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Sample records for late virological monitoring

  1. Therapy of chronic hepatitis C: Virologic response monitoring

    Directory of Open Access Journals (Sweden)

    Kuljić-Kapulica Nada

    2010-01-01

    Full Text Available Background/Aim. Virological testing is considered to be essential in the management of hepatitis C virus (HCV infection in order to diagnose infection, and, most importantly, as a quide for treatment decisions and assess the virological response to antiviral therapy. The aim of this study was to determine the rate of a sustained virological response (SVR and various factors associated with response rates in chronic hepatitis C infected patients treated with pegiinterferon alpha (PEGINF and ribavirin (RBV combination therapy. Methods. A total of 34 patients, treated with PEG-IFN and RBV were studied. Serum HCV-RNA was measured before the treatment, 12 weeks following the start of the therapy and 6 weeks after the treatment cessation. SVR was defined as undetectable serum HCV-RNA 6 months of post-treatment follow-up, virologic relapse (VR as relapse of HCV-RNA during the post-treatment follow-up. Serum HCV-RNA was measured with the Cobas Amplicor test. Results. At the end of post-treatment follow-up 19 (55.8% patients demonstrated a SVR. The majority of the patients were genotype 1 (27, and the other were genotype 3 (5 patients and genotype 4 (2 patients. There was VR in 6 patients 6 months after the therapy. In 9 patients HCV-RNA was positive after 12 weeks. Conclusion. We demonstrated that patients with chronic HCV infection can be successfully treated with combination of PEG-INF and RBV. This result emphasizes also that post-treatment follow-up to identify patients with SVR or VR could be important.

  2. Diagnostic value of different adherence measures using electronic monitoring and virologic failure as reference standards.

    Science.gov (United States)

    Deschamps, Ann E; De Geest, Sabina; Vandamme, Anne-Mieke; Bobbaers, Herman; Peetermans, Willy E; Van Wijngaerden, Eric

    2008-09-01

    Nonadherence to antiretroviral therapy is a substantial problem in HIV and jeopardizes the success of treatment. Accurate measurement of nonadherence is therefore imperative for good clinical management but no gold standard has been agreed on yet. In a single-center prospective study nonadherence was assessed by electronic monitoring: percentage of doses missed and drug holidays and by three self reports: (1) a visual analogue scale (VAS): percentage of overall doses taken; (2) the Swiss HIV Cohort Study Adherence Questionnaire (SHCS-AQ): percentage of overall doses missed and drug holidays and (3) the European HIV Treatment Questionnaire (EHTQ): percentage of doses missed and drug holidays for each antiretroviral drug separately. Virologic failure prospectively assessed during 1 year, and electronic monitoring were used as reference standards. Using virologic failure as reference standard, the best results were for (1) the SHCS-AQ after electronic monitoring (sensitivity, 87.5%; specificity, 78.6%); (2) electronic monitoring (sensitivity, 75%; specificity, 85.6%), and (3) the VAS combined with the SHCS-AQ before electronic monitoring (sensitivity, 87.5%; specificity, 58.6%). The sensitivity of the complex EHTQ was less than 50%. Asking simple questions about doses taken or missed is more sensitive than complex questioning about each drug separately. Combining the VAS with the SHCS-AQ seems a feasible nonadherence measure for daily clinical practice. Self-reports perform better after electronic monitoring: their diagnostic value could be lower when given independently.

  3. 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.

  4. Performance and Logistical Challenges of Alternative HIV-1 Virological Monitoring Options in a Clinical Setting of Harare, Zimbabwe

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    Pascale Ondoa

    2014-01-01

    Full Text Available We evaluated a low-cost virological failure assay (VFA on plasma and dried blood spot (DBS specimens from HIV-1 infected patients attending an HIV clinic in Harare. The results were compared to the performance of the ultrasensitive heat-denatured p24 assay (p24. The COBAS AmpliPrep/COBAS TaqMan HIV-1 test, version 2.0, served as the gold standard. Using a cutoff of 5,000 copies/mL, the plasma VFA had a sensitivity of 94.5% and specificity of 92.7% and was largely superior to the VFA on DBS (sensitivity = 61.9%; specificity = 99.0% or to the p24 (sensitivity = 54.3%; specificity = 82.3% when tested on 302 HIV treated and untreated patients. However, among the 202 long-term ART-exposed patients, the sensitivity of the VFA decreased to 72.7% and to 35.7% using a threshold of 5,000 and 1,000 RNA copies/mL, respectively. We show that the VFA (either on plasma or on DBS and the p24 are not reliable to monitor long-term treated, HIV-1 infected patients. Moreover, achieving acceptable assay sensitivity using DBS proved technically difficult in a less-experienced laboratory. Importantly, the high level of virological suppression (93% indicated that quality care focused on treatment adherence limits virological failure even when PCR-based viral load monitoring is not available.

  5. 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

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

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    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).

  7. Virological response and resistance among HIV-infected children receiving long-term antiretroviral therapy without virological monitoring in Uganda and Zimbabwe: Observational analyses within the randomised ARROW trial.

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    Alexander J Szubert

    2017-11-01

    receiving first-line ART in sub-Saharan Africa without real-time VL monitoring had good virological and resistance outcomes over 4 years, regardless of CD4 monitoring strategy. Many children with detectable low-level viraemia spontaneously resuppressed, highlighting the importance of confirming virological failure before switching to second-line therapy. Children experiencing rebound ≥5,000 copies/ml were much less likely to resuppress, but NRTI resistance increased only slowly. These results are relevant to the increasing numbers of HIV-infected children receiving first-line ART in sub-Saharan Africa with limited access to virological monitoring.ISRCTN Registry, ISRCTN24791884.

  8. Electronic medication monitoring-informed counselling to improve adherence to combination antiretroviral therapy and virologic treatment outcomes: a meta-analysis

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    Nienke eLangebeek

    2015-05-01

    Full Text Available Background: Adherence to combination antiretroviral therapy (cART for HIV infection is a primary determinant of treatment success, but is often suboptimal. Previous studies have suggested that electronic medication monitoring-informed counselling is among the most effective adherence intervention components. Our objective was to review available evidence about the effectiveness of monitoring-informed counselling and to aggregate findings into quantitative estimates of the effect of such intervention on medication adherence and virologic treatment outcomes.Methods: We searched PubMed for papers reporting on randomized controlled trials (RCTs comparing intervention groups receiving monitoring-informed counselling as one of the intervention components versus control groups not receiving such counselling for their effect on medication adherence and viral load concentrations. The standardized mean difference (SMD in adherence and the odds ratio (OR of undetectable HIV RNA in intervention versus control groups were the common effect sizes. Random-effect models with inverse variance weights were used to aggregate findings into pooled effect estimates with 95% confidence limits. Results: A total of 13 studies were included. Adherence was significantly higher in intervention groups than in control groups (SMD 0.51, 95% CI 0.31 to 0.71. Patients in intervention groups were significantly more likely to have undetectable HIV RNA concentrations than patients in control groups (OR 1.35, 95% CI 1.12 to 1.63. However, in studies in which monitoring-informed counselling was the only intervention component, the difference in adherence and virologic response between intervention and control groups was not statistically significant.Conclusion: Electronic monitoring-informed counselling improved adherence and virologic response compared with control groups not receiving such counselling in studies in which it was one out of multiple intervention components, but not

  9. Electronic medication monitoring-informed counseling to improve adherence to combination anti-retroviral therapy and virologic treatment outcomes: a meta-analysis.

    Science.gov (United States)

    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 objective was to review available evidence about the effectiveness of monitoring-informed counseling and to aggregate findings into quantitative estimates of the effect of such intervention on medication adherence and virologic treatment outcomes. We searched PubMed for papers reporting on randomized controlled trials comparing intervention groups receiving monitoring-informed counseling as one of the intervention components versus control groups not receiving such counseling for their effect on medication adherence and viral load concentrations. The standardized mean difference (SMD) in adherence and the odds ratio (OR) of undetectable HIV RNA in intervention versus control groups were the common effect sizes. Random-effect models with inverse variance weights were used to aggregate findings into pooled effect estimates with 95% confidence limits (CI). A total of 13 studies were included. Adherence was significantly higher in intervention groups than in control groups (SMD 0.51, 95% CI 0.31-0.71). Patients in intervention groups were significantly more likely to have undetectable HIV RNA concentrations than patients in control groups (OR 1.35, 95% CI 1.12-1.63). However, in studies in which monitoring-informed counseling was the only intervention component, the difference in adherence and virologic response between intervention and control groups was not statistically significant. Electronic monitoring-informed counseling improved adherence and virologic response compared with control groups not receiving such counseling in studies in which it was one out of multiple intervention components, but not in studies where it was the only intervention component.

  10. Detecting virological failure in HIVinfected Tanzanian children ...

    African Journals Online (AJOL)

    Background. The performance of clinical and immunological criteria to predict virological failure in HIV-infected children receiving antiretroviral therapy (ART) is not well documented. Objective. To determine the validity of clinical and immunological monitoring in detecting virological failure in children on ART. Methods.

  11. 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

    : Virologic response (viral load SIDA patients. Analyses were stratified by region (south, central west, north, east) or time started cART (early, 1996-1997; mid, 1998-1999; late, 2000-1904). RESULTS: Virologic...

  12. Regional changes over time in initial virological response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, W; Kirk, O; Gatell, J

    2006-01-01

    : Virologic response (viral load SIDA patients. Analyses were stratified by region (south, central west, north, east) or time started cART (early, 1996-1997; mid, 1998-1999; late, 2000-1904). RESULTS: Virologic...

  13. Economics of Home Monitoring for Apnea in Late Preterm Infants.

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    Montenegro, Brian L; Amberson, Michael; Veit, Lauren; Freiberger, Christina; Dukhovny, Dmitry; Rhein, Lawrence M

    2017-01-01

    Apnea of prematurity affects a small proportion but large absolute number of late preterm infants, with out-patient management variably utilized despite relative clinical equipoise and potential for improved cost-effectiveness. Over a 5-y period, from 2009 to 2013, infants born at ≥34 weeks gestational age at a level IIIB academic center in Boston, Massachusetts, with discharge-delaying apnea, bradycardia, and desaturation (ABD) events were identified. In-patient costs for discharge-delaying ABD events were compared with hypothetical out-patient management. Out-patient costs took into account 4-10 d of in-patient observation for ABD events before caffeine initiation, 3-5 d of additional in-patient observation before discharge, daily caffeine until 43 weeks corrected gestational age, home pulse oximetry monitoring until 44 weeks corrected gestational age, and consideration of variable readmission rates ranging from 0 to 10%. A total of 425 late preterm and term infants were included in our analysis. Utilization of hypothetical out-patient management resulted in cost savings per eligible patient ranging from $2,422 to $62, dependent upon variable periods of in-patient observation. Sensitivity analysis demonstrated few instances of decreased relative cost-effectiveness. Out-patient management of discharge-delaying ABD events in a late preterm and term population was a cost-effective alternative to prolonged in-patient observation. Copyright © 2017 by Daedalus Enterprises.

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

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    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

  15. The Early vs. Late Infantile Strabismus Surgery Study: Monitoring Report

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    H.J. Simonsz (Huib)

    1995-01-01

    textabstractAbstract: The Early vs. Late Infantile Strabismus Surgery Study Group is a group of strabismologists and orthoptists who investigate whether early or late surgery is preferable in infantile strabismus, in a non-randomized, prospective, multi-center trial. Infants between six and 18

  16. 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). ...

  17. Central-peripheral Temperature Monitoring as a Marker for Diagnosing Late-onset Neonatal Sepsis.

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    Leante-Castellanos, José Luis; Martínez-Gimeno, Antonio; Cidrás-Pidré, Manuel; Martínez-Munar, Gerardo; García-González, Ana; Fuentes-Gutiérrez, Carmen

    2017-12-01

    The prognosis for late-onset sepsis depends largely on a timely diagnosis. We assess central-peripheral temperature difference monitoring as a marker for late-onset neonatal sepsis diagnosis. We performed a prospective, observational study focusing on a cohort of 129 very low-birth-weight infants. Thermal gradient alteration was defined as a difference of > 2°C maintained during 4 hours. We then determined its association with the late-onset sepsis variable through logistic regression. We enrolled 129 preterm babies in 52 months. Thermal gradient alterations showed an adjusted odds ratio for late-onset sepsis of 23.60 (95% confidence interval [CI], 6.80-81.88), with a sensitivity of 83% and negative predictive value of 94%. In 71% of cases, thermal gradient alteration was the first clinical sign of sepsis, while C-reactive protein was peripheral temperature differences are an early sign of evolving late-onset sepsis.

  18. Performance of immunological response in predicting virological failure.

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    Ingole, Nayana; Mehta, Preeti; Pazare, Amar; Paranjpe, Supriya; Sarkate, Purva

    2013-03-01

    In HIV-infected individuals on antiretroviral therapy (ART), the decision on when to switch from first-line to second-line therapy is dictated by treatment failure, and this can be measured in three ways: clinically, immunologically, and virologically. While viral load (VL) decreases and CD4 cell increases typically occur together after starting ART, discordant responses may be seen. Hence the current study was designed to determine the immunological and virological response to ART and to evaluate the utility of immunological response to predict virological failure. All treatment-naive HIV-positive individuals aged >18 years who were eligible for ART were enrolled and assessed at baseline, 6 months, and 12 months clinically and by CD4 cell count and viral load estimations. The patients were categorized as showing concordant favorable (CF), immunological only (IO), virological only (VO), and concordant unfavorable responses (CU). The efficiency of immunological failure to predict virological failure was analyzed across various levels of virological failure (VL>50, >500, and >5,000 copies/ml). At 6 months, 87(79.81%), 7(5.5%), 13 (11.92%), and 2 (1.83%) patients and at 12 months 61(69.3%), 9(10.2%), 16 (18.2%), and 2 (2.3%) patients had CF, IO, VO, and CU responses, respectively. Immunological failure criteria had a very low sensitivity (11.1-40%) and positive predictive value (8.3-25%) to predict virological failure. Immunological criteria do not accurately predict virological failure resulting in significant misclassification of therapeutic responses. There is an urgent need for inclusion of viral load testing in the initiation and monitoring of ART.

  19. Structural health monitoring tools for late and end of life management of offshore wind turbines

    DEFF Research Database (Denmark)

    McGugan, Malcolm; McKirdy, Scott

    2016-01-01

    The late and end of life stages in an offshore wind turbines (OWT) life cycle have unique features that must be considered. The initial focus on risks associated with start-up issues due to design, manufacturing or process elements gives way to a stable period of operation and maintenance...... margins and the predominance of low redundancy structures, accurate structural health monitoring can play a strong role in safe management and enable increased operating time at end of life and decommissioning. Late life operations of offshore wind farms can pose significant challenges, balancing...

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. Molecular virology of feline calicivirus.

    Science.gov (United States)

    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.

  5. Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia

    DEFF Research Database (Denmark)

    Abdissa, Alemseged; Yilma, Daniel; Fonager, Jannik

    2014-01-01

    BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub-Saharan Af...... mutations among failing patients justify increased vigilance by improving the availability and systematic use of VL testing to monitor ART response, and underlines the need for rapid, inexpensive tests to identify the most common drug resistance mutations....

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

    Science.gov (United States)

    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.

  7. 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...

  8. IRAC Monitoring of the Late Heavy Comet Bombardment in the eta Corvi System

    Science.gov (United States)

    Marengo, Massimo; Lisse, Carey; Stapelfeldt, Karl; Hulsebus, Alan

    2014-12-01

    The nearby sun-like star eta Corvi (F2V, d=18 pc, age =1.2 Gyr) has long been known to possess a bright, dusty Kuiper Belt that has now been resolved with Herschel PACS. A warm inner dust belt indicated by an IRAS 12 micron excess and has recently been resolved as a 3-AU scale structure by VLT observations. In 2012 Lisse et al. further characterized this warm dust using Spitzer IRS, identifying the signatures of ice, organics and silicate dust in this system's Terrestrial Habitability Zone (THZ). The system appears to be undergoing a Late Heavy Bombardment (LHB), delivering primitive, water- and organic-rich material from the Kuiper Belt to the THZ, at roughly the same relative age as the solar system's LHB. Our data also showed an upturn in the excess flux shortwards of 6 micron ? evidence for a surprisingly large amount of icy dust scattering in the inner system (fscat/fstar ~ 1.0%). This results is corroborated by our recent 2-5 micron NASA/IRTF SpeX spectroscopy. In 2012 we have obtained Spitzer/IRAC photometric data for the system, detecting the disk at 3.6 and 4.5 micron in two separate epochs, followed by a third epoch in 2013. We now propose to continue our photometric monitoring with 15 additional visits to be scheduled within cycle 11, in order to extend our temporal coverage to 4 years on a variety of timescales ranging from days, to weeks, to months. The proposed campaign will allow us to test the two competing hypothesis for the origin of the warm disk: (1) single collison event leading to the breakup of a large Kuiper Belt object in the system or (2) continual raining of small comets scattered towards the inner system.

  9. Recommendations on the diagnosis, treatment and monitoring of late-onset hypogonadism in men - a suggested update.

    Science.gov (United States)

    Lunenfeld, Bruno; Mskhalaya, George; Kalinchenko, Svetlana; Tishova, Yulia

    2013-12-01

    Recommendations on the diagnosis, treatment and monitoring of late-onset hypogonadism (LOH) in men were first published by ISSAM in 2002 In 2005, and, in 2008, updated recommendations were published in the International Journal of Andrology, the Journal of Andrology, the Aging Male and European Urology. Towards discussions at the next ISSAM/ESSAM meeting in Moscow, 29 November 2013, we suggest the following update.

  10. 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.

  11. Monitoring bentazone concentrations in the uppermost groundwater after late season applications

    NARCIS (Netherlands)

    Cornelese AA; Linden AMA vd; LBG

    1998-01-01

    The herbicide bentazone has been detected in groundwater in several monitoring programs with most of the findings possibly be related to applications early in the growth season. Because of a very low sorption constant bentazone can be transported in soil with the waterflow very easily. This means

  12. 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...

  13. 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.

  14. Applications of Next-Generation Sequencing Technologies to Diagnostic Virology

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. The late posterior negativity in ERP studies of episodic memory: action monitoring and retrieval of attribute conjunctions.

    Science.gov (United States)

    Johansson, Mikael; Mecklinger, Axel

    2003-10-01

    The focus of the present paper is a late posterior negative slow wave (LPN) that has frequently been reported in event-related potential (ERP) studies of memory. An overview of these studies suggests that two broad classes of experimental conditions tend to elicit this component: (a) item recognition tasks associated with enhanced action monitoring demands arising from response conflict and (b) memory tasks that require the binding of items with contextual information specifying the study episode. A combined stimulus- and response-locked analysis of data from two studies mapping onto these classes allowed a temporal and functional decomposition of the LPN. While only the LPN observed in the item recognition task could be attributed to the involvement of a posteriorly distributed response-locked error-related negativity (or error negativity; ERN/Ne) occurring immediately after the response, the source-memory task was associated with a stimulus-locked negative slow wave occurring prior and during response execution that was evident when data were matched for response latencies. We argue that the presence of the former reflects action monitoring due to high levels of response conflict, whereas the latter reflects retrieval processes that may act to reconstruct the prior study episode when task-relevant attribute conjunctions are not readily recovered or need continued evaluation.

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

    Directory of Open Access Journals (Sweden)

    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

  18. Kinetics and Determining Factors of the Virologic Response to Antiretrovirals during Pregnancy

    Directory of Open Access Journals (Sweden)

    Adriana Weinberg

    2009-01-01

    Full Text Available HIV-infected pregnant women with undetectable plasma HIV RNA concentrations at delivery pose a minimal risk of vertical transmission. We studied the kinetics and the determinants of the virologic response to antiretroviral therapy in 117 consecutive pregnancies. Patients who initiated therapy during pregnancy had a VL decrease of 2 and 2.5 log10 after 4 and 24 weeks, respectively. Therapeutic drug monitoring (TDM of the protease inhibitors administered in doses recommended for nonpregnant adults resulted in below-target concentrations in 29%, 35%, and 44% of 1st, 2nd, and 3rd trimester measurements, respectively, but low drug concentrations did not correlate with virologic failure. Demographic characteristics, antiretroviral experience prior to pregnancy, baseline VL, or use of specific antiretrovirals did not affect the virologic response. Adherence to ≥95% of prescribed doses and utilization of psychosocial services were associated with undetectable plasma HIV RNA at delivery. In conclusion, the virologic responses of pregnant and nonpregnant adults share similar charactersitics.

  19. 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

  20. 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.

  1. The continuous automatic monitoring network installed in Tuscany (Italy) since late 2002, to study earthquake precursory phenomena

    Science.gov (United States)

    Pierotti, Lisa; Cioni, Roberto

    2010-05-01

    Since late 2002, a continuous automatic monitoring network (CAMN) was designed, built and installed in Tuscany (Italy), in order to investigate and define the geochemical response of the aquifers to the local seismic activity. The purpose of the investigation was to identify eventual earthquake precursors. The CAMN is constituted by two groups of five measurement stations each. A first group has been installed in the Serchio and Magra graben (Garfagnana and Lunigiana Valleys, Northern Tuscany), while the second one, in the area of Mt. Amiata (Southern Tuscany), an extinct volcano. Garfagnana, Lunigiana and Mt. Amiata regions belong to the inner zone of the Northern Apennine fold-and-thrust belt. This zone has been involved in the post-collision extensional tectonics since the Upper Miocene-Pliocene. Such tectonic activity has produced horst and graben structures oriented from N-S to NW-SE that are transferred by NE-SW system. Both Garfagnana (Serchio graben) and Lunigiana (Magra graben) belong to the most inner sector of the belt where the seismic sources, responsible for the strongest earthquakes of the northern Apennine, are located (e.g. the M=6.5 earthquake of September 1920). The extensional processes in southern Tuscany have been accompanied by magmatic activity since the Upper Miocene, developing effusive and intrusive products traditionally attributed to the so-called Tuscan Magmatic Province. Mt. Amiata, whose magmatic activity ceased about 0.3 M.y. ago, belongs to the extensive Tyrrhenian sector that is characterized by high heat flow and crustal thinning. The whole zone is characterized by wide-spread but moderate seismicity (the maximum recorded magnitude has been 5.1 with epicentre in Piancastagnaio, 1919). The extensional regime in both the Garfagnana-Lunigiana and Mt. Amiata area is confirmed by the focal mechanisms of recent earthquakes. An essential phase of the monitoring activities has been the selection of suitable sites for the installation of

  2. 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.

  3. Wavelength-dependent backscattering measurements for quantitative monitoring of apoptosis, Part 1: early and late spectral changes are indicative of the presence of apoptosis in cell cultures

    Science.gov (United States)

    Mulvey, Christine S.; Zhang, Kexiong; Liu, Wei-Han Bobby; Waxman, David J.; Bigio, Irving J.

    2011-11-01

    Apoptosis, a form of programmed cell death with unique morphological and biochemical features, is dysregulated in cancer and is activated by many cancer chemotherapeutic drugs. Noninvasive assays for apoptosis in cell cultures can aid in screening of new anticancer agents. We have previously demonstrated that elastic scattering spectroscopy can monitor apoptosis in cell cultures. In this report we present data on monitoring the detailed time-course of scattering changes in a Chinese hamster ovary (CHO) and PC-3 prostate cancer cells treated with staurosporine to induce apoptosis. Changes in the backscattering spectrum are detectable within 10 min, and continue to progress up to 48 h after staurosporine treatment, with the magnitude and kinetics of scattering changes dependent on inducer concentration. Similar responses were observed in CHO cells treated with several other apoptosis-inducing protocols. Early and late scattering changes were observed under conditions shown to induce apoptosis via caspase activity assay and were absent under conditions where apoptosis was not induced. Finally, blocking caspase activity and downstream apoptotic morphology changes prevented late scattering changes. These observations demonstrate that early and late changes in wavelength-dependent backscattering correlate with the presence of apoptosis in cell cultures and that the late changes are specific to apoptosis.

  4. 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.

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

    Science.gov (United States)

    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'.

  6. 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

  7. 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.

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

    Science.gov (United States)

    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.

  9. 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 ...

  10. 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…

  11. Virological response without CD4 recovery | Madide | Southern ...

    African Journals Online (AJOL)

    The objective of antiretroviral therapy (ART) is to suppress viral replication so that immune restoration can occur. Failure of immune restoration is usually associated with poor virological suppression. In children a good immunological and clinical response to ART is often achieved despite incomplete viral suppression.

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. 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.

  15. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

    Science.gov (United States)

    Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick CK; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher KC; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    Introduction First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥2 TAMs; and 32 with M184V+≥1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤200 cells/µL at genotyping (OR=4.43, 95% CI [1.59–12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. Conclusions Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving

  16. Next-Generation Sequencing and Genome Editing in Plant Virology

    Directory of Open Access Journals (Sweden)

    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

  17. Factors influencing the virological testing of cornea donors.

    Science.gov (United States)

    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.

  18. 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.

  19. Late Holocene climate and environmental change from Asiul cave speleothems: interpretations in light of modern cave monitoring.

    Science.gov (United States)

    Smith, Andrew; Wynn, Peter; Barker, Philip; Leng, Melanie; Noble, Steve; Tych, Wlodek

    2017-04-01

    Northern Iberia offers an excellent location to study fluctuations in North Atlantic Ocean (NA) conditions and the impact that changes in the NA have on atmospheric systems, which dominate Europe's climate. Two speleothems from Cueva de Asiul (Matienzo, N. Spain) have been used to reconstruct rainfall variability in N. Spain throughout the Holocene (Smith et al., 2016a). The carbonate δ18O records from these speleothems are interpreted in the light of a rigorous modern cave monitoring program undertaken at Cueva de Asiul (Smith et al., 2016b). Drip water δ18O reflects a modern rainfall amount effect whilst δ13C appears influenced by Prior Calcite Precipitation (PCP) in the short term and changes in vegetation at long timescales. The speleothem δ18O shows that long duration ( 1500 year) cycles in wetting and drying are prevalent in N. Spain during the Holocene and that dry climate phases are related to the timing of cold events (Bond et al., 2001) in the NA. Here we look in more detail at one of these speleothems, assessing both δ18O and δ13C during the last two thousand years. We show that Cueva de Asiul speleothems not only preserve long duration climate cycles in δ18O, but that they also appear influenced by shorter duration changes in the North Atlantic Oscillation (NAO), in-sync with other NAO archives (Olsen et al., 2012). However, the Cueva de Asiul record does not appear to preserve a predominately positive NAO signal during the Medieval Climate Anomaly (MCA) as is common within many European archives (Trouet et al., 2009), possibly due to the sites' close proximity to the NA and localised oceanic weather systems (Moreno et al., 2012). Alongside climatic changes, the speleothem δ13C shows a clear transition toward higher isotope values around 360 years BP (BP=1950), signalling a major environmental change in the region possibly due to anthropogenic removal of vast swathes of natural forest to support ship building and industry related to the Spanish

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

    Directory of Open Access Journals (Sweden)

    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.

  1. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia.

    Science.gov (United States)

    Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick C K; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher K C; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance - Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥ 2 TAMs; or M184V+≥ 1 TAM. Virological suppression was defined as viral load (VL) failure and (2) factors associated with virological suppression after 12 months on second-line. A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥ 1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥ 2 TAMs; and 32 with M184V+≥ 1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤ 200 cells/µL at genotyping (OR=4.43, 95% CI [1.59-12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39-16.36], pfailure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Personal historical chronicle of six decades of basic and applied research in virology, immunology, and vaccinology.

    Science.gov (United States)

    Hilleman, M R

    1999-08-01

    The sciences of vaccinology and of immunology were created just two centuries ago by Jenner's studies of prevention of smallpox by inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th and early 20th centuries biomedical sciences. The period from 1930 to 1950 was a transitional era with the introduction of chick embryos and minced tissues for propagating viruses and rickettsiae in vitro for vaccines. Modern era vaccinology began about 1950 as a continuum of notable advances made during the 1940s and World War II. Present vaccinology is based largely on breakthroughs in cell culture, bacterial polysaccharide chemistry, molecular biology, and immunology. By invitation, the author, who is a microbe hunter in fact, was asked to chronicle his six decades of pioneering achievements in basic and applied virology, bacteriology, immunology, molecular biology, epidemiology, and cancer, with special reference to the pioneering creation of most of the present day vaccines. Knowledge of the past may guide the present and future. This chronicle will have achieved its legacy if it helps others to understand the why and how of the past that may help to create the substance of the future.

  5. 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....

  6. 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.

  7. Late Budgets

    DEFF Research Database (Denmark)

    Andersen, Asger Lau; Lassen, David Dreyer; Nielsen, Lasse Holbøll Westh

    are negative rather than positive; and when there is divided government. We test the hypotheses of the model using a unique data set of late budgets for US state governments, based on dates of budget approval collected from news reports and a survey of state budget o¢ cers for the period 1988...

  8. Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?

    Science.gov (United States)

    Basara, N; Rasche, F-M; Schwalenberg, T; Wickenhauser, C; Maier, M; Ivovic, J; Niederwieser, D; Lindner, T H

    2010-01-01

    We report here a case of acute lymphoblastic leukemia in remission presenting a late-onset bilateral hydronephrosis probably due to polyoma BK virus-induced proliferation of bladder endothelium on both ostii. The diagnosis was made virologically by BK virus Polymerase Chain Reaction (PCR) detection in the absence of any other bladder disease. Awareness of this late complication is necessary not only in patients after renal transplantation but also in patients after hematopoietic stem cell transplantation from matched unrelated donor.

  9. Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?

    Science.gov (United States)

    Basara, N.; Rasche, F.-M.; Schwalenberg, T.; Wickenhauser, C.; Maier, M.; Ivovic, J.; Niederwieser, D.; Lindner, T. H.

    2010-01-01

    We report here a case of acute lymphoblastic leukemia in remission presenting a late-onset bilateral hydronephrosis probably due to polyoma BK virus-induced proliferation of bladder endothelium on both ostii. The diagnosis was made virologically by BK virus Polymerase Chain Reaction (PCR) detection in the absence of any other bladder disease. Awareness of this late complication is necessary not only in patients after renal transplantation but also in patients after hematopoietic stem cell transplantation from matched unrelated donor. PMID:20936157

  10. Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?

    OpenAIRE

    Basara, N.; Rasche, F.-M.; Schwalenberg, T.; Wickenhauser, C.; Maier, M.; Ivovic, J.; Niederwieser, D.; Lindner, T. H.

    2010-01-01

    We report here a case of acute lymphoblastic leukemia in remission presenting a late-onset bilateral hydronephrosis probably due to polyoma BK virus-induced proliferation of bladder endothelium on both ostii. The diagnosis was made virologically by BK virus Polymerase Chain Reaction (PCR) detection in the absence of any other bladder disease. Awareness of this late complication is necessary not only in patients after renal transplantation but also in patients after hematopoietic stem cell tra...

  11. 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

  12. Virologic response at week 8 of combined treatment as a predictor of ...

    African Journals Online (AJOL)

    Ali Monis

    2012-04-16

    Apr 16, 2012 ... in non rapid virologic response, chronic HCV genotype 4 infected patients .... Other liver diseases as alcoholic liver disease, non alco- holic fatty liver disease .... penses and limit the side-effects associated with drug exposure.

  13. 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....

  14. 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.

  15. 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

  16. Late Raphael

    OpenAIRE

    Henry, Tom F. K.; Joannides, Paul; González Mozo, Ana; Martín, Bruno

    2012-01-01

    Exhibition catalogue (co-authored with P. Joannides) in English, Spanish and French by the Museo del Prado and the Musée du Louvre, 2012. English edition, publisher: Museo Nacional del Prado (ISBN 978-84-8480-237-2). 382 pages, of which 300 were co-authored with P. Joannides. This publication was the catalogue of the major exhibtion of Raphael's late work which was at the Prado and the Louvre in 2012-13. The exhibition was seen by more than 650,000 visitors, and was widely reviewed in the int...

  17. Geoinformation technology for radioecological monitoring and rehabilitation of the agricultural territories on the late stage of the Chernobyl accident in Ukraine

    International Nuclear Information System (INIS)

    Lev, T.D.; Garger, E.; Tabachny, L.

    2002-01-01

    The complex analysis of the radioecological situation on the polluted agricultural territories of Ukrainian Polissya was carried out on the data of the Radiation Monitoring System during 1996-1999 using GIS technologies. The critical territories for implementation of countermeasures and conservative measures for reduction of product level contamination by radionuclides are selected. The results of the statistical and spatial analysis of the data on product contamination have allowed to elaborate the schedule of the products monitoring. (author)

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. 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.

  2. 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...

  3. 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...

  4. Regional changes over time in initial virological response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, W; Kirk, O; Gatell, J

    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.......026) and time (P changes were observed (south, P = 0.061; central west, P ....001; north: P = 0.070; east, P = 0.001). CONCLUSIONS: There was some evidence of regional differences in initial virologic response to cART. Improvements over time were observed, suggesting that so far, the effect of primary resistance has not been of sufficient magnitude to prevent increasing suppression...

  5. prevalence of clinical, immunological and virological failure among ...

    African Journals Online (AJOL)

    Esem

    ABSTRACT. Background: There is increasing evidence that the current clinical and immunological monitoring tools are not sufficient to identify early enough patients who are failing on treatment. Development of resistance to the limited treatment options for children and premature switching are the dangers. The objective of ...

  6. 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.

    Science.gov (United States)

    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.

  7. Role of IL-28B polymorphisms in virologic response to combined ...

    African Journals Online (AJOL)

    Amira Youssef Shaala

    2014-10-17

    Oct 17, 2014 ... of cirrhosis showed higher risk of failed response at 3 and 6 months (p = 0.016 and 0.020 respec- tively). Also .... Sustained virologic response is defined as non .... nicity, body mass index, insulin resistance, hepatic steatosis,.

  8. 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.

  9. The value of Institute of Human Virology meeting abstracts and beyond

    Directory of Open Access Journals (Sweden)

    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.

  10. 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...

  11. 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.

  12. Risk factors of virologic failure and slow response to art among HIV ...

    African Journals Online (AJOL)

    Risk factors of virologic failure and slow response to art among HIV-infected children and adolescents in Nairobi. J. M. Kabogo, S. Gupta, A. K. Maina, M. Ochwoto, R. W. Omange, R. N. Musoke, R. W. Lihana, E. Muniu, F. W. Wamunyokoli, B. Liang, E. M. Songok ...

  13. 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....

  14. Exploring Late Globalization

    DEFF Research Database (Denmark)

    Turcan, Romeo V.

    2016-01-01

    literature on late globalization from sociocultural and economic perspectives. It illustrates in a vignette the character and features of late globalization observable in the withdrawal from foreign locations or deinternationalization of universities, as late globalizing entitis. The paper discusses...

  15. 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.

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

    Science.gov (United States)

    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.

  17. 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.

  18. Fish mercury levels appear to be increasing lately: a report from 40 years of monitoring in the province of Ontario, Canada.

    Science.gov (United States)

    Gandhi, Nilima; Tang, Rex W K; Bhavsar, Satyendra P; Arhonditsis, George B

    2014-05-20

    Recent mercury levels and trends reported for North America suggest a mixed (positive/negative) outlook for the environmental mercury problem. Using one of the largest consistent monitoring data sets in the world, here we present long-term and recent mercury trends in Walleye, Northern Pike, and Lake Trout from the Province of Ontario, Canada, which contains about one-third of the world's fresh water and covers a wide geographical area (1.5 and 3 times larger than France and Germany, respectively). Overall, the results indicate that the fish mercury levels either declined (0.01-0.07 μg/g decade) or remained stable between the 1970s and 2012. The rates of mercury decline were substantially greater (mostly 0.05-0.31 μg/g decade) during the 1970s/80s possibly in response to reductions in mercury emissions. However, Walleye and Pike levels have generally increased (0.01-0.27 μg/g decade) in recent years (1995-2012), especially for northern Ontario (effect sizes for differences between the two periods ranged from 0.39 to 1.04). Proportions of Walleye and Pike locations showing a flat or increasing trend increased from 26-44% to 59-73% between the 1970s/80s and 1995-2012. Mercury emissions in North America have declined over the last few decades, and as such it is logical to expect recovery in fish mercury levels; however, other factors such as global emissions, climate change, invasive species, and local geochemistry are likely affecting the response time and magnitude.

  19. 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.

  20. Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?

    Directory of Open Access Journals (Sweden)

    N. Basara

    2010-01-01

    Full Text Available We report here a case of acute lymphoblastic leukemia in remission presenting a late-onset bilateral hydronephrosis probably due to polyoma BK virus-induced proliferation of bladder endothelium on both ostii. The diagnosis was made virologically by BK virus Polymerase Chain Reaction (PCR detection in the absence of any other bladder disease. Awareness of this late complication is necessary not only in patients after renal transplantation but also in patients after hematopoietic stem cell transplantation from matched unrelated donor.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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.

  4. 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...

  5. 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

  6. Nucleocapsid promotes localization of HIV-1 gag to uropods that participate in virological synapses between T cells.

    Science.gov (United States)

    Llewellyn, G Nicholas; Hogue, Ian B; Grover, Jonathan R; Ono, Akira

    2010-10-28

    T cells adopt a polarized morphology in lymphoid organs, where cell-to-cell transmission of HIV-1 is likely frequent. However, despite the importance of understanding virus spread in vivo, little is known about the HIV-1 life cycle, particularly its late phase, in polarized T cells. Polarized T cells form two ends, the leading edge at the front and a protrusion called a uropod at the rear. Using multiple uropod markers, we observed that HIV-1 Gag localizes to the uropod in polarized T cells. Infected T cells formed contacts with uninfected target T cells preferentially via HIV-1 Gag-containing uropods compared to leading edges that lack plasma-membrane-associated Gag. Cell contacts enriched in Gag and CD4, which define the virological synapse (VS), are also enriched in uropod markers. These results indicate that Gag-laden uropods participate in the formation and/or structure of the VS, which likely plays a key role in cell-to-cell transmission of HIV-1. Consistent with this notion, a myosin light chain kinase inhibitor, which disrupts uropods, reduced virus particle transfer from infected T cells to target T cells. Mechanistically, we observed that Gag copatches with antibody-crosslinked uropod markers even in non-polarized cells, suggesting an association of Gag with uropod-specific microdomains that carry Gag to uropods. Finally, we determined that localization of Gag to the uropod depends on higher-order clustering driven by its NC domain. Taken together, these results support a model in which NC-dependent Gag accumulation to uropods establishes a preformed platform that later constitutes T-cell-T-cell contacts at which HIV-1 virus transfer occurs.

  7. Nucleocapsid promotes localization of HIV-1 gag to uropods that participate in virological synapses between T cells.

    Directory of Open Access Journals (Sweden)

    G Nicholas Llewellyn

    2010-10-01

    Full Text Available T cells adopt a polarized morphology in lymphoid organs, where cell-to-cell transmission of HIV-1 is likely frequent. However, despite the importance of understanding virus spread in vivo, little is known about the HIV-1 life cycle, particularly its late phase, in polarized T cells. Polarized T cells form two ends, the leading edge at the front and a protrusion called a uropod at the rear. Using multiple uropod markers, we observed that HIV-1 Gag localizes to the uropod in polarized T cells. Infected T cells formed contacts with uninfected target T cells preferentially via HIV-1 Gag-containing uropods compared to leading edges that lack plasma-membrane-associated Gag. Cell contacts enriched in Gag and CD4, which define the virological synapse (VS, are also enriched in uropod markers. These results indicate that Gag-laden uropods participate in the formation and/or structure of the VS, which likely plays a key role in cell-to-cell transmission of HIV-1. Consistent with this notion, a myosin light chain kinase inhibitor, which disrupts uropods, reduced virus particle transfer from infected T cells to target T cells. Mechanistically, we observed that Gag copatches with antibody-crosslinked uropod markers even in non-polarized cells, suggesting an association of Gag with uropod-specific microdomains that carry Gag to uropods. Finally, we determined that localization of Gag to the uropod depends on higher-order clustering driven by its NC domain. Taken together, these results support a model in which NC-dependent Gag accumulation to uropods establishes a preformed platform that later constitutes T-cell-T-cell contacts at which HIV-1 virus transfer occurs.

  8. Trends on epidemiological, virological, and clinical features among newly diagnosed HIV-1 persons in Northwest Spain over the last 10 years.

    Science.gov (United States)

    Pernas, B; Mena, A; Cañizares, A; Grandal, M; Castro-Iglesias, A; Pértega, S; Pedreira, J D; Poveda, E

    2015-08-01

    To describe temporal trend and characteristics of newly HIV-diagnosed patients in a medical care area in Northwest Spain over the last 10 years. All newly diagnosed patients for HIV-infection from 2004 to 2013 at a reference medical care area in Northwest of Spain were identified. Epidemiological, virological, immunological, and clinical data, as well as HIV genotype and drug resistance information were recorded. A total of 565 newly HIV-diagnosed patients were identified. The number of new cases increased in the last 5 years (66 cases/year). Overall, 53.1% had a median CD4 counts study period was 3.7%, but a decreased to 2.6% was observed in the last 5 years. The most prevalent TDR mutations were: T215 revertants (1.5%), K219QENR (1.2%), for NRTIs; K103N (1.9%), for NNRTIs; L90M (0.3%), for PIs. Overall, 73.2% of patients started antiretroviral treatment and 9.9% of patients died during follow-up. The number of newly HIV diagnosed patients increased since year 2009. There is a high prevalence of late diagnosis (53%) and 33% had an AIDS defining criteria. Interestingly, the most prevalent non-B subtype in our population was F (25.8%). These findings support the need to facilitate the access for HIV testing to reduce the rate of late HIV diagnosis, improve the clinical outcome and prevent HIV transmission. © 2015 Wiley Periodicals, Inc.

  9. Late effects of childhood leukemia therapy.

    Science.gov (United States)

    Fulbright, Joy M; Raman, Sripriya; McClellan, Wendy S; August, Keith J

    2011-09-01

    As survival rates for children treated for childhood cancers become significantly better, the focus is increasingly on determining the late effects of treatments and the best ways to monitor for them and prevent their occurrence. This review focuses on recent literature discussing the late effects of treatment in patients treated for acute myeloid leukemia and acute lymphoblastic leukemia during childhood. The late effects of therapy for childhood leukemia include secondary malignancy, cardiotoxicity, obesity, endocrine abnormalities, reproductive changes, neurocognitive deficits, and psychosocial effects. As clinicians have become more aware of the late effects of therapy, treatment regimens have been changed to decrease late effects, but patients still require long-term follow-up for their prevention and treatment.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Comparing Measures of Late HIV Diagnosis in Washington State

    Directory of Open Access Journals (Sweden)

    Laura Saganic

    2012-01-01

    Full Text Available As more US HIV surveillance programs routinely use late HIV diagnosis to monitor and characterize HIV testing patterns, there is an increasing need to standardize how late HIV diagnosis is measured. In this study, we compared two measures of late HIV diagnosis, one based on time between HIV and AIDS, the other based on initial CD4+ results. Using data from Washington's HIV/AIDS Reporting System, we used multivariate logistic regression to identify predictors of late HIV diagnosis. We also conducted tests for trend to determine whether the proportion of cases diagnosed late has changed over time. Both measures lead us to similar conclusions about late HIV diagnosis, suggesting that being male, older, foreign-born, or heterosexual increase the likelihood of late HIV diagnosis. Our findings reaffirm the validity of a time-based definition of late HIV diagnosis, while at the same time demonstrating the potential value of a lab-based measure.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. Personality in Late Midlife

    DEFF Research Database (Denmark)

    Mortensen, Erik Lykke; Flensborg-Madsen, Trine; Molbo, Drude

    2014-01-01

    To analyze associations in late midlife between sex, age, education and social class, and the Big Five personality traits; to analyze associations between personality traits and cognitive ability in late midlife; and to evaluate how these associations are influenced by demographic factors....

  20. 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

  1. Raltegravir versus lopinavir/ritonavir for treatment of HIV-infected late-presenting pregnant women.

    Science.gov (United States)

    Brites, Carlos; Nóbrega, Isabella; Luz, Estela; Travassos, Ana Gabriela; Lorenzo, Cynthia; Netto, Eduardo M

    2018-06-01

    Background Late-presenting pregnant women pose a challenge in the prevention of HIV-1 mother-to-child-transmission. We compared the safety and efficacy of raltegravir and lopinavir/ritonavir for this population. Methods We did a single-center, pilot, open-label, randomized trial in Brazil (N = 44). We randomly allocated late-presenting HIV-infected pregnant women (older than 18 years with a plasma HIV-1 RNA >1000 copies/mL) to receive raltegravir 400 mg twice a day or lopinavir/ritonavir 400/100 mg twice a day plus zidovudine and lamivudine (1:1). The primary endpoint was virological suppression at delivery (HIV-1 RNA HIV-infected late-presenting pregnant women.

  2. 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...

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

    DEFF Research Database (Denmark)

    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...

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

    Directory of Open Access Journals (Sweden)

    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

  5. 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.

  6. 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...

  7. Una Perspectiva sobre la Situación Actual de la Virología

    Directory of Open Access Journals (Sweden)

    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.

  8. [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.

  9. 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)

  10. 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.

  11. 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

  12. 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...

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

    DEFF Research Database (Denmark)

    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...

  14. 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...

  15. 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,

  16. 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...

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

    DEFF Research Database (Denmark)

    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...

  18. 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...

  19. 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

  20. 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

  1. 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...

  2. 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.

  3. 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

  4. Late-Stage Caregiving

    Science.gov (United States)

    ... Caregiving Middle-Stage Caregiving Late-Stage Caregiving Behaviors Aggression & Anger Anxiety & Agitation Depression Hallucinations Memory Loss & Confusion Repetition Sleep Issues & Sundowning Suspicion & Delusions Wandering Abuse Start Here What You Need to Know Online ...

  5. Impact of early, late, and no ST-segment resolution measured by continuous ST Holter monitoring on left ventricular ejection fraction and infarct size as determined by cardiovascular magnetic resonance imaging

    NARCIS (Netherlands)

    Haeck, Joost D. E.; Verouden, Niels J. W.; Kuijt, Wichert J.; Koch, Karel T.; Majidi, Mohamed; Hirsch, Alexander; Tijssen, Jan G. P.; Krucoff, Mitchell W.; de Winter, Robbert J.

    2011-01-01

    Background: The goal of this study is to determine the predictive value of ST-segment resolution (STR) early after percutaneous coronary intervention (PCI), late STR, and no STR for left ventricular ejection fraction (LVEF) and infarct size (IS) by cardiovascular magnetic resonance (CMR) at

  6. Epidemiological and virological assessment of influenza activity in Europe, during the 2004-2005 winter.

    NARCIS (Netherlands)

    Meijer, A.; Paget, W.J.; Meerhoff, T.J.; Brown, C.S.; Meuwissen, L.E.; Velden, J. van der

    2006-01-01

    The 2004-2005 influenza season in Europe started in late December 2004 and the first influenza activity occurred in the west and southwest (Spain, United Kingdom and Ireland). Influenza activity then moved gradually east across Europe during January and early February 2005, and from late February

  7. 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

  8. 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

  9. 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.

  10. Late onset endophthalmitis

    Directory of Open Access Journals (Sweden)

    Abdulaziz AlHadlaq

    2016-04-01

    Full Text Available We report an extremely rare presentation of late-onset endophthalmitis in a young adult patient with an unexposed Ahmed tube implant. The implant was inserted 11 years prior to presentation. There was no history of trauma or any obvious exposure on clinical examination and the tube plate was filled with purulent material. After aqueous and vitreous tap, the patient underwent intracameral, intravitreal subconjunctival antibiotic injections and was started on systemic antibiotics with good response. Endophthalmitis associated with tube drainage device can present as late as 11 years and even without an unexposed tube.

  11. Lateness to School Remediation Game

    Science.gov (United States)

    Ugwuegbulam, Charles N.; Ibrahim, Haj. Naheed

    2015-01-01

    Primary and secondary school in Nigeria encourage punctuality to school yet a good number of the learners came late to school. This is especially true in the case of day students. Learners who come late to school are usually punished in one way or the other yet the lateness to school phenomenon still persist. Lateness to school behaviour affects…

  12. Dynamics of Pathological and Virological Findings During Experimental Calpox Virus Infection of Common Marmosets (Callithrix jacchus

    Directory of Open Access Journals (Sweden)

    Anne Schmitt

    2017-11-01

    Full Text Available Experimental intranasal infection of marmosets (Callithrix jacchus with calpox virus results in fatal disease. Route and dose used for viral inoculation of the test animals mimics the natural transmission of smallpox, thus representing a suitable model to study pathogenesis and to evaluate new vaccines against orthopoxvirus infection. However, the pathogenic mechanisms leading to death are still unclear. Therefore, our study aimed at investigating the kinetics of pathological alterations to clarify the pathogenesis in calpox virus infection. Following intranasal inoculation with two different viral doses, common marmosets were sacrificed on days 3, 5, 7, 10 and 12 post inoculation. Collected tissue was screened using histopathology, immunohistochemistry, transmission electron microscopy, and virological assays. Our data suggest that primary replication took place in nasal and bronchial epithelia followed by secondary replication in submandibular lymph nodes and spleen. Parallel to viremia at day 7, virus was detectable in many organs, mainly located in epithelial cells and macrophages, as well as in endothelial cells. Based on the onset of clinical signs, the histological and ultrastructural lesions and the immunohistochemical distribution pattern of the virus, the incubation period was defined to last 11 days, which resembles human smallpox. In conclusion, the data indicate that the calpox model is highly suitable for studying orthopoxvirus-induced disease.

  13. 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

  14. Type A viral hepatitis: A summary and update on the molecular virology, epidemiology, pathogenesis and prevention.

    Science.gov (United States)

    Lemon, Stanley M; Ott, Jördis J; Van Damme, Pierre; Shouval, Daniel

    2017-09-05

    Although epidemic jaundice was well known to physicians of antiquity, it is only in recent years that medical science has begun to unravel the origins of hepatitis A virus (HAV) and the unique pathobiology underlying acute hepatitis A in humans. Improvements in sanitation and the successful development of highly efficacious vaccines have markedly reduced the worldwide prevalence and incidence of this enterically-transmitted infection over the past quarter century, yet the virus persists in vulnerable populations and remains a common cause of food-borne disease outbreaks in economically-advantaged societies. Reductions in the prevalence of HAV have led to increases in the median age at which infection occurs, often resulting in more severe disease in affected persons and paradoxical increases in disease burden in some developing nations. Here, we summarize recent advances in the molecular virology of HAV, an atypical member of the Picornaviridae family, survey what is known of the pathogenesis of hepatitis A in humans and the host-pathogen interactions that typify the infection, and review medical and public health aspects of immunisation and disease prevention. Copyright © 2017. Published by Elsevier B.V.

  15. 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.

  16. 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.

  17. 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

  18. Late effecten van kankerbehandeling

    NARCIS (Netherlands)

    Langeveld, Nelia E.

    2004-01-01

    In dit artikel wordt ingegaan op de lange termijn effecten van kanker op de kinderleeftijd. Vervolgens wordt een kort overzicht gegeven van de belangrijkste late gevolgen die kunnen optreden na een oncologische behandeling met radio- en/of chemotherapie toegepast in de kinderleeftijd. Er wordt kort

  19. Late-modern hipsters

    DEFF Research Database (Denmark)

    Andersen, Bjørn Schiermer

    2014-01-01

    The article deals with the cultural significance of a new figure in late-modern Western culture: the hipster. The current hipster culture, so I argue, can be used as a magnifying glass that makes impending changes to our conception of culture and of cultural development visible. It ushers...

  20. Big Java late objects

    CERN Document Server

    Horstmann, Cay S

    2012-01-01

    Big Java: Late Objects is a comprehensive introduction to Java and computer programming, which focuses on the principles of programming, software engineering, and effective learning. It is designed for a two-semester first course in programming for computer science students.

  1. Late Embryogenesis Abundant Proteins

    NARCIS (Netherlands)

    Shih, M.D.; Hoekstra, F.A.; Hsing, Y.I.C.

    2008-01-01

    During the late maturation stage of seed development, water content decreases greatly. One of the most striking characteristics of mature orthodox seeds is their ability to withstand severe desiccation. Mechanisms of plant drought/desiccation tolerance have been studied by numerous groups, and a

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  7. 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

  8. 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.

  9. 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.

  10. 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?

    DEFF Research Database (Denmark)

    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....

  11. Late-successional forests and northern spotted owls: how effective is the Northwest Forest Plan?

    Science.gov (United States)

    Miles Hemstrom; Martin G. Raphael

    2000-01-01

    This paper describes the late-successional and old-growth forest and the northern spotted owl effectiveness monitoring plans for the Northwest Forest Plan. The effectiveness monitoring plan for late-successional and old-growth forests will track changes in forest spatial distribution, and within-stand structure and composition, and it will predict future trends.

  12. Risk factors and outcomes for late presentation for HIV-positive persons in europe

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Lundgren, Jens D; Sabin, Miriam Lewis

    2013-01-01

    Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality.......Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality....

  13. Monitoring Completed Navigation Projects Program

    National Research Council Canada - National Science Library

    Bottin, Jr., Robert R

    2001-01-01

    ... (MCNP) Program. The program was formerly known as the Monitoring Completed Coastal Projects Program, but was modified in the late 1990s to include all navigation projects, inland as well as coastal...

  14. Late-Onset Asthma

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli

    2017-01-01

    Late-onset asthma is common, associated with poor outcome, underdiagnosed and undertreated, possibly due to the modifying effect of ageing on disease expression. Although the diagnostic work-up in elderly individuals suspected of having asthma follows the same steps as in younger individuals (case......, to objectively confirm asthma. If necessary, a trial of oral or inhaled corticosteroid might be necessary. Asthma can be diagnosed when increased airflow variability is identified in a symptomatic patient, and if the patient does not have a history of exposure, primarily smoking, known to cause chronic...... obstructive pulmonary disease, the diagnosis is asthma even if the patient does not have fully reversible airflow obstruction. Pharmacological therapy in patients with late-onset asthma follows international guidelines, including treatment with the lowest effective dose of inhaled corticosteroid to minimize...

  15. Late Babylonian Astrology

    Science.gov (United States)

    Steele, John M.

    The last five centuries BC saw the development of several new forms of astrology in Babylonia. Key to these new astrological techniques was the invention of the zodiac in about 400 BC. These new forms of astrology include personal horoscopes, astral medicine, and the exploitation of geometrical relationships between the position of heavenly bodies. Several Late Babylonian astrological doctrines were later adopted within Greek astrology.

  16. Late Palaeozoic plants.

    Science.gov (United States)

    Feng, Zhuo

    2017-09-11

    Land plants are one of the major constituents of terrestrial ecosystems on Earth, and play an irreplaceable role in human activities today. If we are to understand the extant plants, it is imperative that we have some understanding of the fossil plants from the deep geological past, particularly those that occurred during their early evolutionary history, in the late Palaeozoic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Late somatic effects

    International Nuclear Information System (INIS)

    Gilbert, E.S.

    1989-01-01

    Late effects are by definition effects that occur at least one year, and in most cases decades, after the time of exposure. The late effects considered in this chapter are limited to latent cancer incidence and mortality, and benign thyroid disease. A model is provided for estimating risks of late effects resulting from the radiation exposure likely to be received in the event of a nuclear power plant accident. It is assumed that exposure to high-LET radiation would be negligible in such an accident, and thus only risks from low-LET exposure are evaluated. Separate estimates are provided for risks of leukemia, bone cancer, lung cancer, gastrointestinal cancers, thyroid cancer, skin cancer, and the residual group of all other cancers; estimates of leukemia and other cancers due to in utero exposure are also provided. Risks are expressed in absolute terms as the number of cancer deaths (or cases) per million persons exposed to a particular dose. Because the time of death is also important in assessing the impact of an accident, and because the quality of life after the occurrence of cancer will often be reduced, the number of years of life lost and the number of years of life lived after the occurrence of cancer are also estimated

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  20. Virological investigation of hand, foot, and mouth disease in a tertiary care center in South India

    Directory of Open Access Journals (Sweden)

    Pavithra M Vijayaraghavan

    2012-01-01

    Full Text Available Context: Hand, foot, and mouth disease (HFMD remains a common problem in India, yet its etiology is largely unknown as diagnosis is based on clinical characteristics. There are very few laboratory-based molecular studies on HFMD outbreaks. Aim: The aim of this study was to characterize HFMD-related isolates by molecular techniques. Settings and Design: Between 2005 and 2008, during two documented HFMD outbreaks, 30 suspected HFMD cases presented at the Outpatient Unit of the Department of Dermatology, Christian Medical College (CMC, Vellore. Seventy-eight clinical specimens (swabs from throat, mouth, rectum, anus, buttocks, tongue, forearm, sole, and foot were received from these patients at the Department of Clinical Virology, CMC, for routine diagnosis of hand, foot, and mouth disease. Materials and Methods: Samples from these patients were cultured in Vero and rhabdomyosarcoma (RD cell lines. Isolates producing enterovirus-like cytopathogenic effect (CPE in cell culture were identified by a nested reverse transcription-based polymerase chain reaction (RT-PCR and sequenced. The nucleotide sequences were analyzed using the BioEdit sequence program. Homology searches were performed using the Basic Local Alignment Search Tool (BLAST algorithm. Statistical Analysis used: The statistical analysis was performed using Epi Info version 6.04b and Microsoft Excel 2002 (Microsoft Office XP. Results: Of the 30 suspected HFMD cases, only 17 (57% were laboratory confirmed and Coxsackievirus A16 (CVA16 was identified as the etiological agent in all these cases. Conclusions: Coxsackievirus A16 (CVA16 was identified as the virus that caused the HFMD outbreaks in Vellore between 2005 and 2008. Early confirmation of HFMD helps to initiate control measures to interrupt virus transmission. In the laboratory, classical diagnostic methods, culture and serological tests are being replaced by molecular techniques. Routine surveillance systems will help understand the

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

    Science.gov (United States)

    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

  2. Clinical and virological descriptive study in the 2011 outbreak of dengue in the Amazonas, Brazil.

    Directory of Open Access Journals (Sweden)

    Valquiria do Carmo Alves Martins

    Full Text Available Dengue is a vector-borne disease in the tropical and subtropical region of the world and is transmitted by the mosquito Aedes aegypti. In the state of Amazonas, Brazil during the 2011 outbreak of dengue all the four Dengue virus (DENV serotypes circulating simultaneously were observed. The aim of the study was to describe the clinical epidemiology of dengue in Manaus, the capital city of the state of the Amazonas, where all the four DENV serotypes were co-circulating simultaneously.Patients with acute febrile illness during the 2011 outbreak of dengue, enrolled at the Fundação de Medicina Tropical Dr. Heitor Viera Dourado (FMT-HVD, a referral centre for tropical and infectious diseases in Manaus, were invited to participate in a clinical and virological descriptive study. Sera from 677 patients were analyzed by RT-nested-PCRs for flaviviruses (DENV 1-4, Saint Louis encephalitis virus-SLEV, Bussuquara virus-BSQV and Ilheus virus-ILHV, alphavirus (Mayaro virus-MAYV and orthobunyavirus (Oropouche virus-OROV.Only dengue viruses were detected in 260 patients (38.4%. Thirteen patients were co-infected with more than one DENV serotype and six (46.1% of them had a more severe clinical presentation of the disease. Nucleotide sequencing showed that DENV-1 belonged to genotype V, DENV-2 to the Asian/American genotype, DENV-3 to genotype III and DENV-4 to genotype II.Co-infection with more than one DENV serotype was observed. This finding should be warning signs to health authorities in situations of the large dispersal of serotypes that are occurring in the world.

  3. Coping – Late Side Effects

    Science.gov (United States)

    Cancer treatment can cause late side effects that may not show up for months or years after treatment. These late effects may include heart and lung problems, bone loss, eye and hearing changes, lymphedema, and other problems

  4. Epidemiological and virological assessment of influenza activity in Europe, during the winter 2005-2006.

    NARCIS (Netherlands)

    Meijer, A.; Meerhoff, T.J.; Meuwissen, L.E.; Velden, J. van der; Paget, W.J.

    2007-01-01

    Influenza activity in Europe during the winter 2005-2006 started late January - early February 2006 and first occurred in the Netherlands, France, Greece and England. Subsequently, countries were affected in a random pattern across Europe and the period of influenza activity lasted till the end of

  5. Response in the late phase to a radiological emergency

    International Nuclear Information System (INIS)

    Morrey, M.; Nisbet, A.; Thome, D.; Savkin, M.; Hoe, S.; Brynildsen, L.

    2004-01-01

    This paper looks at the key issues that need to be addressed during the transition from the emergency phase to the late phase of a radioactive release, and the development of the initial late phase strategy. It discusses the extent to which current national plans and international advice address the needs of decision makers following contamination of inhabited areas and food production systems. Based on this the following recommendations are made: (1) the issues that will arise at the start of the late phase response to a radioactive release require preparation work in advance of any release; (2) this preparation should consider the adequacy of legislation, technical data and modelling, options for waste storage and disposal, resources for monitoring and implementing clean up; (3) late phase preparedness requires regular exercising and (4) the possibility of terrorist releases adds further emphasis to the need for preparedness for the late phase. (authors)

  6. Late induced abortion.

    Science.gov (United States)

    Savage, W

    1990-09-01

    In the UK in 1988, 13.3% of abortions were performed at 13 weeks' gestation or later. Reasons for this delay, in addition to the diagnosis through amniocentesis of a fetal abnormality, include late recognition of pregnancy, a change of mind about completing the pregnancy, a failure of primary care physicians to entertain the diagnosis of pregnancy, travel or financial problems, and referral difficulties and scheduling delays. Women with little education and very young women are most likely to present for late abortions. From 13-16 weeks, dilatation and evacuation is the safest method of pregnancy termination. The procedure can be made easier through preparation of the cervix with a prostaglandin pessary or Foley catheter. After 16 weeks, an instillation method is recommended; prostaglandin administration can be intro- or extra-amniotic. Complication rates at 13-19 weeks are 14.5/1000 for vaginal methods of abortion and 7.2/1000 for prostaglandin methods. The risk of complications is 3 times higher for women who have 2nd-trimester abortions through the National Health Service. Although it is not realistic to expect that late abortions ever can be eliminated, improved sex education and contraceptive reliability as well as reforms in the National Health Service could reduce the number substantially. To reduce delay, it is suggested that the National Health Service set up satellite day care units and 1-2 central units in each region to deal quickly with midtrimester abortions. Delays would be further reduced by legislation to allow abortion on request in at least the 1st trimester of pregnancy.

  7. [Guidelines for monitoring late-onset Pompe disease.Sociedad Española de Medicina Interna (SEMI), Sociedad Española de Neurología (SEN) y Sociedad Española de Neumología y CirugíaTorácica (SEPAR)].

    Science.gov (United States)

    Gutiérrez-Rivas, Eduardo; Illa, Isabel; Pascual-Pascual, Samuel I; Pérez-López, Jordi; Vílchez-Padilla, Juan J; Bautista-Lorite, Juan; Barrot, Emilia; López de Munain, Adolfo

    2015-04-01

    Although treatment with alglucosidase alfa has helped improve the prognosis of patients with late-onset Pompe disease, both the development of the disease and the effectiveness of the treatment need to be monitored on a regular basis. This is the reason that has led a committee of Spanish experts to draw up a series of guidelines on how to follow up these patients. The committee proposes a model of follow-up tests for late-onset Pompe disease. First of all, the nutritional status and swallowing function must be evaluated. Second, and due to the variability of the clinical features, the committee recommends the simultaneous use of several scales to measure different functions and parameters. Thus, muscular force is assessed with the Medical Research Council scale; motor functioning, with the six-minute walk test and timed tests; disability, with the Rasch-built Pompe-specific Activity scale; respiratory functioning, with measurement of the forced vital capacity and oxygen saturation; and fatigue, with the fatigue intensity scale. Lastly, the safety and tolerability of enzyme replacement therapy are controlled by registering and treating the potential side effects and measurement of the anti-alglucosidase alfa antibodies. A number of different general recommendations are also included.

  8. Late Washing efficiency

    International Nuclear Information System (INIS)

    Morrissey, M.F.

    1992-01-01

    Interim Waste Technology has demonstrated the Late Washing concept on the Experimental Laboratory Filter (ELF) at TNX. In two tests, washing reduced the [NO 2 - ] from 0.08 M to approximately 0.01 M on slurries with 2 year equivalent radiation exposures and 9.5 wt. % solids. For both washes, the [NO 2 - ] decreased at rates near theoretical for a constant volume stirred vessel, indicating approximately l00% washing efficiency. Permeate flux was greater than 0.05 gpm/ft 2 for both washes at a transmembrane pressure of 50 psi and flow velocity of 9 ft/sec

  9. Late-onset hypogonadism

    Directory of Open Access Journals (Sweden)

    Piotr Dudek

    2017-06-01

    Full Text Available In Poland, the number of men over the age of 50 years exceeds 6 million. It is estimated that about 2-6% of this population develops symptoms of late-onset hypogonadism (LOH. In men, testosterone deficiency increases slightly with age. LOH is a clinically and biochemically defined disease of older men with serum testosterone level below the reference parameters of younger healthy men and with symptoms of testosterone deficiency, manifested by pronounced disturbances of quality of life and harmful effects on multiple organ systems. Testosterone replacement therapy may give several benefits regarding body composition, metabolic control, and psychological and sexual parameters.

  10. Early and late motherhood

    DEFF Research Database (Denmark)

    Christoffersen, Mogens; Lausten, Mette

    2009-01-01

    The study investigates parental child rearing methods, structural factors relating to the family during adolescence geographic segregation, individual resource deficits and social background of first time late live births among 32 to 37 years old women and compare to teenagers before becoming...... economic and social gradient for first-time teenage mothers. Teenagers who had experienced family separation or who were formerly in out-of-home care in particular had an increased risk of early childbearing. Results showed that teenage mothers were in every respect in a more disadvantaged position than...

  11. Epidemiological and virological investigation of a Norovirus outbreak in a resort in Puglia, Italy

    Directory of Open Access Journals (Sweden)

    Coscia Maria

    2007-11-01

    uncommon practice of saving clinical samples for virological analysis after bacteriological testing.

  12. Early and late arrhythmogenic effects of doxorubicin.

    Science.gov (United States)

    Kilickap, Saadettin; Barista, Ibrahim; Akgul, Ebru; Aytemir, Kudret; Aksoy, Sercan; Tekuzman, Gulten

    2007-03-01

    To determine the incidence of early and late arrhythmogenic effects of doxorubicin-containing chemotherapy regimens. A prospective study including 29 patients who were treated with doxorubicin-containing regimens. Cardiac evaluation was based on 24-hour electrocardiographic monitorization (Holter), which was performed during the first cycle of doxorubicin-containing regimens, as well as after the last cycle of chemotherapy. The mean age of the patients was 45.8 +/- 15.1 (range 18-69). Holter records obtained during the first cycle of treatment revealed varying arrhythmias in 19 patients (65.5%) and in 18 (62.1%) patients after completion of therapy. One patient presented with syncope and both Mobitz Type 2 atrioventricular block and complete atrioventricular block were demonstrated. The patient subsequently underwent permanent pacemaker implantation. Doxorubicin may result in arrhythmias both in early and late periods of treatment. These arrhythmias are rarely life threatening.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  15. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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

  19. Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen.

    Science.gov (United States)

    Piketty, C; Weiss, L; Thomas, F; Mohamed, A S; Belec, L; Kazatchkine, M D

    2001-05-01

    Within a prospective cohort of 150 human immunodeficiency virus (HIV)-infected patients who began first-line protease inhibitor therapy in 1996, the outcome of 42 patients with discrepant virologic and immunologic responses to antiretroviral treatment at 12 months was analyzed at 30 months of treatment. The incidence of AIDS-defining events and deaths (14%) in the group of patients with immunologic responses in the absence of a virologic response was higher than that in full-responder patients (2%); yet, the incidence in this group was lower than that in patients with no immunologic response, despite a virologic response (21%), and was lower than that in patients without an immunologic or virologic response (67%; P<.0001, log-rank test). Differences in outcome were significant (relative risk, 6.9; 95% confidence interval, 1.9-39.3) when factors for progression were compared with those of responder patients. The results support the relevance of the CD4 cell marker over plasma HIV load for predicting clinical outcome in patients who do not achieve full immunologic and virologic responses.

  20. 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.

  1. Late-Modern Symbolism

    DEFF Research Database (Denmark)

    Andersen, Bjørn Schiermer

    2015-01-01

    Through analysis of key texts, I seek to demonstrate the explanative potential of Durkheim’s sociology of religion in the present context. I critically readdress the idea, found in his early work, that modernity is characterized by a rupture with pre-modern forms of solidarity. First, I investigate...... the ways in which Durkheim sets up a stark distinction between the pre-modern and the modern in his early work, and how this distinction is further cemented by his orthodox critique of the modern economy and its negative effects on social life. Second, I show how another timeless and positive understanding...... of “mechanical” solidarity is to be found behind the “symbolist” template crystalizing in Durkheim’s late work. Third, I develop this template for a modern context by critically addressing and removing other obstacles and prejudices on Durkheim’s part....

  2. Late somatic effects

    International Nuclear Information System (INIS)

    Gilbert, E.

    1985-01-01

    A model is provided for estimating risks of late effects resulting from low-LET radiation exposure likely to be received in the event of a nuclear power plant accident. Separate estimates are provided for risks of leukemia, cancers of the bones, lungs, gastrointestinal tract, thyroid, skin, and the residual group of all other cancers; estimates of leukemia and other cancers due to in utero exposure are also provided. Risks are expressed in absolute terms as the number of cancer deaths (or cases) per million persons exposed to a particular dose. In addition, the number of years of life lost and the number of years of life lived after the occurrence of cancer are also estimated. The model used in the earlier Reactor Safety Study has been modified to reflect additional epidemiological data and these changes are described in detail. 37 references, 1 figure, 13 tables

  3. 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.

  4. 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.

  5. 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

  6. 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.

    Science.gov (United States)

    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.

  7. 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...

  8. Late Carboniferous to Late Permian carbon isotope stratigraphy

    DEFF Research Database (Denmark)

    Buggisch, Werner; Krainer, Karl; Schaffhauser, Maria

    2015-01-01

    An integrated study of the litho-, bio-, and isotope stratigraphy of carbonates in the Southern Alps was undertaken in order to better constrain δ13C variations during the Late Carboniferous to Late Permian. The presented high resolution isotope curves are based on 1299 δ13Ccarb and 396 δ13Corg...

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

    Science.gov (United States)

    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.

  10. 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...

  11. Late arrival in hospital during labour: any correlation with materno ...

    African Journals Online (AJOL)

    Background: Late arrival in labour is a common occurrence in my centre, It has been said to be associated with poor maternal and foetal outcome because of the lack of intrapartum materno-foetal monitoring. It gave me a great concern why booked patients should deliver in vehicles in 21st century. Objectives: Is to ...

  12. The late administration of surfactant

    African Journals Online (AJOL)

    HMD and 4 as having congenital pneumonia. Overall there was a significant and sustained improvement ... 3 infants weighing> 2 400 g with congenital pneumonia responded to a single delayed dose of SRT. Late SRT is ..... pneumonia and meconium aspiration syndrome.' It does not appear that late SRT compromised the ...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. 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...

  19. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 7 CFR 920.112 - Late payments.

    Science.gov (United States)

    2010-01-01

    ... Miscellaneous Provisions § 920.112 Late payments. Pursuant to § 920.41(a), interest will be charged at a 1.5 percent monthly simple interest rate. Assessments for kiwifruit shall be deemed late if not received... late charge will be assessed when payment becomes 30 days late. Interest and late payment charges shall...

  6. 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

  7. 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

  8. 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...

  9. 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

  10. [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.

  11. 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....

  12. 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

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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....

  18. 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.

  19. 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 ...

  20. Vaginal bleeding in late pregnancy

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000627.htm Vaginal bleeding in late pregnancy To use the sharing ... JavaScript. One out of 10 women will have vaginal bleeding during their 3rd trimester. At times, it ...

  1. Late prematurity: a systematic review

    Directory of Open Access Journals (Sweden)

    Luís Carlos Machado Júnior

    2014-06-01

    Full Text Available Objective: this study aimed to review the literature regarding late preterm births (34 weeks to 36 weeks and 6 days of gestation in its several aspects. Sources: the MEDLINE, LILACS, and Cochrane Library databases were searched, and the references of the articles retrieved were also used, with no limit of time. Data synthesis: numerous studies showed a recent increase in late preterm births. In all series, late preterm comprised the majority of preterm births. Studies including millions of births showed a strong association between late preterm birth and neonatal mortality. A higher mortality in childhood and among young adults was also observed. Many studies found an association with several neonatal complications, and also with long-term disorders and sequelae: breastfeeding problems, cerebral palsy, asthma in childhood, poor school performance, schizophrenia, and young adult diabetes. Some authors propose strategies to reduce late preterm birth, or to improve neonatal outcome: use of antenatal corticosteroids, changes in some of the guidelines for early delivery in high-risk pregnancies, and changes in neonatal care for this group. Conclusions: numerous studies show greater mortality and morbidity in late preterm infants compared with term infants, in addition to long-term disorders. More recent studies evaluated strategies to improve the outcomes of these neonates. Further studies on these strategies are needed.

  2. Late effects from hadron therapy

    Energy Technology Data Exchange (ETDEWEB)

    Blakely, Eleanor A.; Chang, Polly Y.

    2004-06-01

    Successful cancer patient survival and local tumor control from hadron radiotherapy warrant a discussion of potential secondary late effects from the radiation. The study of late-appearing clinical effects from particle beams of protons, carbon, or heavier ions is a relatively new field with few data. However, new clinical information is available from pioneer hadron radiotherapy programs in the USA, Japan, Germany and Switzerland. This paper will review available data on late tissue effects from particle radiation exposures, and discuss its importance to the future of hadron therapy. Potential late radiation effects are associated with irradiated normal tissue volumes at risk that in many cases can be reduced with hadron therapy. However, normal tissues present within hadron treatment volumes can demonstrate enhanced responses compared to conventional modes of therapy. Late endpoints of concern include induction of secondary cancers, cataract, fibrosis, neurodegeneration, vascular damage, and immunological, endocrine and hereditary effects. Low-dose tissue effects at tumor margins need further study, and there is need for more acute molecular studies underlying late effects of hadron therapy.

  3. Salt Marshes as Monitors of Late Holocene Outlet Glacier Retreat

    Science.gov (United States)

    Wake, L. M.; Woodroffe, S.; Long, A. J.; Milne, G. A.

    2014-12-01

    New proxy sea-level records extracted from salt marshes in the vicinity of Jakobshavn Isbrae (Pakitsoq; 69.51°N, 50.74°W) and at previous sites in central western Greenland (Sisimiut; 66.47°N, 53.61°W and Aasiaat; 68.69°N, 52.88°W) are analyzed with respect to their ability to act as proximal tide gauges detecting mass balance changes in nearby outlet glaciers associated with the transition from the Little Ice Age ("LIA", 1400-1850AD) to the Industrial Period (>1850AD). Data at Pakitsoq demonstrate that sea-level rose at a rate of 3.5 ±1.7 mm/yr prior to 1850AD and slowed to 0.3 ±0.6mm/yr thereafter, producing a slowdown in sea level of 3.2 ± 1.8 mm/yr. A similar slowdown, occurring at 1600AD, is observed at Aasiaat and Sisimiut. We interpret these observed changes using a glacial isostatic adjustment model of sea-level change truncated at degree and order 4096, with an aim to determine if the sea-level data can be used to place constraints on changes in Jakobshavn Isbrae and/or Kangiata Nunaata Sermia (Nuuk fjord) during this period. Modelled sea level at Pakitsoq is insensitive to the location of thickening (thinning) associated with grounding line advance (retreat) and the rate of advance and retreat but is sensitive to the change point in time between periods of growth associated with LIA expansion (sea level rise) and the onset of 19th century recession (sea level fall) of Jakobshavn Isbrae. We conclude that the change in sea-level rate observed at Pakitsoq circa 1850AD marks the onset of post LIA retreat of this outlet glacier. Conversely, the modelled sea-level response to the retreat of Kangiata Nunaata Sermia from its LIA maximum at ca. 1761AD is below the detection threshold of the salt marsh record at Sisimiut.

  4. 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

    Directory of Open Access Journals (Sweden)

    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

  5. 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.

  6. Late toxicity in breast cancer radiotherapy

    International Nuclear Information System (INIS)

    Gonzalez Coletti, F.; Rafailovici, L.; Filomia, M.L.; Chiozza, J.; Dosoretz, B.

    2008-01-01

    Full text: The aim of this study is to describe and classify chronic complications due to radiotherapy in breast cancer. Also the impact of radiotherapy on the quality of life of patients is evaluated. Materials and methods: 50 patients with breast cancer at early stages (78% in situ, 22% I and II) treated with radiotherapy in breast volume plus boost (45/50 Gy + 18/20 Gy) with a follow up over 5 years. Acute toxicities were found retrospectively and chronic toxicities were assessed though physical examination and review of complementary studies. To facilitate data collection, pre printed forms were used. Bibliographic searches were made. Results: 10% received chemotherapy and 64% tamoxifen. The predominant chronic toxicity were found in skin (66%), although grade I and II (hyperpigmentation 26%, dryness 22%, telangiectasia 10% fibrosis, 4%, other 4%). A 50% of the patients showed hypoesthesia in ipsilateral upper limb. The other toxicities were presented in low rate and magnitude: mastodynia 16%; actinic pneumonitis 4%, pyrosis 4%, Tachycardia 2%, among others. Of the patients with acute toxicity, only 30% were grade III. The 70% of the patients had a positive impact of radiotherapy on quality of life. Conclusions: We found low rates and degrees of late toxicity. It was noticed a relationship between acute and chronic toxicity, because those who presented adverse effects during treatment developed late effects. It reflects the importance of integrating monitoring as part of radiation treatment. It should be adopted a single score of late toxicity measurement to unify data from different series. (authors) [es

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  9. Factors Associated with Low-Level Viraemia and Virological Failure: Results from the Austrian HIV Cohort Study.

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    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.

  10. 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

  11. Recent casualties of late globalization

    DEFF Research Database (Denmark)

    Turcan, Romeo V.

    2016-01-01

    In this essay I will expand my thoughts on universities as ‘late globalizers’ and the impact ‘being late’ has on university internationalization or globalization activities. In my earlier essay I viewed universities as ‘late globalizers’ and briefly introduced the impact of being ‘late’, e.g., wi.......g., withdrawal or de-internationalization of universities due to incompatibility between university autonomy and the context in the target country or universities unwillingness to compromise on their freedom and autonomy....

  12. Eco-virological survey of Aedes mosquito larvae in selected dengue outbreak areas in Malaysia.

    Science.gov (United States)

    Rohani, A; Aidil Azahary, A R; Malinda, M; Zurainee, M N; Rozilawati, H; Wan Najdah, W M A; Lee, H L

    2014-12-01

    BACKGROUND & OBJECTIVESI: Transovarial transmission of dengue virus in the Aedes vectors is now a well-documented phenomenon reported from many parts of the endemic areas in the world, which played an important role in initiating and maintaining the outbreak in human populations. This study investigated the factors affecting breeding habitats and the relationship with transovarial dengue virus in larvae of Aedes aegypti and Ae. albopictus. Larval surveillance was conducted in dengue outbreak areas in Malaysia from 2008 until 2009. Sampling was carried out based on habitat type, water condition (substrate type), canopy coverage, temperature and pH at breeding habitats. RT-PCR was performed to detect presence of transovarial dengue virus in larvae collected in the study areas. A total of 789 breeding habitats were identified during this study and the majority of these breeding sites were plastic containers (57.46%). Aedes albopictus dominated most of the water condition surveyed, while Ae. aegypti indicated preference toward habitats with clear water. Aedes aegypti was selective in selecting ovipositional sites compared to Ae. albopictus where shaded areas were shown to be the most preferred. From a total of 363 mosquito larvae pools, 23 (6.3%) pools were positive for dengue virus where 18 of them were from Ae. albopictus and five were from Ae. aegypti mosquito larvae pools. This study indicated the presence of transovarial transmission of dengue virus in immature Ae. aegypti and Ae. albopictus in the field. This study also showed that combination of water conditions, canopy coverage, temperature and pH of breeding habitats were the factors affecting the larval population. The study suggested that larval survey programme could serve as a tool not only to monitor the local dengue vector distribution but also to provide objective information for taking appropriate action by the community against dengue vectors.

  13. 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...

  14. Two years of surveillance of influenza a virus infection in a swine herd. Results of virological, serological and pathological studies.

    Science.gov (United States)

    Cappuccio, Javier; Dibarbora, Marina; Lozada, Inés; Quiroga, Alejandra; Olivera, Valeria; Dángelo, Marta; Pérez, Estefanía; Barrales, Hernán; Perfumo, Carlos; Pereda, Ariel; Pérez, Daniel R

    2017-02-01

    Swine farms provide a dynamic environment for the evolution of influenza A viruses (IAVs). The present report shows the results of a surveillance effort of IAV infection in one commercial swine farm in Argentina. Two cross-sectional serological and virological studies (n=480) were carried out in 2011 and 2012. Virus shedding was detected in nasal samples from pigs from ages 7, 21 and 42-days old. More than 90% of sows and gilts but less than 40% of 21-days old piglets had antibodies against IAV. In addition, IAV was detected in 8/17 nasal swabs and 10/15 lung samples taken from necropsied pigs. A subset of these samples was further processed for virus isolation resulting in 6 viruses of the H1N2 subtype (δ2 cluster). Pathological studies revealed an association between suppurative bronchopneumonia and necrotizing bronchiolitis with IAV positive samples. Statistical analyses showed that the degree of lesions in bronchi, bronchiole, and alveoli was higher in lungs positive to IAV. The results of this study depict the relevance of continuing long-term active surveillance of IAV in swine populations to establish IAV evolution relevant to swine and humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. PENGAMATAN SERO—VIROLOGI BEBERAPA JENIS ANTIGEN VIRUS PADA SERUM TALIPUSAT BAYI DI RS. CIPTO MANGUNKUSUMO, JAKARTA

    Directory of Open Access Journals (Sweden)

    Djoko Yuwono

    2012-09-01

    Full Text Available Perinatal infection due to viral agents from mother to neonate is still a major cause of viral transmis­sion in developing countries. Several type of viruses which are known to be transmitted vertieally or perinatally from mother to neonates are: Hepatitis B virus, Herpes simplex, Rubella and Cytomegalovi­rus. In attempt to estimate the real problem of viral diseases which are vertically or perinatally transmis­sible among infants, a survey on sero-virology of several type viral antigens among neonates who were borned in Dr. Cipto Mangunkusumo hospital, was carried out. A total of 227 blood samples of umbillical cord were examined for the presence of their viral anti­gens such as: Hepatitis B surface antigen (HBsAg, Herpes simplex type 1 and type 2, and anti-rubella IgM as an indicator of early infection due to rubella virus in the fetus. The detection of antigens and anti-rubella IgM in the serum.were done by ELISA methode using reagents which are commercially available. The result of the study indicated that there was a possibility of perinatal infection due to related viruses, i.e.: 2.2%; 1.9% and 14.3% due to HBsAg; Herpes simplex type 1 and type 2 respectivelly, however none of the serum indicated seropositive IgM against rubella virus: infection.

  16. HTLV-3/4 and simian foamy retroviruses in humans: discovery, epidemiology, cross-species transmission and molecular virology.

    Science.gov (United States)

    Gessain, Antoine; Rua, Réjane; Betsem, Edouard; Turpin, Jocelyn; Mahieux, Renaud

    2013-01-05

    Non-human primates are considered to be likely sources of viruses that can infect humans and thus pose a significant threat to human population. This is well illustrated by some retroviruses, as the simian immunodeficiency viruses and the simian T lymphotropic viruses, which have the ability to cross-species, adapt to a new host and sometimes spread. This leads to a pandemic situation for HIV-1 or an endemic one for HTLV-1. Here, we present the available data on the discovery, epidemiology, cross-species transmission and molecular virology of the recently discovered HTLV-3 and HTLV-4 deltaretroviruses, as well as the simian foamy retroviruses present in different human populations at risk, especially in central African hunters. We discuss also the natural history in humans of these retroviruses of zoonotic origin (magnitude and geographical distribution, possible inter-human transmission). In Central Africa, the increase of the bushmeat trade during the last decades has opened new possibilities for retroviral emergence in humans, especially in immuno-compromised persons. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Evaluation of Virological Microparticle Enzyme Immunoassay According to the ISO 15189: Real-Life Experience in a University Hospital.

    Science.gov (United States)

    Lafontaine, Sophie; Prin-Mathieu, Christine; Velay, Aurélie; Agulles, Odette; Schvoerer, Evelyne; Jeulin, Hélène

    2016-01-01

    The International Standard ISO 15189 based on the ISO 9001:2008 emphasizes specific requirements for quality and ability of medical laboratories. The accreditation of medical laboratories according to ISO 15189 includes the validation of biological methods, which depends on collection of bibliographic data and experimental proofs. Moreover, these results must be compared to provider data sheets and independent scientific data. In the immunodiagnostic field, independent published data are deeply lacking. The aim of our work was to share experience of method validation for virological immune markers on the widely used Architect i2000sr. After risk analysis, intra- and inter-assay variability, and inter-sample contamination were evaluated for each method, and sensitivity was investigated for antigen detection tests. A comparison between the two Architect i2000sr available in our laboratory was also performed. All tested methods were consistent with the manufacturer data (from the data sheet). No inter-sample contamination was observed. Both devices are broadly equivalent and can be used indifferently or as a backup solution of the other. To our knowledge, those results are the first independent complete data on the reliability of the Architect i2000sr in real-life experience. These data are needed to the accreditation of our platform and potentially useful for the accreditation of other laboratories using the same equipment.

  18. 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.

  19. 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...

  20. 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...

  1. Epidemiological and Virological Characteristics of Influenza Viruses Circulating in Cambodia from 2009 to 2011

    Science.gov (United States)

    Ly, Sovann; Heng, Seng; Vong, Sirenda; Kitsutani, Paul; Ieng, Vannra; Tarantola, Arnaud; Ly, Sowath; Sar, Borann; Chea, Nora; Sokhal, Buth; Barr, Ian; Kelso, Anne; Horwood, Paul F.; Timmermans, Ans; Hurt, Aeron; Lon, Chanthap; Saunders, David; Ung, Sam An; Asgari, Nima; Roces, Maria Concepcion; Touch, Sok; Komadina, Naomi; Buchy, Philippe

    2014-01-01

    Background The Cambodian National Influenza Center (NIC) monitored and characterized circulating influenza strains from 2009 to 2011. Methodology/Principal Findings Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from patients who fulfilled case definitions for influenza-like illness, acute lower respiratory infections and event-based surveillance. Each year in Cambodia, influenza viruses were detected mainly from June to November, during the rainy season. Antigenic analysis show that A/H1N1pdm09 isolates belonged to the A/California/7/2009-like group. Circulating A/H3N2 strains were A/Brisbane/10/2007-like in 2009 before drifting to A/Perth/16/2009-like in 2010 and 2011. The Cambodian influenza B isolates from 2009 to 2011 all belonged to the B/Victoria lineage represented by the vaccine strains B/Brisbane/60/2008 and B/Malaysia/2506/2004. Sequences of the M2 gene obtained from representative 2009–2011 A/H3N2 and A/H1N1pdm09 strains all contained the S31N mutation associated with adamantanes resistance except for one A/H1N1pdm09 strain isolated in 2011 that lacked this mutation. No reduction in the susceptibility to neuraminidase inhibitors was observed among the influenza viruses circulating from 2009 to 2011. Phylogenetic analysis revealed that A/H3N2 strains clustered each year to a distinct group while most A/H1N1pdm09 isolates belonged to the S203T clade. Conclusions/Significance In Cambodia, from 2009 to 2011, influenza activity occurred throughout the year with peak seasonality during the rainy season from June to November. Seasonal influenza epidemics were due to multiple genetically distinct viruses, even though all of the isolates were antigenically similar to the reference vaccine strains. The drug susceptibility profile of Cambodian influenza strains revealed that neuraminidase inhibitors would be the drug of choice for

  2. Late onset globoid cell leukodystrophy.

    OpenAIRE

    Grewal, R P; Petronas, N; Barton, N W

    1991-01-01

    A 29 year old male with onset of globoid cell leukodystrophy at age 14 is described. This is the first case of enzymatically confirmed globoid cell leukodystrophy with onset of symptoms after the age of ten. This patient is unique because of the late onset and slow progression and extends the clinical spectrum of globoid cell leukodystrophy.

  3. Late onset globoid cell leukodystrophy.

    Science.gov (United States)

    Grewal, R P; Petronas, N; Barton, N W

    1991-11-01

    A 29 year old male with onset of globoid cell leukodystrophy at age 14 is described. This is the first case of enzymatically confirmed globoid cell leukodystrophy with onset of symptoms after the age of ten. This patient is unique because of the late onset and slow progression and extends the clinical spectrum of globoid cell leukodystrophy.

  4. Early and Late Retirement Exits

    Science.gov (United States)

    Brougham, Ruby R.; Walsh, David A.

    2009-01-01

    The current study proposes that personal need fulfillment (relatedness, generativity, identity, growth, and finances) predicts early and late retirement intentions. The personal needs of 160 full-time older employees were measured by personal goals, job satisfactions, job characteristics, and intrinsic motivation. Results suggest that the personal…

  5. Late onset startle induced tics

    NARCIS (Netherlands)

    Tijssen, MAJ; Brown, P; Morris, HR; Lees, A

    1999-01-01

    Three cases of late onset Gilles de la Tourette's syndrome are presented. The motor ties were mainly induced by an unexpected startling stimulus, but the startle reflex was not exaggerated. The ties developed after physical trauma or a period of undue emotional stress. Reflex ties may occur in

  6. Late onset startle induced tics

    NARCIS (Netherlands)

    Tijssen, M. A.; Brown, P.; Morris, H. R.; Lees, A.

    1999-01-01

    Three cases of late onset Gilles de la Tourette's syndrome are presented. The motor tics were mainly induced by an unexpected startling stimulus, but the startle reflex was not exaggerated. The tics developed after physical trauma or a period of undue emotional stress. Reflex tics may occur in

  7. 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.

  8. 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.

  9. 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.

    Science.gov (United States)

    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.

  10. 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.

  11. 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.

  12. 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....

  13. Radiation monitoring

    International Nuclear Information System (INIS)

    Larsson, L.Eh.; B'yuli, D.K.; Karmikel, Dzh.Kh.E.

    1985-01-01

    Recommendations on radiation monitoring of personnel, used medical ionizing radiation source, are given. The necessity to carry out radiation monitoring of situation at medical personnel's positions and personnel dosimetry is marked. It is convenient to subdivide radiation monitoring into 3 types: usual, surgical and special. Usual monitoring is connected with current work; surgical monitoring is carried out to receive information during a concrete operation; special monitoring is used to detect possible deviation from standard conditions of work or when suspecting them

  14. 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

  15. 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

  16. 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

  17. Late baryogenesis faces primordial nucleosynthesis

    International Nuclear Information System (INIS)

    Delbourgo-Salvador, P.; Audouze, J.; Salati, P.

    1991-11-01

    Since the sphalleron mechanism present in the standard theory of electro-weak interactions violates B+L, models have been suggested where baryogenesis takes place at late epochs and is concomitant with primordial nucleosynthesis. The possibility for the baryon asymmetry to be generated was numerically investigated at the same time as the light elements are cooked. The primordial yields of D, 3 He, 4 He and 7 Li were shown to exceed the upper limits inferred from observation, unless baryogenesis is anterior to the freeze-out of the weak interactions. This implies strong constraints on scenarios where the baryon asymmetry originates from the late decay of massive gravitinos. (author) 18 refs., 6 figs

  18. 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.

  19. African Ancestry Influences CCR5 –2459G>A Genotype-Associated Virologic Success of Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Cheruvu, Vinay K.; Igo, Robert P.; Jurevic, Richard J.; Serre, David; Zimmerman, Peter A.; Rodriguez, Benigno; Mehlotra, Rajeev K.

    2014-01-01

    Introduction In a North American, HIV-positive, highly active antiretroviral therapy (HAART)-treated, adherent cohort of self-identified white and black patients, we previously observed that chemokine (C-C motif) receptor 5 (CCR5) –2459G>A genotype had a strong association with time to achieve virologic success (TVLS) in black but not in white patients. Methods Using 128 genome-wide ancestry informative markers, we performed a quantitative assessment of ancestry in these patients (n = 310) to determine (1) whether CCR5 –2459G>A genotype is still associated with TVLS of HAART when ancestry, not self-identified race, is considered and (2) whether this association is influenced by varying African ancestry. Results We found that the interaction between CCR5 –2459G>A genotype and African ancestry (≤0.125 vs. ≥0.425 and A genotype and TVLS was stronger in patients with African ancestry ≥0.71 than in patients with African ancestry ≥0.452, in both Kaplan-Meier (log-rank P = 0.039 and 0.057, respectively, for AA, GA, and GG) and Cox proportional hazards regression (relative hazard for GG compared with AA 2.59 [95% CI, 1.27–5.22; P = 0.01] and 2.26 [95% CI, 1.18–4.32; P = 0.01], respectively) analyses. Conclusions We observed that the association between CCR5 –2459G>A genotype and TVLS of HAART increased with stronger African ancestry. Understanding the genomic mechanisms by which African ancestry influences this association is critical, and requires further studies. PMID:24714069

  20. 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.

  1. Virological surveillance and preliminary antigenic characterization of influenza viruses in pigs in five European countries from 2006 to 2008.

    Science.gov (United States)

    Kyriakis, C S; Brown, I H; Foni, E; Kuntz-Simon, G; Maldonado, J; Madec, F; Essen, S C; Chiapponi, C; Van Reeth, K

    2011-03-01

    This study presents the results of the virological surveillance for swine influenza viruses (SIVs) in Belgium, UK, Italy, France and Spain from 2006 to 2008. Our major aims were to clarify the occurrence of the three SIV subtypes - H1N1, H3N2 and H1N2 - at regional levels, to identify novel reassortant viruses and to antigenically compare SIVs with human H1N1 and H3N2 influenza viruses. Lung tissue and/or nasal swabs from outbreaks of acute respiratory disease in pigs were investigated by virus isolation. The hemagglutinin (HA) and neuraminidase (NA) subtypes were determined using standard methods. Of the total 169 viruses, 81 were classified as 'avian-like' H1N1, 36 as human-like H3N2 and 47 as human-like H1N2. Only five novel reassortant viruses were identified: two H1N1 viruses had a human-like HA and three H1N2 viruses an avian-like HA. All three SIV subtypes were detected in Belgium, Italy and Spain, while only H1N1 and H1N2 viruses were found in UK and Northwestern France. Cross-hemagglutination inhibition (HI) tests with hyperimmune sera against selected older and recent human influenza viruses showed a strong antigenic relationship between human H1N1 and H3N2 viruses from the 1980s and H1N2 and H3N2 human-like SIVs, confirming their common origin. However, antisera against human viruses isolated during the last decade did not react with currently circulating H1 or H3 SIVs, suggesting that especially young people may be, to some degree, susceptible to SIV infections. © 2009 Blackwell Verlag GmbH.

  2. Plasma lopinavir concentrations predict virological failure in a cohort of South African children initiating a protease-inhibitor-based regimen

    Science.gov (United States)

    Moholisa, Retsilisitsoe R; Schomaker, Michael; Kuhn, Louise; Meredith, Sandra; Wiesner, Lubbe; Coovadia, Ashraf; Strehlau, Renate; Martens, Leigh; Abrams, Elaine J; Maartens, Gary; Mcllleron, Helen

    2014-01-01

    Background Poor adherence to antiretroviral therapy contributes to pharmacokinetic variability and is the major determinant of virological failure. However, measuring treatment adherence is difficult, especially in children. We investigated the relationship between plasma lopinavir concentrations, pretreatment characteristics and viral load >400 copies/ml. Methods A total of 237 HIV-infected children aged 4–42 months on lopinavir/ritonavir oral solution were studied prospectively and followed for up to 52 weeks. Viral load and lopinavir concentration were measured at clinic visits 12, 24, 36 and 52 weeks after starting treatment. Cox multiple failure events models were used to estimate the crude and adjusted effect of lopinavir concentrations on the hazard of viral load >400 copies/ml. Results The median (IQR) pretreatment CD4+ T-lymphocyte percentage was 18.80% (12.70–25.35) and 53% of children had a pretreatment viral load >750,000 copies/ml. The median (IQR) weight-for-age and height-for-age z-scores were −2.17 (−3.35–−2.84) and −3.34 (−4.57–−3.41), respectively. Median (IQR) lopinavir concentrations were 8.00 mg/l (4.11–12.42) at median (IQR) 3.50 h (2.67–4.25) after the dose. The hazard of viral load >400 copies/ml was increased with lopinavir concentrations <1 mg/l versus ≥1 mg/l (adjusted hazard ratio 2.3 [95% CI 1.63, 3.26]) and lower height-for-age z-scores. Conclusions Low lopinavir concentrations (<1 mg/l) are associated with viraemia in children. This measure could be used as a proxy for adherence and to determine which children are more likely to fail. PMID:24518130

  3. 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.

  4. Point-of-Care Virologic Testing to Improve Outcomes of HIV-Infected Children in Zambia: A Clinical Trial Protocol.

    Science.gov (United States)

    Chibwesha, Carla J; Ford, Catherine E; Mollan, Katie R; Stringer, Jeffrey S A

    2016-08-01

    In the absence of early infant diagnosis (EID) and immediate antiretroviral therapy (ART), some 50% of untreated HIV-infected infants die before age 2. Conventional EID requires sophisticated instruments that are typically placed in centralized or reference laboratories. In low-resource settings, centralized systems often lead to result turnaround times of several months, long delays in diagnosis, and adverse outcomes for HIV-infected children. Our clinical trial tests the effectiveness of a new point-of-care (POC) diagnostic technology to identify HIV-infected infants and start providing them life-saving ART as soon as possible. The study uses a randomized, controlled design to test whether the Alere q platform for HIV DNA polymerase chain reaction (PCR) testing improves outcomes of HIV-infected children in Zambia. We aim to enroll 2867 HIV-exposed infants aged 4-12 weeks and to follow those who are HIV infected for 12 months as they receive HIV care at 6 public health facilities in Lusaka. The trial's primary endpoint is the proportion of HIV-infected infants in each study arm who start ART and remain alive, in care, and virally suppressed 12 months after their diagnostic blood draw. Our trial will provide evidence for the incremental benefit of implementing a POC EID strategy in low-resource settings where only off-site PCR services are currently available. The results will be useful in guiding future decisions regarding investments in POC virologic testing as part of overall pediatric AIDS mitigation strategies in sub-Saharan Africa. clinicaltrials.gov NCT02682810.

  5. High Rates of Baseline Drug Resistance and Virologic Failure Among ART-naive HIV-infected Children in Mali.

    Science.gov (United States)

    Crowell, Claudia S; Maiga, Almoustapha I; Sylla, Mariam; Taiwo, Babafemi; Kone, Niaboula; Oron, Assaf P; Murphy, Robert L; Marcelin, Anne-Geneviève; Traore, Ban; Fofana, Djeneba B; Peytavin, Gilles; Chadwick, Ellen G

    2017-11-01

    Limited data exist on drug resistance and antiretroviral treatment (ART) outcomes in HIV-1-infected children in West Africa. We determined the prevalence of baseline resistance and correlates of virologic failure (VF) in a cohort of ART-naive HIV-1-infected children baseline (before ART) and at 6 months. Resistance was defined according to the Stanford HIV Genotypic Resistance database. VF was defined as viral load ≥1000 copies/mL after 6 months of ART. Logistic regression was used to evaluate factors associated with VF or death >1 month after enrollment. Post hoc, antiretroviral concentrations were assayed on baseline samples of participants with baseline resistance. One-hundred twenty children with a median age 2.6 years (interquartile range: 1.6-5.0) were included. Eighty-eight percent reported no prevention of mother-to-child transmission exposure. At baseline, 27 (23%), 4 (3%) and none had non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor or protease inhibitor resistance, respectively. Thirty-nine (33%) developed VF and 4 died >1 month post-ART initiation. In multivariable analyses, poor adherence [odds ratio (OR): 6.1, P = 0.001], baseline NNRTI resistance among children receiving NNRTI-based ART (OR: 22.9, P baseline NNRTI resistance (OR: 5.8, P = 0.018) were significantly associated with VF/death. Ten (38%) with baseline resistance had detectable levels of nevirapine or efavirenz at baseline; 7 were currently breastfeeding, but only 2 reported maternal antiretroviral use. Baseline NNRTI resistance was common in children without reported NNRTI exposure and was associated with increased risk of treatment failure. Detectable NNRTI concentrations were present despite few reports of maternal/infant antiretroviral use.

  6. Avian influenza A H5N1 infections in Bali Province, Indonesia: a behavioral, virological and seroepidemiological study.

    Science.gov (United States)

    Santhia, Ketut; Ramy, Ayu; Jayaningsih, Putri; Samaan, Gina; Putra, Anak Agung Gde; Dibia, Nyoman; Sulaimin, Cynthia; Joni, Gusti; Leung, Connie Y H; Sriyal, Joseph; Peiris, Malik; Wandra, Toni; Kandun, Nyoman

    2009-05-01

    Bali Province was affected by avian influenza H5N1 outbreaks in birds in October 2003. Despite ongoing circulation of the virus, no human infection had been identified by December 2005. To assess behavioral patterns associated with poultry rearing in Bali, and to identify potential risk factors for H5N1 infection in humans and in household chickens, ducks and pigs. A behavioral, virological and seroepidemiologic survey in 38 villages and three live bird markets was completed in December 2005. A multi-stage cluster design was used to select 291 households with 841 participants from all nine districts in Bali. Specimens were collected from participants as well as a maximum of three pigs, chickens and ducks from each household. Eighty-seven market vendors participated, where specimens were collected from participants as well as chickens and ducks. Twenty out of the 38 villages sampled had H5N1 outbreaks. Despite exposure to H5N1 outbreaks, none of the participants from villages or markets were seropositive for H5N1. None of the pigs tested were positive for H5N1. Virus isolation rate in ducks and chicken in markets was higher than in households. Transport of poultry in or out of villages was a risk factor for outbreaks in household chickens and ducks. The study highlighted that the market chain and associated behaviors may play a role in maintaining the virus in household flocks. The study adds evidence that transmission of H5N1 to humans remains a rare event despite high level handling of both healthy and sick birds.

  7. Late radiation pathology of mammals

    Energy Technology Data Exchange (ETDEWEB)

    Alexandrov, S N

    1982-01-01

    The comprehensive monograph on delayed radiation effects in mammals including man comprises 3 main chapters dealing with non-neoplastic as well as neoplastic manifestations of late radiation pathology, with the prophylaxis of delayed radiation effects, and with the therapy of radiation injuries. Alterations induced by whole-body irradiation and delayed radiation effects caused by partial body irradiation are described in detail. The developmental mechanisms and pathogenesis of non-neoplastic pathological changes and of radiation-induced neoplasms are elaborated.

  8. LATE NEUROSYPHILIS: TRENDS AND CHALLENGES.

    Directory of Open Access Journals (Sweden)

    Ivan Dimitrov

    2015-09-01

    Full Text Available Background: Syphilis is not only a disease of historical importance. It has been recognized that nowadays, in the era of AIDS, it still remains a serious challenge. For the last two decades there has been a resumption of neurosyphilis cases. This has revived the interest in the diagnostic and therapeutic challenges that the disease presents to clinical practice and to healthcare systems. Material/Methods: We present the overall picture of newly registered cases of syphilis in Varna municipality between 2009 and 2013, and report a case of neurosyphilis diagnosed at the first clinic of neurological diseases of St. Marina University Hospital during this period. Results: For the 5-year period, newly registered cases of syphilis in Varna have shown a tendency towards a decrease. Patients were typically in the early stages of the disease, primary and secondary. Late manifestations dropped from 29 in 2009 to 0 in 2010, but increased again to 15 in 2013. Only 1 case of neurosyphilis was registered during the 5-year period, in 2013. Conclusions: Neurological syndromes observed in cases of late neurosyphilis, presenting in different clinical forms, require a broad spectrum of differential diagnoses. Attention in everyday clinical practice should be focused on these cases which, though rare, are of high medical and social importance. Clinical cases of late neurosyphilis are often atypical and the early consideration of serologic tests or even biopsy may be of critical importance.

  9. The late-M dwarfs

    International Nuclear Information System (INIS)

    Bessell, M.S.

    1991-01-01

    Far-red spectra and VRIJHK photometry have been obtained for a sample of late-M dwarfs selected on the basis of large reduced red magnitudes from the LHS Catalog. Half of the stars in the three faintest 1 mag bins are late-M stars, the other red stars are metallic-hydride subdwarfs. Relations between various colors for the late-M dwarfs are investigated. Of all the colors I - K most reliably correlates with spectral type. FeH bands near 9900 A are clearly seen in the spectra of all dwarf stars later than M5. Two stars cooler than VB10, and similar in temperature to LHS2924 have been identified; both have H-alpha in emission and appear variable in magnitude and R - I color; one is a flare star. The other stars are of earlier spectral type and resemble W359 and VB8. The observed MI, I - K main sequence is in good agreement with the IG theoretical main sequence of Stringfellow, and the faintest stars could be about 0.09 solar mass red dwarfs or lower mass brown dwarfs. 65 refs

  10. Progression of Late-Onset Stargardt Disease.

    Science.gov (United States)

    Lambertus, Stanley; Lindner, Moritz; Bax, Nathalie M; Mauschitz, Matthias M; Nadal, Jennifer; Schmid, Matthias; Schmitz-Valckenberg, Steffen; den Hollander, Anneke I; Weber, Bernhard H F; Holz, Frank G; van der Wilt, Gert Jan; Fleckenstein, Monika; Hoyng, Carel B

    2016-10-01

    Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression as an outcome measure. We performed a retrospective cohort study collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt, defined by clinical phenotype, at least one ABCA4 mutation, and age at disease onset ≥ 45 years. We analyzed RPE atrophy progression on fundus autofluorescence and near-infrared reflectance imaging using semiautomated software and a linear mixed model. We performed sample size calculations to assess the power in a simulated 2-year interventional study and assessed visual endpoints using time-to-event analysis. Over time, progression of RPE atrophy was observed (mean: 0.22 mm/year, 95% confidence interval [CI]: 0.19-0.27). By including only patients with bilateral RPE atrophy in a future trial, 32 patients are needed to reach a power of 83.9% (95% CI: 83.1-84.6), assuming a fixed therapeutic effect size of 30%. We found a median interval between disease onset and visual acuity decline to 20/32, 20/80, and 20/200 of 2.74 (95% CI: 0.54-4.41), 10.15 (95% CI: 6.13-11.38), and 11.38 (95% CI: 6.13-13.34) years, respectively. We show that RPE atrophy represents a robust biomarker to monitor disease progression in future therapeutic trials. In contrast, the variability in terms of the course of visual acuity was high.

  11. Hot Executive Function Following Moderate-to-Late Preterm Birth: Altered Delay Discounting at 4 Years of Age

    Science.gov (United States)

    Hodel, Amanda S.; Brumbaugh, Jane E.; Morris, Alyssa R.; Thomas, Kathleen M.

    2016-01-01

    Interest in monitoring long-term neurodevelopmental outcomes of children born moderate-to-late preterm (32-36 weeks gestation) is increasing. Moderate-to-late preterm birth has a negative impact on academic achievement, which may relate to differential development of executive function (EF). Prior studies reporting deficits in EF in preterm…

  12. Late Effects of Polio: An Overview

    Science.gov (United States)

    ... Polio Wellness Retreats For Health Professionals The Late Effects of Polio: An Overview FRENCH | GERMAN | PORTUGUESE POLIOMYELITIS ( ... largest and most inclusive category is called Late Effects of Polio or Polio Sequelae and is defined ...

  13. Late prematurity: a systematic review

    Directory of Open Access Journals (Sweden)

    Luís Carlos Machado, Júnior

    2014-05-01

    Full Text Available Objective: this study aimed to review the literature regarding late preterm births (34 weeks to 36 weeks and 6 days of gestation in its several aspects. Sources: the MEDLINE, LILACS, and Cochrane Library databases were searched, and the references of the articles retrieved were also used, with no limit of time. Data synthesis: numerous studies showed a recent increase in late preterm births. In all series, late preterm comprised the majority of preterm births. Studies including millions of births showed a strong association between late preterm birth and neonatal mortality. A higher mortality in childhood and among young adults was also observed. Many studies found an association with several neonatal complications, and also with long-term disorders and sequelae: breastfeeding problems, cerebral palsy, asthma in childhood, poor school performance, schizophrenia, and young adult diabetes. Some authors propose strategies to reduce late preterm birth, or to improve neonatal outcome: use of antenatal corticosteroids, changes in some of the guidelines for early delivery in high-risk pregnancies, and changes in neonatal care for this group. Conclusions: numerous studies show greater mortality and morbidity in late preterm infants compared with term infants, in addition to long-term disorders. More recent studies evaluated strategies to improve the outcomes of these neonates. Further studies on these strategies are needed. Resumo: Objetivo: revisar a literatura sobre prematuridade tardia (nascimentos de 34 semanas a 36 semanas e seis dias em seus vários aspectos. Fonte dos dados: buscas nas bases MEDLINE, LILACS e Biblioteca Cochrane, sem limite de tempo, e nas referências bibliográficas dos artigos encontrados. Síntese dos dados: muitos estudos mostram aumento na taxa de prematuridade tardia nos últimos anos. Em todas as séries, os prematuros tardios correspondem à maioria dos nascimentos prematuros. Estudos envolvendo análises de milhões de

  14. Late-onset CMV disease following CMV prophylaxis.

    LENUS (Irish Health Repository)

    Donnelly, C

    2012-02-01

    BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic infection after solid-organ transplantation, increasing morbidity and mortality. Three months of oral valganciclovir have been shown to provide effective prophylaxis. Late-onset CMV disease, occurring after the discontinuation of prophylaxis, is now increasingly recognised. AIMS: To investigate the incidence and the time of detection of CMV infections in liver transplant recipients who received CMV prophylaxis. METHODS: Retrospective review of 64 high- and moderate-risk patients with 1 year of follow-up. RESULTS: The incidence of CMV infection was 12.5%, with 4.7% disease. All cases of symptomatic CMV disease were of late-onset. CONCLUSIONS: The incidence of CMV infections in this study was low compared with literature reports; however, the late-onset disease is an emerging problem. Detection of late-onset disease may be delayed because of less frequent clinic follow-up visits. Increased regular laboratory monitoring may allow earlier detection at the asymptomatic infection stage.

  15. A randomized controlled trial comparing the effects of counseling and alarm device on HAART adherence and virologic outcomes.

    Directory of Open Access Journals (Sweden)

    Michael H Chung

    2011-03-01

    virologic treatment failure during 18-month follow-up, while use of an alarm device had no effect. As antiretroviral treatment clinics expand to meet an increasing demand for HIV care in sub-Saharan Africa, adherence counseling should be implemented to decrease the development of treatment failure and spread of resistant HIV.

  16. 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

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Antibiotics in late clinical development.

    Science.gov (United States)

    Fernandes, Prabhavathi; Martens, Evan

    2017-06-01

    Most pharmaceutical companies have stopped or have severely limited investments to discover and develop new antibiotics to treat the increasing prevalence of infections caused by multi-drug resistant bacteria, because the return on investment has been mostly negative for antibiotics that received marketing approved in the last few decades. In contrast, a few small companies have taken on this challenge and are developing new antibiotics. This review describes those antibiotics in late-stage clinical development. Most of them belong to existing antibiotic classes and a few with a narrow spectrum of activity are novel compounds directed against novel targets. The reasons for some of the past failures to find new molecules and a path forward to help attract investments to fund discovery of new antibiotics are described. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. 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

  6. The regulated secretory pathway in CD4(+ T cells contributes to human immunodeficiency virus type-1 cell-to-cell spread at the virological synapse.

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  9. History of the department of virology and molecular and biological methods of investigation of pediatric research and clinical center for infectious diseases

    Directory of Open Access Journals (Sweden)

    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. 

  10. Nucleocapsid promotes localization of HIV-1 gag to uropods that participate in virological synapses between T cells.

    OpenAIRE

    G Nicholas Llewellyn; Ian B Hogue; Jonathan R Grover; Akira Ono

    2010-01-01

    T cells adopt a polarized morphology in lymphoid organs, where cell-to-cell transmission of HIV-1 is likely frequent. However, despite the importance of understanding virus spread in vivo, little is known about the HIV-1 life cycle, particularly its late phase, in polarized T cells. Polarized T cells form two ends, the leading edge at the front and a protrusion called a uropod at the rear. Using multiple uropod markers, we observed that HIV-1 Gag localizes to the uropod in polarized T cells. ...

  11. Late Onset Bipolar Disorder: Case Report

    OpenAIRE

    Filipa Araújo; Adriana Horta

    2016-01-01

    Background: Bipolar disorder affects approximately 1% of the population, with diagnosis often being made during late adolescence and early adulthood, and only rarely (0.1%) in the elderly. Late onset bipolar disorder in the elderly has a impact on the nature and course of bipolar disorder. Aims: The authors report a case of bipolar disorder emerging in late life  (76years old) with no cleary identified organic cause. Conclusion: This case highlights the importance of a broad different...

  12. Late complications of radiation therapy

    International Nuclear Information System (INIS)

    Masaki, Norie

    1998-01-01

    There are cases in which, although all traces of acute radiation complications seem to have disappeared, late complications may appear months or years to become apparent. Trauma, infection or chemotherapy may sometimes recall radiation damage and irreversible change. There were two cases of breast cancer that received an estimated skin dose in the 6000 cGy range followed by extirpation of the residual tumor. The one (12 y.o.) developed atrophy of the breast and severe teleangiectasis 18 years later radiotherapy. The other one (42 y.o.) developed severe skin necrosis twenty years later radiotherapy after administration of chemotherapy and received skin graft. A case (52 y.o.) of adenoidcystic carcinoma of the trachea received radiation therapy. The field included the thoracic spinal cord which received 6800 cGy. Two years and 8 months after radiation therapy she developed complete paraplegia and died 5 years later. A truly successful therapeutic outcome requires that the patient be alive, cured and free of significant treatment-related morbidity. As such, it is important to assess quality of life in long-term survivors of cancer treatment. (author)

  13. Late Disciform Endotheliitis after LASIK

    Directory of Open Access Journals (Sweden)

    Faik Oruçoğlu

    2013-08-01

    Full Text Available Clinical and imaging features of the patient with late herpetic keratouveitis after LASIK were investigated. A 25-year-old male patient applied with a chief complaint of blurred vision and photophobia in the left eye. He had a history of herpetic keratitits and elsewhere underwent LASIK procedure in 2005. Oral and topical acyclovir treatments were started a week ago when his complaints started. His corrected distance visual acuity was 0.2 and intraocular pressure was 14 mmHg on the left eye. Slit-lamp revealed deep central disciform edema, keratic precipitates, and 2 positive cells in the anterior chamber. Although the patient had myopic LASIK ablation, the central corneal thickness was 652 microns. Scheimpflug imaging was drawing attention to the thickening of the posterior cornea and the keratic precipitates. Sagital and anterior elevation maps were not affected, however, posterior elevation map showed marked central flattening. Asphericity value Q was within normal limits anteriorly (Q=-0.14 and it was in oblate appearance posteriorly (Q=+5.24. In addition to the antiviral medications, a topical dexamethasone treatment was started. The vision improved to 0.6, and the edema was markedly reduced after 4 days of treatment. Scheimpflug imaging parameters were significantly improved. (Turk J Ophthalmol 2013; 43: 282-5

  14. Late complications of radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Masaki, Norie [Osaka Prefectural Center for Adult Diseases (Japan)

    1998-03-01

    There are cases in which, although all traces of acute radiation complications seem to have disappeared, late complications may appear months or years to become apparent. Trauma, infection or chemotherapy may sometimes recall radiation damage and irreversible change. There were two cases of breast cancer that received an estimated skin dose in the 6000 cGy range followed by extirpation of the residual tumor. The one (12 y.o.) developed atrophy of the breast and severe teleangiectasis 18 years later radiotherapy. The other one (42 y.o.) developed severe skin necrosis twenty years later radiotherapy after administration of chemotherapy and received skin graft. A case (52 y.o.) of adenoidcystic carcinoma of the trachea received radiation therapy. The field included the thoracic spinal cord which received 6800 cGy. Two years and 8 months after radiation therapy she developed complete paraplegia and died 5 years later. A truly successful therapeutic outcome requires that the patient be alive, cured and free of significant treatment-related morbidity. As such, it is important to assess quality of life in long-term survivors of cancer treatment. (author)

  15. Severe Anaemia during Late Pregnancy

    Directory of Open Access Journals (Sweden)

    Mahenaz Akhtar

    2012-01-01

    Full Text Available Vitamin B12 deficiency is uncommon in pregnancy, it occurs in 10–28% of uncomplicated pregnancies, and is associated with a few complications. We present a case report of a 21-year-old patient with severe anaemia during late pregnancy caused by vitamin B12 deficiency. At 38 weeks gestation and with a BMI of 48.9, a history of rupture of membranes was given but not confirmed. On examination, she appeared pale and therefore full blood counts were done. Interestingly her haemoglobin (Hb levels were 3.7 g/dL. Folate and vitamin B12 levels were also found to be low, and the diagnosis of anaemia caused by vitamin B12 deficiency was made. After treatment with vitamin B12 injections, folic acid and blood transfusions, the patient’s haemoglobin levels improved from 3.7 g/dL to 10.7 g/dL. The conclusion is that effective history taking, diagnosis, and management can prevent many complications that are usually associated with vitamin B12 deficiency anaemia.

  16. Clozapine-induced late leukopenia.

    LENUS (Irish Health Repository)

    Latif, Z

    2012-03-01

    A patient with a 28-year history of schizophrenia was treated with a wide range of antipsychotic medications since diagnosis. She had experienced no clinically significant symptomatic relief until she commenced treatment on clozapine. Her psychotic symptoms, self care, and general sense of well-being improved significantly. After 6 years of successful treatment, she developed leukopenia and clozapine was discontinued. The following issues will be discussed in the article: rechallenge with clozapine following leukopenia during previous therapy and the choice of and haematological monitoring needs with other antipsychotic medications after clozapine-induced blood dyscrasia.

  17. Personnel monitoring

    International Nuclear Information System (INIS)

    1965-01-01

    This film stresses the need for personnel monitoring in work areas where there is a hazard of exposure to radiation. It illustrates the use of personnel monitoring devices (specially the film dosimeter), the assessment of exposure to radiation and the detailed recording of the results on personnel filing cards

  18. Mobility Monitor

    DEFF Research Database (Denmark)

    Schæbel, Anne-Lise; Dybbro, Karina Løvendahl; Andersen, Lisbeth Støvring

    2015-01-01

    Undersøgelse af digital monitorering af plejehjemsbeboeres vendinger under søvn på Fremtidens Plejehjem, Nørresundby......Undersøgelse af digital monitorering af plejehjemsbeboeres vendinger under søvn på Fremtidens Plejehjem, Nørresundby...

  19. Personnel monitoring

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1966-12-31

    This film stresses the need for personnel monitoring in work areas where there is a hazard of exposure to radiation. It illustrates the use of personnel monitoring devices (specially the film dosimeter), the assessment of exposure to radiation and the detailed recording of the results on personnel filing cards

  20. Childhood abuse in late-life depression

    NARCIS (Netherlands)

    Comijs, Hannie C; van Exel, Eric; van der Mast, Roos C; Paauw, Anna; Oude Voshaar, Richard; Stek, Max L

    Background: Little is known about the role of childhood abuse in late-life depression. The aim of the study is therefore to study whether childhood abuse is associated with late-life depression according to its onset, and which clinical characteristics play a role in this association. Methods: Data

  1. Are we ready to predict late effects?

    DEFF Research Database (Denmark)

    Salz, Talya; Baxi, Shrujal S; Raghunathan, Nirupa

    2015-01-01

    BACKGROUND: After completing treatment for cancer, survivors may experience late effects: consequences of treatment that persist or arise after a latent period. PURPOSE: To identify and describe all models that predict the risk of late effects and could be used in clinical practice. DATA SOURCES:...

  2. Process monitoring

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    Many of the measurements and observations made in a nuclear processing facility to monitor processes and product quality can also be used to monitor the location and movements of nuclear materials. In this session information is presented on how to use process monitoring data to enhance nuclear material control and accounting (MC and A). It will be seen that SNM losses can generally be detected with greater sensitivity and timeliness and point of loss localized more closely than by conventional MC and A systems if process monitoring data are applied. The purpose of this session is to enable the participants to: (1) identify process unit operations that could improve control units for monitoring SNM losses; (2) choose key measurement points and formulate a loss indicator for each control unit; and (3) describe how the sensitivities and timeliness of loss detection could be determined for each loss indicator

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

    Science.gov (United States)

    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.

  4. 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

  5. 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.

  6. Late effects on normal tissues: oesophagus

    International Nuclear Information System (INIS)

    Pavy, J.J.; Bosset, J.F.

    1997-01-01

    Radiation-induced late effects of oesophagus are observed after treatment of various cancers. Acute reactions, mainly oesophagitis, are well known and accurately described; late effects share, for most of these, a common consequence: alteration of the main oesophageal function, namely to conduct the food bolus; clinically they are impaired in terms of mobility and stenosis. More rarely, ulcerations and pseudodiverticulae can be observed. Chemotherapy further increases the risk of late effects, especially in case of concomitant chemo-radiotherapy. All numbers and statistical data on oesophagus late effects should be regarded with caution due to recent changes in the therapeutic attitudes (more and more combined chemotherapy-radiotherapy) and some progress in given cancer locations. A common scale like the LENT-SOMA should enable the clinician to better know these late effects on oesophagus which is required to initiate effective prevention measures and adapted treatments. (authors)

  7. Late Abortion: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Sheng Chiang

    2005-12-01

    Full Text Available Late termination of pregnancy (LTOP is defined as an abortion carried out beyond 24 gestational weeks, when the fetus has arguably attained viability. In Taiwan, the current abortion law, bearing a eugenic title, allows LTOP on certain medical grounds. However, the fetal and maternal conditions that constitute medical grounds are not clarified and remain legally untested. Professional debate on the abortion issue is also lacking in academia in Taiwan, despite societal concerns. With the advent of technology to detect fetal abnormalities, obstetricians are now confronted more frequently with acute dilemmas regarding LTOP. Quite often, they sail in an uncharted sea with no clinical guidelines from their professional societies or affiliated hospitals. Recently, LTOP at 35 gestational weeks for a fetus with Down syndrome, complicated with polyhydramnios and tetralogy of Fallot, triggered media scrutiny and aroused much public attention. Although the clinical decision making for pregnancies with fetal abnormalities entails increasingly balanced information and consideration in terms of the medical, ethical, legal, psychologic, and societal aspects, society at large is unaware of the complexity and intertwined nature of various abortion issues, especially LTOP. Obstetricians are now in a vulnerable position in Taiwanese society, where litigations relevant to the practice of early abortions are not rare. Therefore, a global and in-depth look into abortion issues from legal and ethical dimensions is indispensable for modern obstetric practice. This review considers the core issues in LTOP, including what conditions constitute a “serious” fetal abnormality to justify LTOP, the incidence of LTOP, legislation regarding LTOP in Western countries, and recent research on ambivalent fetal pain. It will also present procedures, some under the auspices of the ethical committee of a Presbyterian hospital in Taiwan, for clinical decision making, particularly

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

    Science.gov (United States)

    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.

  9. Experience of Conducting Microbiology, Virology and Immunology Classes in the Form of the Round Table with Foreign Students, Who are Studying in Ukrainian

    Directory of Open Access Journals (Sweden)

    D.V. Rotar

    2015-09-01

    Full Text Available The article discussed the advantages of active learning methods for foreign students studying in Ukrainian, when studying the subject «Microbiology, virology and Immunology», namely the round table. During these sessions, there is an active exchange of knowledge, the students formed professional ability to express opinions, to argue their reasoning, to justify the proposed decisions and to defend their beliefs, despite the language barrier. At this, there is increased activity, increasing the number of statements, the possibility of individual inclusion of each student in the discussion, increased motivation, non-verbal means of communication, such as facial expressions, gestures, emotional expression, are also included, and all of this subsequently leads to proper consolidation of knowledge.

  10. 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...

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

    DEFF Research Database (Denmark)

    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...

  12. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. Eco-virological approach for assessing the role of wild birds in the spread of avian influenza H5N1 along the central Asian flyway

    Science.gov (United States)

    Newman, Scott H.; Hill, Nichola J.; Spragens, Kyle A.; Janies, Daniel; Voronkin, Igor O.; Prosser, Diann J.; Yan, Baoping; Lei, Fumin; Batbayar, Nyambayar; Natsagdorj, Tseveenmyadag; Bishop, Charles M.; Butler, Patrick J.; Wikelski, Martin; Balachandran, Sivananinthaperumal; Mundkur, Taej; Douglas, David C.; Takekawa, John Y.

    2012-01-01

    A unique pattern of highly pathogenic avian influenza (HPAI) H5N1 outbreaks has emerged along the Central Asia Flyway, where infection of wild birds has been reported with steady frequency since 2005. We assessed the potential for two hosts of HPAI H5N1, the bar-headed goose (Anser indicus) and ruddy shelduck (Tadorna tadorna), to act as agents for virus dispersal along this ‘thoroughfare’. We used an eco-virological approach to compare the migration of 141 birds marked with GPS satellite transmitters during 2005–2010 with: 1) the spatio-temporal patterns of poultry and wild bird outbreaks of HPAI H5N1, and 2) the trajectory of the virus in the outbreak region based on phylogeographic mapping. We found that biweekly utilization distributions (UDs) for 19.2% of bar-headed geese and 46.2% of ruddy shelduck were significantly associated with outbreaks. Ruddy shelduck showed highest correlation with poultry outbreaks owing to their wintering distribution in South Asia, where there is considerable opportunity for HPAI H5N1 spillover from poultry. Both species showed correlation with wild bird outbreaks during the spring migration, suggesting they may be involved in the northward movement of the virus. However, phylogeographic mapping of HPAI H5N1 clades 2.2 and 2.3 did not support dissemination of the virus in a northern direction along the migration corridor. In particular, two subclades (2.2.1 and 2.3.2) moved in a strictly southern direction in contrast to our spatio-temporal analysis of bird migration. Our attempt to reconcile the disciplines of wild bird ecology and HPAI H5N1 virology highlights prospects offered by both approaches as well as their limitations.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Eco-Virological Approach for Assessing the Role of Wild Birds in the Spread of Avian Influenza H5N1 along the Central Asian Flyway

    Science.gov (United States)

    Newman, Scott H.; Hill, Nichola J.; Spragens, Kyle A.; Janies, Daniel; Voronkin, Igor O.; Prosser, Diann J.; Yan, Baoping; Lei, Fumin; Batbayar, Nyambayar; Natsagdorj, Tseveenmyadag; Bishop, Charles M.; Butler, Patrick J.; Wikelski, Martin; Balachandran, Sivananinthaperumal; Mundkur, Taej; Douglas, David C.; Takekawa, John Y.

    2012-01-01

    A unique pattern of highly pathogenic avian influenza (HPAI) H5N1 outbreaks has emerged along the Central Asia Flyway, where infection of wild birds has been reported with steady frequency since 2005. We assessed the potential for two hosts of HPAI H5N1, the bar-headed goose (Anser indicus) and ruddy shelduck (Tadorna tadorna), to act as agents for virus dispersal along this ‘thoroughfare’. We used an eco-virological approach to compare the migration of 141 birds marked with GPS satellite transmitters during 2005–2010 with: 1) the spatio-temporal patterns of poultry and wild bird outbreaks of HPAI H5N1, and 2) the trajectory of the virus in the outbreak region based on phylogeographic mapping. We found that biweekly utilization distributions (UDs) for 19.2% of bar-headed geese and 46.2% of ruddy shelduck were significantly associated with outbreaks. Ruddy shelduck showed highest correlation with poultry outbreaks owing to their wintering distribution in South Asia, where there is considerable opportunity for HPAI H5N1 spillover from poultry. Both species showed correlation with wild bird outbreaks during the spring migration, suggesting they may be involved in the northward movement of the virus. However, phylogeographic mapping of HPAI H5N1 clades 2.2 and 2.3 did not support dissemination of the virus in a northern direction along the migration corridor. In particular, two subclades (2.2.1 and 2.3.2) moved in a strictly southern direction in contrast to our spatio-temporal analysis of bird migration. Our attempt to reconcile the disciplines of wild bird ecology and HPAI H5N1 virology highlights prospects offered by both approaches as well as their limitations. PMID:22347393

  20. 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.

  1. 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.

  2. TLR-4 engagement of dendritic cells confers a BST-2/tetherin-mediated restriction of HIV-1 infection to CD4+ T cells across the virological synapse

    Directory of Open Access Journals (Sweden)

    Blanchet Fabien P

    2013-01-01

    Full Text Available Abstract Background Dendritic cells and their subsets, located at mucosal surfaces, are among the first immune cells to encounter disseminating pathogens. The cellular restriction factor BST-2/tetherin (also known as CD317 or HM1.24 potently restricts HIV-1 release by retaining viral particles at the cell surface in many cell types, including primary cells such as macrophages. However, BST-2/tetherin does not efficiently restrict HIV-1 infection in immature dendritic cells. Results We now report that BST-2/tetherin expression in myeloid (myDC and monocyte-derived dendritic cells (DC can be significantly up-regulated by IFN-α treatment and TLR-4 engagement with LPS. In contrast to HeLa or 293T cells, infectious HIV-1 release in immature DC and IFN-α–matured DC was only modestly affected in the absence of Vpu compared to wild-type viruses. Strikingly, immunofluorescence analysis revealed that BST-2/tetherin was excluded from HIV containing tetraspanin-enriched microdomains (TEMs in both immature DC and IFN-α–matured DC. In contrast, in LPS-mediated mature DC, BST-2/tetherin exerted a significant restriction in transfer of HIV-1 infection to CD4+ T cells. Additionally, LPS, but not IFN-α stimulation of immature DC, leads to a dramatic redistribution of cellular restriction factors to the TEM as well as at the virological synapse between DC and CD4+ T cells. Conclusions In conclusion, we demonstrate that TLR-4 engagement in immature DC significantly up-regulates the intrinsic antiviral activity of BST-2/tetherin, during cis-infection of CD4+ T cells across the DC/T cell virological synapse. Manipulating the function and potency of cellular restriction factors such as BST-2/tetherin to HIV-1 infection, has implications in the design of antiviral therapeutic strategies.

  3. Monitoring Hadoop

    CERN Document Server

    Singh, Gurmukh

    2015-01-01

    This book is useful for Hadoop administrators who need to learn how to monitor and diagnose their clusters. Also, the book will prove useful for new users of the technology, as the language used is simple and easy to grasp.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. LATE VISION: PROCESSES AND EPISTEMIC STATUS

    Directory of Open Access Journals (Sweden)

    Athanassios eRaftopoulos

    2011-12-01

    Full Text Available In this paper, I examine the processes that occur in late vision and address the problem of whether late vision should be construed as a properly speaking perceptual stage, or as a thought-like discursive stage. Specifically, I argue that late vision, its (partly conceptual nature notwithstanding, neither is constituted by nor does it implicate what I call pure thoughts, that is, propositional structures that are formed in the cognitive areas of the brain through, and participate in, discursive reasoning and inferences. At the same time, the output of late vision, namely an explicit belief concerning the identity and category membership of an object (that is, a recognitional belief or its features, eventually enters into discursive reasoning. Using Jackendoff’s distinction between visual awareness, which characterizes perception, and visual understanding, which characterizes pure thought, I claim that the contents of late vision belong to visual awareness and not to visual understanding and that although late vision implicates beliefs, either implicit or explicit, these beliefs are hybrid visual/conceptual constructs and not pure thoughts. Distinguishing between these hybrid representations and pure thoughts and delineating the nature of the representations of late vision lays the ground for examining, among other things, the process of conceptualization that occurs in visual processing and the way concepts modulate perceptual content affecting either its representational or phenomenal character. I also do not discuss the epistemological relations between the representations of late vision and the perceptual judgments they ‘support’, or ‘guide’ or ‘render possible’ or ‘evidence’ or ‘entitle’. However, the specification of the epistemology of late vision lays the ground for attacking that problem as well.

  9. Late Onset Bipolar Disorder: Case Report

    Directory of Open Access Journals (Sweden)

    Filipa Araújo

    2016-07-01

    Full Text Available Background: Bipolar disorder affects approximately 1% of the population, with diagnosis often being made during late adolescence and early adulthood, and only rarely (0.1% in the elderly. Late onset bipolar disorder in the elderly has a impact on the nature and course of bipolar disorder. Aims: The authors report a case of bipolar disorder emerging in late life  (76years old with no cleary identified organic cause. Conclusion: This case highlights the importance of a broad differential diagnosis and pharmacologic management when approaching new-onset manic/depressive symptoms among geriatric patients.

  10. Late washing filter cleaning cycle demonstration

    International Nuclear Information System (INIS)

    Meyer, M.L.; McCabe, D.J.

    1992-01-01

    The DWPF Late Washing Facility will filter cesium and potassium tetraphenyl borate (TPB) solids using a Mott sintered metal filter, identical to the filter now used in the In-tank Precipitation Facility. The purpose of the late wash step is primarily to remove the nitrite salts from the slurry prior to delivery to DWPF. Periodic chemical cleaning of the filter will be required, presumably after each batch although the actual required frequency could not be determined on the lab-scale. Minimization of chemical cleaning solution volumes is key to maximizing the attainment of the Late Wash facility. This report summarizes work completed in experiments designed to identify minimum cleaning solution requirements

  11. 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.

  12. Nephrogenic systemic fibrosis: late skin manifestations

    DEFF Research Database (Denmark)

    Bangsgaard, Nannie; Marckmann, Peter; Rossen, Kristian

    2009-01-01

    BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a serious disease that occurs in patients with severe renal disease and is believed to be caused by gadolinium-containing contrast agents. A detailed description of the late skin manifestations of NSF is important to help dermatologists...... and nephrologists recognize the disease. OBSERVATIONS: We studied 17 patients with NSF late in the disease. All patients showed epidermal atrophy and hairlessness of the affected regions, primarily the lower legs. Affected areas were symmetrically distributed and hyperpigmented in most cases. Eleven patients showed......: This descriptive case series of patients with NSF gives a detailed clinical picture of the skin manifestations late in the disease. It demonstrates that the clinical picture in the late stage has a varied presentation and that NSF has a significant effect on the quality of life....

  13. Late onset depression: A recent update

    Directory of Open Access Journals (Sweden)

    Ananya Mahapatra

    2015-01-01

    Full Text Available Late onset depression has recently emerged as a serious mental health issue in the geriatric population with significant public health implications. It is often challenging to diagnose and treat this entity. Various theories have been postulated to elucidate the etiology of late onset depression, but a unifying hypothesis is lacking. Although the vascular hypothesis is most researched; a complex interaction of multiple vulnerability factors is the current focus of attention. Numerous psychosocial variables have been implicated to play a significant role in predicting the onset and severity of late-life depression. Phenomenological differences have been delineated from depression occurring at a younger age, but the findings are equivocal. A better understanding of the natural trajectory of depression in the elderly is required for early diagnosis and effective treatment. This review attempts to summarize the current status of evidence regarding epidemiology, etiology, clinical features, and treatment options available for late-onset depression.

  14. Early- and Late-Onset Inherited Erythromelalgia

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-08-01

    Full Text Available A genotype-phenotype relationship at the clinical, cellular and molecular levels is shown in a case of erythromelalgia of relatively late onset, in a study at Yale University School of Medicine, and centers in China.

  15. Progression of Late-Onset Stargardt Disease

    OpenAIRE

    Lambertus, Stanley; Lindner, Moritz; Bax, Nathalie M.; Mauschitz, Matthias M.; Nadal, Jennifer; Schmid, Matthias; Schmitz-Valckenberg, Steffen; den Hollander, Anneke I.; Weber, Bernhard H. F.; Holz, Frank G.; van der Wilt, Gert Jan; Fleckenstein, Monika; Hoyng, Carel B.

    2016-01-01

    Purpose: Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression as an outcome measure. Methods: We performed a retrospective cohort study collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt, defined by clinical phenotype...

  16. Overexpression Analysis of emv2 gene coding for Late Embryogenesis Abundant Protein from Vigna radiata (Wilczek

    Directory of Open Access Journals (Sweden)

    Rajesh S.

    2008-10-01

    Full Text Available Late embryogenesis abundant (LEA proteins are speculated to protect against water stress deficit in plants. An over expression system for mungbean late embryogenesis abundant protein, emv2 was constructed in a pET29a vector, designated pET-emv2 which is responsible for higher expression under the transcriptional/translational control of T7/lac promoter incorporated in the Escherichia coli BL21 (DE3.Induction protocol was optimized for pET recombinants harboring the target gene. Overexpressed EMV2 protein was purified to homogeneity and the protein profile monitored by SDS-PAGE.

  17. Treaty Monitoring

    DEFF Research Database (Denmark)

    Canty, M.; Jasani, B.; Lingenfelder, I.

    2009-01-01

    of remote sensing technologies. The book therefore comprises management aspects (issues and priorities of security research, crisis response), applied methodologies and process chains (treaty monitoring, estimation of population densities and characteristics, border permeability models, damage assessment...... companies, national research institutions and international organizations, all of whom were brought together under the aegis of the European research project GMOSS (Global Monitoring for Security and Stability). This book is tailored for the scientific community that deals with the application of EO data...... of civil security. Written for: Scientists, researchers in spatial sciences as well as practitioners, politicians, decision makers at NGO's in the field of security, crisis management, risk assessment and vulnerability....

  18. Quantification of late complications after radiation therapy

    International Nuclear Information System (INIS)

    Jung, Horst; Beck-Bornholdt, Hans-Peter; Svoboda, Vladimir; Alberti, Winfried; Herrmann, Thomas

    2001-01-01

    Background: An increasing number of patients survive cancer after having received radiation therapy. Therefore, the occurrence of late normal tissue complications among long-term survivors is of particular concern. Methods: Sixty-three patients treated by radical surgery and irradiation for rectal carcinoma were subjected to an unconventional sandwich therapy. Preoperative irradiation was given in four fractions of 5 Gy each applied within 2 or 3 days; postoperative irradiation consisted mostly of 15x2 Gy (range, 20-40 Gy). A considerable proportion of these patients developed severe late complications (Radiother Oncol 53 (1999) 177). The data allowed a detailed analysis of complication kinetics, leading to a new model which was tested using data from the literature. Results: Data on late complications were obtained for eight different organs with a follow-up of up to 10 years. For the various organs, the percentage of patients being free from late complications, plotted as a function of time after start of radiation therapy, was adequately described by exponential regression. From the fit, the parameter p a was obtained, which is the percentage of patients at risk in a given year of developing a complication in a given organ during that year. The rate p a remained about constant with time. Following sandwich therapy, the annual incidence of complications in the bladder, ileum, lymphatic and soft tissue, and ureters was about the same (p a =10-14%/year), whereas complications in bone or dermis occurred at lower rates (4.7 or 7.5%/year, respectively). Discussion: Numerous data sets collected from published reports were analyzed in the same way. Many of the data sets studied were from patients in a series where there was a high incidence of late effects. Three types of kinetics for the occurrence of late effects after radiotherapy were identified: Type 1, purely exponential kinetics; Type 2, exponential kinetics, the slope of which decreased exponentially with time

  19. Monitoring apparatus

    International Nuclear Information System (INIS)

    Keats, A.B.

    1981-01-01

    An improved monitoring apparatus for use with process plants, such as nuclear reactors, is described. System failure in the acquisition of data from the plant, owing to stuck signals, is avoided by arranging input signals from transducers in the plant in a test pattern. (U.K.)

  20. Monitor 1979

    International Nuclear Information System (INIS)

    Grisham, D.L.; Ekberg, E.L.; Lambert, J.E.; Meyer, R.E.; Stroik, P.J.; Wickham, M.D.

    1979-01-01

    The status, improvements, and accomplishments of the Monitor remote-handling system previously reported are updated. It also outlines the goals for the future to improve the efficiency and speed of remote-maintenance operations at the Clinton P. Anderson Meson Physics Facility

  1. Monitoring programme

    International Nuclear Information System (INIS)

    1994-06-01

    Her Majesty's Inspectorate of Pollution's 1992 report on its programme of monitoring radioactive substances is presented. Site operators' returns are verified and the report provides independent data on the environmental impact of authorized disposal of radioactive wastes. Radiation doses which may have been received by members of the public, fall well below the International Commission for Radiological Protection's (ICRP) recommended annual doses. (UK)

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

    Science.gov (United States)

    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.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Paradox of Prescribing Late Chemotherapy: Oncologists Explain.

    Science.gov (United States)

    Bluhm, Minnie; Connell, Cathleen M; De Vries, Raymond G; Janz, Nancy K; Bickel, Kathleen E; Silveira, Maria J

    2016-12-01

    The value of chemotherapy for patients with cancer in the last weeks of life warrants examination. Late chemotherapy may not improve survival or quality of life but typically precludes hospice enrollment and may result in additional symptoms, increased use of other aggressive treatments, and worsening quality of life. Few studies have explored oncologists' rationales for administering chemotherapy near death. This study examines the self-reported factors that influence oncologists' decisions about late chemotherapy. In-depth individual interviews were conducted with 17 oncologists through a semistructured interview guide. Interviews were audio recorded and transcribed verbatim. Transcripts were coded and analyzed using conventional content analysis, a qualitative method that allows the detection and analysis of patterns in the data. Clinical factors take priority in determining late chemotherapy decisions when clear treatment choices exist. When clinical factors are ambiguous, emotion becomes a highly salient influence. Oncologists view late chemotherapy to be patient driven and use it to palliate emotional distress and maintain patient hope even when physical benefit is unexpected. Oncologists experience unique and difficult challenges when caring for dying patients, including emotionally draining communication, overwhelming responsibility for life/death, limitations of oncology to heal, and prognostic uncertainty. These challenges are also eased by offering late chemotherapy. The findings reveal a nuanced understanding of why oncologists find it difficult to refuse chemotherapy treatment for patients near death. Optimal end-of-life treatment decisions require supportive interventions and system change, both of which must take into account the challenges oncologists face.

  6. The polyimage poetics in Ibsen's late plays

    Directory of Open Access Journals (Sweden)

    Wang Yuli

    2015-02-01

    Full Text Available The unique poetics of polyimage implied in Ibsen’s late plays can be excavated with aesthetic reading. The term polyimage is coined to describe Ibsen’s original design in aesthetic form and ingenious realm in aesthetic reaction in his late plays; that is, beyond an imagery realm, another imagery realm exists, which construct a deep vision of significance. In each of the excellent late plays, what Ibsen creates is one or more veiled holistic imagery realms in addition to an ordinary entire imagery realm perceived by most audiences. The “layers of imagery realm” result from Ibsen’s “double self-examinations”, including self-examination of soul and of art. It is these “double self-examinations” that make polyimage possible in his late plays and generates the attribute of “meta-art” in these works. Compared with polyphony in Dostoevsky’s novels, the polyimage in Ibsen’s late plays contains a unique modernity, which is of great significance to modern artistic creation.

  7. Pathological review of late cerebral radionecrosis

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko

    2008-01-01

    Late cerebral radionecrosis may be considered to be a specific chronic inflammatory response, although it is unknown whether the initial damage by brain irradiation is to an endothelial cell or a glial cell. I discuss the pathological specificity of late cerebral radionecrosis by studying the published literature and a case that I experienced. In late cerebral radionecrosis, there are typical coagulation necrosis areas containing fibrinoid necrosis with occlusion of the lumina and poorly active inflammatory areas with many inflammatory ghost cells, focal perivascular lymphocytes, hyalinized vessels, and telangiectatic vascularization near and in the necrotic tissue, and more active inflammatory areas formed as a partial rim of the reactive zone by perivascular lymphocytes, much vascularization, and glial fibrillary acidic protein (GFAP)-positive astrocytes at the corticomedullary border adjacent to necrotic tissue in the white matter. It is difficult to believe that coagulation necrosis occurs without first disordering the vascular endothelial cells because fibrinoid necrosis is a main feature and a diffusely multiple lesion in late cerebral radionecrosis. Because various histological findings do develop, progress, and extend sporadically at different areas and times in the irradiated field of the brain for a long time after radiation, uncontrolled chronic inflammation containing various cytokine secretions may also play a key role in progression of this radionecrosis. Evaluation of the mechanism of the development/aggravation of late cerebral radionecrosis requires a further study for abnormal cytokine secretions and aberrant inflammatory reactions. (author)

  8. Early- versus Late-Onset Dysthymia

    Science.gov (United States)

    Sansone, Lori A.

    2009-01-01

    In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared to those with late-onset dysthymia, early-onset patients are more likely to harbor psychiatric comorbidity both on Axis I and II, exhibit less psychological resilience, and have more prominent family loadings for mood disorders. These findings suggest that this distinction is meaningful and that the early-onset subtype of dysthymia is more difficult to effectively treat. PMID:20049145

  9. Mobile ICT Acceptance in Late Adopter Countries

    DEFF Research Database (Denmark)

    Gimpel, Gregory; Sudzina, Frantisek; Petrovcikova, Katarina

    2014-01-01

    Despite the rapid global diffusion of the smartphone, some countries have experienced much slower uptake of the technology. The low smartphone penetration within Slovakia provides the opportunity to explore what drives smartphone use in late majority countries. Slovakia is a central European nation...... and part of the Eurozone. It has advanced telecommunications infrastructure and is subject to the same telecommunications regulations as other EU members. While neighbours have high smartphone penetration, Slovakia is a late majority adopter. This study uses Triandis’ theory of interpersonal behavior...... to investigate the question: What drives the use of smartphones in late majority countries? By studying the differences between current and potential smartphone users, the study revisits Karahanna et al.’s research question: Do potential adopters and users of IT hold the same behavioral and normative beliefs...

  10. Climate predictors of late quaternary extinctions

    DEFF Research Database (Denmark)

    Nogués-Bravo, David; Ohlemüller, Ralf; Batra, Persaram

    2010-01-01

    Between 50,000 and 3,000 years before present (BP) 65% of mammal genera weighing over 44 kg went extinct, together with a lower proportion of small mammals. Why species went extinct in such large numbers is hotly debated. One of the arguments proposes that climate changes underlie Late Quaternary...... extinctions, but global quantitative evidence for this hypothesis is still lacking. We test the potential role of global climate change on the extinction of mammals during the Late Quaternary. Our results suggest that continents with the highest climate footprint values, in other words, with climate changes...... of greater magnitudes during the Late Quaternary, witnessed more extinctions than continents with lower climate footprint values, with the exception of South America. Our results are consistent across species with different body masses, reinforcing the view that past climate changes contributed to global...

  11. Energy Monitoring

    DEFF Research Database (Denmark)

    Hansen, Claus T.; Madsen, Dines; Christiensen, Thomas

    Energy measurement has become an important aspect of our daily lives since we have learned that energy consumption, is one of the main source of global warming. Measuring instruments varies from a simple watt-meter to more sophisticated microprocessor control devices. The negative effects...... that fossil fuels induce on our environment has forced us to research renewable energy such as sunlight, wind etc. This new environmental awareness has also helped us to realize the importance of monitoring and controlling our energy use. The main purpose in this research is to introduce a more sophisticated...... but affordable way to monitor energy consumption of individuals or groups of home appliances. By knowing their consumption the utilization can be regulated for more efficient use. A prototype system has been constructed to demonstrate our idea....

  12. Personal monitoring

    International Nuclear Information System (INIS)

    1995-01-01

    Sources of ionizing radiation have innumerable applications in the workplace. The potential exposures of the individual workers involved may need to be routinely monitored and records kept of their cumulative radiation doses. There are also occasions when it is necessary to retrospectively determine a dose which may have been received by a worker. This Module explains the basic terminology associated with personal monitoring and describes the principal types of dosimeters and other related techniques and their application in the workplace. The Manual will be of most benefit if it forms part of more comprehensive training or is supplemented by the advice of a qualified expert in radiation protection. Most of the dosimeters and techniques described in this Module can only be provided by qualified experts

  13. Sewage Monitors

    Science.gov (United States)

    1987-01-01

    Every U.S. municipality must determine how much waste water it is processing and more importantly, how much is going unprocessed into lakes and streams either because of leaks in the sewer system or because the city's sewage facilities were getting more sewer flow than they were designed to handle. ADS Environmental Services, Inc.'s development of the Quadrascan Flow Monitoring System met the need for an accurate method of data collection. The system consists of a series of monitoring sensors and microcomputers that continually measure water depth at particular sewer locations and report their findings to a central computer. This provides precise information to city managers on overall flow, flow in any section of the city, location and severity of leaks and warnings of potential overload. The core technology has been expanded upon in terms of both technical improvements, and functionality for new applications, including event alarming and control for critical collection system management problems.

  14. Late effects of thoracic irradiation in children

    Energy Technology Data Exchange (ETDEWEB)

    Boelling, T.; Koenemann, S.; Ernst, I.; Willich, N. [Dept. of Radiotherapy, Univ. Hospital of Muenster (Germany)

    2008-06-15

    Purpose: to summarize the literature regarding the late effects of radiotherapy to the thorax in childhood and adolescence with special emphasis on cardiac and pulmonary impairment. Material und methods: the literature was critically reviewed using the PubMed {sup registered} database with the key words 'late effects', 'late sequelae', 'child', 'childhood', 'adolescence', 'radiation', 'radiotherapy', 'thorax', 'lung', 'heart', and 'pulmonary'. Results: 17 publications dealing with radiation-induced pulmonary and cardiac late sequelae in children could be identified and were analyzed in detail. 29 further publications with additional information were also included in the analysis. Pulmonary function impairment after mediastinal irradiation arose in one third of all pediatric patients, even when treatment was performed with normofractionated lower doses (15-25 Gy). Whole lung irradiation was regularly followed by pulmonary function impairment with differing rates in several reports. However, clinically symptomatic function impairment like dyspnea was less frequent. Irradiation of up to 25 Gy (single doses {<=} 2 Gy) to the heart showed little or no cardiac toxicity in analyses of irradiated children (median follow-up 1.3-14.3 years). Doses of > 25 Gy (single doses {<=} 2-3.3 Gy) led to several cardiac dysfunctions. However, new data from adults with longer follow-up may indicate threshold doses as low as 1 Gy. Impairment of skeletal growth, breast hypoplasia, and secondary malignancy were further potential late sequelae. Conclusion: several retrospective reports described radiation-associated late sequelae in children. However, there is still a lack of sufficient data regarding the characterization of dose-volume effects. (orig.)

  15. Material monitoring

    International Nuclear Information System (INIS)

    Kotter, W.; Zirker, L.; Hancock, J.A.

    1995-01-01

    Waste Reduction Operations Complex (WROC) facilities are located at the Idaho National Engineering Laboratory (INEL). The overall goal for the Pollution Prevention/Waste Minimization Unit is to identify and establish the correct amount of waste generated so that it can be reduced. Quarterly, the INEL Pollution Prevention (P2) Unit compares the projected amount of waste generated per process with the actual amount generated. Examples of waste streams that would be addresses for our facility would include be are not limited to: Maintenance, Upgrades, Office and Scrap Metal. There are three potential sources of this variance: inaccurate identification of those who generate the waste; inaccurate identification of the process that generates the waste; and inaccurate measurement of the actual amount generated. The Materials Monitoring Program was proposed to identify the sources of variance and reduce the variance to an acceptable level. Prior to the implementation of the Material Monitoring Program, all information that was gathered and recorded was done so through an informal estimation of waste generated by various personnel concerned with each processes. Due to the inaccuracy of the prior information gathering system, the Material Monitoring Program was established. The heart of this program consists of two main parts. In the first part potential waste generators provide information on projected waste generation process. In the second part, Maintenance, Office, Scrap Metal and Facility Upgrade wastes from given processes is disposed within the appropriate bin dedicated to that process. The Material Monitoring Program allows for the more accurate gathering of information on the various waste types that are being generated quarterly

  16. Novel marmoset (Callithrix jacchus model of human Herpesvirus 6A and 6B infections: immunologic, virologic and radiologic characterization.

    Directory of Open Access Journals (Sweden)

    Emily Leibovitch

    2013-01-01

    Full Text Available Human Herpesvirus 6 (HHV-6 is a ubiquitous virus with an estimated seroprevalence of 95% in the adult population. HHV-6 is associated with several neurologic disorders, including multiple sclerosis, an inflammatory demyelinating disease affecting the CNS. Animal models of HHV-6 infection would help clarify its role in human disease but have been slow to develop because rodents lack CD46, the receptor for cellular entry. Therefore, we investigated the effects of HHV-6 infections in a non-human primate, the common marmoset Callithrix jacchus. We inoculated a total of 12 marmosets with HHV-6A and HHV-6B intravenously and HHV-6A intranasally. Animals were monitored for 25 weeks post-inoculation clinically, immunologically and by MRI. Marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms and generated virus-specific antibody responses, while those inoculated intravenously with HHV-6B were asymptomatic and generated comparatively lower antibody responses. Viral DNA was detected at a low frequency in paraffin-embedded CNS tissue of a subset of marmosets inoculated with HHV-6A and HHV-6B intravenously. When different routes of HHV-6A inoculation were compared, intravenous inoculation resulted in virus-specific antibody responses and infrequent detection of viral DNA in the periphery, while intranasal inoculation resulted in negligible virus-specific antibody responses and frequent detection of viral DNA in the periphery. Moreover, marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms, while marmosets inoculated with HHV-6A intranasally were asymptomatic. We demonstrate that a marmoset model of HHV-6 infection can serve to further define the contribution of this ubiquitous virus to human neurologic disorders.

  17. Clinical and virological characteristics of calves experimentally infected with a Brazilian isolate of bovine viral diarrhea virus type 1a

    Directory of Open Access Journals (Sweden)

    Luana Marchi Quadros

    Full Text Available ABSTRACT: To study the pathogenicity of the Brazilian bovine viral diarrhea virus (BVDV type 1a 241.10 isolate, four calves were intranasally inoculated with a viral suspension containing 107.2 TCID50 mL-1. One calf was left uninoculated and kept in contact with the other calves to investigate viral transmissibility. After inoculation, the animals were monitored daily for clinical signs of infection. The presence of the virus in the blood and nasal secretions was confirmed by virus isolation in cell culture. White blood cells were quantified prior to and every 3 days after infection, and the presence of antibodies was checked every 7 days, starting at day 0 until day 42 post-inoculation (pi. After infection, nasal and ocular serous secretions were observed between days 1 and 5 pi, along with a mild cough from days 2 to 4 pi; however, no severe clinical signs were present. Body temperature was slightly elevated between days 4 and 6 pi. The control calf did not develop any of the signs observed in the infected animals. Cell culture-mediated virus isolation confirmed viremia between days 4 and 8 pi and the presence of the virus in the nasal secretions between days 1 and 10 pi. All infected animals showed a decrease in white blood cell count. Antibodies could be detected from day 14 pi, and these levels remained high until day 35 pi. The control calf had no viremia, viral presence in nasal secretions, or positive serology, indicating the absence of viral transmission. Thus, isolate BVDV 1a 241.10 has low pathogenicity and transmissibility but retains immunosuppressive capacity.

  18. Individual monitoring

    International Nuclear Information System (INIS)

    2004-01-01

    This Practical Radiation Technical Manual is one of a series which has been designed to provide guidance on radiological protection for employers, Radiation Protection Officers, managers and other technically competent persons who have a responsibility to ensure the safety of employees working with ionizing radiation. The Manual may be used together with the appropriate IAEA Practical Radiation Safety Manual to provide adequate training, instruction or information on individual monitoring for all employees engaged in work with ionizing radiations. Sources of ionizing radiation have a large number of applications in the workplace. The exposures of the individual workers involved may need to be routinely monitored and records kept of their cumulative radiation doses. There are also occasions when it is necessary to retrospectively determine a dose which may have been received by a worker. This Manual explains the basic terminology associated with individual monitoring and describes the principal types of dosimeters and other related techniques and their application in the workplace. The Manual will be of most benefit if it forms part of more comprehensive training or is supplemented by the advice of a qualified expert in radiation protection. Most of the dosimeters and techniques described in this Manual can only be provided by qualified experts

  19. Late Cretaceous vicariance in Gondwanan amphibians.

    Directory of Open Access Journals (Sweden)

    Ines Van Bocxlaer

    Full Text Available Overseas dispersals are often invoked when Southern Hemisphere terrestrial and freshwater organism phylogenies do not fit the sequence or timing of Gondwana fragmentation. We used dispersal-vicariance analyses and molecular timetrees to show that two species-rich frog groups, Microhylidae and Natatanura, display congruent patterns of spatial and temporal diversification among Gondwanan plates in the Late Cretaceous, long after the presumed major tectonic break-up events. Because amphibians are notoriously salt-intolerant, these analogies are best explained by simultaneous vicariance, rather than by oceanic dispersal. Hence our results imply Late Cretaceous connections between most adjacent Gondwanan landmasses, an essential concept for biogeographic and palaeomap reconstructions.

  20. A case of late-onset oligomeganephronia

    Directory of Open Access Journals (Sweden)

    Rafael José Vargas Alves

    2012-12-01

    Full Text Available A 33-year old caucasian man was investigated for pain in the right flank, proteinuria, hemathuria and an elevated serum creatinine level. He also presented an abnormal ultrasonography, which revealed asymmetric kidneys. Through renal biopsy, the diagnosis of oligomeganephronia (OMN was confirmed. OMN is a very rare form of renal hypoplasia, and late-onset in adulthood is even rarer. In the pediatric population, OMN leads to end-stage-renal-failure(ESRF in a few years. This is the sixth case related in the literature of a late-onset OMN who have not yet developed ESRF.

  1. Late complication after radiotherapy for testicular tumor

    Energy Technology Data Exchange (ETDEWEB)

    Mineyama, Hirotada; Komatsubara, Shuichi; Sakata, Yasunosuke; Abe, Norio (Niigata Prefectural Cancer Center (Japan). Niigata Hospital)

    1983-12-01

    During the past 21 years, 105 patients with germinal testicular tumor were treated in our hospital; 86 out of 105 patients were irradiated postoperatively. Late radiation injury was observed in 14 patients: Cutaneosigmoidal fistula in 1 patient, ileus (jejunum necrosis) in 1 patient, gastric ulcer in 1 patient, duodenal ulcer and stenosis in 1 patient, lung fibrosis in 1 patient, radiation cystitis in 1 patient, severe lymph edema of lower extremity in 1 patient, muscle atrophy of lower extremity in 1 patient, lower extremity growth disturbances in 3 children and severe abdominal cutancosubcutaneal fibrosis in 3 patient. Two cases of late radiation injury are presented and discussed.

  2. 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

    Directory of Open Access Journals (Sweden)

    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.

  3. Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Jesse J R Masson

    Full Text Available Metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and mitochondrial biogenesis in subpopulations of CD4+ and CD8+ T cells from 18 virologically-suppressed HIV-positive individuals on combination antiretroviral therapy (cART; median CD4+ cell count: 728 cells/μl and 13 HIV seronegative controls. Mitochondrial membrane potential (MMP and reactive oxygen species (ROS production were also analysed in total CD4+ and CD8+ T cells. Among HIV+/cART individuals, expression of glucose transporter (Glut1 and mitochondrial density were highest within central memory and naïve CD4+ T cells, and lowest among effector memory and transitional memory T cells, with similar trends in HIV-negative controls. Compared to HIV-negative controls, there was a trend towards higher percentage of circulating CD4+Glut1+ T cells in HIV+/cART participants. There were no significant differences in mitochondrial dynamics between subject groups. Glut1 expression was positively correlated with mitochondrial density and MMP in total CD4+ T cells, while MMP was also positively correlated with ROS production in both CD4+ and CD8+ T cells. Our study characterizes specific metabolic features of CD4+ and CD8+ T cells in HIV-negative and HIV+/cART individuals and will invite future studies to explore the immunometabolic consequences of HIV infection.

  4. The impact of nevirapine- versus protease inhibitor-based regimens on virological markers of HIV-1 persistence during seemingly suppressive ART.

    Science.gov (United States)

    Kiselinova, Maja; Anna, Maria; Malatinkova, Eva; Vervish, Karen; Beloukas, Apostolos; Messiaen, Peter; Bonczkowski, Pawel; Trypsteen, Wim; Callens, Steven; Verhofstede, Chris; De Spiegelaere, Ward; Vandekerckhove, Linos

    2014-01-01

    The source and significance of residual plasma HIV-1 RNA detection during suppressive ART remain controversial. It has been proposed that nevirapine (NVP)-based regimens achieve a greater HIV-1 RNA suppression than regimens containing a protease inhibitor (PI). The aim of this study was to compare the effect of receiving NVP- vs PI-based ART on the virological markers of HIV persistence in peripheral blood. The study population comprised 161 HIV-1 infected patients receiving either NVP-based (n=81) or PI-based (n=80) ART and showing a HIV-1 RNA load stably suppressed ART, with median (IQR) levels of 5 (3-6) and 5 (3-8) copies/mL, respectively. HIV-1 RNA detection was associated with shorter duration of suppressive ART regardless of treatment arm (p=0.007), and lower CD4 nadir (p=0.015). HIV-1 DNA levels were median 282 (120-484) and 213 (87-494) copies/106 PBMCs in the two groups respectively, and were lowest (ART HIV-1 RNA load (p=0.0001). In this comprehensive characterization of patients on long-term suppressive ART, we did not observe evidence for a greater suppressive activity of NVP-based over PI-based therapy on plasma and intracellular markers of virus persistence. Overall excellent correlation was observed between the markers, allowing the identification of a subset of treated patients with low HIV-1 expression as an important cohort for future HIV cure studies.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Virological Surveillance of Dengue in Saint Martin and Saint Barthélemy, French West Indies, Using Blood Samples on Filter Paper

    Science.gov (United States)

    Matheus, Séverine; Chappert, Jean-Loup; Cassadou, Sylvie; Berger, Franck; Labeau, Bhetty; Bremand, Laetitia; Winicki, Alain; Huc-Anais, Patricia; Quenel, Philippe; Dussart, Philippe

    2012-01-01

    To strengthen active dengue surveillance in Saint Martin and Saint Barthélemy, two French Caribbean islands, we evaluated the epidemiological usefulness of collecting blood samples from NS1-positive dengue patients on filter paper to identify the dengue serotypes circulating in these regions during a 27-month period. This approach allowed dengue serotypes to be identified by reverse transcriptase-polymerase chain reaction in 90.1% of the total set of 666 samples analyzed and, in 95.5% of the samples collected during the acute phase of the disease. This prospective virological surveillance using blood samples absorbed onto filter paper, which were stored at 4°C and shipped at ambient temperature to a specialized laboratory for analysis, allowed us to avoid the logistic and financial costs associated with shipping frozen venous blood samples. This surveillance system offers a low-cost alternative for reinforcing dengue prevention in areas where specialized laboratories do not exist, notably by facilitating the early detection of potentially new dengue serotypes. PMID:22232467

  10. 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....

  11. Technology monitoring; Technologie-Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Eicher, H.; Rigassi, R. [Eicher und Pauli AG, Liestal (Switzerland); Ott, W. [Econcept AG, Zuerich (Switzerland)

    2003-07-01

    This study made for the Swiss Federal Office of Energy (SFOE) examines ways of systematically monitoring energy technology development and the cost of such technologies in order to pave the way to a basis for judging the economic development of new energy technologies. Initial results of a survey of the past development of these technologies are presented and estimates are made of future developments in the areas of motor-based combined heat and power systems, fuel-cell heating units for single-family homes and apartment buildings, air/water heat pumps for new housing projects and high-performance thermal insulation. The methodology used for the monitoring and analysis of the various technologies is described. Tables and diagrams illustrate the present situation and development potential of various fields of technology.

  12. Hypothyroidism in late-onset Pompe disease

    Directory of Open Access Journals (Sweden)

    Joseph Schneider

    2016-09-01

    Conclusions: Hypothyroidism was found at a higher prevalence in patients with late-onset Pompe disease compared to the general adult population at UMMC. Studies in larger populations of patients with Pompe disease would be needed to confirm an association of Pompe disease and hypothyroidism. Challenges include finding an adequate sample size, due the rarity of Pompe disease.

  13. Progression of Late-Onset Stargardt Disease

    NARCIS (Netherlands)

    Lambertus, S.; Lindner, M.; Bax, N.M.; Mauschitz, M.M.; Nadal, J.; Schmid, M.; Schmitz-Valckenberg, S.; Hollander, A.I. den; Weber, B.H.; Holz, F.G.; Wilt, G.J. van der; Fleckenstein, M.; Hoyng, C.B.

    2016-01-01

    Purpose: Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy

  14. Late effects of radiation: host factors

    International Nuclear Information System (INIS)

    Fry, R.J.M.; Storer, J.B.

    1983-01-01

    The paper discusses the influence of host factors on radiation late effects and in particular cancer. Radiation induces cellular changes that result in initiated cells with a potential to become cancers. The expression of the initiated cells as tumors is influenced, if not determined, by both tissue and systemic factors that are sex-, age-, and species-dependent

  15. 30 CFR 870.21 - Late payments.

    Science.gov (United States)

    2010-07-01

    ... Government. The Treasury current value of funds rate is published annually in the Federal Register and on... fees and interest. (c) When a reclamation fee debt is more than 91 days overdue, a 6 percent annual... fee was owed are subject to interest. Late reclamation fee payments are subject to interest at the...

  16. Late time phase transition as dark energy

    Indian Academy of Sciences (India)

    Abstract. We show that the dark energy field can naturally be described by the scalar condensates of a non-abelian gauge group. This gauge group is unified with the standard model gauge groups and it has a late time phase transition. The small phase transition explains why the positive acceleration of the universe is ...

  17. Late Miocene magnetostratigraphy in the Mediterranean

    NARCIS (Netherlands)

    Langereis, C.G.

    1984-01-01

    Reversals of the geomagnetic field In the geological past are recorded globally in the natural remanent magnetization (NRM) of igneous and sedimentary rock sequences. The accurate and rei iable reconstruction of this record is the basis of magnetostratigraphy. The magnetostratigraphy of Late

  18. Late Miocene magnetostratigraphy in the Mediterranean

    NARCIS (Netherlands)

    Langereis, C.G.

    1984-01-01

    Reversals of the geomagnetic field In the geological past are recorded globally in the natural remanent magnetization (NRM) of igneous and sedimentary rock sequences. The accurate and rei iable reconstruction of this record is the basis of magnetostratigraphy. The magnetostratigraphy of Late Miocene

  19. Language Control Abilities of Late Bilinguals

    Science.gov (United States)

    Festman, Julia

    2012-01-01

    Although all bilinguals encounter cross-language interference (CLI), some bilinguals are more susceptible to interference than others. Here, we report on language performance of late bilinguals (Russian/German) on two bilingual tasks (interview, verbal fluency), their language use and switching habits. The only between-group difference was CLI:…

  20. Causes for Late onset Alcohol Use Disorder

    DEFF Research Database (Denmark)

    Emiliussen, Jakob; Nielsen, Anette Søgaard; Andersen, Kjeld

    the studies. The results of this review are generally inconclusive. In spite of the low quality scores, we did find that chronic stress, role/identity loss and friends approval of drinking, was associated with an increased risk for late-onset AUD whereas retirement, death of spouse or close relative does...

  1. 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.

  2. Late complications after radiotherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jung, H. [University Hospital Hamburg-Eppendorf (Germany). Inst. of Biophysics and Radiobiology; University Hospital Hamburg-Eppendorf (Germany). Lab. of Radiobiology and Experimental Radiooncology; Beck-Bornholdt, H.P. [University Hospital Hamburg-Eppendorf (Germany). Inst. of Biophysics and Radiobiology; Svoboda, V. [University Hospital Hamburg-Eppendorf (Germany). Inst. of Biophysics and Radiobiology; Portsmouth Oncology Centre, Saint Mary' s Hospital (United Kingdom). Dept. of Radiotherapy; Alberti, W. [University Hospital Hamburg-Eppendorf (Germany). Dept. of Radiotherapy and Radiooncology; Herrmann, T. [Technical Univ. Dresden (Germany). Dept. of Radiotherapy and Radiooncology

    2012-11-15

    Background: The aim of the present study was to analyze in detail the time course of the incidence of radiation-induced late effects. For this purpose, unpublished data of patients treated by radiation therapy in Hamburg in the late 1980s were analyzed. Relatively large volumes were exposed to comparatively high doses, thus leading to a high rate of treatment-related side effects. Patients and methods: A total of 180 consecutive patients received radiotherapy for prostate cancer. The median age was 66 years (range 41-88 years). The median of the maximum dose was 77.5 Gy (range 56.3-95 Gy) and overall treatment time was 51 days (range 28-128 days). Endpoints analyzed were late complications of grade 3 or higher, overall and disease-free survival, local tumor control, and distant metastases. Data analysis was actuarial and the log-rank test was used to compare the various subgroups. Results After 2 years, 80.5 {+-} 3.2% of the patients were without any complications of grade 3 or higher, and after 5 years a constant level of 70.3 {+-} 4.0% was approached. When multiple lesions occurred per patient, the later events were disregarded. A total of 66 complications occurred in 42 patients. The percentage of patients being free from late complications, plotted as a function of time after start of radiation therapy, was adequately described by an exponential function and a constant fraction. Complications approached a constant level of 70.3% at a rate of 5.3% per month. This means that patients who will develop a complication do so at exponential kinetics and at a relatively high rate, whereas about 70% of the patients will never experience a late effect even over long observation periods. After subdividing the maximum dose into three equal dose groups of 55 patients each (< 73.3 Gy, 73.3-80 Gy, > 80 Gy), the constant fraction decreased from 85.7 to 72.8% and 52.2%, whereas the incidence rate was 4.3%, 7.7%, and 5.6% per month and, thus, almost independent of radiation dose

  3. The late Cainozoic East Antarctic ice sheet

    International Nuclear Information System (INIS)

    Colhoun, E.A.

    1999-01-01

    A review, mainly of East Antarctic late Cainozoic (post 40 Ma) geological and geomorphological evidence, supports the hypothesis of the continuous presence of an ice sheet, of about the present size, since the late Miocene. Evidence is presented and the view advanced that, during the late Wisconsin maximum of isotope stage 2, ice was not nearly as thick or extensive over the continental shelf as required by the model of 'maximum' Antarctic glaciation. Some of the factors influencing the contribution of Antarctica to post-glacial sea-level rise are discussed. It is considered that Antarctica's contribution was probably considerably less than previously estimated. The dating of marine and freshwater sequences in the Vestfold and Bunger Hills is consistent with deglaciation around the Pleistocene Holocene boundary, after the Late Wisconsin maximum. A date of ∼25 ka BP from permafrost in the Larsemann Hills means that either the Larsemann Hills were not glaciated during the Late Wisconsin or the ice failed to erode much of the permafrost surface. The degree of weathering of rock and glacial drifts in the Vestfold, Larsemann and Bunger Hills suggests a long time for formation, perhaps considerably longer than indicated by the dated marine and freshwater sediment sequences. Cosmogenic isotope dating in the Vestfold Hills has provided equivocal ages for deglaciation. While the results could indicate deglaciation before 80 ka BP, they do not confirm such early deglaciation. If the ice cover was thin and failed to remove the previous rock exposure profile, then the assays could predate the last ice advance. Weathered iron crust fragments in the till suggest little erosion. The raised beaches of the oases are Holocene. Assuming they have been produced by post Late Wisconsin isostatic uplift and by the Holocene transgression, calculations show that the Antarctic continental ice sheet could not have been more than ∼500 m thicker in the inner shelf-coastal zone. The

  4. Ammonia Monitor

    Science.gov (United States)

    Sauer, Richard L. (Inventor); Akse, James R. (Inventor); Thompson, John O. (Inventor); Atwater, James E. (Inventor)

    1999-01-01

    Ammonia monitor and method of use are disclosed. A continuous, real-time determination of the concentration of ammonia in an aqueous process stream is possible over a wide dynamic range of concentrations. No reagents are required because pH is controlled by an in-line solid-phase base. Ammonia is selectively transported across a membrane from the process stream to an analytical stream to an analytical stream under pH control. The specific electrical conductance of the analytical stream is measured and used to determine the concentration of ammonia.

  5. Oscillator monitor

    International Nuclear Information System (INIS)

    McNeill, G.A.

    1981-01-01

    Present high-speed data acquisition systems in nuclear diagnostics use high-frequency oscillators to provide timing references for signals recorded on fast, traveling-wave oscilloscopes. An oscillator's sinusoidal wave shape is superimposed on the recorded signal with each cycle representing a fixed time increment. During data analysis the sinusoid is stripped from the signal, leaving a clean signal shape with known timing. Since all signal/time relationships are totally dependant upon working oscillators, these critical devices must have remote verification of proper operation. This manual presents the newly-developed oscillator monitor which will provide the required verification

  6. 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)

  7. Reproductive rights: Current issues of late abortion

    Directory of Open Access Journals (Sweden)

    Mujović-Zornić Hajrija

    2009-01-01

    Full Text Available This article considers the legal issues surrounding induced late abortion in cases when severe medical, therapeutic or ethical reasons have not been in dispute. Generally discussing the essential question about abortion today, it means not anymore legality of abortion but, in the first place, safety of abortion. From the aspect of woman health the most important aim is to detect and avoid possible risks of medical intervention, such as late abortion present. This is the matter of medical law context and also the matter of the woman's reproductive rights, here observed through legislation and court practice. The gynecologist has an obligation to obtain the informed consent of each patient. Information's should be presented in reasonably understandable terms and include alternative modes of treatment, objectives, risks, benefits, possible complications, and anticipated results of such treatment. Pregnant woman should receive supportive counseling before and particularly after the procedure. The method chosen for all terminations should ensure that the fetus is born dead. This should be undertaken by an appropriately trained practitioner. Reform in abortion law, making it legally accessible to woman, is not necessarily the product of a belief in woman's rights, but can be a means of bringing the practice of abortion back under better control. Counseling and good medical practice in performing late abortion are the instruments to drive this point even further home. It does not undermine the woman who wants to make a positive decision about her life and its purpose is not to produce feelings of insecurity and guilt. It concludes that existing law should not be changed but that clear rules should be devised and board created to review late term abortion. In Serbia, this leads to creation and set up guidelines for reconciling medical justification for late abortion with existing law, especially with solutions which brings comparative law. .

  8. LATE RENAL GRAFT REJECTION: PATHOLOGY AND PROGNOSIS

    Directory of Open Access Journals (Sweden)

    E.S. Stolyarevich

    2014-01-01

    Full Text Available Rejection has always been one of the most important cause of late renal graft dysfunction. Aim of the study was to analyze the prevalence of different clinico-pathological variants of rejection that cause late graft dysfunction, and evaluate their impact on long-term outcome. Materials and methods. This is a retrospective study that analyzed 294 needle core biopsy specimens from 265 renal transplant recipients with late (48,8 ± 46,1 months after transplantation allograft dysfunction caused by late acute rejection (LAR, n = 193 or chronic rejection (CR, n = 78 or both (n = 23. C4d staining was performed by immunofl uorescence (IF on frozen sections using a standard protocol. Results. Peritubular capillary C4d deposition was identifi ed in 36% samples with acute rejection and in 62% cases of chronic rejection (including 67% cases of transplant glomerulopathy, and 50% – of isolated chronic vasculopathy. 5-year graft survival for LAR vs CR vs their combination was 47, 13 and 25%, respectively. The outcome of C4d– LAR was (p < 0,01 better than of C4d+ acute rejection: at 60 months graft survival for diffuse C4d+ vs C4d− was 33% vs 53%, respectively. In cases of chronic rejection C4d+ vs C4d– it was not statistically signifi cant (34% vs 36%. Conclusion. In long-term allograft biopsy C4d positivity is more haracteristic for chronic rejection than for acute rejection. Only diffuse C4d staining affects the outcome. C4d– positivity is associated with worse allograft survival in cases of late acute rejection, but not in cases of chronic rejection. 

  9. Support Vector Machine Based Monitoring of Cardio-Cerebrovascular Reserve during Simulated Hemorrhage

    NARCIS (Netherlands)

    van der Ster, Björn J. P.; Bennis, Frank C.; Delhaas, Tammo; Westerhof, Berend E.; Stok, Wim J.; van Lieshout, Johannes J.

    2018-01-01

    Introduction: In the initial phase of hypovolemic shock, mean blood pressure (BP) is maintained by sympathetically mediated vasoconstriction rendering BP monitoring insensitive to detect blood loss early. Late detection can result in reduced tissue oxygenation and eventually cellular death. We

  10. 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.

  11. [Analysis of a proposal for changing the educational paradigm in bacteriology and virology. Facultad de Ciencias Médicas, Universidad Nacional de Córdoba].

    Science.gov (United States)

    Márquez, E; González, S; López, T; Giayetto, V; Littvik, A; Cannistraci, R; Pavan, J

    2000-01-01

    The productive character of the scientific thought points out a methodological means that include the demand of the students' job about the information and not his mere reception and reproduction. It is essential to give the students the opportunity of discovering the cognitive processes used in the production of the scientific knowledge. In this work, we present the result of the starting of a workshop dynamic in a basic subject, the students' answers, and the analysis of the subject. In the Chair of Medical Bacteriology and Virology of the School of Medical Sciences, the National University of Córdoba, 1700 students attended classes in 1997. The subject was developed with the activities that worked the same contents from two different learning conceptions: (I) workshop activity, non obligatory, constructive, and (II) theorico-practical activity, obligatory and traditional. Two voluntary and anonymous interviews were done about the valuation that the student gave to these two activities and their basis, one in the middle and the other at the end of the course. 90.55% classified the traditional activity as positive, and 9.45% as negative. Regarding the workshop activity, the 60.5% classified it as positive and the 39.5% as negative. The same developed content with two activities made possible the analysis of the impact that the two different methodologies produced on the students. The student's answer to the traditional activity was better than the workshop activity (p < 0.001). The differences in the student's acceptance between the two option revealed the major difficulty of an alternative methodological strategy in the current educational model.

  12. Clinical and virological improvement of hepatitis B virus-related or hepatitis C virus-related chronic hepatitis with concomitant hepatitis A virus infection.

    Science.gov (United States)

    Sagnelli, Evangelista; Coppola, Nicola; Pisaturo, Mariantonietta; Pisapia, Raffaella; Onofrio, Mirella; Sagnelli, Caterina; Catuogno, Antonio; Scolastico, Carlo; Piccinino, Felice; Filippini, Pietro

    2006-06-01

    We evaluated the clinical and virological characteristics of hepatitis A virus infection in persons concomitantly infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). We enrolled 21 patients with acute hepatitis A and chronic hepatitis with no sign of liver cirrhosis, 13 patients who were positive for hepatitis B surface antigen (case B group), 8 patients who were anti-HCV positive (case C group), and 21 patients with acute hepatitis A without a preexisting liver disease (control A group). Two control groups of patients with chronic hepatitis B (control B group) or C (control C group) were also chosen. All control groups were pair-matched by age and sex with the corresponding case group. Fulminant hepatitis A was never observed, and hepatitis A had a severe course in 1 patient in the case B group and in 1 patient in the control A group. Both patients recovered. On admission, HBV DNA was detected in 1 patient in the case B group (7.7%) and in 13 patients (50%) in the control B group; HCV RNA was found in no patient in the case C group and in 16 patients (81.2%) in the control C group. Of 9 patients in the case B group who were followed up for 6 months, 3 became negative for hepatitis B surface antigen and positive for hepatitis B surface antibody, 2 remained positive for hepatitis B surface antigen and negative for HBV DNA, and 4 became positive for HBV DNA with a low viral load [corrected] Of 6 patients in the case C group who were followed up for 6 months, 3 remained negative for HCV RNA, and 3 had persistently low viral loads. Concomitant hepatitis A was always self-limited, associated with a marked inhibition of HBV and HCV genomes, and possibly had a good prognosis for the underlying chronic hepatitis.

  13. Clinical and virologic outcomes after changes in first antiretroviral regimen at 7 sites in the Caribbean, Central and South America Network (CCASAnet)

    Science.gov (United States)

    Wolff, Marcelo; Shepherd, Bryan E.; Cortés, Claudia; Rebeiro, Peter; Cesar, Carina; Cardoso, Sandra Wagner; Pape, Jean W.; Padgett, Denis; Sierra-Madero, Juan; Echevarria, Juan; McGowan, Catherine C.

    2015-01-01

    Background HIV-infected persons in lower income countries may experience high rates of antiretroviral therapy (ART) change, particularly due to toxicity or other non-failure reasons. Few reports address patient outcomes after these modifications. Methods HIV-infected adults from 7 Caribbean, Central and South America network (CCASAnet) clinical cohorts who modified > or = 1 drug from first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. Results 5,565 ART-naïve HAART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 due to toxicity and 11% due to 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[aHR]=1.5 vs. failure, 95% confidence interval[CI]=1.0–2.1). 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 start of ART-2, and starting ART-2 because of failure (aHR=2.1 vs. toxicity, 95% CI=1.5–2.8). Conclusions Among patients modifying 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. PMID:26761273

  14. 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.

  15. 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.

  16. Epidemiological, Clinicopathological and Virological Features of Merkel Cell Carcinomas in Medical Center of University of Pécs, Hungary (2007-2012).

    Science.gov (United States)

    Horváth, Katalin Barbara; Pankovics, Péter; Kálmán, Endre; Kádár, Zsolt; Battyáni, Zita; Lengyel, Zsuzsanna; Reuter, Gábor

    2016-01-01

    Merkel cell carcinoma (MCC) is a rare, highly aggressive skin tumour. In 2008, a Merkel cell polyomavirus (MC) was identified in MCCs as a potential etiological factor of MCC. The aims of this retrospective study were to investigate the epidemiological, clinicopathological and virological features of MCCs. Between 2007 and 2012, 11 patients had been diagnosed with MCC by histological methods in University of Pécs, Hungary. In eight MCC cases MC was tested by PCR (in primary skin lesions, lymph nodes/cutan metastases, MCC neighboring carcinomas). Clinicopathological characteristics (age, histological pattern, lymphovascular invasion, co-morbidities) of MC-positive and MC-negative cases were compared. MC was detected in three (37.5%) out of eight patients' primary tumour or metastasis. The average age was 73.8 (64.3 in MC-positive group). Except the youngest, 55 year-old patient (the primary tumour appeared on his leg), all tumours were found at the head and neck region. Immunosuppression (steroid therapy, chronic lymphoid leukaemia, chronic obstructive pulmonary disease) and/or old age were characteristic for all cases. Histological pattern was different in MC-positive and in MC-negative groups: MCCs with MC showed more homogeneous histological pattern, lack of lymphovascular invasion and were associated with better prognosis (mortality rate: 33% versus 80%). MCC associated with oncogenic virus is a newly recognized clinical entity. However, MC could not be detected in all histologically proven MCCs. The well-defined selection of patients/disease groups and better characterization of differences between MC-positive and negative cases is an important step towards the recognition of the etiology and pathogenesis of all MCCs.

  17. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe.

    Science.gov (United States)

    Judd, A; Lodwick, R; Noguera-Julian, A; Gibb, D M; Butler, K; Costagliola, D; Sabin, C; van Sighem, A; Ledergerber, B; Torti, C; Mocroft, A; Podzamczer, D; Dorrucci, M; De Wit, S; Obel, N; Dabis, F; Cozzi-Lepri, A; García, F; Brockmeyer, N H; Warszawski, J; Gonzalez-Tome, M I; Mussini, C; Touloumi, G; Zangerle, R; Ghosn, J; Castagna, A; Fätkenheuer, G; Stephan, C; Meyer, L; Campbell, M A; Chene, G; Phillips, A

    2017-03-01

    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. 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 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection 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 was 9.6% [95% confidence interval (CI) 7.0-12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9-5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10-14 years when starting ART (27.7%; 95% CI 13.2-42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10-14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development. © 2016 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

  18. Late Bronze Age hoard studied by PIXE

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez Neira, P.C., E-mail: carolina.gutierrez@uam.es [CMAM, Universidad Autonoma de Madrid, c/Farady 3, E-28049 Madrid (Spain); Zucchiatti, A., E-mail: alessandro.zucchiatti@uam.es [CMAM, Universidad Autonoma de Madrid, c/Farady 3, E-28049 Madrid (Spain); Montero-Ruiz, I., E-mail: ignacio.montero@cchs.csic.es [CCHS-CSIC, Albasanz 26-28, E 28037 Madrid (Spain); Vilaca, R., E-mail: rvilaca@fl.uc.pt [University of Coimbra, Largo da Porta Ferrea, 3000-447 Coimbra (Portugal); Bottaini, C., E-mail: keret18@yahoo.it [University of Coimbra, Largo da Porta Ferrea, 3000-447 Coimbra (Portugal); Gener, M., E-mail: marc.gener@cchs.csic.es [CCHS-CSIC, Albasanz 26-28, E 28037 Madrid (Spain); Climent-Font, A., E-mail: acf@uam.es [CMAM, Universidad Autonoma de Madrid, c/Farady 3, E-28049 Madrid (Spain); Department of Applied Physics, Universidad Autonoma de Madrid, Campus Cantobalanco, E-28049 Madrid (Spain)

    2011-12-15

    The hoards of metallic objects belonging to the Late European Bronze Age can be interpreted differently depending on the type, number and composition of the artefacts. PIXE analysis has been performed in nine items from the Hoard of Freixanda in Portugal comprising four socket axes, a palstave axe, a ring, a chisel, a dagger, and a casting debris. Besides the composition of the main matrix elements, that is Cu and Sn, the amount of trace elements of interest like, As, Pb, Ni, and Ag has been determined using this ion beam technique. The high tin content alloy and the high purity of the metals from the Freixanda hoard are characteristic of the Portuguese and Spanish Late Bronze Age metallurgy, supporting the idea of a regional production.

  19. Features of Social Cognition in Late Adulthood

    Directory of Open Access Journals (Sweden)

    Melehin A.I.

    2015-12-01

    Full Text Available The paper presents outcomes of researches on the central component of social cognition — theory of mind in late adulthood. The outcomes show that, in normal aging, in advanced adulthood (55—74 years as well as in old age (75—90 years there are several qualitative changes in the affective (understanding and differentiation of emotions and cognitive (understanding irony and deceit components of theory of mind. Also, at these ages individuals may develop various forms of theory of mind deficits. They may encounter difficulties with reading facial expressions and recognizing other people’s emotions. It becomes harder for them to recognize negative emotions (such as sorrow, fear, anger than positive ones (joy. The paper describes features of pragmatic interpretation of events and understanding of deceit and irony in late adulthood.

  20. Educating Citizens in Late Modern Societies

    DEFF Research Database (Denmark)

    Christensen, Torben Spanget

    2011-01-01

    One way or the other democratic states need to take on the task of educating its rising generation in governmental affairs, societal matters and citizenship in order to sustain the democracy itself. This article presents a model for analysing civic education in late modern, globalised world....... The model is based on the fundamental belief that the overall aim of civic education in democratic, late modern and global societies is empowerment of the citizen in order to establish a self governing citizen who simultaneous is capable of managing and keeping together partly contradictory citizens tasks...... studies and evaluations of the Danish upper secondary school completed at my department at University of Southern Denmark in recent years, especially connected to a quite far reaching curriculum reform from 2005. It is assumed that this Danish development is an expression of a more general phenomenon...

  1. Late presentation of posterior urethral valves.

    Science.gov (United States)

    Jalbani, Imran Khan; Biyabani, Syed Raziuddin

    2014-05-01

    Presence of posterior urethral valves (PUV) is the most common cause of urinary tract obstruction in the male neonate. Late presentation occurs in 10% of cases. We present a case of PUVs in an adult male who presented with history of obstructive lower urinary tract symptoms and hematuria. On evaluation, he was found to have raised serum creatinine level. A voiding cystourethrogram (VCUG) could not be completely performed because of narrowing in the posterior urethra. A rigid urethrocystoscopy was performed at which he was found to have type-I posterior urethral valve which were fulgurated. A repeat uroflowmetry revealed maximum flow rate of 12 ml/second. This case highlights that PUVs is not solely a disease of infancy but may also present late. VCUG is the radiological investigation of choice but the diagnosis may be missed. A urethrocystoscopy is advised if there is a high index of suspicion.

  2. Multimodal brain monitoring in fulminant hepatic failure

    Science.gov (United States)

    Paschoal Jr, Fernando Mendes; Nogueira, Ricardo Carvalho; Ronconi, Karla De Almeida Lins; de Lima Oliveira, Marcelo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

    2016-01-01

    Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting. PMID:27574545

  3. [Late primary abdominal pregnancy. Case report].

    Science.gov (United States)

    Farías, Emigdio Torres; Gómez, Luis Guillermo Torres; Allegre, René Márquez; Higareda, Salvador Hernández

    2008-09-01

    Abdominal advanced pregnancy is an obstetric complication that put at risk maternal and fetal life. We report a case of advanced abdominal pregnancy with intact ovaries and fallopian tubes, without ureteroperitoneal fistulae and, late prenatal diagnosis, in a multiparous patient without risk factors, with alive newborn, and whose pregnancy was attended at Unidad Medica de Alta Especialidad, Hospital de Gineco-Obstetricia, Centro Medico Nacional de Occidente del IMSS, Guadalajara, Jalisco, México.

  4. Hypothyroidism in late-onset Pompe disease.

    Science.gov (United States)

    Schneider, Joseph; Burmeister, Lynn A; Rudser, Kyle; Whitley, Chester B; Jarnes Utz, Jeanine

    2016-09-01

    In Pompe disease, a deficiency of acid α-glucosidase enzyme activity leads to pathologic accumulation of glycogen in tissues. Phenotype heterogeneity in Pompe includes an infantile form and late-onset forms (juvenile- and adult-onset forms). Symptoms common to all phenotypes include progressive muscle weakness and worsening respiratory function. Patients with late-onset forms of Pompe disease commonly complain of chronic fatigue and generalized muscle weakness prior to being diagnosed with Pompe disease, and this may lead to consideration of hypothyroidism in the differential diagnosis. This study aimed to evaluate the prevalence of hypothyroidism in the adult-onset form of Pompe disease. Electronic chart review was performed at the Advanced Therapies Clinic at the University of Minnesota Medical Center (UMMC) to identify patients with late-onset Pompe disease. The identified charts were reviewed for a co-diagnosis of hypothyroidism. A query was made to the clinical data repository at UMMC searching diagnosis ICD9 code 244.9 (hypothyroidism not otherwise specified) and/or presence of levothyroxine from 2011 to 2014 in patients 18 years of age and older. The clinical data repository found a prevalence of hypothyroidism of 3.15% (56,072 of 1,782,720 patients) in the adult patient population at UMMC. Ten adult patients with Pompe disease were identified, five with the diagnosis of hypothyroidism (50%, 95% CI: 23.7, 76.3, p Hypothyroidism was found at a higher prevalence in patients with late-onset Pompe disease compared to the general adult population at UMMC. Studies in larger populations of patients with Pompe disease would be needed to confirm an association of Pompe disease and hypothyroidism. Challenges include finding an adequate sample size, due the rarity of Pompe disease.

  5. Early- versus Late-Onset Systemic Sclerosis

    Science.gov (United States)

    Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard

    2014-01-01

    Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463

  6. A Late Pleistocene sea level stack

    OpenAIRE

    Spratt Rachel M; Lisiecki Lorraine E

    2016-01-01

    Late Pleistocene sea level has been reconstructed from ocean sediment core data using a wide variety of proxies and models. However, the accuracy of individual reconstructions is limited by measurement error, local variations in salinity and temperature, and assumptions particular to each technique. Here we present a sea level stack (average) which increases the signal-to-noise ratio of individual reconstructions. Specifically, we perform principal componen...

  7. The Accelerated Late Adsorption of Pulmonary Surfactant

    OpenAIRE

    Loney, Ryan W.; Anyan, Walter R.; Biswas, Samares C.; Rananavare, Shankar B.; Hall, Stephen B.

    2011-01-01

    Adsorption of pulmonary surfactant to an air−water interface lowers surface tension (γ) at rates that initially decrease progressively, but which then accelerate close to the equilibrium γ. The studies here tested a series of hypotheses concerning mechanisms that might cause the late accelerated drop in γ. Experiments used captive bubbles and a Wilhelmy plate to measure γ during adsorption of vesicles containing constituents from extracted calf surfactant. The faster fall in γ reflects faster...

  8. Intermediate Inflation or Late Time Acceleration?

    International Nuclear Information System (INIS)

    Sanyal, A.K.

    2008-01-01

    The expansion rate of intermediate inflation lies between the exponential and power law expansion but corresponding accelerated expansion does not start at the onset of cosmological evolution. Present study of intermediate inflation reveals that it admits scaling solution and has got a natural exit form it at a later epoch of cosmic evolution, leading to late time acceleration. The corresponding scalar field responsible for such feature is also found to behave as a tracker field for gravity with canonical kinetic term.

  9. Late haemorrhagic disease of the newborn.

    Science.gov (United States)

    Zengin, Emine; Sarper, Nazan; Türker, Gülcan; Corapçioğlu, Funda; Etuş, Volkan

    2006-09-01

    Late haemorrhagic disease of the newborn (HDN) can occur owing to a lack of vitamin K prophylaxis, as a manifestation of an underlying disorder or idiopatically from the 8th day to 12 weeks after birth. Eight infants admitted to Kocaeli University Hospital with nine episodes of late HDN between January 2002 and April 2005 were evaluated retrospectively from hospital records. The median age at presentation was 46 (26-111) days. All the infants were born at full-term to healthy mothers and were exclusively breast-fed. All had an uneventful perinatal history, except one who had meconium aspiration. Four patients had received no vitamin K prophylaxis and another three had uncertain histories. At presentation, six had intracranial bleeding and the remainder had bleeding either from the venepuncture site or the gastro-intestinal tract. The presenting signs and symptoms were irritability, vomiting, bulging or full fontanelle, convulsions and diminished or absent neonatal reflexes. Galactosaemia was detected in a 2-month-old infant with prolonged jaundice. There was no surgery-related mortality or complications but one survived for only 2 days on ventilatory support following surgery. Only one of the six survivors had severe neurological sequelae. Late HDN frequently presents with intracranial haemorrhage, leading to high morbidity and mortality. HDN can be the manifestation of an underlying metabolic disorder. Vitamin K prophylaxis of the newborn should be routine in developing countries.

  10. VERY LATE PHOTOMETRY OF SN 2011fe

    International Nuclear Information System (INIS)

    Kerzendorf, W. E.; Taubenberger, S.; Seitenzahl, I. R.; Ruiter, A. J.

    2014-01-01

    The Type Ia supernova SN 2011fe is one of the closest supernovae of the past decades. Due to its proximity and low dust extinction, this object provides a very rare opportunity to study the extremely late time evolution (>900 days) of thermonuclear supernovae. In this Letter, we present our photometric data of SN 2011fe taken at an unprecedented late epoch of ≈930 days with GMOS-N mounted on the Gemini North telescope (g = 23.43 ± 0.28, r = 24.14 ± 0.14, i = 23.91 ± 0.18, and z = 23.90 ± 0.17) to study the energy production and retention in the ejecta of SN 2011fe. Together with previous measurements by other groups, our result suggests that the optical supernova light curve can still be explained by the full thermalization of the decay positrons of 56 Co. This is in spite of theoretical predicted effects (e.g., infrared catastrophe, positron escape, and dust) that advocate a substantial energy redistribution and/or loss via various processes that result in a more rapid dimming at these very late epochs

  11. Late-time cosmological phase transitions

    International Nuclear Information System (INIS)

    Schramm, D.N.

    1990-11-01

    It is shown that the potential galaxy formation and large-scale structure problems of objects existing at high redshifts (Z approx-gt 5), structures existing on scales of 100M pc as well as velocity flows on such scales, and minimal microwave anisotropies (ΔT/T) approx-lt 10 -5 can be solved if the seeds needed to generate structure form in a vacuum phase transition after decoupling. It is argued that the basic physics of such a phase transition is no more exotic than that utilized in the more traditional GUT scale phase transitions, and that, just as in the GUT case, significant random gaussian fluctuations and/or topological defects can form. Scale lengths of ∼100M pc for large-scale structure as well as ∼1 M pc for galaxy formation occur naturally. Possible support for new physics that might be associated with such a late-time transition comes from the preliminary results of the SAGE solar neutrino experiment, implying neutrino flavor mixing with values similar to those required for a late-time transition. It is also noted that a see-saw model for the neutrino masses might also imply a tau neutrino mass that is an ideal hot dark matter candidate. However, in general either hot or cold dark matter can be consistent with a late-time transition. 47 refs., 2 figs

  12. Anatomy of the late radiation encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    De Reuck, J; vander Eecken, H

    1975-01-01

    The clinico-pathological data and the topography of the lesions were determined in 13 cases of late radiation encephalopathy. In one case the arterial vascularisation was studied by the translucidation technique after filling of the blood vessels with a colloidal barium sulphate solution. The radiation lesions consisted of areas of focal necrosis and of diffuse demyelination and necrosis of the deep cerebral structures and the brain stem. Demyelination was predominantly present in cases of late appearance of the neurological symptoms while necrosis was found in cases with a short latency period. The cerebral cortex and the arcuate fibres were always the most preserved structures. The topography of the focal lesions in the cerebral hemispheres and in the brain stem corresponded well to the vascular supply areas of the deep perforating arteries, while the diffuse lesions always had a predominant distribution in the periventricular arterial end- and border-zones. These observations were also confirmed by a post mortem angiographic study. The present report argues once more for a vascular aetiology as cause of the late radiation encephalopathy.

  13. Luminosity monitor

    International Nuclear Information System (INIS)

    Underwood, D. G.

    1998-01-01

    Luminosity monitors are needed in each experiment doing spin physics at RHIC. They concentrate on the luminosity aspects here because, for example, with a 10 -3 raw asymmetry in an experiment, an error of 10 -4 in the luminosity is as significant as a 10% polarization error. Because luminosity is a property of how two beams overlap, the luminosity at an interaction region must be measured at that interaction region in order to be relevant to the experiment at that interaction region. The authors will have to do the physics and the luminosity measurements by using labels on the event sums according to the polarization labels on the colliding bunches. Most likely they will not have independent polarization measurement on each bunch, but only on all the filled bunches in a ring, or perhaps all the bunches that are actually used in an experiment. Most analyses can then be handled by using the nine combinations gotten from three kinds of bunches in each ring, +, - and empty bunches. The empty bunches are needed to measure beam-gas background, (and some, like six in a row, are needed for the beam abort). Much of the difficulty comes from the fact that they must use a physics process to represent the luminosity. This process must have kinematic and geometric cuts both to reduce systematics such as beam-gas backgrounds, and to make it representative of the part of the interaction diamond from which the physics events come

  14. Contamination monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Alamares, A L [Philippine Nuclear Research Inst., Diliman, Quezon City (Philippines)

    1997-06-01

    By virture of Republic Act 2067, as amended the Philippine Atomic Energy Commission (PAEC), now renamed Philippine Nuclear Research Institute (PNRI) is the government agency charged with the regulations and control of radioactive materials in the Philippines. The protection against the hazards of non-ionizing radiation is being monitored by the Radiological Health Service (RHS) of the Department of Health pursuant to the provision of Presidental Decree 480. The RHS issues licenses for possession, handling, and use of x-ray machines and equipment, both industrial and medical, and provide radiation protection training to x-ray technologists and technicians. As part of its regulatory function, the PNRI is charged with the responsibility of assuring that the radiation workers and the public are protected from the hazards associated with the possession, handling, production, manufacturing, and the use of radioactive materials and atomic energy facilities in the Philippines. The protection of radiation workers from the hazards of ionizing radiation has always been a primary concern of PNRI and by limiting the exposure of radiation workers, the risk to population is kept to within acceptable level. In this paper, the following items are described: radiation protection program, radiation protection services, radiation control, and problems encountered/recommendation. (G.K.)

  15. Reactor monitor

    International Nuclear Information System (INIS)

    Takada, Tamotsu.

    1992-01-01

    The device of the present invention monitors a reactor so that each of the operations for the relocation of fuel assemblies and the withdrawal and the insertion of control rods upon exchange of fuel assemblies and control rods in the reactor. That is, when an operator conducts relocating operation by way of a fuel assembly operation section, the device of the present invention judges whether the operation indication is adequate or not, based on the information of control rod arrangement in a control rod memory section. When the operation indication is wrong, a stop signal is sent to a fuel assembly relocating device. Further, when the operator conducts control rod operation by way of a control rod operation section, the device of the present invention judges in the control rod withdrawal judging section, as to whether the operation indication given by the operator is adequate or not by comparing it with fuel assembly arrangement information. When the operation indication is wrong, a stop signal is sent to control rod drives. With such procedures, increase of nuclear heating upon occurrence of erroneous operation can be prevented. (I.S.)

  16. Quantified Effects of Late Pregnancy and Lactation on the Osmotic ...

    African Journals Online (AJOL)

    Quantified Effects of Late Pregnancy and Lactation on the Osmotic Stability of ... in the composition of erythrocyte membranes associated with the physiologic states. Keywords: Erythrocyteosmotic stability, osmotic fragility, late pregnancy, ...

  17. Requests for late termination of pregnancy: Tower Hamlets, 1983.

    OpenAIRE

    Savage, W

    1985-01-01

    The case histories of all women seeking late (more than 20 weeks' gestation) abortion in the NHS district of Tower Hamlets in 1983 were assessed. Of 12 women requesting late abortion, seven underwent termination of pregnancy. All the women had severe social or psychological problems, or both. The main reasons for late presentation were denial of pregnancy, youth, and mental disorder. In a small group of atypical women late abortion seems to be justified for reasons other than fetal abnormality.

  18. 48 CFR 852.273-70 - Late offers.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Late offers. 852.273-70... SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 852.273-70 Late offers. As prescribed in 873.110(a), insert the following provision: Late Offers (JAN 2003) This provision replaces...

  19. Comparative virology and AIDS (review).

    Science.gov (United States)

    Kodama, M; Kodama, T

    1996-03-01

    The scientific debate between pros and cons of the HIV criminal theory of AIDS still remains unsettled. The purpose of this review is to promote resolution of the problem by extracting a common principle of the host-virus relation using data resources for each of 4 viruses as follows: a) polyoma virus, b) Marek's disease virus, c) Ebola virus, d) Korean hemorrhagic fever virus. Conclusions drawn from this study are given as follows: i) Environment emerged as the cardinal factor to modify the process of virus infection in all of the 4 viruses studied. Above all, an accelerating effect of environmental stress on the progression of virus infection was noted in vivo in the majority of viral diseases. ii) Evidence is available to indicate that a healthy cell (or a healthy individual) may harbor virus genes of multiple species without manifesting any pathologic sign. iii) Evidence also suggests that the biological property as well as morphological structure of a virus may vary in reponse to a change of the bioenvironment. On the basis of the above information, we propose to renounce 2 assumptions of classical infection model: a) the hereditarily determined virulence of a microorganism (including virus) be the sole determinant of infection to the effect that its invasion into the host should automatically complete the programmed course of infection; b) virus, a quasi-living creature, should reserve its behavioral independence irrespective of a change of the bioenvironment. The new infection model was constructed on the basis of the selfish gene concept that had been invented by Richard Dawkins to explain the altruistic behavior of an individual. That is, the fate of an exogenous or endogenous virus is under the dual control of the host genome (selfish gene) and the outer environment. The progression of virus infection is conditioned by a crosstalk between them. The selfish gene may use virus (a lifeless substance) as a magic bullet to induce a designated host response. In that sense, virus is not allowed to retain behavioral independence in the practice of its task. The above new model of virus infection was tested for its validity in the recent data of AIDS epidemiology.

  20. 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.

  1. The late biological effects of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1978-06-15

    Full text: The principal objective of the symposium was to review the current status of understanding of the late biological effects of ionizing radiation from external and internal sources. A second objective was to critically evaluate information obtained from epidemiological studies of human population groups as well as from animal experimentation in order to provide a solid scientific basis upon which problems of current concern, such as radiation protection standards and risk-benefit analysis, could be deliberated. Eighty-one papers were presented in 10 sessions which covered epidemiological studies of late effects in human populations exposed to internal and/or external ionizing radiation; quantitative and qualitative data from animal experimentation of late effects; methodological problems and modern approaches; factors influencing susceptibility or expression of late radiation injury; comparative evaluation of late effects induced by radiation and other environmental pollutants, and problems of risk assessment. In addition, there were two evening sessions for free discussion of problems of interpreting animal data, and of the epidemiological studies of occupationally exposed populations. Reports on atomic bomb survivors showed that these epidemiological studies are providing dependable data, such as dose-related excess infant mortality. The reports also revealed the need for consensus in the method employed in the interpretation of data. That was also the case with studies on occupationally exposed populations at Hanford plant, where disparate results were presented on radiation-induced neoplasia among radiation workers. These data are, however, considered not so significant in relative terms when compared to risks involved in other industries. It was recommended that national registry systems for the dosimetry and medical records of radiation workers be established and co-ordinated internationally in order to facilitate reliable epidemiological

  2. Late onset corneal ectasia after LASIK surgery.

    Science.gov (United States)

    Said, Ashraf; Hamade, Issam H; Tabbara, Khalid F

    2011-07-01

    To report late onset corneal ectasia following myopic LASIK. A retrospective cohort case series. Nineteen patients with late onset corneal ectasia following LASIK procedure were examined at The Eye Center, Riyadh, Saudi Arabia. Patients underwent LASIK for myopia with spherical equivalent ranging from -1.4 to -13.75 diopters. Age and gender, history of systemic or local diseases, and time of onset of corneal ectasia were recorded. Eye examination and corneal topographical analyses were done before and after LASIK surgery. Nineteen patients (29 eyes) with late onset corneal ectasia were identified from 1998 to 2008 in 13 male and six female patients. The mean follow-up period was 108 ± 23 months (range 72-144 months). No patient had pre-operative identifiable risk factors for corneal ectasia and the mean time of onset was 57 ± 24 months (range 24-120 months after LASIK). The pre-operative values included mean central pachymetry 553 ± 25 μm, mean keratometry reading of 42.9 ± 1.5 diopters, average oblique cylinder of 1.4 ± 1.2 diopters, posterior surface elevation of 26 ± 2.1 diopters, corneal flap thickness of 160 μm, mean spherical equivalent of -5.6 ± 3.6 diopters, and calculated residual corneal stromal bed thickness was 288 ± 35 μm. Three (5 eyes) patients developed ectasia after pregnancy. Three (4 eyes) patients developed corneal ectasia following severe adenoviral keratoconjunctivitis and had positive PCR for adenovirus type 8. Corneal ectasia may develop many years after LASIK surgery and symptoms could go undetected for some time. Pregnancy and adenoviral keratoconjunctivitis occurred post-operatively in six patients.

  3. Computed tomography of late-onset epilepsy

    International Nuclear Information System (INIS)

    Kim, Young Sik; Im, Jae Yung; Joo, Yang Goo; Park, Sam Kyoon

    1982-01-01

    Epilepsy can be divided into idiopathic epilepsy and symptomatic epilepsy according to the existence of underlying organic brain disease. It has been said that the incidence of the symptomatic epilepsy caused by underlying organic brain disease is higher in late-onset epilepsy after the age of 20 than in childhood-onset epilepsy. CT is very sensitive and non-invasive method for detection of organic brain disease. 168 cases of late-onset epilepsy after the age of of 20 were studied by CT in recent 2 years were analyzed. The results were as follows: 1. The 3rd decade was the most frequent age group, and the ratio of male to female was 2.5 : 1. 2. Structural abnormality on brain CT was demonstrated in 51.8% of the patient. 3. The older onset of age was, the higher the ratio of abnormal CT findings, except 5th decade which showed less CT abnormality than 4th decade. 4. The most frequent history related to epilepsy was trauma. 63.1% of patients had no relevant history: and they showed CT findings of brain tumor, atrophy and infraction in decreasing order of frequency. 5. Abnormal CT findings was demonstrated in 49.2% of normal neurologic examination and in 46.4% of normal EEG study. 6. The most frequent lesion of abnormal CT scan in late-onset epilepsy was 30 cases (18.4%) of brain atrophy. The next frequent lesion was 18 cases (10.7%) of brain tumor. Infarction, parasites and calcification were other frequent lesions

  4. Reconstructing the genetic history of late Neanderthals.

    Science.gov (United States)

    Hajdinjak, Mateja; Fu, Qiaomei; Hübner, Alexander; Petr, Martin; Mafessoni, Fabrizio; Grote, Steffi; Skoglund, Pontus; Narasimham, Vagheesh; Rougier, Hélène; Crevecoeur, Isabelle; Semal, Patrick; Soressi, Marie; Talamo, Sahra; Hublin, Jean-Jacques; Gušić, Ivan; Kućan, Željko; Rudan, Pavao; Golovanova, Liubov V; Doronichev, Vladimir B; Posth, Cosimo; Krause, Johannes; Korlević, Petra; Nagel, Sarah; Nickel, Birgit; Slatkin, Montgomery; Patterson, Nick; Reich, David; Prüfer, Kay; Meyer, Matthias; Pääbo, Svante; Kelso, Janet

    2018-03-29

    Although it has previously been shown that Neanderthals contributed DNA to modern humans, not much is known about the genetic diversity of Neanderthals or the relationship between late Neanderthal populations at the time at which their last interactions with early modern humans occurred and before they eventually disappeared. Our ability to retrieve DNA from a larger number of Neanderthal individuals has been limited by poor preservation of endogenous DNA and contamination of Neanderthal skeletal remains by large amounts of microbial and present-day human DNA. Here we use hypochlorite treatment of as little as 9 mg of bone or tooth powder to generate between 1- and 2.7-fold genomic coverage of five Neanderthals who lived around 39,000 to 47,000 years ago (that is, late Neanderthals), thereby doubling the number of Neanderthals for which genome sequences are available. Genetic similarity among late Neanderthals is well predicted by their geographical location, and comparison to the genome of an older Neanderthal from the Caucasus indicates that a population turnover is likely to have occurred, either in the Caucasus or throughout Europe, towards the end of Neanderthal history. We find that the bulk of Neanderthal gene flow into early modern humans originated from one or more source populations that diverged from the Neanderthals that were studied here at least 70,000 years ago, but after they split from a previously sequenced Neanderthal from Siberia around 150,000 years ago. Although four of the Neanderthals studied here post-date the putative arrival of early modern humans into Europe, we do not detect any recent gene flow from early modern humans in their ancestry.

  5. Late-presenting congenital diaphragmatic hernia

    Directory of Open Access Journals (Sweden)

    Raashid Hamid

    2014-01-01

    Full Text Available Background: This study was undertaken to highlight the clinical profile, misdiagnosis, surgical treatment,and prognosis of late-presenting congenital diaphragmatic hernia (CDH cases in a tertiary level hospital. Patients and Methods: This retrospective study included all the babies and children >1 month of age with CDH who were admitted in our Hospital (Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India during the period between January 2008 and December 2013. Babies with age <1 month were excluded from the study. Data regarding clinical profile, operative records, and follow-up was reviewed and analysed statistically. Results: A total of 20 patients were included in this study. The clinical picture ranged from respiratory distress (13 patients to non-specific gastrointestinal complaints (5 patients. In two patients, CDH was misdiagnosed as pneumothorax and had got chest tube inserted in other hospitals before referral to this tertiary care centre. In 14 patients chest, X-ray revealed the diagnosis of CDH and in remaining five patients (including the two patients with misdiagnosis further investigations were undertaken to establish the diagnosis. Age ranged from 45 days to 17 years with an average age of 58.9 months. There were 12 male and 8 female patients. In all the 20 patients, surgical procedures were undertaken with the retrieval of herniated contents from the thoracic cavity and repair of the diaphragmatic defect. There was no mortality in our series. All the 20 patients were followed-up for a period ranging from 6 months to 5 years (median 3.1 years. Conclusions: Late-presenting CDH can have diverse clinical presentation. Late diagnosis and misdiagnosis can result in significant morbidity and potential mortality if these cases are not managed properly at an appropriate stage. Outcome is favourable if these patients are expeditiously identified and surgically repaired.

  6. Virologic versus cytologic triage of women with equivocal Pap smears: a meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia.

    Science.gov (United States)

    Arbyn, Marc; Buntinx, Frank; Van Ranst, Marc; Paraskevaidis, Evangelos; Martin-Hirsch, Pierre; Dillner, Joakim

    2004-02-18

    The appropriate management of women with minor cytologic lesions in their cervix is unclear. We performed a meta-analysis to assess the accuracy of human papillomavirus (HPV) DNA testing as an alternative to repeat cytology in women who had equivocal results on a previous Pap smear. Data were extracted from articles published between 1992 and 2002 that contained results of virologic and cytologic testing followed by colposcopically directed biopsy in women with an index smear showing atypical cells of undetermined significance (ASCUS). Fifteen studies were identified in which HPV triage and the histologic outcome (presence or absence of a cervical intraepithelial neoplasia of grade II or worse [CIN2+]) was documented. Nine, seven, and two studies also documented the accuracy of repeat cytology when the cutoff for abnormal cytology was set at a threshold of ASCUS or worse, low-grade squamous intraepithelial lesion (LSIL) or worse, or high-grade squamous intraepithelial lesion (HSIL) or worse, respectively. Random-effects models were used for pooling of accuracy parameters in case of interstudy heterogeneity. Differences in accuracy were assessed by pooling the ratio of the sensitivity (or specificity) of HPV testing to that of repeat cytology. The sensitivity and specificity were 84.4% (95% confidence interval [CI] = 77.6% to 91.1%) and 72.9% (95% CI = 62.5% to 83.3%), respectively, for HPV testing overall and 94.8% (95% CI = 92.7% to 96.9%) and 67.3% (95% CI = 58.2% to 76.4%), respectively, for HPV testing in the eight studies that used the Hybrid Capture II assay. Sensitivity and specificity of repeat cytology at a threshold for abnormal cytology of ASCUS or worse was 81.8% (95% CI = 73.5% to 84.3%) and 57.6% (95% CI = 49.5% to 65.7%), respectively. Repeat cytology that used higher cytologic thresholds yielded substantially lower sensitivity but higher specificity than triage with the Hybrid Capture II assay. The ratio of the sensitivity of the Hybrid Capture II

  7. 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

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

    Directory of Open Access Journals (Sweden)

    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

  9. 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

  10. Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study.

    Science.gov (United States)

    Thibault, Vincent; Gaudy-Graffin, Catherine; Colson, Philippe; Gozlan, Joël; Schnepf, Nathalie; Trimoulet, Pascale; Pallier, Coralie; Saune, Karine; Branger, Michel; Coste, Marianne; Thoraval, Francoise Roudot

    2013-03-15

    Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia. A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated. Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected. Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management

  11. Epidemiology and virologic investigation of human enterovirus 71 infection in the Republic of Korea from 2007 to 2012: a nationwide cross-sectional study.

    Science.gov (United States)

    Kim, Hye-Jin; Hyeon, Ji-Yeon; Hwang, Seoyeon; Lee, Yong-Pyo; Lee, Sang Won; Yoo, Jung Sik; Kang, Byunghak; Ahn, Jeong-Bae; Jeong, Yong-Seok; Lee, June-Woo

    2016-08-18

    Enterovirus (EV) 71 is the main pathogen associated with hand, foot and mouth disease (HFMD) or herpangina. Outbreaks of HFMD caused by EV71 infection are associated severe neurological disease and high mortality rates in children. Several sporadic cases of EV71 infection occurred in the Republic of Korea (ROK) in 2000, and EV71 infections were not reported thereafter until 2006. In this prospective study, we report the epidemic and virologic characteristics of the EV71 endemic from 2007 to 2012 in the Republic of Korea. We analyzed characteristics of the EV71 infection-associated epidemic from collected specimens and clinical information from 9987 patients with suspected EV infection from the National EV Surveillance System in ROK. To identify the EV71 subgenotype, the homology of viral protein 1 sequences obtained using reverse transcription polymerase chain reaction was compared with the sequences on other countries available from GenBank database. EV71 was detected in 585 (16.7 %) specimens (cerebrospinal fluid, stool or rectal swabs, throat swabs and blood) during study period and was most frequently observed during epidemic seasons in 2009-2012. Major manifestations due to EV71 infection were HFMD (62.2 %) and HFMD with severe neurological complications (28.4 %). Five deaths (0.9 %) due to EV71 infection occurred, with an increased mortality rate during the period after 2009. Most patients (476; 81.4 %) were less than 5 years of age. Analysis of the monthly distribution showed that there was an obvious seasonal pattern to the epidemics, with infections appearing from June to August. The major subgenotype of EV71 isolates circulating in ROK was the C4a strain, which has also appeared in China, Japan and Vietnam. This surveillance provided valuable data on the epidemic characteristics of EV71 infections in ROK during a 6-year period. Our findings provide data to assist during future outbreaks of EV71 and associated acute neurologic disease.

  12. Late complications following cryotherapy of lattice degeneration.

    Science.gov (United States)

    Benson, W E; Morse, P H; Nantawan, P

    1977-10-01

    We observed 341 patients who had received cryotherapy for lattice degeneration in order to identify possible late complications. Sequelae such as retinal tears posterior to an operculum or flap tears within treated areas showed that treatment did not necessarily prevent subsequent vitreous traction. Moreover, the newly created flap tears may extend beyond the treated area and can cause retinal detachment. Even scleral buckling did not necesserily prevent further traction. Therefore, we concluded that when cryotherapy is used to treat lattice degeneration, an adequate margin of surrounding retina should be treated and the treatment should extend to the ora serrata.

  13. An ovarian teratoma of late Roman age.

    Science.gov (United States)

    Armentano, Núria; Subirana, Mercè; Isidro, Albert; Escala, Oscar; Malgosa, Assumpció

    2012-12-01

    We report here a very unusual pelvic calcification recovered from the remains of a 30-40-year-old woman found at the late Roman period archeological site of La Fogonussa (Lleida, Catalonia). Although differential diagnoses for calcifications of the pelvis are complicated in archeological contexts, the precise localization, macroscopic features, and the presence of teeth along with part of a small bone led us to identify this case as an ovarian teratoma, based upon gross observations and computerized tomography (CT). Copyright © 2012 Elsevier Inc. All rights reserved.

  14. 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

  15. 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

  16. 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.

  17. 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.

    Science.gov (United States)

    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.

  18. 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.

  19. 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

  20. Implementación de un Sistema de Gestión de la Calidad en la Unidad de Diagnóstico de Virología Animal

    OpenAIRE

    Obret, Yalainne; Vega, Armando; Perera, Carmen Laura; Betancourt, Arsenio

    2016-01-01

    La Organización Mundial de Salud Animal (OIE) recomienda a los laboratorios de diagnóstico realizar sus ensayos en correspondencia con un Sistema de Gestión de la Calidad (SGC). La Unidad de Diagnóstico de Virología Animal (UDVA) se propuso la planificación del SGC bajo los requisitos de la NC ISO/IEC 17025: 2006 y se incluyeron requisitos de Bioseguridad establecidos en la Resolución 180/2007 sobre Seguridad Biológica. Se estableció el sistema de documentación, como soporte del sistema de ge...

  1. Cross-Sectional Analysis of Late HAART Initiation in Latin America and the Caribbean: Late Testers and Late Presenters

    Science.gov (United States)

    Crabtree-Ramírez, Brenda; Caro-Vega, Yanink; Shepherd, Bryan E.; Wehbe, Firas; Cesar, Carina; Cortés, Claudia; Padgett, Denis; Koenig, Serena; Gotuzzo, Eduardo; Cahn, Pedro; McGowan, Catherine; Masys, Daniel; Sierra-Madero, Juan

    2011-01-01

    Background Starting HAART in a very advanced stage of disease is assumed to be the most prevalent form of initiation in HIV-infected subjects in developing countries. Data from Latin America and the Caribbean is still lacking. Our main objective was to determine the frequency, risk factors and trends in time for being late HAART initiator (LHI) in this region. Methodology Cross-sectional analysis from 9817 HIV-infected treatment-naïve patients initiating HAART at 6 sites (Argentina, Chile, Haiti, Honduras, Peru and Mexico) from October 1999 to July 2010. LHI had CD4+ count ≤200cells/mm3 prior to HAART. Late testers (LT) were those LHI who initiated HAART within 6 months of HIV diagnosis. Late presenters (LP) initiated after 6 months of diagnosis. Prevalence, risk factors and trends over time were analyzed. Principal Findings Among subjects starting HAART (n = 9817) who had baseline CD4+ available (n = 8515), 76% were LHI: Argentina (56%[95%CI:52–59]), Chile (80%[95%CI:77–82]), Haiti (76%[95%CI:74–77]), Honduras (91%[95%CI:87–94]), Mexico (79%[95%CI:75–83]), Peru (86%[95%CI:84–88]). The proportion of LHI statistically changed over time (except in Honduras) (p≤0.02; Honduras p = 0.7), with a tendency towards lower rates in recent years. Males had increased risk of LHI in Chile, Haiti, Peru, and in the combined site analyses (CSA). Older patients were more likely LHI in Argentina and Peru (OR 1.21 per +10-year of age, 95%CI:1.02–1.45; OR 1.20, 95%CI:1.02–1.43; respectively), but not in CSA (OR 1.07, 95%CI:0.94–1.21). Higher education was associated with decreased risk for LHI in Chile (OR 0.92 per +1-year of education, 95%CI:0.87–0.98) (similar trends in Mexico, Peru, and CSA). LHI with date of HIV-diagnosis available, 55% were LT and 45% LP. Conclusion LHI was highly prevalent in CCASAnet sites, mostly due to LT; the main risk factors associated were being male and older age. Earlier HIV-diagnosis and earlier treatment initiation

  2. Can Mustard Gas Induce Late Onset Polyneuropathy?

    Directory of Open Access Journals (Sweden)

    SJ. Mousavi

    2007-11-01

    Full Text Available Background:Mustard gas, lethal in high doses, affects multiple organs such as skin, eye and respiratory system. We studied the development of late onset mustardinduced polyneuropathy among chemically wounded Iranian veterans.Methods:In this descriptive study,100 chemically wounded Iranian veterans with severe eye involvement were examined for any signs and symptoms of polyneuropathy by an internist.20 patients were suspected to have neurological symptoms or signs.These patients were examined by a neurologist again. 13 showed abnormal neurological symptoms. Electrodiagnostic exams were performed for this group by another physician.Results:13 veterans had abnormal neurological exam results with prominent sensory signs and symptoms in almost all of them. Brisk deep tendon reflexes were found in 3 cases. Electrodiagnostic studies were compatible with axonal type distal sensory polyneuropathy in 6 subjects. Conclusion: To the best of our knowledge, this is the first report of late onset polyneuropathy among chemically-wounded victims who were exposed to mustard gas. The pathophysiology of this form of neuropathy is still unknown. Unlike most toxic neuropathies,obvious clinical signs and symptoms appeared several years after exposure. No specific treatment for.polyneuropathy due to chemical weapons exposure has been described to date.

  3. The Accelerated Late Adsorption of Pulmonary Surfactant

    Science.gov (United States)

    2011-01-01

    Adsorption of pulmonary surfactant to an air−water interface lowers surface tension (γ) at rates that initially decrease progressively, but which then accelerate close to the equilibrium γ. The studies here tested a series of hypotheses concerning mechanisms that might cause the late accelerated drop in γ. Experiments used captive bubbles and a Wilhelmy plate to measure γ during adsorption of vesicles containing constituents from extracted calf surfactant. The faster fall in γ reflects faster adsorption rather than any feature of the equation of state that relates γ to surface concentration (Γ). Adsorption accelerates when γ reaches a critical value rather than after an interval required to reach that γ. The hydrophobic surfactant proteins (SPs) represent key constituents, both for reaching the γ at which the acceleration occurs and for producing the acceleration itself. The γ at which rates of adsorption increase, however, is unaffected by the Γ of protein in the films. In the absence of the proteins, a phosphatidylethanolamine, which, like the SPs, induces fusion of the vesicles with the interfacial film, also causes adsorption to accelerate. Our results suggest that the late acceleration is characteristic of adsorption by fusion of vesicles with the nascent film, which proceeds more favorably when the Γ of the lipids exceeds a critical value. PMID:21417351

  4. Late Quaternary climate change shapes island biodiversity.

    Science.gov (United States)

    Weigelt, Patrick; Steinbauer, Manuel Jonas; Cabral, Juliano Sarmento; Kreft, Holger

    2016-04-07

    Island biogeographical models consider islands either as geologically static with biodiversity resulting from ecologically neutral immigration-extinction dynamics, or as geologically dynamic with biodiversity resulting from immigration-speciation-extinction dynamics influenced by changes in island characteristics over millions of years. Present climate and spatial arrangement of islands, however, are rather exceptional compared to most of the Late Quaternary, which is characterized by recurrent cooler and drier glacial periods. These climatic oscillations over short geological timescales strongly affected sea levels and caused massive changes in island area, isolation and connectivity, orders of magnitude faster than the geological processes of island formation, subsidence and erosion considered in island theory. Consequences of these oscillations for present biodiversity remain unassessed. Here we analyse the effects of present and Last Glacial Maximum (LGM) island area, isolation, elevation and climate on key components of angiosperm diversity on islands worldwide. We find that post-LGM changes in island characteristics, especially in area, have left a strong imprint on present diversity of endemic species. Specifically, the number and proportion of endemic species today is significantly higher on islands that were larger during the LGM. Native species richness, in turn, is mostly determined by present island characteristics. We conclude that an appreciation of Late Quaternary environmental change is essential to understand patterns of island endemism and its underlying evolutionary dynamics.

  5. Late neurotoxicity after nasopharyngeal carcinoma treatment

    International Nuclear Information System (INIS)

    Siala, W.; Mnejja, W.; Daoud, J.; Khabir, A.; Boudawara, T.; Ben Mahfoudh, K.; Ghorbel, A.; Frikha, M.

    2009-01-01

    Purpose A retrospective analysis of risk factors for late neurological toxicity after nasopharyngeal carcinoma radiotherapy. Patients and methods Between 1993 and 2004, 239 patients with non metastatic nasopharyngeal carcinoma were treated by radiotherapy associated or not to chemotherapy. Radiotherapy was delivered with two modalities: hyperfractionated for 82 patients and conventional fractionation for 157 patients. We evaluated the impact of tumour stage, age, gender, radiotherapy schedule and chemotherapy on neurological toxicity. Results After a mean follow-up of 107 months (35-176 months), 21 patients (8.8%) developed neurological complications, such as temporal necrosis in nine cases, brain stem necrosis in five cases, optics nerve atrophy in two cases and myelitis in one case. Five- and ten-year free of toxicity survival was 95 and 84% respectively. Young patients had greater risk of temporal necrosis, and hyperfractionated radiotherapy was associated with a significantly higher risk of neurological complications (14.6% vs 5.7%, p = 0.02). On multivariate analysis, hyperfractionation and age were insignificant. Conclusion Late neurological toxicity after radiotherapy for nasopharyngeal carcinoma was rare. Younger age and hyperfractionation were considered as risk factors of neurological toxicity in our study

  6. Late-onset Bartter syndrome type II.

    Science.gov (United States)

    Gollasch, Benjamin; Anistan, Yoland-Marie; Canaan-Kühl, Sima; Gollasch, Maik

    2017-10-01

    Mutations in the ROMK1 potassium channel gene ( KCNJ1 ) cause antenatal/neonatal Bartter syndrome type II (aBS II), a renal disorder that begins in utero , accounting for the polyhydramnios and premature delivery that is typical in affected infants, who develop massive renal salt wasting, hypokalaemic metabolic alkalosis, secondary hyperreninaemic hyperaldosteronism, hypercalciuria and nephrocalcinosis. This BS type is believed to represent a disorder of the infancy, but not in adulthood. We herein describe a female patient with a remarkably late-onset and mild clinical manifestation of BS II with compound heterozygous KCNJ1 missense mutations, consisting of a novel c.197T > A (p.I66N) and a previously reported c.875G > A (p.R292Q) KCNJ1 mutation. We implemented and evaluated the performance of two different bioinformatics-based approaches of targeted massively parallel sequencing [next generation sequencing (NGS)] in defining the molecular diagnosis. Our results demonstrate that aBS II may be suspected in patients with a late-onset phenotype. Our experimental approach of NGS-based mutation screening combined with Sanger sequencing proved to be a reliable molecular approach for defining the clinical diagnosis in our patient, and results in important differential diagnostic and therapeutic implications for patients with BS. Our results could have a significant impact on the diagnosis and methodological approaches of genetic testing in other patients with clinical unclassified phenotypes of nephrocalcinosis and congenital renal electrolyte abnormalities.

  7. Late-onset Huntington's disease: diagnostic and prognostic considerations.

    Science.gov (United States)

    Koutsis, Georgios; Karadima, Georgia; Kladi, Athina; Panas, Marios

    2014-07-01

    To address diagnostic and prognostic issues in patients with late-onset Huntington's disease (HD). We analyzed a cohort of 41 late-onset (≥60 years) HD patients and compared them to 39 late-onset patients referred for HD testing that were negative for the HD-expansion and to 290 usual-onset (20-59 years) HD patients. Disease severity was assessed by the Total Functional Capacity Scale. Late-onset HD comprised 11.5% of our HD cohort. In total, 70.7% of late-onset HD patients had positive family history compared to 15.4% of late-onset expansion-negative patients (p < 0.001). Clinical features at onset or presentation could not usefully distinguish between late-onset expansion-positive and negative patients, excepting hemichorea, which was absent from the HD group (p = 0.024). Chorea was the first clinical feature in 53.7% and a presenting feature in 90.2% of late-onset HD. The mutation hit rate for late-onset patients was 51.3%, lower than in usual-onset patients (p = 0.04). Frequencies of chorea, cognitive impairment and psychiatric manifestations at onset or presentation were not significantly different between late-onset and usual-onset HD patients. Gait unsteadiness however was more common at presentation in late-onset HD (p = 0.007). Late-onset HD patients reached a severe stage of illness on average 2.8 years earlier than usual-onset HD patients (p = 0.046). A positive family history suggestive of HD, although absent in a third of patients, remains a helpful clue in diagnosing late-onset HD. Prognosis of late-onset HD in terms of Total Functional Capacity appears no better and shows a trend of being somewhat less favorable compared to usual-onset HD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Takaka Fossil Cave : a stratified Late Glacial to Late Holocene deposit from Takaka Hill, New Zealand

    International Nuclear Information System (INIS)

    Worthy, T.H.; Roscoe, D.

    2003-01-01

    A rich terrestrial vertebrate fauna from the pitfall trap deposit of Takaka Fossil Cave on Takaka Hill, South Island, New Zealand, is described. Radiocarbon ages on moa bones bracket the onset of sedimentation in the site to between 12361 and 11354 14 C yrs BP. Euryapteryx geranoides was in the Late Glacial moa fauna that predates the onset of sedi-mentation in the site, but was absent in younger faunas. The moa Anomalopteryx didiformis was present in the Late Glacial fauna as well throughout the Holocene. A total of 1633 bones from 25 species of birds and a further 895 bones of 154 individuals of vertebrates other than birds (two species of frog, one tuatara, three lizards, two bats, and a rat) were identified in the total recovered fauna. A well-preserved partial skeleton of Haast's eagle (Harpagornis moorei) of Late Glacial age had severe arthritis. Unusually small specimens of Euryapteryx were morphologically diagnosed as E. geranoides, and confirmed as such by mitochondrial DNA analysis. The molluscan fauna contained two aquatic, troglobitic hydrobiids and 29 taxa of land snails. While there is little change in species diversity between lower and upper layers, there are marked changes in relative abundance of some taxa that suggest the environment was drier in the Early and Middle Holocene than it was in the Late Holocene. (author). 26 refs., 3 figs., 4 tabs

  9. Late-modern transformation of Islam or Islamic transformation of Late-modern Religiosity?

    DEFF Research Database (Denmark)

    Riexinger, Martin Thomas

    2017-01-01

    The Turkish author Muhammed Bozdağ, who has no formal religious education, has been popular since the late 1990s because of his self-help seminars and self-help books. Though they are based on the adaptation of Western New Age-inspired models, Bozdağ uses many of the models’ parascientific concepts...

  10. Cohort Profile: The Danish Testicular Cancer Late Treatment Effects Cohort (DaTeCa-LATE

    Directory of Open Access Journals (Sweden)

    Michael Kreiberg

    2018-02-01

    Full Text Available The cohort was set up in order to analyze late effects in long-term testicular cancer survivors (TCS and to contribute to the design of future follow-up programs addressing and potentially preventing late effects. Data for this cross-sectional study were collected between January 1, 2014, and December 31, 2016, among living Danish TCS and 60% agreed to participate in the cohort (N = 2,572. Mean time since testicular cancer (TC diagnosis was 18 years (range 7–33 and mean age of participants was 53 years (range 25–95. Data consist of results of a questionnaire with patient reported outcomes which covers a broad range of items on late-effects. The study also included data obtained through linkages to Danish registries, a biobank, and clinical data from hospital files and pathology reports originating from the Danish Testicular Cancer Database (DaTeCa. The treatment during the observation period has been nearly the same for all stages of TC and is in agreement with today’s standard treatment, this allows for interesting analysis with a wide timespan. We have extensive data on non-responders and are able to validate our study findings. Data from a Danish reference population (N = 162,283 allow us to compare our findings with a Danish background population. The cohort can easily be extended to access more outcomes, or include new TCS. A limitation of the present study is the cross-sectional design and despite the large sample size, The Danish Testicular Cancer Late Treatment Effects Cohort (DaTeCa-LATE lacks statistical power to study very rare late effects. Since it was voluntary to participate in the study we have some selection bias, for instance, we lack responders who were not in a paired relationship, but we would still argue that this cohort of TCSs is representative for TCSs in Denmark.Collaboration and data accessResearches interested in collaboration with the DaTeCa-LATE study group please contact Professor Gedske Daugaard

  11. Development of web monitoring radiation area monitor

    International Nuclear Information System (INIS)

    Jung, Hoon Jin; Lee, Jun Hee; Namkoong, Phil; Lee, Dong Hoon; Lee, Su Hong; Lee, Gun Bae

    2005-01-01

    Recently the increasing number of radioisotope industry and nuclear facility have ever raised the possibility of radiation safety accident. As such a result, radioisotope companies and nuclear facility operators have become to be much interested in radiation area monitoring for efficient radiation protection. At present, almost of the radiation area monitors which are imported products are outdated in aspect of their functions. Diversification of the monitoring work is urgently demanding additional functions to be added. Thus we have developed new-type digital area monitor which enables remote web monitoring with image and radiation dose rate value at distant places through using internet, the latest IT technology, and radiation measurement technology

  12. Late graft explants in endovascular aneurysm repair.

    Science.gov (United States)

    Turney, Eric J; Steenberge, Sean P; Lyden, Sean P; Eagleton, Matthew J; Srivastava, Sunita D; Sarac, Timur P; Kelso, Rebecca L; Clair, Daniel G

    2014-04-01

    With more than a decade of use of endovascular aneurysm repair (EVAR), we expect to see a rise in the number of failing endografts. We review a single-center experience with EVAR explants to identify patterns of presentation and understand operative outcomes that may alter clinical management. A retrospective analysis of EVARs requiring late explants, >1 month after implant, was performed. Patient demographics, type of graft, duration of implant, reason for removal, operative technique, length of stay, complications, and in-hospital and late mortality were reviewed. During 1999 to 2012, 100 patients (91% men) required EVAR explant, of which 61 were placed at another institution. The average age was 75 years (range, 50-93 years). The median length of time since implantation was 41 months (range, 1-144 months). Explanted grafts included 25 AneuRx (Medtronic, Minneapolis, Minn), 25 Excluder (W. L. Gore & Associates, Flagstaff, Ariz), 17 Zenith (Cook Medical, Bloomington, Ind), 15 Talent (Medtronic), 10 Ancure (Guidant, Indianapolis, Ind), 4 Powerlink (Endologix, Irvine, Calif), 1 Endurant (Medtronic), 1 Quantum LP (Cordis, Miami Lakes, Fla), 1 Aorta Uni Iliac Rupture Graft (Cook Medical, Bloomington, Ind), and 1 homemade tube graft. Overall 30-day mortality was 17%, with an elective case mortality of 9.9%, nonelective case mortality of 37%, and 56% mortality for ruptures. Endoleak was the most common indication for explant, with one or more endoleaks present in 82% (type I, 40%; II, 30%; III, 22%; endotension, 6%; multiple, 16%). Other reasons for explant included infection (13%), acute thrombosis (4%), and claudication (1%). In the first 12 months, 23 patients required explants, with type I endoleak (48%) and infection (35%) the most frequent indication. Conversely, 22 patients required explants after 5 years, with type I (36%) and type III (32%) endoleak responsible for most indications. The rate of EVAR late explants has increased during the past decade at our

  13. Monitoring Knowledge Base (MKB)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Monitoring Knowledge Base (MKB) is a compilation of emissions measurement and monitoring techniques associated with air pollution control devices, industrial...

  14. Monitoring the vegetation recovery in Østerild Plantage 2013. Part 1

    DEFF Research Database (Denmark)

    Wind, Peter

    The trees in a part of Østerild Plantage have been cut down to give room for a national test center. Before the afforestation DCE has performed a baseline monitoring in the summer of 2011. DCE has in late summer 2013 re-monitored the recovery of the vegetation cover in the northernmost part...

  15. Late presentation for HIV care across Europe

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Lundgren, Jens; Antinori, Andrea

    2015-01-01

    Late presentation (LP) for HIV care across Europe remains a significant issue. We provide a cross-European update from 34 countries on the prevalence and risk factors of LP for 2010-2013. People aged ≥ 16 presenting for HIV care (earliest of HIV-diagnosis, first clinic visit or cohort enrollment......) after 1 January 2010 with available CD4 count within six months of presentation were included. LP was defined as presentation with a CD4 count HIV diagnosis. Logistic regression investigated changes in LP over time. A total.......02-1.32), and a significant decline in LP in northern Europe (aOR/year later 0.89; 95% CI: 0.85-0.94). Further improvements in effective HIV testing strategies, with a focus on vulnerable groups, are required across the European continent....

  16. Dysphagia lusoria: a late onset presentation.

    Science.gov (United States)

    Bennett, Alice Louise; Cock, Charles; Heddle, Richard; Morcom, Russell Kym

    2013-04-21

    Dysphagia lusoria is a term used to describe dysphagia secondary to vascular compression of the oesophagus. The various embryologic anomalies of the arterial brachial arch system often remain unrecognised and asymptomatic, but in 30%-40% of cases can result in tracheo-oesophageal symptoms, which in the majority of cases manifest as dysphagia. Diagnosis of dysphagia lusoria is via barium swallow and chest Computed tomography scan. Manometric abnormalities are variable, but age-related manometric changes may contribute to clinically relevant dysphagia lusoria in patients who present later in life. Our report describes a case of late-onset dysphagia secondary to a right aortic arch with an aberrant left subclavian artery, which represents a rare variant of dysphagia lusoria. The patient had proven additional oesophageal dysmotility with solid bolus only and a clinical response to dietary modification.

  17. Late Ordovician brachiopods from eastern North Greenland

    DEFF Research Database (Denmark)

    Mac Ørum Rasmussen, Christian

    2013-01-01

    Late Ordovician rhynchonelliformean brachiopods, typical of the North American Red River fauna, are found sporadically in the BOrglum River Formation of the Centrum SO area, Kronprins Christian Land, eastern North Greenland. The geographical distribution of this characteristic brachiopod fauna......) to younger strata exclusively yielding specimens of H.gigas. As H.gigas occurs in the upper part of the Cape Calhoun Formation in Washington Land, it indicates that the upper boundary of the Cape Calhoun Formation is considerably younger than previous estimates, reaching into the uppermost Katian (middle...... (Richmondian), it possesses a strong provincial signal during the later Ordovician. The new occurrences indicate that this fauna extended to the north-eastern margin of the Laurentian Craton. It lived in close association with cosmopolitan faunal elements that may have been the earliest sign of the succeeding...

  18. Spectroscopy of late type giant stars

    Science.gov (United States)

    Spaenhauer, A.; Thevenin, F.

    1984-06-01

    An attempt to calibrate broadband RGU colors of late type giant stars in terms of the physical parameters of the objects is reported. The parameters comprise the effective temperature, surface gravity and global metal abundance with respect to the sun. A selection of 21 giant star candidates in the Basel fields Plaut 1, Centaurus III and near HD 95540 were examined to obtain a two color plot. Attention is focused on the G-R color range 1.5-2.15 mag, i.e., spectral types K0-K5. A relationship between R and the metallicity is quantified and shown to have a correlation coefficient of 0.93. No correlation is found between metallicity and gravity or R and the effective temperature.

  19. Phylogenetic paleobiogeography of Late Ordovician Laurentian brachiopods

    Directory of Open Access Journals (Sweden)

    Jennifer E. Bauer

    2014-12-01

    Full Text Available Phylogenetic biogeographic analysis of four brachiopod genera was used to uncover large-scale geologic drivers of Late Ordovician biogeographic differentiation in Laurentia. Previously generated phylogenetic hypotheses were converted into area cladograms, ancestral geographic ranges were optimized and speciation events characterized as via dispersal or vicariance, when possible. Area relationships were reconstructed using Lieberman-modified Brooks Parsimony Analysis. The resulting area cladograms indicate tectonic and oceanographic changes were the primary geologic drivers of biogeographic patterns within the focal taxa. The Taconic tectophase contributed to the separation of the Appalachian and Central basins as well as the two midcontinent basins, whereas sea level rise following the Boda Event promoted interbasinal dispersal. Three migration pathways into the Cincinnati Basin were recognized, which supports the multiple pathway hypothesis for the Richmondian Invasion.

  20. Neuropsychological functioning in late-life depression

    Directory of Open Access Journals (Sweden)

    Gro Strømnes Dybedal

    2013-06-01

    Full Text Available Background: The literature describing neurocognitive function in patients with late-life depression (LLD show inconsistent findings in regard to incidence and main deficits. Reduced information processing speed is in some studies found to explain deficits in higher order cognitive function, while other studies report specific deficits in memory and executive function. Our aim was to determine the characteristics of neuropsychological functioning in non-demented LLD patients.Methods; A comprehensive neuropsychological battery was administered to a group of hospitalized LLD patients and healthy control subjects. Thirty-nine patients without dementia, 60 years or older meeting DSM-IV criteria for current episode of major depression, and 18 nondepressed control subjects were included. The patient group was characterized by having a long lasting current depressive episode of late-onset depression and by being non-responders to treatment with antidepressants. Neurocognitive scores were calculated for the domains of information processing speed, verbal memory, visuospatial memory, executive function, and language. Number of impairments (performance below the 10th percentile of the control group per domain for each participant was calculated. Results: Nearly half of the patients had a clinically significant cognitive impairment in at least one neurocognitive domain. Relative to healthy control subjects, LLD patients performed significantly poorer in the domains of information processing speed and executive function. Executive abilities were most frequently impaired in the patient group (39 % of the patients. Even when controlling for differences in processing speed, patients showed more executive deficits than controls. CONCLUSIONS: Controlling for processing speed, patients still showed impaired executive function compared to healthy controls. Reduced executive function thus appears to be the core neurocognitive deficit in LLD. Executive function seems

  1. Late renal function following whole abdominal irradiation

    International Nuclear Information System (INIS)

    Irwin, C.; Fyles, A.; Wong, S.C.; Cheung, C.M.; Zhu, Y.

    1996-01-01

    Sixty patients treated with whole abdominal radiotherapy who had remained disease-free since completion of treatment participated in a study to assess the late clinical and biochemical effects of bilateral renal irradiation. Minimum follow-up was 5 years with a maximum of 20 years and a median of 9 years. Fifty-two patients in the study group were treated for primary ovarian cancer. Seven had non-Hodgkins lymphoma arising in the gastrointestinal tract and one patient had a carcinoid tumour arising in small bowel. None of the patients received chemotherapy. Abdominal radiation was given using an open beam technique to a mean dose of 22.92 Gy (range 6.68-27.54 Gy) in 1.02 to 1.25 Gy fractions treated once daily. Posterior kidney shields were used in order to limit the renal dose to <20 Gy. Mean radiation dose to both kidneys (retrospectively calculated) was 19.28 Gy (range 6.68-22.99 Gy). Patients ranged in age from 32-81 years with a median of 61 years. No patient had clinical evidence of renal impairment. Nine patients were hypertensive prior to radiotherapy and a further five patients became hypertensive after treatment. Serum creatinine values ranged from 44-123 μmol/l, with a mean of 87 μmol/l. Creatinine clearance ranged from 0.61-2.38 ml/s (mean 1.28 ml/s). Tubular function tests revealed one borderline high 24-h protein excretion and normal 24-h phosphorous and uric acid. Using a multiple linear regression analysis with creatinine clearance as the endpoint, age was the only significant variable (P < 0.00001) and renal dose and interval from treatment were not independently significant. There was no evidence of late renal toxicity more than 5 years after whole abdominal radiotherapy delivered with this technique and dose/fractionation schedule, and using the clinical and biochemical endpoints assessed in this study

  2. Plate tectonics in the late Paleozoic

    Directory of Open Access Journals (Sweden)

    Mathew Domeier

    2014-05-01

    Full Text Available As the chronicle of plate motions through time, paleogeography is fundamental to our understanding of plate tectonics and its role in shaping the geology of the present-day. To properly appreciate the history of tectonics—and its influence on the deep Earth and climate—it is imperative to seek an accurate and global model of paleogeography. However, owing to the incessant loss of oceanic lithosphere through subduction, the paleogeographic reconstruction of ‘full-plates’ (including oceanic lithosphere becomes increasingly challenging with age. Prior to 150 Ma ∼60% of the lithosphere is missing and reconstructions are developed without explicit regard for oceanic lithosphere or plate tectonic principles; in effect, reflecting the earlier mobilistic paradigm of continental drift. Although these ‘continental’ reconstructions have been immensely useful, the next-generation of mantle models requires global plate kinematic descriptions with full-plate reconstructions. Moreover, in disregarding (or only loosely applying plate tectonic rules, continental reconstructions fail to take advantage of a wealth of additional information in the form of practical constraints. Following a series of new developments, both in geodynamic theory and analytical tools, it is now feasible to construct full-plate models that lend themselves to testing by the wider Earth-science community. Such a model is presented here for the late Paleozoic (410–250 Ma together with a review of the underlying data. Although we expect this model to be particularly useful for numerical mantle modeling, we hope that it will also serve as a general framework for understanding late Paleozoic tectonics, one on which future improvements can be built and further tested.

  3. 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

    DEFF Research Database (Denmark)

    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...

  4. Late Ebola virus relapse causing meningoencephalitis: a case report.

    Science.gov (United States)

    Jacobs, Michael; Rodger, Alison; Bell, David J; Bhagani, Sanjay; Cropley, Ian; Filipe, Ana; Gifford, Robert J; Hopkins, Susan; Hughes, Joseph; Jabeen, Farrah; Johannessen, Ingolfur; Karageorgopoulos, Drosos; Lackenby, Angie; Lester, Rebecca; Liu, Rebecca S N; MacConnachie, Alisdair; Mahungu, Tabitha; Martin, Daniel; Marshall, Neal; Mepham, Stephen; Orton, Richard; Palmarini, Massimo; Patel, Monika; Perry, Colin; Peters, S Erica; Porter, Duncan; Ritchie, David; Ritchie, Neil D; Seaton, R Andrew; Sreenu, Vattipally B; Templeton, Kate; Warren, Simon; Wilkie, Gavin S; Zambon, Maria; Gopal, Robin; Thomson, Emma C

    2016-07-30

    There are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2). A 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood. The patient was readmitted to hospital 9 months after discharge with symptoms of acute meningitis, and was found to have Ebola virus in cerebrospinal fluid (CSF). She was treated with supportive therapy and experimental antiviral drug GS-5734 (Gilead Sciences, San Francisco, Foster City, CA, USA). We monitored Ebola virus RNA in CSF and plasma, and sequenced the viral genome using an unbiased metagenomic approach. On admission, reverse transcriptase PCR identified Ebola virus RNA at a higher level in CSF (cycle threshold value 23.7) than plasma (31.3); infectious virus was only recovered from CSF. The patient developed progressive meningoencephalitis with cranial neuropathies and radiculopathy. Clinical recovery was associated with addition of high-dose corticosteroids during GS-5734 treatment. CSF Ebola virus RNA slowly declined and was undetectable following 14 days of treatment with GS-5734. Sequencing of plasma and CSF viral genome revealed only two non-coding changes compared with the original infecting virus. Our report shows that previously unanticipated, late, severe relapses of Ebola virus can occur, in this case in the CNS. This finding fundamentally redefines what is known about the natural history of Ebola virus infection. Vigilance should be maintained in the thousands of Ebola survivors

  5. High rates of chronic HBV genotype E infection in a group of migrants in Italy from West Africa: Virological characteristics associated with poor immune clearance.

    Science.gov (United States)

    Malagnino, Vincenzo; Salpini, Romina; Maffongelli, Gaetano; Battisti, Arianna; Fabeni, Lavinia; Piermatteo, Lorenzo; Colagrossi, Luna; Fini, Vanessa; Ricciardi, Alessandra; Sarrecchia, Cesare; Perno, Carlo Federico; Andreoni, Massimo; Svicher, Valentina; Sarmati, Loredana

    2018-01-01

    Hepatitis B virus (HBV) genotype E almost exclusively occurs in African people, and its presence is more commonly associated with the development of chronic HBV (CHB) infection. Moreover, an epidemiological link has been found between the distribution of HBV genotype E infection and African countries with high incidences of hepatocellular carcinoma. As part of a programme for the health assessment of migrants, we evaluated 358 young African subjects for HBV infection; 58.1% (208/358) were positive for an HBV marker, and 54 (25.5%) had CHB. Eighty-one percent of the CHB subjects were infected with HBV genotype E, with a median serum HBV-DNA of 3.2 (IQR: 2.7-3.6) logIU/ml. All patients had high serum HBsAg titres (10,899 [range 5,359-20,272] IU/ml), and no correlation was found between HBsAg titres and HBV-DNA plasma levels. RT sequence analysis showed the presence of a number of immune escape mutations: strains from all of the patients had a serine at HBsAg position 140; 3 also had T116N, Y100C, and P142L+S143L substitutions; and 1 had a G112R substitution. Six (18%) patients had stop-codons at position 216. In 5 of the 9 (26.5%) CHB patients, ultrasound liver biopsy, quantification of total intrahepatic HBV-DNA and cccDNA, and RT/HBsAg sequencing were performed. The median (IQR) total intrahepatic HBV-DNA was 766 (753-1139) copies/1000 cells, and the median (IQR) cccDNA was 17 (10-27) copies/1000 cells. Correlations were observed for both total intrahepatic HBV-DNA and cccDNA with serum HBV-DNA, while no correlation was found for the HBsAg titres. A difference of 2.5/1,000 nucleotides was found in the HBsAg sequences obtained from plasma and from liver tissue, with 3 cases of possible viral anatomical compartmentalization. In conclusion, a high rate of CHB infection due to the E genotype was demonstrated in a group of immigrants from Western Africa. An analysis of the viral strains obtained showed the virological characteristics of immune escape, which may be the

  6. Gratkorn - A new late Middle Miocene vertebrate fauna from Styria (Late Sarmatian, Austria)

    Science.gov (United States)

    Gross, M.; Böhme, M.; Prieto, J.

    2009-04-01

    Integrated stratigraphic approaches provide precise correlations of global standard stages with regional Paratethys stages. Nevertheless, higher resolution stratigraphic matching of terrestrial deposits remains challenging due to the lack of a practical continental biostratigraphy. The mostly used tool for biostratigraphic correlation of non-marine deposits in the Old World is still the concept of Neogene Mammal-zones (MN-zones). However, at higher biostratigraphic resolution (reptiles (scincids, lacertids, gekkonids, anguids, varanids, colubrids, testudinids, emydids), birds (coliiformes), rodents and lagomorphs (cricetids, glirids, eomyids, sciurids, castorids), insectivores and chiropterans (erinaceids, soricids, talpids), and large mammals (suids, tragulids, moschids, cervids, ?palaeomerycids, equids, chalicotheriids, rhinos, proboscidians, carnivors). Litho- and biostratigraphy (terrestrial gastropods) as well as magnetostratigraphic data and the sequence stratigraphic and geodynamic frame indicate an age of 12-12.2 Ma (early Late Sarmatian s.str., chron 5An.1n) for the locality. Therefore, Gratkorn is one of richest and most complete fauna of the late Middle Miocene of Central Europe and will be confidentially one of the key faunas for a high-resolution continental biostratigraphy and the comprehension of the faunal succession and interchanges near the Middle/Late Miocene transition. Acknowledgements This is a preliminary overview of the Gratkorn vertebrate fauna. Several taxa are still under investigation. We are especially grateful to Gudrun Daxner-Höck, Ursula Göhlich (both Natural History Museum Vienna) and Getrud Rössner (University of Munich) for their comments to the rodents, ruminants, proboscidians and bird remains. References Böhme, M., Ilg, A., Winklhofer, M. 2008. Late Miocene "washhouse" climate in Europe.- Earth and Planetary Science Letters, 275: 393-401. Gross, M., 2008. A limnic ostracod fauna from the surroundings of the Central

  7. Light curve analysis of the late type binary V523 Cassiopeiae

    Directory of Open Access Journals (Sweden)

    Latković O.

    2009-01-01

    Full Text Available We present the analysis of V and R light curves of the late type contact binary V523 Cas for the season of 2006. These observations make part of the monitoring program aimed at studying the long-term light curve variability in this system. Our results confirm that the system is in an over contact configuration, and include a bright spot in the neck region of the cooler and larger primary. We compare these results with the previous solution, obtained for the season 2005 dataset and discuss the differences.

  8. Late injury of cancer therapy on the female reproductive tract

    International Nuclear Information System (INIS)

    Grigsby, Perry W.; Russell, Anthony; Bruner, Deborah; Eifel, Patricia; Koh, Wui-Jin; Spanos, William; Stetz, Joann; Stitt, Judith Anne; Sullivan, Jessie

    1995-01-01

    The purpose of this article is to review the late effects of cancer therapy on the female reproductive tract. The anatomic sites detailed are the vulva, vagina, cervix, uterus, fallopian tubes, and ovaries. The available pathophysiology is discussed. Clinical syndromes are presented. Tolerance doses of irradiation for late effects are rarely presented in the literature and are reviewed where available. Management strategies for surgical, radiotherapeutic, and chemotherapeutic late effects are discussed. Endpoints for evaluation of therapeutic late effects have been formulated utilizing the symptoms, objective, management, and analytic (SOMA) format. Late effects on the female reproductive tract from cancer therapy should be recognized and managed appropriately. A grading system for these effects is presented. Endpoints for late effects and tolls for the evaluation need to be further developed

  9. Body position and late postoperative nocturnal hypoxaemia

    DEFF Research Database (Denmark)

    Rosenberg-Adamsen, S; Stausholm, K; Edvardsen, L

    1997-01-01

    Thirteen patients were monitored for nocturnal body position (supine vs. side) and arterial oxygen saturation pre-operatively and on the second postoperative night after major abdominal surgery. The number of positional changes were significantly decreased after operation (p ... position than on the side (p movements....... towards more time spent in the supine position (p = 0.1). Individual mean arterial oxygen saturation decreased postoperatively (p positions (p = 0.9). Pre-operatively, episodic desaturations were significantly more frequent in the supine...

  10. Monitor resultaten geluid 2000

    NARCIS (Netherlands)

    Jabben J; Potma CJM; Swart WJR; LLO

    2001-01-01

    As part of an enhanced effort in monitoring the environmental quality in 1999, the RIVM set up a noise monitoring programme. This programme forms part of the project, "Development of a monitoring system for noise and disturbance", which aims at establishing a number of permanent sites for monitoring

  11. Radioactive surface contamination monitors

    International Nuclear Information System (INIS)

    Aoyama, Kei; Minagoshi, Atsushi; Hasegawa, Toru

    1994-01-01

    To reduce radiation exposure and prevent contamination from spreading, each nuclear power plant has established a radiation controlled area. People and articles out of the controlled area are checked for the surface contamination of radioactive materials with surface contamination monitors. Fuji Electric has repeatedly improved these monitors on the basis of user's needs. This paper outlines typical of a surface contamination monitor, a personal surface contamination monitor, an article surface contamination monitor and a laundry monitor, and the whole-body counter of an internal contamination monitor. (author)

  12. Sirtinol abrogates late phase of cardiac ischemia preconditioning in rats.

    Science.gov (United States)

    Safari, Fereshteh; Shekarforoosh, Shahnaz; Hashemi, Tahmineh; Namvar Aghdash, Simin; Fekri, Asefeh; Safari, Fatemeh

    2017-07-01

    The aim of this study was to investigate the effect of sirtinol, as an inhibitor of sirtuin NAD-dependent histone deacetylases, on myocardial ischemia reperfusion injury following early and late ischemia preconditioning (IPC). Rats underwent sustained ischemia and reperfusion (IR) alone or proceeded by early or late IPC. Sirtinol (S) was administered before IPC. Arrhythmias were evaluated based on the Lambeth model. Infarct size (IS) was measured using triphenyltetrazolium chloride staining. The transcription level of antioxidant-coding genes was assessed by real-time PCR. In early and late IPC groups, IS and the number of arrhythmia were significantly decreased (P < 0.05 and P < 0.01 vs IR, respectively). In S + early IPC, incidences of arrhythmia and IS were not different compared with the early IPC group. However, in S + late IPC the IS was different from the late IPC group (P < 0.05). In late IPC but not early IPC, transcription levels of catalase (P < 0.01) and Mn-SOD (P < 0.05) increased, although this upregulation was not significant in the S + late IPC group. Our results are consistent with the notion that different mechanisms are responsible for early and late IPC. In addition, sirtuin NAD-dependent histone deacetylases may be implicated in late IPC-induced cardioprotection.

  13. Paradoxical physiological transitions from aging to late life in Drosophila.

    Science.gov (United States)

    Shahrestani, Parvin; Quach, Julie; Mueller, Laurence D; Rose, Michael R

    2012-02-01

    In a variety of organisms, adulthood is divided into aging and late life, where aging is a period of exponentially increasing mortality rates and late life is a period of roughly plateaued mortality rates. In this study we used ∼57,600 Drosophila melanogaster from six replicate populations to examine the physiological transitions from aging to late life in four functional characters that decline during aging: desiccation resistance, starvation resistance, time spent in motion, and negative geotaxis. Time spent in motion and desiccation resistance declined less quickly in late life compared to their patterns of decline during aging. Negative geotaxis declined at a faster rate in late life compared to its rate of decline during aging. These results yield two key findings: (1) Late-life physiology is distinct from the physiology of aging, in that there is not simply a continuation of the physiological trends which characterize aging; and (2) late life physiology is complex, in that physiological characters vary with respect to their stabilization, deceleration, or acceleration in the transition from aging to late life. These findings imply that a correct understanding of adulthood requires identifying and appropriately characterizing physiology during properly delimited late-life periods as well as aging periods.

  14. Late style as exile: De/colonising the life course.

    Science.gov (United States)

    Hartung, Heike

    2016-12-01

    In the collection of essays On Late Style, Edward Said reflects on the new idiom achieved by great artists in their work near the end of their lives as "late style." Drawing on Adorno's essay on Beethoven's late style, Said also focuses on the aesthetic aspects of lateness. Defining the late works of artists as "a form of exile," however, Said moves beyond Adorno's aesthetic conception of late style. Highlighting the artist's abandonment of communication with the established social order, who achieves a contradictory, alienated relationship with it instead, Said compares artistic lateness with the experience of the subject in exile. Drawing on the analogy provided by Said, this article argues that the relationship between "self" and "other" in the different theoretical contexts of Postcolonial Studies and Age Studies can be usefully combined in the composite concept of "late style as exile." In order to explore how the concept of lateness correlates with that of exile, this contribution turns to theoretical and autobiographical texts by Edward Said. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Comparative Earth history and Late Permian mass extinction

    Science.gov (United States)

    Knoll, A. H.; Bambach, R. K.; Canfield, D. E.; Grotzinger, J. P.

    1996-01-01

    The repeated association during the late Neoproterozoic Era of large carbon-isotopic excursions, continental glaciation, and stratigraphically anomalous carbonate precipitation provides a framework for interpreting the reprise of these conditions on the Late Permian Earth. A paleoceanographic model that was developed to explain these stratigraphically linked phenomena suggests that the overturn of anoxic deep oceans during the Late Permian introduced high concentrations of carbon dioxide into surficial environments. The predicted physiological and climatic consequences for marine and terrestrial organisms are in good accord with the observed timing and selectivity of Late Permian mass extinction.

  16. Monitoring of transport contamination

    International Nuclear Information System (INIS)

    Turkin, N.F.

    1980-01-01

    Organization of monitoring of transport contamination is considered. A particularly thorough monitoring is recommended to be carried out in loading-unloading operations. The monitoring is performed when leaving loading-unloading site and zone under control and prior to preventive examination, technical service or repair. The method of monitoring of auto transport contamination with high-energy β-emitters by means of a special stand permitting the automation of the monitoring process is described [ru

  17. Surfactant therapy in late preterm infants

    Directory of Open Access Journals (Sweden)

    Murat Yurdakök

    2013-06-01

    Full Text Available Late preterm (LPT neonates are at a high risk for respiratory distress soon after birth due to respiratory distress syndrome (RDS, transient tachypnea of the newborn, persistent pulmonary hypertension, and pneumonia along with an increased need for surfactant replacement therapy, continuous positive airway pressure, and ventilator support when compared with the term neonates. In the past, studies on outcomes of infants with respiratory distress have primarily focused on extremely premature infants, leading to a gap in knowledge and understanding of the developmental biology and mechanism of pulmonary diseases in LPT neonates. Surfactant deficiency is the most frequent etiology of RDS in very preterm and moderately preterm infants, while cesarean section and lung infection play major roles in RDS development in LPT infants. The clinical presentation and the response to surfactant therapy in LPT infants may be different than that seen in very preterm infants. Incidence of pneumonia and occurrence of pneumothorax are significantly higher in LPT and term infants. High rates of pneumonia in these infants may result in direct injury to the type II alveolar cells of the lung with decreasing synthesis, release, and processing of surfactant. Increased permeability of the alveolar capillary membrane to both fluid and solutes is known to result in entry of plasma proteins into the alveolar hypophase, further inhibiting the surface properties of surfactant. However, the oxygenation index value do not change dramatically after ventilation or surfactant administration in LPT infants with RDS compared to very preterm infants. These finding may indicate a different pathogenesis of RDS in late preterm and term infants. In conclusion, surfactant therapy may be of significant benefit in LPT infants with serious respiratory failure secondary to a number of insults. However, optimal timing and dose of administration are not so clear in this group. Additional

  18. Solar-Geophysical Data Number 546, February 1990. Part 1 (prompt reports). data for January 1990, December 1989, and late data

    International Nuclear Information System (INIS)

    Coffey, H.E.

    1990-02-01

    Contents include: detailed index for 1989-1990; data for January 1990--solar-terrestrial environment, IUWDS alert periods (advance and worldwide), solar activity indices, solar flares, solar radio emission, Stanford mean solar magnetic field; data for December 1989--solar-active regions, sudden ionospheric disturbances, solar radio spectral observations, cosmic-ray measurements by neutron monitor, geomagnetic indices; late data--cosmic-ray measurements by neutron monitor, reprint of halftone-page Kitt Peak solar magnetic field synoptic chart November 1989

  19. Solar-Geophysical Data Number 539, July 1989. Part 1 (prompt reports). Data for June, May 1989, and late data

    International Nuclear Information System (INIS)

    Coffey, H.E.

    1989-07-01

    Contents include: detailed index for 1988-1989; data for June 1989 -- IUWDS alert periods (advance and worldwide), solar-activity indices, solar flares, solar radio emission, Stanford mean solar magnetic field; data for May 1989 -- solar active regions, sudden ionospheric disturbances, solar radio spectral observations, cosmic-ray measurements by neutron monitor, geomagnetic indices; late data -- solar radio emission (Nancay 169-MHz solar interferometric chart, May 1989)

  20. Solar-Geophysical Data Number 551, July 1990. Part 1 (prompt reports). Data for June, May 1990 and late data

    International Nuclear Information System (INIS)

    Coffey, H.E.

    1990-07-01

    ;Contents: Detailed index for 1989-1990; Data for June 1990--Solar-terrestrial environment, IUWDS alert periods (Advance and worldwide), Solar activity indices, Solar flares, Solar radio emission, Stanford mean solar magnetic field; Data for May 1990--Solar active regions, Sudden ionospheric disturbances, Solar radio spectral observations, Cosmic ray measurements by neutron monitor, Geomagnetic indices; Late data--Geomagnetic indices February-April 1990--sudden commencements/solar flare effects