A measurement of the spectrum of cosmic ray electrons between 20 MeV and 4 BeV in 1968 - Further evidence for extensive time variations of this component

Cosmic ray electron intensity and spectrum measurements between 20 MeV and 4 BeV - 196

Hepatitis C virus treatment in the real world: optimising treatment and access to therapies

Chronic HCV infections represent a major worldwide public health problem and are responsible for a large proportion of liver related deaths, mostly because of HCV-associated hepatocellular carcinoma and cirrhosis. The treatment of HCV has undergone a rapid and spectacular revolution. In the past 5 years, the launch of direct acting antiviral drugs has seen sustained virological response rates reach 90% and above for many patient groups. The new treatments are effective, well tolerated, allow for shorter treatment regimens and offer new opportunities for previously excluded groups. This therapeutic revolution has changed the rules for treatment of HCV, moving the field towards an interferon-free era and raising the prospect of HCV eradication. This manuscript addresses the new challenges regarding treatment optimisation in the real world, improvement of antiviral efficacy in `hard-to-treat' groups, the management of patients whose direct acting antiviral drug treatment was unsuccessful, and access to diagnosis and treatment in different parts of the world

Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

Prevalence and risk factors of Hepatitis C among individuals presenting to HIV testing centers, Hawassa city, Southern Ethiopia

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV), either alone or in combination with Human Immunodeficiency virus (HIV), constitutes a major public health concern. This study was conducted to describe the prevalence and risk factors for HCV infection in people with and without HIV infection.</p> <p>Methods</p> <p>Blood samples and data on socio-demographic and risk factors for HCV infection were collected from consecutive 400 HIV- positive and 400 HIV- negative individuals attending HIV testing centers in Hawassa city, from October to December, 2008. All sera were tested for antibody to HCV infection (anti-HCV) using enzyme linked immunosorbent assay (ELISA). Sera positive for anti-HCV were further tested for viral ribonucleic acid (RNA) levels using real-time polymerase chain reaction.</p> <p>Results</p> <p>The rate of anti-HCV positivity was 10.5% in the HIV- infected individuals compared with 6% in the HIV negative group (p = 0.002). HCV-RNA was detected in 9.1% of anti-HCV positive samples and rates were comparable between HIV- infected and HIV<b>- </b>non<b>-</b>infected individuals. There was no significant difference in odds of HCV infection in participants with and without HCV risk factors in either HIV sero-group.</p> <p>Conclusion</p> <p>HIV infected individuals had significantly higher rate of anti-HCV although most of them showed no evidence of viraemia. Hence, while priority should be given for HIV infected patients, testing those with anti-HCV for HCV-RNA remains important.</p

The Interstellar Environment of our Galaxy

We review the current knowledge and understanding of the interstellar medium of our galaxy. We first present each of the three basic constituents - ordinary matter, cosmic rays, and magnetic fields - of the interstellar medium, laying emphasis on their physical and chemical properties inferred from a broad range of observations. We then position the different interstellar constituents, both with respect to each other and with respect to stars, within the general galactic ecosystem.Comment: 39 pages, 12 figures (including 3 figures in 2 parts

Modified bibenzimidazole ligands as spectator ligands in photoactive molecular functional Ru-polypyridine units? Implications from spectroscopy

The photophysical properties of Ruthenium-bipyridine complexes bearing a bibenzimidazole ligand were investigated. The nitrogens on the bibenzimidazole-ligand were protected, by adding either a phenylene group or a 1,2-ethandiyl group, to remove the photophysical dependence of the complex on the protonation state of the bibenzimidazole ligand. This protection results in the bibenzimidazole ligand contributing to the MLCT transition, which is experimentally evidenced by (resonance) Raman scattering in concert with DFT calculations for a detailed mode assignment in the (resonance) Raman spectra

Survey of both hepatitis B virus (HBsAg) and hepatitis C virus (HCV-Ab) coinfection among HIV positive patients

<p>Abstract</p> <p>Background</p> <p>HIV, HBVand HCV is major public health concerns. Because of shared routes of transmission, HIV-HCV coinfection and HIV-HBV coinfection are common. HIV-positive individuals are at risk of coinfection with HBV and HCV infections. The prevalence rates of coinfection with HBV and HCV in HIV-patients have been variable worldwide depending on the geographic regions, and the type of exposure.</p> <p>Aim</p> <p>This study aimed to examine HBV and HCV coinfection serologically and determine the shared and significant factors in the coinfection of HIV-positive patients.</p> <p>Methods</p> <p>This descriptive, cross-sectional study was carried out on 391 HIV-positive patients including 358 males and 33 females in Lorestan province, west Iran, to survey coinfection with HBsAg and anti-HCV. The retrospective demographic data of the subjects was collected and the patients' serums were analyzed by ELISA kits including HBsAg and anti-HCV. The collected data was analyzed with SPSS software (15) and Chi-square. Fisher's exact test with 5% error intervals was used to measure the correlation of variables and infection rates.</p> <p>Results</p> <p>The results of the study indicated that the prevalence of coinfection in HIV-positive patients with hepatitis viruses was 94.4% (370 in 391), out of whom 57 (14.5%) cases were HBsAg positive, 282 (72%) cases were anti-HCV positive, and 31 (7.9%) cases were both HBsAg and anti-HCV positive.</p> <p>Conclusion</p> <p>There was a significant correlation between coinfection with HCV and HBV and/or both among HIV-positive patients depending on different variables including sex, age, occupation, marital status, exposure to risk factors.(p < 0.001).</p

Circulating sCD14 Is Associated with Virological Response to Pegylated-Interferon-Alpha/Ribavirin Treatment in HIV/HCV Co-Infected Patients

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

HCV Coinfection Associated with Slower Disease Progression in HIV-Infected Former Plasma Donors Naïve to ART

It remains controversial how HCV coinfection influences the disease progression during HIV-1 infection. This study aims to define the influence of HCV infection on the replication of HIV-1 and the disease progression in HIV-infected former plasma donors (FPDs) naïve to ART.168 HIV-1-infected FPDs were enrolled into a cohort study from Anhui province in central China, and thereafter monitored at month 3, 9, 15, 21 and 33. Fresh whole blood samples were used for CD4+ T-cell counting. Their plasma samples were collected and stored for quantification of HIV-1 viral loads and for determination of HCV and Toxoplasma. Out of 168 HIV-infected FBDs, 11.9% (20 cases), 80.4% (135 cases) and 7.7% (13 cases) were infected with HIV-1 alone, HIV-1/HCV and HIV/HCV/Toxoplasma, respectively. During the 33-month follow-up, only 35% (7 out of 20 cases) HIV-1 mono-infected subjects remained their CD4+ T-cell counts above 200 cells/µl and retained on the cohort study, which was significantly lower than 56% (75 out of 135 cases) for HIV/HCV group and 69% (9 out of 13 cases) for HIV/HCV/Toxoplasma group (p<0.05). CD4+ T cells in HIV mono infection group were consistently lower than that in HIV/HCV group (p = 0.04, 0.18, 0.03 and 0.04 for baseline, month 9, month 21 and month 33 visit, respectively). In accordance with those observations, HIV viral loads in HIV mono-infection group were consistently higher than that in HIV/HCV group though statistical significances were only reached at baseline (p = 0.04).These data indicated HCV coinfection with HIV-1 is associated with the slower disease progression at the very late stage when comparing with HIV-1 mono-infection. The coinfection of Toxoplasma with HIV and HCV did not exert additional influence on the disease progression. It will be highly interesting to further explore the underlying mechanism for this observation in the future