Population-Level Benefits from Providing Effective HIV Prevention Means to Pregnant Women in High Prevalence Settings

Background:HIV prevalence among pregnant women in Southern Africa is extremely high. Epidemiological studies suggest that pregnancy increases the risk of HIV sexual acquisition and that HIV infections acquired during pregnancy carry higher risk of mother-to-child transmission (MTCT). We analyze the potential benefits from extending the availability of effective microbicide to pregnant women (in addition to non-pregnant women) in a wide-scale intervention.Methods and Findings:A transmission dynamic model was designed to assess the impact of microbicide use in high HIV prevalence settings and to estimate proportions of new HIV infections, infections acquired during pregnancy, and MTCT prevented over 10 years. Our analysis suggests that consistent use of microbicide with 70% efficacy by 60% of non-pregnant women may prevent approximately 40% and 15% of new infections in women and men respectively over 10 years, assuming no additional increase in HIV risk to either partner during pregnancy (RRHIV/preg = 1). It may also prevent 8-15% MTCT depending on the increase in MTCT risk when HIV is acquired during pregnancy compared to before pregnancy (RRMTCT/preg). Extending the microbicides use during pregnancy may improve the effectiveness of the intervention by 10% (RRHIV/preg = 1) to 25% (RRHIV/preg = 2) and reduce the number of HIV infections acquired during pregnancy by 40% to 70% in different scenarios. It may add between 6% (RRHIV/preg = 1, RRMTCT/preg = 1) and 25% (RRHIV/preg = 2, RRMTCT/preg = 4) to the reduction in the residual MTCT.Conclusion:Providing safe and effective microbicide to pregnant women in the context of wide-scale interventions would be desirable as it would increase the effectiveness of the intervention and significantly reduce the number of HIV infections acquired during pregnancy. The projected benefits from covering pregnant women by the HIV prevention programs is more substantial in communities in which the sexual risk during pregnancy is elevated. © 2013 Dimitrov et al

Global Nonradial Instabilities of Dynamically Collapsing Gas Spheres

Self-similar solutions provide good descriptions for the gravitational collapse of spherical clouds or stars when the gas obeys a polytropic equation of state, $p=K\rho^\gamma$ (with $\gamma\le 4/3$). We study the behaviors of nonradial perturbations in the similarity solutions of Larson, Penston and Yahil, which describe the evolution of the collapsing cloud prior to core formation. Our global stability analysis reveals the existence of unstable bar-modes ($l=2$) when $\gamma\le 1.09$. In particular, for the collapse of isothermal spheres, which applies to the early stages of star formation, the $l=2$ density perturbation relative to the background, $\delta\rho({\bf r},t)/\rho(r,t)$, increases as $(t_0-t)^{-0.352}\propto \rho_c(t)^{0.176}$, where $t_0$ denotes the epoch of core formation, and $\rho_c(t)$ is the cloud central density. Thus, the isothermal cloud tends to evolve into an ellipsoidal shape (prolate bar or oblate disk, depending on initial conditions) as the collapse proceeds. In the context of Type II supernovae, core collapse is described by the $\gamma\simeq 1.3$ equation of state, and our analysis indicates that there is no growing mode (with density perturbation) in the collapsing core before the proto-neutron star forms, although nonradial perturbations can grow during the subsequent accretion of the outer core and envelope onto the neutron star. We also carry out a global stability analysis for the self-similar expansion-wave solution found by Shu, which describes the post-collapse accretion (``inside-out'' collapse) of isothermal gas onto a protostar. We show that this solution is unstable to perturbations of all $l$'s, although the growth rates are unknown.Comment: 28 pages including 7 ps figures; Minor changes in the discussion; To be published in ApJ (V.540, Sept.10, 2000 issue

Ferrihidrita ferrimagnética: una historia de serendipia y radiación de sincrotón

II Encuentro sobre nanociencia y nanotecnología de investigadores y tecnólogos de la Universidad de Córdoba. NANOUC

The circumnuclear environment of the peculiar galaxy NGC 3310

Gas and star velocity dispersions have been derived for eight circumnuclear star-forming regions (CNSFRs) and the nucleus of the spiral galaxy NGC3310 using high resolution spectroscopy in the blue and far red. Stellar velocity dispersions have been obtained from the CaII triplet in the near-IR, using cross-correlation techniques, while gas velocity dispersions have been measured by Gaussian fits to the Hb 4861A and [OIII]5007A emission lines. The CNSFRs stellar velocity dispersions range from 31 to 73 km/s. These values, together with the sizes measured on archival HST images, yield upper limits to the dynamical masses for the individual star clusters between 1.8 and 7.1 x 10$^6$ M$_\odot$, for the whole CNSFR between 2 x 10$^7$ and 1.4 x 10$^8$ M$_\odot$, and 5.3 x 10$^7$ M$_\odot$ for the nucleus inside the inner 14.2 pc. The masses of the ionizing stellar population responsible for the HII region gaseous emission have been derived from their published Ha luminosities and are found to be between 8.7 x 10$^5$ and 2.1 x 10$^6$ M$_\odot$ for the star-forming regions, and 2.1 x 10$^5$ M$_\odot$ for the galaxy nucleus; they therefore constitute between 1 and 7 per cent of the total dynamical mass. The ionized gas kinematics is complex; two different kinematical components seem to be present as evidenced by different line widths and Doppler shifts.Comment: 24 pages, accepted by MNRA

Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis

Background More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against human papillomavirus on HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia grade 2+ (CIN2+)to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination.Methods In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks.Findings We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+.After 5\u20138 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0\ub717, 95% CI 0\ub711\u20130\ub725) among girls aged 13\u201319 years, and decreased significantly by 66% (RR 0\ub734, 95% CI 0\ub723\u20130\ub749) among women aged 20\u201324 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0\ub746, 95% CI 0\ub733\u20130\ub766) among girls aged 13\u201319 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0\ub733, 95% CI 0\ub724\u20130\ub746) among girls aged 15\u201319 years, decreased significantly by 54% (RR 0\ub746, 95% CI 0.36\u20130.60) among women aged 20\u201324 years, and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub753\u20130\ub789) among women aged 25\u201329 years. Among boys aged 15\u201319 years anogenital wart diagnoses decreased significantly by 48% (RR 0\ub752, 95% CI 0\ub737\u20130\ub775) and among men aged 20\u201324 years they decreased significantly by 32% (RR 0\ub768, 95% CI 0\ub747\u20130\ub798). After 5\u20139 years of vaccination, CIN2+ decreased significantly by 51% (RR 0\ub749, 95% CI 0\ub742\u20130\ub758) among screened girls aged 15\u201319 years and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub757\u20130\ub784) among women aged 20\u201324 years.Interpretation This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects

Evaluating Human Papillomavirus Vaccination Programs

Human papillomavirus (HPV) has been implicated as the primary etiologic agent of cervical cancer. Potential vaccines against high-risk HPV types are in clinical trials. We evaluated vaccination programs with a vaccine against HPV-16 and HPV-18. We developed disease transmission models that estimated HPV prevalence and infection rates for the population overall, by age group, by level of sexual activity within each age group, and by sex. Data were based on clinical trials and published and unpublished sources. An HPV-16/18 vaccine for 12-year-old girls would reduce cohort cervical cancer cases by 61.8%, with a cost-effectiveness ratio of $14,583 per quality-adjusted life year (QALY). Including male participants in a vaccine rollout would further reduce cervical cancer cases by 2.2$442,039/QALY compared to female-only vaccination. Vaccination against HPV-16 and HPV-18 can be cost-effective, although including male participants in a vaccination program is generally not cost-effective, compared to female-only vaccination

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

Spiral anchoring in anisotropic media with multiple inhomogeneities: a dynamical system approach

Various PDE models have been suggested in order to explain and predict the dynamics of spiral waves in excitable media. In two landmark papers, Barkley noticed that some of the behaviour could be explained by the inherent Euclidean symmetry of these models. LeBlanc and Wulff then introduced forced Euclidean symmetry-breaking (FESB) to the analysis, in the form of individual translational symmetry-breaking (TSB) perturbations and rotational symmetry-breaking (RSB) perturbations; in either case, it is shown that spiral anchoring is a direct consequence of the FESB. In this article, we provide a characterization of spiral anchoring when two perturbations, a TSB term and a RSB term, are combined, where the TSB term is centered at the origin and the RSB term preserves rotations by multiples of $\frac{2\pi}{\jmath^*}$, where $\jmath^*\geq 1$ is an integer. When $\jmath^*>1$ (such as in a modified bidomain model), it is shown that spirals anchor at the origin, but when $\jmath^* =1$ (such as in a planar reaction-diffusion-advection system), spirals generically anchor away from the origin.Comment: Revised versio

A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction

Calorie restriction delays brain senescence and prevents neurodegeneration, but critical regulators of these beneficial responses other than the NAD(+)-dependent histone deacetylase Sirtuin-1 (Sirt-1) are unknown. We report that effects of calorie restriction on neuronal plasticity, memory and social behavior are abolished in mice lacking cAMP responsive-element binding (CREB)-1 in the forebrain. Moreover, CREB deficiency drastically reduces the expression of Sirt-1 and the induction of genes relevant to neuronal metabolism and survival in the cortex and hippocampus of dietary-restricted animals. Biochemical studies reveal a complex interplay between CREB and Sirt-1: CREB directly regulates the transcription of the sirtuin in neuronal cells by binding to Sirt-1 chromatin; Sirt-1, in turn, is recruited by CREB to DNA and promotes CREB-dependent expression of target gene peroxisome proliferator-activated receptor-\u3b3 coactivator-1\u3b1 and neuronal NO Synthase. Accordingly, expression of these CREB targets is markedly reduced in the brain of Sirt KO mice that are, like CREB-deficient mice, poorly responsive to calorie restriction. Thus, the above circuitry, modulated by nutrient availability, links energy metabolism with neurotrophin signaling, participates in brain adaptation to nutrient restriction, and is potentially relevant to accelerated brain aging by overnutrition and diabetes

A Modified Protocol for Bisulfite Genomic Sequencing of Difficult Samples

The bisulfite genomic sequencing protocol is a widely used method for analyzing DNA methylation. It relies on the deamination of unmethylated cytosine residues to uracil; however, its high rates of DNA degradation and incomplete cytosine to uracil conversion often lead to failed experiments, uninformative results, and false positives. Here, we report the addition of a single-step multiple restriction enzyme digestion (MRED) designed to differentially digest polymerase chain reaction products amplified from unconverted DNA while leaving those of converted DNA intact. We show that for our model system, RARB2 P2 promoter, use of MRED increased informative sequencings ninefold, and MRED did not alter the clonal representation in one fully methylated cell line, H-596, treated or not with 5-azadeoxycytidine, a methylation inhibitor. We believe that this method may easily be adapted for analyzing other genes and provide guidelines for selecting the most appropriate MRED restriction enzymes