The Diaphragm and Lubricant Gel for Prevention of Cervical Sexually Transmitted Infections: Results of a Randomized Controlled Trial

BACKGROUND: We evaluated the effectiveness of the Ortho All-Flex Diaphragm, lubricant gel (Replens) and condoms compared to condoms alone on the incidence of chlamydial and gonococcal infections in an open-label randomized controlled trial among women at risk of HIV/STI infections. METHODS: We randomized 5045 sexually-active women at three sites in Southern Africa. Participants who tested positive for curable STIs were treated prior to enrollment as per local guidelines. Women were followed quarterly and tested for Chlamydia trachomatis (CT) or Neisseria gonorrhoeae (GC) infection by nucleic-acid amplification testing (Roche Amplicor) using first-catch urine specimens. STIs detected at follow-up visits were treated. We compared the incidence of first infection after randomization between study arms in both intent-to-treat (ITT) and per-protocol populations. FINDINGS: Baseline demographic, behavioral and clinical characteristics were balanced across study arms. Nearly 80% of participants were under 35 years of age. Median follow-up time was 21 months and the retention rate was over 93%. There were 471 first chlamydia infections, 247 in the intervention arm and 224 in the control arm with an overall incidence of 6.2/100 woman-years (wy) (relative hazard (RH) 1.11, 95% Confidence Interval (CI): 0.93-1.33; p = 0.25) and 192 first gonococcal infections, 95 in the intervention arm and 97 in the control arm with an overall incidence of 2.4/100wy (RH 0.98, 95%CI: 0.74-1.30; p = 0.90). Per protocol results indicated that when diaphragm adherence was defined as "always use" since the last visit, there was a significant reduction in the incidence of GC infection among women randomized to the intervention arm (RH 0.61, 95%CI: 0.41-0.91, P = 0.02). INTERPRETATION: There was no difference by study arm in the rate of acquisition of CT or GC. However, our per-protocol results suggest that consistent use of the diaphragm may reduce acquisition of GC. TRIAL REGISTRATION: ClinicalTrials.gov NCT00121459

Evaluation of Analytical Methods to Study Aquifer Properties with Pumping Tests in Coastal Aquifers with Numerical Modelling (Motril-Salobreña Aquifer)

Two pumping tests were performed in the unconfined Motril-Salobreña detrital aquifer in a 250 m-deep well 300 m from the coastline containing both freshwater and saltwater. It is an artesian well as it is in the discharge zone of this coastal aquifer. The two observation wells where the drawdowns are measured record the influence of tidal fluctuations, and the well lithological columns reveal high vertical heterogeneity in the aquifer. The Theis and Cooper-Jacob approaches give average transmissivity (T) and storage coefficient (S) values of 1460 m2 /d and 0.027, respectively. Other analytical solutions, modified to be more accurate in the boundary conditions found in coastal aquifers, provide similar T values to those found with the Theis and Cooper-Jacob methods, but give very different S values or could not estimate them. Numerical modelling in a synthetic model was applied to analyse the sensitivity of the Theis and Cooper-Jacob approaches to the usual boundary conditions in coastal aquifers. The T and S values calculated from the numerical modelling drawdowns indicate that the regional flow, variable pumping flows, and tidal effect produce an error of under 10 % compared to results obtained with classic methods. Fluids of different density (freshwater and saltwater) cause an error of 20 % in estimating T and of over 100 % in calculating S. The factor most affecting T and S results in the pumping test interpretation is vertical heterogeneity in sediments, which can produce errors of over 100 % in both parameters.This research has been financed by Project CGL2012-32892 (Ministerio de Economía y Competitividad of Spain) and by the Research Group Sedimentary Geology and Groundwater (RNM-369) of the Junta de Andalucía

Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse

<p>Abstract</p> <p>Background</p> <p>Several active ingredients proposed as vaginal microbicides have been shown paradoxically to <it>increase </it>susceptibility to infection in mouse genital herpes (HSV-2) vaginal susceptibility models and in clinical trials. In addition, "inactive ingredients" (or excipients) used in topical products to formulate and deliver the active ingredient might also cause epithelial toxicities that increase viral susceptibility. However, excipients have not previously been tested in susceptibility models.</p> <p>Methods</p> <p>Excipients commonly used in topical products were formulated in a non-toxic vehicle (the "HEC universal placebo"), or other formulations as specified. Twelve hours after exposure to the excipient or a control treatment, mice were challenged with a vaginal dose of HSV-2, and three days later were assessed for infection by vaginal lavage culture to assess susceptibility.</p> <p>Results</p> <p>The following excipients markedly increased susceptibility to HSV-2 after a single exposure: 5% glycerol monolaurate (GML) formulated in K-Y^®Warming Jelly, 5% GML as a colloidal suspension in phosphate buffered saline, K-Y Warming Jelly alone, and both of its humectant/solvent ingredients (neat propylene glycol and neat PEG-8). For excipients formulated in the HEC vehicle, 30% glycerin significantly increased susceptibility, and a trend toward increased HSV-2 susceptibility was observed after 10% glycerin, and 0.1% disodium EDTA, but not after 0.0186% disodium EDTA. The following excipients did not increase susceptibility: 10% propylene glycol, 0.18%, methylparaben plus 0.02% propylparaben, and 1% benzyl alcohol.</p> <p>Conclusions</p> <p>As reported with other surfactants, the surfactant/emulsifier GML markedly increased susceptibility to HSV-2. Glycerin at 30% significantly increased susceptibility, and, undiluted propylene glycol and PEG-8 greatly increased susceptibility.</p

Dynamic factor model with infinite-dimensional factor space:forecasting

The paper compares the pseudo real-time forecasting performance of three Dynamic Factor Models: (i) The standard principal-component model introduced by Stock and Watson in 2002, (ii) The model based on generalized principal components, introduced by Forni, Hallin, Lippi and Reichlin in 2005, (iii) The model recently proposed by Forni, Hallin, Lippi and Zaffaroni in 2015. We employ a large monthly dataset of macroeconomic and financial time series for the U.S. economy, which includes the Great Moderation, the Great Recession and the subsequent recovery (an update of the so-called Stock and Watson dataset). Using a rolling window for estimation and prediction, we find that (iii) significantly outperforms (i) and (ii) in the Great Moderation period for both Industrial Production and Inflation, that (iii) is also the best method for Inflation over the full sample. However, (iii) is outperformed by (ii) and (i) over the full sample for Industrial Production

Hydrogeological typologies of the Indo-Gangetic basin alluvial aquifer, South Asia

The Indo-Gangetic aquifer is one of the world’s most important transboundary water resources, and the most heavily exploited aquifer in the world. To better understand the aquifer system, typologies have been characterized for the aquifer, which integrate existing datasets across the Indo-Gangetic catchment basin at a transboundary scale for the first time, and provide an alternative conceptualization of this aquifer system. Traditionally considered and mapped as a single homogenous aquifer of comparable aquifer properties and groundwater resource at a transboundary scale, the typologies illuminate significant spatial differences in recharge, permeability, storage, and groundwater chemistry across the aquifer system at this transboundary scale. These changes are shown to be systematic, concurrent with large-scale changes in sedimentology of the Pleistocene and Holocene alluvial aquifer, climate, and recent irrigation practices. Seven typologies of the aquifer are presented, each having a distinct set of challenges and opportunities for groundwater development and a different resilience to abstraction and climate change. The seven typologies are: (1) the piedmont margin, (2) the Upper Indus and Upper-Mid Ganges, (3) the Lower Ganges and Mid Brahmaputra, (4) the fluvially influenced deltaic area of the Bengal Basin, (5) the Middle Indus and Upper Ganges, (6) the Lower Indus, and (7) the marine-influenced deltaic areas

Prior mucosal exposure to heterologous cells alters the pathogenesis of cell-associated mucosal feline immunodeficiency virus challenge

<p>Abstract</p> <p>Background</p> <p>Several lines of research suggest that exposure to cellular material can alter the susceptibility to infection by HIV-1. Because sexual contact often includes exposure to cellular material, we hypothesized that repeated mucosal exposure to heterologous cells would induce an immune response that would alter the susceptibility to mucosal infection. Using the feline immunodeficiency virus (FIV) model of HIV-1 mucosal transmission, the cervicovaginal mucosa was exposed once weekly for 12 weeks to 5,000 heterologous cells or media (control) and then cats were vaginally challenged with cell-associated or cell-free FIV.</p> <p>Results</p> <p>Exposure to heterologous cells decreased the percentage of lymphocytes in the mucosal and systemic lymph nodes (LN) expressing L-selectin as well as the percentage of CD4+ CD25+ T cells. These shifts were associated with enhanced ex-vivo proliferative responses to heterologous cells. Following mucosal challenge with cell-associated, but not cell-free, FIV, proviral burden was reduced by 64% in cats previously exposed to heterologous cells as compared to media exposed controls.</p> <p>Conclusions</p> <p>The pathogenesis and/or the threshold for mucosal infection by infected cells (but not cell-free virus) can be modulated by mucosal exposure to uninfected heterologous cells.</p

Forecasting Bond Risk Premia Using Technical Analysis

This paper is selected as one of the Top Ten Paper in Forecasting in SSRN