Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals.

Studies have demonstrated that intensive ART alone is not capable of eradicating HIV-1, as the virus rebounds within a few weeks upon treatment interruption. Viral rebound may be induced from several cellular subsets; however, the majority of proviral DNA has been found in antigen experienced resting CD4+ T cells. To achieve a cure for HIV-1, eradication strategies depend upon both understanding mechanisms that drive HIV-1 persistence as well as sensitive assays to measure the frequency of infected cells after therapeutic interventions. Assays such as the quantitative viral outgrowth assay (QVOA) measure HIV-1 persistence during ART by ex vivo activation of resting CD4+ T cells to induce latency reversal; however, recent studies have shown that only a fraction of replication-competent viruses are inducible by primary mitogen stimulation. Previous studies have shown a correlation between the acquisition of effector memory phenotype and HIV-1 latency reversal in quiescent CD4+ T cell subsets that harbor the reservoir. Here, we apply our mechanistic understanding that differentiation into effector memory CD4+ T cells more effectively promotes HIV-1 latency reversal to significantly improve proviral measurements in the QVOA, termed differentiation QVOA (dQVOA), which reveals a significantly higher frequency of the inducible HIV-1 replication-competent reservoir in resting CD4+ T cells

More Evidence of Professionalism and Professional Engagement

Type: Lette

Reviews

The following publications have been reviewed by the mentioned authors;Getting Things Right Design and Realization by Adrian Marden, reviewed by Michael RobertsVisual Messages: An Introduction to Graphics by C. J. Breckon, L. J. Jones and C. E. Moorhouse, reviewed by John BaleErgonomics in the Computerized Office by Etienne Grandjean, reviewed by T. LawleyTeaching GCSE Craft, Design and Technology by David Rees, reviewed by Brian OppenheimComputers at Work by H. Scott, B. Frost, S. Alexander and G. Bowie, reviewed by S.R. St. J. NeillScience Report for Teachers: 10 Metals at age 15, reviewed by David BarlexThe Anti-Colouring Book by Susan Striker & Edward Kimmel, reviewed by Marshall HughesUnderstanding and Using Technology by A. Todd, C. McRory and D. Todd, reviewed by David Perry

Oral administration of morphine versus ibuprofen to manage postfracture pain in children: A randomized trial

Background: Recent warnings from Health Canada regarding codeine for children have led to increased use of nonsteroidal anti-inflammatory drugs and morphine for common injuries such as fractures. Our objective was to determine whether morphine administered orally has superior efficacy to ibuprofen in fracture-related pain

Why do only some people who support parties actually join them? Evidence from Britain

What makes people join a political party is one of the most commonly studied questions in research on party members. Nearly all this research, however, is based on talking to people who have actually joined parties. This article simultaneously analyses surveys of members of political parties in Britain and surveys of non-member supporters of those same parties. This uniquely enables us to model the decision to join parties. The results suggest that most of the elements that constitute the influential ‘General Incentives Model’ are significant. But it also reveals that, while party supporters imagine that selective benefits, social norms and opposing rival parties’ policies are key factors in members’ decisions to join a party, those who actually do so are more likely to say they are motivated by attachments to their party’s values, policies and leaders, as well as by an altruistic desire to support democracy more generally

Liberal market economies, business, and political finance: Britain under New Labour

The extent and nature of business financing of parties is an important feature of political finance. Britain’s transparent and permissive regulatory system provides an excellent opportunity to study business financing of parties. Business donations have been very important to the Conservative party over the last decade, and of only marginal importance to Labour. Unlike other Conservative contributors, business donors are more likely to contribute when the party is popular. In contrast to the previous period of Conservative government, the biggest British businesses tended to abstain from political finance under New Labour. However, their bias towards the Conservatives is affected by the party’s popularity and the closeness of an election. Britain shares the political importance of business financing of parties and its mixture of ideological and pragmatic motivations with other liberal market economies. However, in Britain the bias towards the right is much stronger and the role of big business more marginal

Electron Energy Partition across Interplanetary Shocks. III. Analysis

An analysis of model fit results of 15,210 electron velocity distribution functions (VDFs), observed within 2 hr of 52 interplanetary (IP) shocks by the Wind spacecraft near 1 au, is presented as the third and final part on electron VDFs near IP shocks. The core electrons and protons dominate in the magnitude and change in the partial-to-total thermal pressure ratio, with the core electrons often gaining as much or more than the protons. Only a moderate positive correlation is observed between the electron temperature and the kinetic energy change across the shock, while weaker, if any, correlations were found with any other macroscopic shock parameter. No VDF parameter correlated with the shock normal angle. The electron VDF evolves from a narrowly peaked core with flaring suprathermal tails in the upstream to either a slightly hotter core with steeper tails or much hotter flattop core with even steeper tails downstream of the weaker and strongest shocks, respectively. Both quasi-static and fluctuating fields are examined as possible mechanisms modifying the VDF, but neither is sufficient alone. For instance, flattop VDFs can be generated by nonlinear ion acoustic wave stochastic acceleration (i.e., inelastic collisions), while other work suggested they result from the combination of quasi-static and fluctuating fields. This three-part study shows that not only are these systems not thermodynamic in nature; even kinetic models may require modification to include things like inelastic collision operators to properly model electron VDF evolution across shocks or in the solar wind.Peer reviewe

Electron Energy Partition across Interplanetary Shocks. II. Statistics

A statistical analysis of 15,210 electron velocity distribution function (VDF) fits, observed within +/- 2 hr of 52 interplanetary (IP) shocks by the Wind spacecraft near 1 au, is presented. This is the second in a three-part series on electron VDFs near IP shocks. The electron velocity moment statistics for the dense, low-energy core, tenuous, hot halo, and field-aligned beam/strahl are a statistically significant list of values illustrated with both histograms and tabular lists for reference and baselines in future work. Given the large statistics in this investigation, the beam/strahl fit results in the upstream are now the most comprehensive attempt to parameterize the beam/strahl electron velocity moments in the ambient solar wind. The median density, temperature, beta, and temperature anisotropy values for the core(halo)[beam/strahl] components, with subscripts ec(eh)[eb], of all fit results, respectively, are n(ec(h)[b]) similar to 11.3(0.36)[0.17] cm(-3), T-ec(h)[b],T-tot similar to 14.6(48.4)[40.2] eV, beta(ec(h)[b],tot) similar to 0.93(0.11)[0.05], and Alpha(ec(h)[b]) similar to 0.98(1.03)[0.93]. This work will also serve as a 1 au baseline and reference for missions like Parker Solar Probe and Solar Orbiter.Peer reviewe

The Temperature, Electron, and Pressure Characteristics of Switchbacks: Parker Solar Probe Observations

Parker Solar Probe (PSP) observes unexpectedly prevalent switchbacks, which are rapid magnetic field reversals that last from seconds to hours, in the inner heliosphere, posing new challenges to understanding their nature, origin, and evolution. In this work, we investigate the thermal states, electron pitch angle distributions, and pressure signatures of both inside and outside switchbacks, separating a switchback into spike, transition region (TR), and quiet period (QP). Based on our analysis, we find that the proton temperature anisotropies in TRs seem to show an intermediate state between spike and QP plasmas. The proton temperatures are more enhanced in spike than in TR and QP, but the alpha temperatures and alpha-to-proton temperature ratios show the opposite trends, implying that the preferential heating mechanisms of protons and alphas are competing in different regions of switchbacks. Moreover, our results suggest that the electron integrated intensities are almost the same across the switchbacks but the electron pitch angle distributions are more isotropic inside than outside switchbacks, implying switchbacks are intact structures but strong scattering of electrons happens inside switchbacks. In addition, the examination of pressures reveals that the total pressures are comparable through a switchback, confirming switchbacks are pressure-balanced structures. These characteristics could further our understanding of ion heating, electron scattering, and the structure of switchbacks.Comment: submitted to Ap