Generation of neutralizing antibodies and divergence of SIVmac239 in cynomolgus macaques following short-term early antiretroviral therapy.

Neutralizing antibodies (NAb) able to react to heterologous viruses are generated during natural HIV-1 infection in some individuals. Further knowledge is required in order to understand the factors contributing to induction of cross-reactive NAb responses. Here a well-established model of experimental pathogenic infection in cynomolgus macaques, which reproduces long-lasting HIV-1 infection, was used to study the NAb response as well as the viral evolution of the highly neutralization-resistant SIVmac239. Twelve animals were infected intravenously with SIVmac239. Antiretroviral therapy (ART) was initiated ten days post-inoculation and administered daily for four months. Viral load, CD4(+) T-cell counts, total IgG levels, and breadth as well as strength of NAb in plasma were compared simultaneously over 14 months. In addition, envs from plasma samples were sequenced at three time points in all animals in order to assess viral evolution. We report here that seven of the 12 animals controlled viremia to below 10(4) copies/ml of plasma after discontinuation of ART and that this control was associated with a low level of evolutionary divergence. Macaques that controlled viral load developed broader NAb responses early on. Furthermore, escape mutations, such as V67M and R751G, were identified in virus sequenced from all animals with uncontrolled viremia. Bayesian estimation of ancestral population genetic diversity (PGD) showed an increase in this value in non-controlling or transient-controlling animals during the first 5.5 months of infection, in contrast to virus-controlling animals. Similarly, non- or transient controllers displayed more positively-selected amino-acid substitutions. An early increase in PGD, resulting in the generation of positively-selected amino-acid substitutions, greater divergence and relative high viral load after ART withdrawal, may have contributed to the generation of potent NAb in several animals after SIVmac239 infection. However, early broad NAb responses correlated with relatively preserved CD4(+) T-cell numbers, low viral load and limited viral divergence

Transparency and trustworthiness in user intentions to follow career recommendations from a learning analytics tool

Abstract Transparency and trustworthiness are among the key requirements for the ethical use of learning analytics (LA) and artificial intelligence (AI) in the context of social inclusion and equity. However, research on these issues pertaining to users is lacking, leaving it unclear as to how transparent and trustworthy current LA tools are for their users and how perceptions of these variables relate to user behaviour. In this study, we investigate user experiences of an LA tool in the context of career guidance, which plays a crucial role in supporting nonlinear career pathways for individuals. We review the ethical challenges of big data, AI, and LA in connection to career guidance and analyze the user experiences (N = 106) of the LA career guidance tool, which recommends study programs and institutions to users. Results indicate that the LA career guidance tool was evaluated as trustworthy but not transparent. Accuracy was found to be a stronger predictor for the intention to follow on the recommendations of the LA guidance tool than was understanding the origins of the recommendation. The user’s age emerged as an important factor in their assessment of transparency. We discuss the implications of these findings and suggest emphasizing accuracy in the development of LA tools for career guidance