A Phase 1 Randomized, Double Blind, Placebo Controlled Rectal Safety and Acceptability Study of Tenofovir 1% Gel (MTN-007)

Objective: Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal), adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel. Methods: Participants were randomized 1:1:1:1 to receive the reduced glycerin formulation of tenofovir 1% gel, a hydroxyethyl cellulose placebo gel, a 2% nonoxynol-9 gel, or no treatment. Each gel was administered as a single dose followed by 7 daily doses. Mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein), microarrays, flow cytometry of mucosal T cell phenotype, and rectal microflora. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response, respectively. Results: Sixty-five participants (45 men and 20 women) were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability) was 87% (reduced glycerin formulation of tenofovir 1% gel), 93% (hydroxyethyl cellulose placebo gel), and 63% (nonoxynol-9 gel). Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms. Conclusions: The reduced glycerin formulation of tenofovir 1% gel was safe and well tolerated rectally and should be advanced to Phase 2 development. Trial Registration: ClinicalTrials.gov NCT01232803

Diagnosis and correction of soil nutrient problems of common beans (Phaseolus vulgaris) in the Usambara mountains of Tanzania

Stages in the diagnosis of an interveinal leaf chlorosis in bean in the Usambara Mountains of northern Tanzania are described. Leaf tissue analysis, soil analysis, a 25 factorial trial with treatments of nitrogen, phosphorus, potassium, the trace elements copper and zinc and lime at one location and data from a series of 43 factorial trials of N, P and K demonstrated the leaf condition to be due to potassium deficiency. Large growth and yield responses to N, P and K were recorded. The responses were accompanied by greater numbers of pods and seeds/pod. The application of N and K increased leaf concentrations of the respective elements but depressed the concentrations of other major and minor elements in leaves. There were no effects of trace elements or lime

NGOs as catalysts for international arms control? The ratification of the Chemical Weapons Convention and the Comprehensive Test Ban Treaty in the United States

The article investigates the role of pro-arms control non-governmental organisations (NGOs) in furthering the domestic ratification of the Chemical Weapons Convention (CWC) and the Comprehensive Test Ban Treaty (CTBT) in the United States. The study starts out from the two-level framework for analysing domestic ratification processes of international agreements, and it introduces the concept of audience gains to complement this framework: being the counterpart of audience costs, audience gains denote positive contributions of domestic non-state actors to formal ratification processes. The article distinguishes two complementary pathways for NGOs to generate audience gains, that is, the pathways of ‘mobilising consensus’ and of ‘persuading veto players’. Two in-depth case studies on the ratification of the CWC and the CTBT in the US explore the extent to which pro-agreement NGOs were indeed successful in employing the two pathways. The evidence of the case studies is that NGOs were more influential catalysts of the ratification of the CWC than with respect to the CTBT. The article's findings on the prospects for NGOs to push the domestic ratification of international agreements are expected to be of more general relevance beyond the field of arms control