees (NE Spain).

Science.gov (United States)

Marco, I; Rosell, R; Cabezón, O; Beneria, M; Mentaberre, G; Casas, E; Hurtado, A; López-Olvera, J R; Lavín, S

2009-08-01

An outbreak of disease associated to a border disease virus was described in the Southern chamois (Rupicapra pyrenaica) in Spain in 2002. Sera and/or spleen samples from 57 mouflon, 15 red deer, 21 roe deer, 3 fallow deer, 55 sheep, 32 cattle, and 68 goats sharing the chamois habitat were studied. An antibody ELISA test yielded an inconclusive result in 2 mouflon and positive results in 5 goat sera. Comparative virus neutralization tests were performed on the 2 inconclusive mouflons, 3 of the 5 seropositive goats, 55 sheep and 32 cattle, using 6 pestivirus strains. Positive results were obtained in 1 mouflon, 2 goats, 69% of sheep and 78% of cattle. Virological investigations performed with an antigen ELISA test yielded negative results in 21 goats and 39 mouflons, the result in 1 mouflon being inconclusive. PCR performed on 12 goats and the inconclusive mouflon gave negative results. These results suggested that it is unlikely that chamois BDV is infecting wild and domestic ruminants.

Immunological monitoring for prediction of clinical response to antitumor vaccine therapy.

Science.gov (United States)

Mikhaylova, Irina N; Shubina, Irina Zh; Chkadua, George Z; Petenko, Natalia N; Morozova, Lidia F; Burova, Olga S; Beabelashvili, Robert Sh; Parsunkova, Kermen A; Balatskaya, Natalia V; Chebanov, Dmitrii K; Pospelov, Vadim I; Nazarova, Valeria V; Vihrova, Anastasia S; Cheremushkin, Evgeny A; Molodyk, Alvina A; Kiselevsky, Mikhail V; Demidov, Lev V

2018-05-11

Immunotherapy has shown promising results in a variety of cancers, including melanoma. However, the responses to therapy are usually heterogeneous, and understanding the factors affecting clinical outcome is still not achieved. Here, we show that immunological monitoring of the vaccine therapy for melanoma patients may help to predict the clinical course of the disease. We studied cytokine profile of cellular Th1 (IL-2, IL-12, IFN-γ) and humoral Th2 (IL-4, IL-10) immune response, vascular endothelial growth factor (VEGFA), transforming growth factor-β 2 (TGF-β 2), S100 protein (S100A1B and S100BB), adhesion molecule CD44 and serum cytokines β2-microglobulin to analyze different peripheral blood mononuclear cell subpopuations of patients treated with dendritic vaccines and/or cyclophosphamide in melanoma patients in the course of adjuvant treatment. The obtained data indicate predominance of cellular immunity in the first adjuvant group of patients with durable time to progression and shift to humoral with low cellular immunity in patients with short-term period to progression (increased levels of IL-4 and IL- 10). Beta-2 microglobulin was differentially expressed in adjuvant subgroups: its higher levels correlated with shorter progression-free survival and the total follow-up time. Immunoregulatory index was overall higher in patients with disease progression compared to the group of patients with no signs of disease progression.

Drought is Coming: Monitoring Vegetation Response to Water Scarcity through Variable Chlorophyll a Fluorescence

Science.gov (United States)

Guadagno, C. R.; Beverly, D.; Pleban, J. R.; Speckman, H. N.; Ewers, B. E.; Weinig, C.

2017-12-01

Aridity is one of the most pronounced environmental limits to plant survival, and understanding how plants respond to drought and recovery is crucial for predicting impacts on managed and natural ecosystems. Changes in soil moisture conditions induce a suite of physiological responses from the cell to ecosystem scale, complicating the assessment of drought effects. Characterizing early indicators of water scarcity across species can inform biophysical models with improved understanding of plant hydraulics. While indexes exist for drought monitoring across scales, many are unable to identify imminent vegetative drought. We explore a method of early diagnosis using leaf-level and kinetic imaging measures of variable chlorophyll a fluorescence. This is a fast and reliable tool capturing leaf physiological changes in advance of changes in NDVI or passive solar induced fluorescence. Both image and leaf level Pulse Amplitude Method (PAM) measurements illustrate the utility of variable chlorophyll a fluorescence for monitoring vegetative drought. Variable fluorescence was monitored across populations of crops, desert shrubs, montane conifers and riparian deciduous trees under variable water regimes. We found a strong correlation (R = 0.85) between the maximum efficiency of photosystem II measured using variable fluorescence (Fv'Fm') and leaf level electrolyte leakage, a proximal cause of drought stress induced by cellular damage in leaves. This association was confirmed in two gymnosperm species (Picea engelmannii and Pinus contorta) and for diverse varieties of the crop species Brassica rapa. The use of chlorophyll a fluorescence per image also allowed for early detection of drought in aspen (Populus tremuloides). These results provide evidence that variable chlorophyll fluorescence decreases between 25% and 70% in mild and severely droughted twigs with respect to ones collected from trees in wet soil conditions. While current systems for monitoring variable fluorescence

Monitoring bottlenose dolphin leukocyte cytokine mRNA responsiveness by qPCR

Science.gov (United States)

Eberle, Kirsten C.; Venn-Watson, Stephanie K.; Jensen, Eric D.; Porter, Tracy J.; Waters, Theresa E.; Sacco, Randy E.

2017-01-01

Both veterinarians caring for dolphins in managed populations and researchers monitoring wild populations use blood-based diagnostics to monitor bottlenose dolphin (Tursiops truncatus) health. Quantitative PCR (qPCR) can be used to assess cytokine transcription patterns of peripheral blood mononuclear cells (PBMC). This can supplement currently available blood tests with information on immune status. Full realization of this potential requires establishment of normal ranges of cytokine gene transcription levels in bottlenose dolphins. We surveyed four dolphins over the span of seven months by serial bleeds. PBMC were stimulated with phytohaemagglutinin (1, 5, and 10 μg/mL) and concanavalin A (1 μg/mL) for 48 H in vitro. RNA from these cultures was probed by qPCR using Tursiops truncatus-specific primers (IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-13, IL-18, IFN-γ and TNF-α). Two blood samples from an additional bottlenose dolphin diagnosed with acute pulmonary disease add further perspective to the data. We observed that mitogen choice made a significant difference in the magnitude of gene transcription observed. On the other hand, most cytokines tested exhibited limited intra-animal variation. However, IL-6 and IL-12p40 differed between older and younger dolphins. Furthermore, the magnitude of mitogenic response clusters the tested cytokines into three groups. The data provide a reference for the selection of target cytokine mRNAs and their expected range of mitogen-stimulated cytokine gene transcription for future studies. PMID:29272269

Monitoring bottlenose dolphin leukocyte cytokine mRNA responsiveness by qPCR.

Directory of Open Access Journals (Sweden)

Amelia Ruth Hofstetter

Full Text Available Both veterinarians caring for dolphins in managed populations and researchers monitoring wild populations use blood-based diagnostics to monitor bottlenose dolphin (Tursiops truncatus health. Quantitative PCR (qPCR can be used to assess cytokine transcription patterns of peripheral blood mononuclear cells (PBMC. This can supplement currently available blood tests with information on immune status. Full realization of this potential requires establishment of normal ranges of cytokine gene transcription levels in bottlenose dolphins. We surveyed four dolphins over the span of seven months by serial bleeds. PBMC were stimulated with phytohaemagglutinin (1, 5, and 10 μg/mL and concanavalin A (1 μg/mL for 48 H in vitro. RNA from these cultures was probed by qPCR using Tursiops truncatus-specific primers (IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-13, IL-18, IFN-γ and TNF-α. Two blood samples from an additional bottlenose dolphin diagnosed with acute pulmonary disease add further perspective to the data. We observed that mitogen choice made a significant difference in the magnitude of gene transcription observed. On the other hand, most cytokines tested exhibited limited intra-animal variation. However, IL-6 and IL-12p40 differed between older and younger dolphins. Furthermore, the magnitude of mitogenic response clusters the tested cytokines into three groups. The data provide a reference for the selection of target cytokine mRNAs and their expected range of mitogen-stimulated cytokine gene transcription for future studies.

Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years

DEFF Research Database (Denmark)

Lodwick, Rebecca; Costagliola, Dominique; Reiss, Peter

2010-01-01

/r) from 1998 onwards. We also focused on TCVF in patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed. RESULTS: Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting...... ART, an estimated 3.4% (95% confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according...... to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF. CONCLUSIONS: The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over...

Estimation of groundwater flow from temperature monitoring in a borehole heat exchanger during a thermal response test

Science.gov (United States)

Yoshioka, Mayumi; Takakura, Shinichi; Uchida, Youhei

2018-05-01

To estimate the groundwater flow around a borehole heat exchanger (BHE), thermal properties of geological core samples were measured and a thermal response test (TRT) was performed in the Tsukuba upland, Japan. The thermal properties were measured at 57 points along a 50-m-long geological core, consisting predominantly of sand, silt, and clay, drilled near the BHE. In this TRT, the vertical temperature in the BHE was also monitored during and after the test. Results for the thermal properties of the core samples and from the monitoring indicated that groundwater flow enhanced thermal transfers, especially at shallow depths. The groundwater velocities around the BHE were estimated using a two-dimensional numerical model with monitoring data on temperature changes. According to the results, the estimated groundwater velocity was generally consistent with hydrogeological data from previous studies, except for the data collected at shallow depths consisting of a clay layer. The reasons for this discrepancy at shallow depths were predicted to be preferential flow and the occurrence of vertical flow through the BHE grout, induced by the hydrogeological conditions.

Regulatory T cells in human immunodeficiency virus-infected patients are elevated and independent of immunological and virological status, as well as initiation of highly active anti-retroviral therapy

DEFF Research Database (Denmark)

Gaardbo, J.C.; Nielsen, S.D.; Vedel, S.J.

2008-01-01

Infection with human immunodeficiency virus (HIV) causes a dysregulation of the immune system. This is caused by HIV-specific as well as non-specific mechanisms and has not been explained fully. In particular, knowledge is lacking about the potential role of host-mediated immunosuppressive mechan......(regs) was found to be independent of both immunological and virological status, indicating that initiation of HAART has minor effects on the T(reg) level in HIV-infected patients....

Conformable amplified lead zirconate titanate sensors with enhanced piezoelectric response for cutaneous pressure monitoring.

Science.gov (United States)

Dagdeviren, Canan; Su, Yewang; Joe, Pauline; Yona, Raissa; Liu, Yuhao; Kim, Yun-Soung; Huang, YongAn; Damadoran, Anoop R; Xia, Jing; Martin, Lane W; Huang, Yonggang; Rogers, John A

2014-08-05

The ability to measure subtle changes in arterial pressure using devices mounted on the skin can be valuable for monitoring vital signs in emergency care, detecting the early onset of cardiovascular disease and continuously assessing health status. Conventional technologies are well suited for use in traditional clinical settings, but cannot be easily adapted for sustained use during daily activities. Here we introduce a conformal device that avoids these limitations. Ultrathin inorganic piezoelectric and semiconductor materials on elastomer substrates enable amplified, low hysteresis measurements of pressure on the skin, with high levels of sensitivity (~0.005 Pa) and fast response times (~0.1 ms). Experimental and theoretical studies reveal enhanced piezoelectric responses in lead zirconate titanate that follow from integration on soft supports as well as engineering behaviours of the associated devices. Calibrated measurements of pressure variations of blood flow in near-surface arteries demonstrate capabilities for measuring radial artery augmentation index and pulse pressure velocity.

SESOTHO trial (“Switch Either near Suppression Or THOusand”) – switch to second-line versus WHO-guided standard of care for unsuppressed patients on first-line ART with viremia below 1000 copies/mL: protocol of a multicenter, parallel-group, open-label, randomized clinical trial in Lesotho, Southern Africa

OpenAIRE

Amstutz, Alain; Nsakala, Bienvenu Lengo; Vanobberghen, Fiona; Muhairwe, Josephine; Glass, Tracy Renée; Achieng, Beatrice; Sepeka, Mamorena; Tlali, Katleho; Sao, Lebohang; Thin, Kyaw; Klimkait, Thomas; Battegay, Manuel; Labhardt, Niklaus Daniel

2018-01-01

Background The World Health Organization (WHO) recommends viral load (VL) measurement as the preferred monitoring strategy for HIV-infected individuals on antiretroviral therapy (ART) in resource-limited settings. The new WHO guidelines 2016 continue to define virologic failure as two consecutive VL ≥1000 copies/mL (at least 3 months apart) despite good adherence, triggering switch to second-line therapy. However, the threshold of 1000 copies/mL for defining virologic failure is based on low-...

IFNL4 ss469415590 Variant Is Associated with Treatment Response in Japanese HCV Genotype 1 Infected Individuals Treated with IFN-Including Regimens

Directory of Open Access Journals (Sweden)

Tatsuo Miyamura

2014-01-01

Full Text Available Aim. Eradication of hepatitis C virus (HCV is still challenging even if interferon- (IFN- free regimens with direct-acting antiviral agents (DAAs for HCV-infected individuals are available in clinical practice. IFNL4 is a newly described protein, associated with human antiviral defenses. We investigated whether IFNL4 ss469415590 variant has an effect on the prediction of treatment response in HCV-infected patients treated with IFN-including regimens. Patients and Methods. In all, 185 patients infected with HCV genotype 1 treated with peg-IFN plus ribavirin, with or without telaprevir, were genotyped for IFNL4 ss469415590. We retrospectively investigated whether the role of IFNL4 ss469415590 variant and other factors could predict sustained virological response (SVR in Japanese patients infected with HCV genotype 1. Results. There were 65.7%, 31.5%, and 2.8% patients in the IFNL4 ss469415590 TT/TT, TT/-G, and -G/-G groups, respectively. SVR rates were 82.1% or 49.3% in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. IFNL4 ss469415590 variant and HCV viral loads or IFNL4 ss469415590 variant and early virological response were better predictors of SVR in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. Conclusion. In the era of DAAs, measurement of IFNL4 ss469415590 variant could help the prediction of SVR in Japanese HCV genotype 1 infected individuals treated with IFN-including regimens.

Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience.

Science.gov (United States)

Lovett, Grace C; Nguyen, Tin; Iser, David M; Holmes, Jacinta A; Chen, Robert; Demediuk, Barbara; Shaw, Gideon; Bell, Sally J; Desmond, Paul V; Thompson, Alexander J

2017-01-08

To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting. We performed a retrospective analysis of treatment outcomes among treatment-naïve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate (TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemical response, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus (HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/mL. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen (HBeAg)/HB surface antigen loss and seroconversion over time. Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo (range 3-114). Mean age was 46 (24-78) years, 64 (70%) were male and 77 (84%) were of Asian origin. 55 (60%) patients were treatment-naïve and 62 patients (67%) were HBeAg-negative. Complete virological suppression was achieved by 45/65 (71%) patients at 12 mo, 37/46 (80%) at 24 mo and 25/28 (89%) at 36 mo. Partial virological response (HBV DNA 20-2000 IU/mL) was achieved by 89/92 (96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level (OR = 0.897, 95%CI

Pooled nucleic acid testing to identify antiretroviral treatment failure during HIV infection.

Science.gov (United States)

May, Susanne; Gamst, Anthony; Haubrich, Richard; Benson, Constance; Smith, Davey M

2010-02-01

Pooling strategies have been used to reduce the costs of polymerase chain reaction-based screening for acute HIV infection in populations in which the prevalence of acute infection is low (less than 1%). Only limited research has been done for conditions in which the prevalence of screening positivity is higher (greater than 1%). We present data on a variety of pooling strategies that incorporate the use of polymerase chain reaction-based quantitative measures to monitor for virologic failure among HIV-infected patients receiving antiretroviral therapy. For a prevalence of virologic failure between 1% and 25%, we demonstrate relative efficiency and accuracy of various strategies. These results could be used to choose the best strategy based on the requirements of individual laboratory and clinical settings such as required turnaround time of results and availability of resources. Virologic monitoring during antiretroviral therapy is not currently being performed in many resource-constrained settings largely because of costs. The presented pooling strategies may be used to significantly reduce the cost compared with individual testing, make such monitoring feasible, and limit the development and transmission of HIV drug resistance in resource-constrained settings. They may also be used to design efficient pooling strategies for other settings with quantitative screening measures.

MONITORING TRAINING LOADS, STRESS, IMMUNE-ENDOCRINE RESPONSES AND PERFORMANCE IN TENNIS PLAYERS

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Rodrigo Vitasovic Gomes

2013-06-01

Full Text Available The study aim was to investigate the effect of a periodised pre-season training plan on internal training load and subsequent stress tolerance, immune-endocrine responses and physical performance in tennis players. Well-trained young tennis players (n = 10 were monitored across the pre-season period, which was divided into 4 weeks of progressive overloading training and a 1-week tapering period. Weekly measures of internal training load, training monotony and stress tolerance (sources and symptoms of stress were taken, along with salivary testosterone, cortisol and immunoglobulin A. One repetition maximum strength, running endurance, jump height and agility were assessed before and after training. The periodised training plan led to significant weekly changes in training loads (i.e. increasing in weeks 3 and 4, decreasing in week 5 and post-training improvements in strength, endurance and agility (P < 0.05. Cortisol concentration and the symptoms of stress also increased in weeks 3 and/or 4, before returning to baseline in week 5 (P < 0.05. Conversely, the testosterone to cortisol ratio decreased in weeks 3 and 4, before returning to baseline in week 5 (P < 0.05. In conclusion, the training plan evoked adaptive changes in stress tolerance and hormonal responses, which may have mediated the improvements in physical performance.

Evaluation of 18F-FDG and 18F-FLT for monitoring therapeutic responses of colorectal cancer cells to radiotherapy

International Nuclear Information System (INIS)

Wang, Hui; Liu, Bo; Tian, Jiahe; Xu, Baixuan; Zhang, Jinming; Qu, Baolin; Chen, Yingmao

2013-01-01

In order to compare the efficacy of 18 F-fluorothymidine (FLT) and 18 F-fluorodeoxyglucose (FDG) for monitoring early responses to irradiation, two human colorectal cancer (CRC) cell lines SW480 and SW620, which were derived from the primary lesions and the metastatic lymph node, underwent X-ray irradiation of 0, 10, or 20 Gy and were examined at 0, 24 and 72 h After irradiation, reduced proliferation of both SW480 and SW620 cells was observed in a dose-dependent manner (P < 0.001), G0-G1 arrest was also noted in both cell types after 72 h in the 20 Gy group (P < 0.001). Although increased apoptosis was observed in both cell lines after irradiation (P < 0.001), a greater percentage of SW480 cells underwent apoptosis in response to irradiation than SW620 cells. Increased Hsp27 and decreased integrin β 3 , Ki67 and VEGFR2 expression was observed over time via immunocytochemistry and Western blot analysis (P < 0.001), however, no significant changes were noted in response to irradiation. Finally, reduced uptake of 18 F-FLT by SW480 or SW620 cells was observed at 24-h post-irradiation, however, reduced 18 F-FDG uptake was only observed after 72 h. Therefore, we conclude that 18 F-FLT is a more suitable positron emission tomography (PET) tracer for monitoring early responses to irradiation in primary and metastatic lymph node CRC cells

The Pajarito Monitor: a high-sensitivity monitoring system for highly enriched uranium

International Nuclear Information System (INIS)

Fehlau, P.E.; Coop, K.; Garcia, C.; Martinez, J.

1984-01-01

The Pajarito Monitor for Special Nuclear Material is a high-sensitivity gamma-ray monitoring system for detecting small quantities of highly enriched uranium transported by pedestrians or motor vehicles. The monitor consists of two components: a walk-through personnel monitor and a vehicle monitor. The personnel monitor has a plastic-scintillator detector portal, a microwave occupancy monitor, and a microprocessor control unit that measures the radiation intensity during background and monitoring periods to detect transient diversion signals. The vehicle monitor examines stationary motor vehicles while the vehicle's occupants pass through the personnel portal to exchange their badges. The vehicle monitor has four groups of large plastic scintillators that scan the vehicle from above and below. Its microprocessor control unit measures separate radiation intensities in each detector group. Vehicle occupancy is sensed by a highway traffic detection system. Each monitor's controller is responsible for detecting diversion as well as serving as a calibration and trouble-shooting aid. Diversion signals are detected by a sequential probability ratio hypothesis test that minimizes the monitoring time in the vehicle monitor and adapts itself well to variations in individual passage speed in the personnel monitor. Designed to be highly sensitive to diverted enriched uranium, the monitoring system also exhibits exceptional sensitivity for plutonium

The Emergency Radiological Monitoring and Analysis Division of the United States Federal Radiological Monitoring and Assessment Center

International Nuclear Information System (INIS)