Incidence and risk factors of severe adverse events with nevirapine-based antiretroviral therapy in HIV-infected women. MTCT-Plus program, Abidjan, Côte d'Ivoire

<p>Abstract</p> <p>Background</p> <p>In resource-limited settings where nevirapine-containing regimen is the preferred regimen in women, data on severe adverse events (SAEs) according to CD4 cell count are limited. We estimated the incidence of SAEs according to CD4 cell count and identify their risk factors in nevirapine-treated women.</p> <p>Methods</p> <p>All HIV-infected women who initiated nevirapine-containing regimen in the MTCT-Plus operational program in Abidjan, Côte d'Ivoire, were eligible for this study. Laboratory and clinical (rash) SAEs were classified as grade 3 and 4. Cox models were used to identify factors associated with the occurrence of SAEs.</p> <p>Results</p> <p>From August 2003 to October 2006, 290 women initiated a nevirapine-containing regimen at a median CD4 cell count of 186 cells/mm³(IQR 124-266). During a median follow-up on treatment of 25 months, the incidence of all SAEs was 19.5/100 patient-years. The 24-month probability of occurrence of hepatotoxicity or rash was not different between women with a CD4 cell count >250 cells/mm³and women with a CD4 cell count ≤250 cells/mm³(8.3% <it>vs</it>. 9.9%, Log-rank test: p = 0.75). In a multivariate proportional hazard model, neither CD4 cell count >250 cells/mm³at treatment initiation nor initiation NVP-based regimen initiated during pregnancy were associated with the occurrence of SAEs.</p> <p>Conclusion</p> <p>CD4 cell count >250 cells/mm³was not associated with a higher risk of severe hepatotoxicity and/or rash, as well as initiation of ART during pregnancy. Pharmacovogilance data as well as meta-analysis on women receiving NVP in these settings are needed for better information about NVP toxicity.</p

Ubiquitous sensorization for multimodal assessment of driving patterns

Sustainability issues and sustainable behaviours are becoming concerns of increasing signi cance in our society. In the case of transportation systems, it would be important to know the impact of a given driving behaviour over sustainability factors. This paper describes a system that integrates ubiquitous mobile sensors available on devices such as smartphones, intelligent wristbands and smartwatches, in order to determine and classify driving patterns and to assess driving e ficiency and driver's moods. It first identi fies the main attributes for contextual information, with relevance to driving analysis. Next, it describes how to obtain that information from ubiquitous mobile sensors, usually carried by drivers. Finally, it addresses the multimodal assessment process which produces the analysis of driving patterns and the classi cation of driving moods, promoting the identifi cation of either regular or aggressive driving patterns, and the classi fication of mood types between aggressive and relaxed. Such an approach enables ubiquitous sensing of personal driving patterns across diff erent vehicles, which can be used in sustainability frameworks, driving alerts and recommendation systems.This work is part-funded by ERDF - European Regional Development Fund through the COMPETE Programme (operational programme for competitiveness) and by National Funds through the FCT Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within project FCOMP-01-0124-FEDER-028980 (PTDC/EEI-SII/1386/2012). It is also supported by a doctoral grant, SFRH/BD/78713/2011, issued by FCT in Portugal

Immunological response to highly active antiretroviral therapy following treatment for prevention of mother to child transmission of HIV-1: a study in Côte d'Ivoire

<p>Abstract</p> <p>Background</p> <p>Information is currently limited on the long-term follow up of HIV-1 infected women who are on highly active antiretroviral therapy (HAART) that contains nevirapine and lamivudine and who were previously exposed to antiretroviral drugs for the prevention of mother to child transmission (PMTCT) of HIV.</p> <p>Methods</p> <p>We studied the 36-month immunological response to HAART in HIV-1 infected women in Côte d'Ivoire. The women were previously exposed to antiretroviral drug regimens for PMTCT, including single-dose nevirapine and/or short-course zidovudine with or without lamivudine. All HAART regimens included a non-nucleoside reverse transcriptase inhibitor.</p> <p>Results</p> <p>At 36 months: the median absolute increase in CD4+ T cell count was +359 cells/mm³(IQR: 210-466) in 200 women who had undergone 36-month follow-up visits; +359 cells/mm³(IQR: 222-491) in 88 women not exposed to PMTCT antiretrovirals; and +363 cells/mm³(IQR: 200-464) in 112 women exposed to at least one antiretroviral PMTCT regimen. Overall, 49 (19.8%) of the 247 women who initiated HAART met the immunological failure criteria at least once during follow up. The overall probability of immunological failure was 0.08 (95% CI: 0.12-0.15) at 12 months, and 0.21 (95% CI: 0.16-0.27) at 36 months. No difference was observed according to the presence or absence of resistance mutations to nevirapine or lamivudine in women tested at four weeks postpartum. In addition, at 36 months, 23% of women were lost to follow up, dead or had stopped their treatment.</p> <p>Conclusions</p> <p>A non-nucleoside reverse transcriptase inhibitor-based antiretroviral regimen, initiated a year or more after PMTCT exposure and that includes nevirapine, remains a good option for at least the first 36 months of treatment.</p

A Viscoelastic model of phase separation

We show here a general model of phase separation in isotropic condensed matter, namely, a viscoelastic model. We propose that the bulk mechanical relaxation modulus that has so far been ignored in previous theories plays an important role in viscoelastic phase separation in addition to the shear relaxation modulus. In polymer solutions, for example, attractive interactions between polymers under a poor-solvent condition likely cause the transient gellike behavior, which makes both bulk and shear modes active. Although such attractive interactions between molecules of the same component exist universally in the two-phase region of a mixture, the stress arising from attractive interactions is asymmetrically divided between the components only in dynamically asymmetric mixtures such as polymer solutions and colloidal suspensions. Thus, the interaction network between the slower components, which can store the elastic energy against its deformation through bulk and shear moduli, is formed. It is the bulk relaxation modulus associated with this interaction network that is primarily responsible for the appearance of the sponge structure peculiar to viscoelastic phase separation and the phase inversion. We demonstrate that a viscoelastic model of phase separation including this new effect is a general model that can describe all types of isotropic phase separation including solid and fluid models as its special cases without any exception, if there is no coupling with additional order parameter. The physical origin of volume shrinking behavior during viscoelastic phase separation and the universality of the resulting spongelike structure are also discussed.Comment: 14 pages, RevTex, To appear in Phys. Rev

Characterizing, modelling and understanding the climate variability of the deep water formation in the North-Western Mediterranean Sea

Observing, modelling and understanding the climate-scale variability of the deep water formation (DWF) in the North-Western Mediterranean Sea remains today very challenging. In this study, we first characterize the interannual variability of this phenomenon by a thorough reanalysis of observations in order to establish reference time series. These quantitative indicators include 31 observed years for the yearly maximum mixed layer depth over the period 1980–2013 and a detailed multi-indicator description of the period 2007–2013. Then a 1980–2013 hindcast simulation is performed with a fully-coupled regional climate system model including the high-resolution representation of the regional atmosphere, ocean, land-surface and rivers. The simulation reproduces quantitatively well the mean behaviour and the large interannual variability of the DWF phenomenon. The model shows convection deeper than 1000 m in 2/3 of the modelled winters, a mean DWF rate equal to 0.35 Sv with maximum values of 1.7 (resp. 1.6) Sv in 2013 (resp. 2005). Using the model results, the winter-integrated buoyancy loss over the Gulf of Lions is identified as the primary driving factor of the DWF interannual variability and explains, alone, around 50 % of its variance. It is itself explained by the occurrence of few stormy days during winter. At daily scale, the Atlantic ridge weather regime is identified as favourable to strong buoyancy losses and therefore DWF, whereas the positive phase of the North Atlantic oscillation is unfavourable. The driving role of the vertical stratification in autumn, a measure of the water column inhibition to mixing, has also been analyzed. Combining both driving factors allows to explain more than 70 % of the interannual variance of the phenomenon and in particular the occurrence of the five strongest convective years of the model (1981, 1999, 2005, 2009, 2013). The model simulates qualitatively well the trends in the deep waters (warming, saltening, increase in the dense water volume, increase in the bottom water density) despite an underestimation of the salinity and density trends. These deep trends come from a heat and salt accumulation during the 1980s and the 1990s in the surface and intermediate layers of the Gulf of Lions before being transferred stepwise towards the deep layers when very convective years occur in 1999 and later. The salinity increase in the near Atlantic Ocean surface layers seems to be the external forcing that finally leads to these deep trends. In the future, our results may allow to better understand the behaviour of the DWF phenomenon in Mediterranean Sea simulations in hindcast, forecast, reanalysis or future climate change scenario modes. The robustness of the obtained results must be however confirmed in multi-model studies

Effect of Composition Changes on the Structural Relaxation of a Binary Mixture

Within the mode-coupling theory for idealized glass transitions, we study the evolution of structural relaxation in binary mixtures of hard spheres with size ratios $\delta$ of the two components varying between 0.5 and 1.0. We find two scenarios for the glassy dynamics. For small size disparity, the mixing yields a slight extension of the glass regime. For larger size disparity, a plasticization effect is obtained, leading to a stabilization of the liquid due to mixing. For all $\delta$, a decrease of the elastic moduli at the transition due to mixing is predicted. A stiffening of the glass structure is found as is reflected by the increase of the Debye-Waller factors at the transition points. The critical amplitudes for density fluctuations at small and intermediate wave vectors decrease upon mixing, and thus the universal formulas for the relaxation near the plateau values describe a slowing down of the dynamics upon mixing for the first step of the two-step relaxation scenario. The results explain the qualitative features of mixing effects reported by Williams and van Megen [Phys. Rev. E \textbf{64}, 041502 (2001)] for dynamical light-scattering measurements on binary mixtures of hard-sphere-like colloids with size ratio $\delta=0.6$

Critical Decay at Higher-Order Glass-Transition Singularities

Within the mode-coupling theory for the evolution of structural relaxation in glass-forming systems, it is shown that the correlation functions for density fluctuations for states at A_3- and A_4-glass-transition singularities can be presented as an asymptotic series in increasing inverse powers of the logarithm of the time t: $\phi(t)-f\propto \sum_i g_i(x)$, where $g_n(x)=p_n(\ln x)/x^n$ with p_n denoting some polynomial and x=ln (t/t_0). The results are demonstrated for schematic models describing the system by solely one or two correlators and also for a colloid model with a square-well-interaction potential.Comment: 26 pages, 7 figures, Proceedings of "Structural Arrest Transitions in Colloidal Systems with Short-Range Attractions", Messina, Italy, December 2003 (submitted

Evidence for Unusual Dynamical Arrest Scenario in Short Ranged Colloidal Systems

Extensive molecular dynamics simulation studies of particles interacting via a short ranged attractive square-well (SW) potential are reported. The calculated loci of constant diffusion coefficient $D$ in the temperature-packing fraction plane show a re-entrant behavior, i.e. an increase of diffusivity on cooling, confirming an important part of the high volume-fraction dynamical-arrest scenario earlier predicted by theory for particles with short ranged potentials. The more efficient localization mechanism induced by the short range bonding provides, on average, additional free volume as compared to the hard-sphere case and results in faster dynamics.Comment: 4 pages, 3 figure