31 research outputs found
Utilization of parallel processing in solving the inviscid form of the average-passage equation system for multistage turbomachinery
A procedure is outlined which utilizes parallel processing to solve the inviscid form of the average-passage equation system for multistage turbomachinery along with a description of its implementation in a FORTRAN computer code, MSTAGE. A scheme to reduce the central memory requirements of the program is also detailed. Both the multitasking and I/O routines referred to are specific to the Cray X-MP line of computers and its associated SSD (Solid-State Disk). Results are presented for a simulation of a two-stage rocket engine fuel pump turbine
Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice
Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides
First Phase 1 Double-Blind, Placebo-Controlled, Randomized Rectal Microbicide Trial Using UC781 Gel with a Novel Index of Ex Vivo Efficacy
Objectives: Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo. Methods: HIV-1 seronegative, sexually-abstinent men and women (N = 36) were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25%) with placebo gel (1:1:1). Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint. Results: All 36 subjects enrolled completed the 7-14 week trial (100% retention) including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm). There were 81 Grade 1 adverse events (AEs) and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1 BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration. Conclusions: Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy. (Registered at ClinicalTrials.gov; #NCT00408538). © 2011 Anton et al
A systematic review of heterosexual anal intercourse and its role in the transmission of HIV and other sexually transmitted infections in Papua New Guinea
Intimate Partner Violence and Anal Intercourse In Young Adult Heterosexual Relationships
CONTEXT: The prevalence of intimate partner violence and anal intercourse is high in young adult relationships, but few have looked the intersection of the two. This paper considers this association within multiple intimate partner violence contexts. METHODS: Using wave 3 of the National Longitudinal Study of Adolescent Health, an analysis was completed on the association of physical and sexual intimate partner violence and anal intercourse in relationships reported by young women. This wave was collected from 2001–2002 when the women were between 18 and 28 years old. A hierarchical random effects model was used to control for the clustered survey design and multiple relationships reported per participant. This analysis included 10,462 relationships reported by 6,280 women. RESULTS: In multivariate analysis, relationships where women perpetrated physical violence (AOR 1.9) and relationships that were reciprocally physically violent (AOR 1.7) were more likely to include anal intercourse than non-abusive relationships. Among those that included anal intercourse, relationships where the woman was a victim of physical violence (AOR 0.2) were less likely to have ever used a condom during anal intercourse. There was no association between sexual violence and condom use. CONCLUSION: These analyses demonstrate that women in violent relationships may be at increased risk of sexually transmitted infections due to unprotected anal intercourse. More information on the context surrounding anal intercourse and intimate partner violence is needed in order to understand the nuances of this association