One popular idea is that, to support maintenance of a set of elements over brief periods of time, the focus of attention rotates among the different elements thereby serially refreshing the content of Working Memory (WM). In the research reported here, probe letters were presented between to-be-remembered letters. Response times to these probes were used to infer the status of the different items in WM. If the focus of attention cycles from one item to the next, its content should be different at different points in time and this should be reflected in a change in the response time patterns over time. Across a set of four experiments, we demonstrate a striking pattern of invariance in the response time patterns over time, suggesting that either the content of the focus of attention did not change over time or that response times cannot be used to infer the content of the focus of attention. We discuss how this pattern constrains models of WM, attention, and human information processing.

Raltegravir is an antiretroviral with potential value for preexposure prophylaxis (PrEP) against HIV, but the intracellular pharmacokinetics in genital tissue have not been described. In this study, healthy, HIV-uninfected nonpregnant women took 400 mg of raltegravir twice daily for 22 days. On day 8, 15, and 22, blood was collected 0, 4, 6, 8, and 12 h and cervical biopsy specimens taken 0, 6, and 12 h after raltegravir dosing. Plasma and intracellular raltegravir concentrations in peripheral blood mononuclear cells (PBMC) and cervical tissue were measured by tandem mass spectrometry. Linear mixed effects models evaluated correlations between different sample types, as well as differences in concentration between phases of the menstrual cycle. Ten women were enrolled: 9 completed all three visits and 1 completed two visits. The age (mean ؎ standard deviation) of participants was 30 ؎ 8 years. Trough plasma concentrations of raltegravir 12 h after a directly observed dose were above the HIV 95% inhibitory concentration (IC 95 ) of 33 nM (14.6 ng/ml) in 96% of measurements, compared to 67% of PBMC and 89% of cervical tissue trough values. Across all measurements, only 2% (3/135) of plasma values fell below the IC 95 , compared to 10% (13/135) for PBMC and 6% (5/81) for cervical tissue. There was no impact of menstrual phase on raltegravir concentrations. In conclusion, cervical tissue raltegravir concentrations were no greater than plasma concentrations, and ϳ10% of all cervical tissue trough values were below the IC 95 , making the current twice-daily formulation of raltegravir impractical for PrEP. P reexposure prophylaxis (PrEP) using antiretroviral medication has proven effective for infants and adults to prevent HIV acquisition. Studies have shown significant reduction in risk of HIV acquisition in high-risk infants born to HIV-infected women (1, 2), men who have sex with men (3), and HIV-1 serodiscordant heterosexual partners (4). The ideal agent for PrEP should have a long half-life and high concentrations in the genital tract at the site of viral exposure, should be nontoxic, and should not be part of first-line HIV regimens. Tenofovir was chosen as a potential PrEP agent in part because it fulfills almost all of these criteria (5). However, tenofovir is part of the first-line HIV treatment regimen in many parts of the world (6), raising concerns about the impact of development of drug resistance if HIV transmission occurs while taking PrEP.Raltegravir is an HIV integrase inhibitor which blocks strand transfer of viral DNA and integration into the host's genome and has minimal adverse effects (7). Genital fluid concentrations of raltegravir are higher than plasma concentrations, an attractive quality for a PrEP agent (8, 9). However, no studies have examined intracellular tissue concentrations of raltegravir in the genital tract, where the level of the drug would be critical to ensuring efficacy (10). Raltegravir is a substrate for P glycoprotein transporter, which is expressed in cervical tissue (11) and...

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