Safety, tolerability, and mechanisms of antiretroviral activity of pegylated interferon Alfa-2a in HIV-1-monoinfected participants: a phase II clinical trial.

BACKGROUND: To our knowledge, the antiviral activity of pegylated interferon alfa-2a has not been studied in participants with untreated human immunodeficiency virus type 1 (HIV-1) infection but without chronic hepatitis C virus (HCV) infection. METHODS: Untreated HIV-1-infected volunteers without HCV infection received 180 microg of pegylated interferon alfa-2a weekly for 12 weeks. Changes in plasma HIV-1 RNA load, CD4(+) T cell counts, pharmacokinetics, pharmacodynamic measurements of 2',5'-oligoadenylate synthetase (OAS) activity, and induction levels of interferon-inducible genes (IFIGs) were measured. Nonparametric statistical analysis was performed. RESULTS: Eleven participants completed 12 weeks of therapy. The median plasma viral load decrease and change in CD4(+) T cell counts at week 12 were 0.61 log(10) copies/mL (90% confidence interval [CI], 0.20-1.18 log(10) copies/mL) and -44 cells/microL (90% CI, -95 to 85 cells/microL), respectively. There was no correlation between plasma viral load decreases and concurrent pegylated interferon plasma concentrations. However, participants with larger increases in OAS level exhibited greater decreases in plasma viral load at weeks 1 and 2 (r = -0.75 [90% CI, -0.93 to -0.28] and r = -0.61 [90% CI, -0.87 to -0.09], respectively; estimated Spearman rank correlation). Participants with higher baseline IFIG levels had smaller week 12 decreases in plasma viral load (0.66 log(10) copies/mL [90% CI, 0.06-0.91 log(10) copies/mL]), whereas those with larger IFIG induction levels exhibited larger decreases in plasma viral load (-0.74 log(10) copies/mL [90% CI, -0.93 to -0.21 log(10) copies/mL]). CONCLUSION: Pegylated interferon alfa-2a was well tolerated and exhibited statistically significant anti-HIV-1 activity in HIV-1-monoinfected patients. The anti-HIV-1 effect correlated with OAS protein levels (weeks 1 and 2) and IFIG induction levels (week 12) but not with pegylated interferon concentrations.

Making marine life count: a new baseline for policy.

The Census of Marine Life aids practical work of the Convention on Biological Diversity, discovers and tracks ocean biodiversity, and supports marine environmental planning.

Implementation of customer relationship management and inventory control software: a multiple case study of small retailers

Gemstone Team Small Business Solutions

Suppression of the Hepatitis C viral load by Phyllanthus niruri extracts

Gemstone Team ANTIDOTE

Multi-touch and keyboard/mouse devices comparison in an information search task: influence on cognitive load and task engagement

Nowadays multi-touch devices (MTD) can be found in all kind of contexts. In the learning context, MTD availability leads many teachers to use them in their class room, to support the use of the devices by students, or to assume that it will enhance the learning processes. Despite the raising interest for MTD, few researches studying the impact in term of performance or the suitability of the technology for the learning context exist. However, even if the use of touch-sensitive screens rather than a mouse and keyboard seems to be the easiest and fastest way to realize common learning tasks (as for instance web surfing behaviour), we notice that the use of MTD may lead to a less favourable outcome. The complexity to generate an accurate fingers gesture and the split attention it requires (multi-tasking effect) make the use of gestures to interact with a touch-sensitive screen more difficult compared to the traditional laptop use. More precisely, it is hypothesized that efficacy and efficiency decreases, as well as the available cognitive resources making the users’ task engagement more difficult. Furthermore, the presented study takes into account the moderator effect of previous experiences with MTD. Two key factors of technology adoption theories were included in the study: familiarity and self-efficacy with the technology.Sixty university students, invited to a usability lab, are asked to perform information search tasks on an online encyclopaedia. The different tasks were created in order to execute the most commonly used mouse actions (e.g. right click, left click, scrolling, zooming, key words encoding…). Two different conditions were created: (1) MTD use and (2) laptop use (with keyboard and mouse). The cognitive load, self-efficacy, familiarity and task engagement scales were adapted to the MTD context. Furthermore, the eye-tracking measurement would offer additional information about user behaviours and their cognitive load.Our study aims to clarify some important aspects towards the usage of MTD and the added value compared to a laptop in a student learning context. More precisely, the outcomes will enhance the suitability of MTD with the processes at stakes, the role of previous knowledge in the adoption process, as well as some interesting insights into the user experience with such devices.

Exploring the benefits of using multi-touch devices in performing information search tasks: An analysis in terms of performance, cognitive load and task engagement

Over the last decade, multi-touch devices (MTD) have spread in a range of contexts. In the learning context, MTD accessibility leads more and more teachers to use them in their classroom, assuming that it will improve the learning activities. Despite a growing interest, only few studies have focused on the impacts of MTD use in terms of performance and suitability in a learning context.However, even if the use of touch-sensitive screens rather than a mouse and keyboard seems to be the easiest and fastest way to realize common learning tasks (as for instance web surfing), we notice that the use of MTD may lead to a less favorable outcome. More precisely, tasks that require users to generate complex and/or less common gestures may increase extrinsic cognitive load and impair performance, especially for intrinsically complex tasks. It is hypothesized that task and gesture complexity will affect users’ cognitive resources and decrease task efficacy and efficiency. Because MTD are supposed to be more appealing, it is assumed that it will also impact cognitive absorption. The present study also takes into account user’s prior knowledge concerning MTD use and gestures by using experience with MTD as a moderator. Sixty university students were asked to perform information search tasks on an online encyclopedia. Tasks were set up so that users had to generate the most commonly used mouse actions (e.g. left/right click, scrolling, zooming, text encoding…). Two conditions were created: MTD use and laptop use (with mouse and keyboard) in order to make a comparison between the two devices. An eye tracking device was used to measure user’s attention and cognitive load. Our study sheds light on some important aspects towards the use of MTD and the added value compared to a laptop in a student learning context.

Age-related immune reconstitution during highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children.

OBJECTIVES: To evaluate the immune reconstitution in HIV-1-infected children in whom highly active antiretroviral therapy (HAART) controlled viral replication and to assess the existence of a relation between the magnitude of this restoration and age. METHODS: All HIV-1-infected children in whom a new HAART decreased plasma viral load below 400 copies/ml after 3 months of therapy were prospectively enrolled in a study of their immune reconstitution. Viral load, lymphocyte phenotyping, determination of CD4+ and CD8+ T cell receptor repertoires and proliferative responses to mitogens and recall antigens were assessed every 3 months during 1 year. RESULTS: Nineteen children were evaluated. Naive and memory CD4+ percentages were already significantly increased after 3 months of HAART. In contrast to memory CD4+ percentages, naive CD4+ percentages continued to rise until 12 months. Age at baseline was inversely correlated with the magnitude of the rise in naive CD4+ cells after 3, 6 and 9 months of therapy but not after 12 months. Although memory and activated CD8+ cells were already decreasing after 3 months, abnormalities of the CD8 T cell receptor repertoire and activation of CD8+ cells persisted at 1 year. HAART increased the response to mitogens as early as 3 months after starting therapy. CONCLUSIONS: In children the recovery of naive CD4+ cells occurs more rapidly if treatment is started at a younger age, but after 1 year of viral replication control, patients of all ages have achieved the same level of restoration. Markers of chronic activation in CD8+ cells persist after 1 year of HAART.

An automatable generic strategy for dynamic load balancing in parallel structured mesh CFD codes

Parallel computing is now widely used in numerical simulation, particularly for application codes based on finite difference and finite element methods. A popular and successful technique employed to parallelize such codes onto large distributed memory systems is to partition the mesh into sub-domains that are then allocated to processors. The code then executes in parallel, using the SPMD methodology, with message passing for inter-processor interactions. In order to improve the parallel efficiency of an imbalanced structured mesh CFD code, a new dynamic load balancing (DLB) strategy has been developed in which the processor partition range limits of just one of the partitioned dimensions uses non-coincidental limits, as opposed to coincidental limits. The ‘local’ partition limit change allows greater flexibility in obtaining a balanced load distribution, as the workload increase, or decrease, on a processor is no longer restricted by the ‘global’ (coincidental) limit change. The automatic implementation of this generic DLB strategy within an existing parallel code is presented in this chapter, along with some preliminary results.

Shape-optimized mesh partitioning and load balancing for parallel adaptive FEM

We present a dynamic distributed load balancing algorithm for parallel, adaptive Finite Element simulations in which we use preconditioned Conjugate Gradient solvers based on domain-decomposition. The load balancing is designed to maintain good partition aspect ratio and we show that cut size is not always the appropriate measure in load balancing. Furthermore, we attempt to answer the question why the aspect ratio of partitions plays an important role for certain solvers. We define and rate different kinds of aspect ratio and present a new center-based partitioning method of calculating the initial distribution which implicitly optimizes this measure. During the adaptive simulation, the load balancer calculates a balancing flow using different versions of the diffusion algorithm and a variant of breadth first search. Elements to be migrated are chosen according to a cost function aiming at the optimization of subdomain shapes. Experimental results for Bramble's preconditioner and comparisons to state-of-the-art load balancers show the benefits of the construction.

Dynamic load-balancing of finite element applications with the DRAMA library

The DRAMA library, developed within the European Commission funded (ESPRIT) project DRAMA, supports dynamic load-balancing for parallel (message-passing) mesh-based applications. The target applications are those with dynamic and solution-adaptive features. The focus within the DRAMA project was on finite element simulation codes for structural mechanics. An introduction to the DRAMA library will illustrate that the very general cost model and the interface designed specifically for application requirements provide simplified and effective access to a range of parallel partitioners. The main body of the paper will demonstrate the ability to provide dynamic load-balancing for parallel FEM problems that include: adaptive meshing, re-meshing, the need for multi-phase partitioning.

Load-balancing for mesh-based applications on heterogeneous cluster computers

This paper discusses load-balancing issues when using heterogeneous cluster computers. There is a growing trend towards the use of commodity microprocessor clusters. Although today's microprocessors have reached a theoretical peak performance in the range of one GFLOPS/s, heterogeneous clusters of commodity processors are amongst the most challenging parallel systems to programme efficiently. We will outline an approach for optimising the performance of parallel mesh-based applications for heterogeneous cluster computers and present case studies with the GeoFEM code. The focus is on application cost monitoring and load balancing using the DRAMA library.

Dynamic mesh partitioning and load-balancing for parallel computational mechanics codes

In this Chapter we discuss the load-balancing issues arising in parallel mesh based computational mechanics codes for which the processor loading changes during the run. We briefly touch on geometric repartitioning ideas and then focus on different ways of using a graph both to solve the load-balancing problem and the optimisation problem, both locally and globally. We also briefly discuss whether repartitioning is always valid. Sample illustrative results are presented and we conclude that repartitioning is an attractive option if the load changes are not too dramatic and that there is a certain trade-off between partition quality and volume of data that the underlying application needs to migrate.

Load sharing in cluster service provision

The factors that are driving the development and use of grids and grid computing, such as size, dynamic features, distribution and heterogeneity, are also pushing to the forefront service quality issues. These include performance, reliability and security. Although grid middleware can address some of these issues on a wider scale, it has also become imperative to ensure adequate service provision at local level. Load sharing in clusters can contribute to the provision of a high quality service, by exploiting both static and dynamic information. This paper is concerned with the presentation of a load sharing scheme, that can satisfy grid computing requirements. It follows a proactive, non preemptive and distributed approach. Load information is gathered continuously before it is needed, and a task is allocated to the most appropriate node for execution. Performance and reliability are enhanced by the decentralised nature of the scheme and the symmetric roles of the nodes. In addition, the scheme exhibits transparency characteristics that facilitate integration with the grid.