The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade, but no tuberculosis-specific drugs have been discovered in 40 years. We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (minimum inhibitory concentration 0.06 mug/ml). In mice, R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit. Substitution of drugs included in the World Health Organization's first-line tuberculosis treatment regimen (rifampin, isoniazid, and pyrazinamide) with R207910 accelerated bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations. A single dose of R207910 inhibited mycobacterial growth for 1 week. Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers. Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate (ATP) synthase.

ViiV Healthcare and Janssen R&D.

Purpose -This article is an edited version of a report commissioned by the British Library and JISC to identify how the specialist researchers of the future (those born after 1993) are likely to access and interact with digital resources in five to ten years' time. The purpose is to investigate the impact of digital transition on the information behaviour of the Google Generation and to guide library and information services to anticipate and react to any new or emerging behaviours in the most effective way. Design/methodology/approach -The study was virtually longitudinal and is based on a number of extensive reviews of related literature, survey data mining and a deep log analysis of a British Library and a JISC web site intended for younger people. Findings -The study shows that much of the impact of ICTs on the young has been overestimated. The study claims that although young people demonstrate an apparent ease and familiarity with computers, they rely heavily on search engines, view rather than read and do not possess the critical and analytical skills to assess the information that they find on the web. Originality/value -The paper reports on a study that overturns the common assumption that the "Google generation" is the most web-literate.

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BACKGROUND Long-acting injectable regimens may simplify therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection. METHODS We conducted a phase 3, randomized, open-label trial in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir-abacavir-lamivudine. Participants who had an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were randomly assigned (1:1) to continue the current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly injections of long-acting cabotegravir plus rilpivirine. The primary end point was the percentage of participants who had an HIV-1 RNA level of 50 copies per milliliter or higher at week 48 (Food and Drug Administration snapshot algorithm). RESULTS At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 participants (2.1%) who received long-acting therapy and in 7 of 283 (2.5%) who received oral therapy (adjusted difference, −0.4 percentage points; 95% confidence interval [CI], −2.8 to 2.1), a result that met the criterion for noninferiority for the primary end point (margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% who received long-acting therapy and in 93.3% who received oral therapy (adjusted difference, 0.4 percentage points; 95% CI, −3.7 to 4.5), a result that met the criterion for noninferiority for this end point (margin, −10 percentage points). Of the participants who received long-acting therapy, 86% reported injection-site reactions (median duration, 3 days; mild or moderate severity, 99% of cases); 4 participants withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, who received long-acting therapy and in 4% and 1% who received oral therapy. Treatment satisfaction increased after participants switched to long-acting therapy; 91% preferred long-acting therapy at week 48. CONCLUSIONS Therapy with long-acting cabotegravir plus rilpivirine was noninferior to oral therapy with dolutegravir-abacavir-lamivudine with regard to maintaining HIV-1 suppression. Injection-site reactions were common. (Funded by ViiV Healthcare and Janssen; FLAIR ClinicalTrials.gov number, NCT02938520.

Ideally, an anti-HIV drug should (1) be highly active against wild-type and mutant HIV without allowing breakthrough; (2) have high oral bioavailability and long elimination half-life, allowing once-daily oral treatment at low doses; (3) have minimal adverse effects; and (4) be easy to synthesize and formulate. R278474, a new diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitor (NNRTI), appears to meet these criteria and to be suitable for high compliance oral treatment of HIV-1 infection. The discovery of R278474 was the result of a coordinated multidisciplinary effort involving medicinal chemists, virologists, crystallographers, molecular modelers, toxicologists, analytical chemists, pharmacists, and many others.

Background Journal editors are responsible for what they publish and therefore have a duty to correct the record if published work is found to be unreliable. One method for such correction is retraction of an article. Anecdotal evidence suggested a lack of consistency in journal policies and practices regarding retraction. In order to develop guidelines, we reviewed retractions in Medline to discover how and why articles were retracted. Methods We retrieved all available Medline retractions from 2005 to 2008 and a one-in-three random selection of those from 1988 to 2004. This yielded 312 retractions (from a total of 870). Details of the retraction including the reason for retraction were recorded by two investigators.

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