Top-down social modulation of interpersonal observation-execution.

Cyclical upper limb movement can involuntarily deviate from its primary movement axis when the performer concurrently observes incongruent biological motion (i.e. interpersonal observation-execution). The current study examined the social modulation of such involuntary motor interference using a protocol that reflected everyday social interactions encountered in a naturalistic social setting. Eighteen participants executed cyclical horizontal arm movements during the observation of horizontal (congruent) or curvilinear (incongruent) biological motion. Both prior to, and during the interpersonal observation-execution task, participants also received a series of social words designed to prime a pro-social or anti-social attitude. The results showed greater orthogonal movement deviation, and thus interference, for the curvilinear compared to horizontal stimuli. Importantly, and opposite to most of the previous findings from work on automatic imitation and mimicry, there was a greater interference effect for the anti-social compared to pro-social prime condition. These findings demonstrate the importance of interpreting the context of social primes, and strongly support predictions of a comparison between the prime construct and the self-concept/-schema and the top-down response modulation of social incentives

Raltegravir-intensified initial antiretroviral therapy in advanced HIV in Africa: a randomized controlled trial

BACKGROUND: In sub-Saharan Africa, severely immunocompromised HIV-infected individuals have high mortality (10%) shortly after starting antiretroviral therapy (ART). This group also have the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster, and hence reduce early mortality, although this strategy could also risk more IRIS events. METHODS AND FINDINGS: In a 2x2x2 factorial open-label parallel-group trial, treatment-naïve HIV-infected adults, adolescents and children >5 years with CD4 0.7), and despite significantly greater VL suppression with raltegravir-intensified-ART at 4-weeks (343/836 (41.0%) vs 113/841 (13.4%) standard-ART, p<0.001) and 12-weeks (567/789 (71.9%) vs 415/803 (51.7%) standard-ART, p<0.001). Through 48-weeks there was no evidence of differences in mortality (aHR=0.98 (95%CI 0.76-1.28) p=0.91); serious (aHR=0.99 (0.81-1.21) p=0.88), grade-4 (aHR=0.88 (0.71-1.09) p=0.29) or ART-modifying (aHR=0.90 (0.63-1.27) p=0.54) adverse events (the latter occurring in occurring in 59 (6.5%) raltegravir-intensified-ART vs 66 (7.3%) standard-ART); in events judged compatible with IRIS (occurring in 89 (9.9%) raltegravir-intensified-ART vs 86 (9.5%) standard-ART, p=0.79) or hospitalizations (aHR=0.94 (95%CI 0.76-1.17) p=0.59). At 12 weeks, one and two raltegravir-intensified participants had predicted intermediate-level and high-level raltegravir resistance respectively. At 48 weeks, the NRTI mutation K219E/Q (p=0.004), and the NNRTI mutations K101E/P (p=0.03) and P225H (p=0.007), were less common in raltegravir-intensified-ART, with weak evidence of less intermediate or high-level resistance to tenofovir (p=0.06), abacavir (p=0.08) and rilpivirine (p=0.07). Limitations were limited clinical, radiological and/or microbiological information for some participants, reflecting available services at the centres, and lack of baseline genotypes. CONCLUSIONS: Although 12-weeks raltegravir-intensification was well-tolerated and reduced HIV viraemia significantly faster than standard triple-drug ART during the time of greatest risk for early death, this strategy did not reduce mortality or clinical events, and is not warranted. There was no excess of IRIS-compatible events, suggesting integrase inhibitors can be used safely as part of standard triple-drug first-line therapy in severely immuno-compromised individuals