Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Activity-based costing in the hospitality industry: Evidence from Greece

The purpose of this article is to provide some empirical evidence of the current general trends regarding the practical consideration, adoption, and use of activity-based costing (ABC) in the hospitality industry. To this end, a survey was conducted with 85 firms of the Greek hotel sector with the use of questionnaires. Results showed that the adoption rate of an ABC system could be considered rather satisfactory. For the hotels that have adopted ABC, the survey showed that they apply it throughout all the core areas of management accounting, especially in pricing decisions and customer's profitability analysis. The nonusers reported that the main reason for rejecting it is the satisfaction of the existing cost accounting system and the high cost of an ABC implementation. © 2009 International Council on Hotel, Restaurant and Institutional Education

Final report on practical assessment of the RESCUE architecture:ICT-619555 RESCUE D4.4 Version 1.0

Abstract This deliverable summarizes the practical assessment of the links-on-the-fly concept. To do so, a software and hardware integration based on GNU Radio and SDR devices has been performed. Intensive verification and validation within three different testing facilities provided a stable framework for the subsequent assessment. The evaluation strategy comprises experiments under controllable and reproducible test conditions considering the OTAinVEE approach followed by field trials in an indoor testbed emulating the public safety use case, as well as outdoor tests emulating the V2V scenario. Finally, the outcomes of the practical evaluations are compared and analyzed jointly. These results are also analyzed in the light of previous outcomes from other work packages within the RESCUE project.Executive summary D4.4 is the final report of WP4. It presents the software and hardware integration into the selected SDR platform as well as the functional validation and first results within the OTAinVEE test facility. Moreover, two real field experimental trials have been planned and conducted for an indoor and outdoor scenario respectively. The deliverable aims to close the performance validation circle envisaged within the RESCUE project: increasing degree of realistic assumptions during the specific validation stages starting from WP1 over to WP2 and WP3 and finally to WP4. However, real field experiments are usually limited by the number of device deployments, capabilities of the selected software and hardware platform as well as limits in the available experimental time-frame. Therefore, the reported experiments cover the basic scenarios TS0 and TS1, consisting of two and three nodes, respectively. The deliverable consists of four main parts. The first part gives a detailed technical background of the software and hardware framework used to incorporate the RESCUE architecture. For this reason, and in order to obtain stable, reproducible and trustable results, the open-source GNU Radio framework and USRPs from Ettus/National Instruments have been selected as a compromise between flexibility, performance, and costs. Standard building blocks from GNU Radio have been customized to provide a basic physical and MAC layout. Contributions from WP2 and WP3 in terms of implemented software blocks were integrated, including the RESCUE coding algorithms (from WP2) and the network protocols (from WP3). Besides iterative bug fixing and code optimization, the challenging tasks during the testbed verification were the frame synchronization, SNR estimation, and calibration of the testbeds between different WP4 partners. The second part summarizes the verification and experiments based on the OTAinVEE (over-the-air in a virtual electromagnetic environment) concept. Within RESCUE, this specific validation stage turned out to be very valuable since the controllable and reproducible test conditions allowed for deep software and hardware verification followed by intensive performance validation before the real field experiments were conducted. The third part of the deliverable focuses on the real field experiments. Initially, trials were planned only for the public safety scenario with a focus on an indoor deployment. For the V2V use case, performance studies based on the OTAinVEE framework had been programmed. However, following the recommendation from the RESCUE reviewers suggesting to study the RESCUE architecture not only under synthesized traffic and propagation conditions but also to conduct real field experiments, the consortium deployed additional efforts for this purpose. Consequently, for both deployments the technical configuration and experimental test plan are detailed in this document. Whereby for the V2V setup one of the challenging parts was to integrate an efficient hence remote access to each mobile node in such a way that the individual measurements could be configured and started while the vehicles were moving. Numerous experiments have been conducted in particular for TS0 PHY and MAC as well as for TS1. However, other scenarios or more intense trials have been limited by the enormous time consumption of each single test to provide enough datasets fulfilling statistical means. The fourth part of D4.4 provides final assessments and conclusions. It aims to bridge the research and validation methods used within the RESCUE project and their subsequent performance results. The considered stages of performance validation balance between realism and simplification while moving from theory to practice. Results from three different WPs: WP2, WP3 as well as WP4 are discussed and related among each other. From the validation method perspective it can be concluded that this project was able to research the capabilities of the links-on-the-fly concept with a very ambitious approach bridging the ineluctable gap between theory and practice. It was found that the gains of this new architecture are impacted by the implementation of more practical-oriented validation methods of increasing complexity. A detailed analysis identifying the potential impact of the validation methodologies on the given results, e.g., the small number of nodes during the experiments or constraints by the software and hardware implementation and integration of the test platform, are left for future study

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection