Low level of virological failure and drug resistance among patients receiving antiretroviral treatment under programme conditions in Maputo, Mozambique

Mexico AIDS Conference 200

The HIV-1 Integrase Mutations Y143C/R Are an Alternative Pathway for Resistance to Raltegravir and Impact the Enzyme Functions

Resistance to HIV-1 integrase (IN) inhibitor raltegravir (RAL), is encoded by mutations in the IN region of the pol gene. The emergence of the N155H mutation was replaced by a pattern including the Y143R/C/H mutations in three patients with anti-HIV treatment failure. Cloning analysis of the IN gene showed an independent selection of the mutations at loci 155 and 143. Characterization of the phenotypic evolution showed that the switch from N155H to Y143C/R was linked to an increase in resistance to RAL. Wild-type (WT) IN and IN with mutations Y143C or Y143R were assayed in vitro in 3′end-processing, strand transfer and concerted integration assays. Activities of mutants were moderately impaired for 3′end-processing and severely affected for strand transfer. Concerted integration assay demonstrated a decrease in mutant activities using an uncleaved substrate. With 3′end-processing assay, IC50 were 0.4 µM, 0.9 µM (FC = 2.25) and 1.2 µM (FC = 3) for WT, IN Y143C and IN Y143R, respectively. An FC of 2 was observed only for IN Y143R in the strand transfer assay. In concerted integration, integrases were less sensitive to RAL than in ST or 3′P but mutants were more resistant to RAL than WT

The epidemiological transition in Antananarivo, Madagascar: an assessment based on death registers (1900–2012)

Background: Madagascar today has one of the highest life expectancies in sub-Saharan Africa, despite being among the poorest countries in the continent. There are relatively few detailed accounts of the epidemiological transition in this country due to the lack of a comprehensive death registration system at the national level. However, in Madagascar's capital city, death registration was established around the start of the 20th century and is now considered virtually complete. Objective: We provide an overview of trends in all-cause and cause-specific mortality in Antananarivo to document the timing and pace of the mortality decline and the changes in the cause-of-death structure. Design: Death registers covering the period 1976–2012 were digitized and the population at risk of dying was estimated from available censuses and surveys. Trends for the period 1900–1976 were partly reconstructed from published sources. Results: The crude death rate stagnated around 30‰ until the 1940s in Antananarivo. Mortality declined rapidly after the World War II and then resurged again in the 1980s as a result of the re-emergence of malaria and the collapse of Madagascar's economy. Over the past 30 years, impressive gains in life expectancy have been registered thanks to the unabated decline in child mortality, despite political instability, a lasting economic crisis and the persistence of high rates of chronic malnutrition. Progress in adult survival has been more modest because reductions in infectious diseases and diseases of the respiratory system have been partly offset by increases in cardiovascular diseases, neoplasms, and other diseases, particularly at age 50 years and over. Conclusions: The transition in Antananarivo has been protracted and largely dependent on anti-microbial and anti-parasitic medicine. The capital city now faces a double burden of communicable and non-communicable diseases. The ongoing registration of deaths in the capital generates a unique database to evaluate the performance of the health system and measure intervention impacts

Beyond capitalism and liberal democracy: on the relevance of GDH Cole’s sociological critique and alternative

This article argues for a return to the social thought of the often ignored early 20th-century English thinker GDH Cole. The authors contend that Cole combined a sociological critique of capitalism and liberal democracy with a well-developed alternative in his work on guild socialism bearing particular relevance to advanced capitalist societies. Both of these, with their focus on the limitations on ‘free communal service’ in associations and the inability of capitalism to yield emancipation in either production or consumption, are relevant to social theorists looking to understand, critique and contribute to the subversion of neoliberalism. Therefore, the authors suggest that Cole’s associational sociology, and the invitation it provides to think of formations beyond capitalism and liberal democracy, is a timely and valuable resource which should be returned to

Can we identify non-stationary dynamics of trial-to-trial variability?"

Identifying sources of the apparent variability in non-stationary scenarios is a fundamental problem in many biological data analysis settings. For instance, neurophysiological responses to the same task often vary from each repetition of the same experiment (trial) to the next. The origin and functional role of this observed variability is one of the fundamental questions in neuroscience. The nature of such trial-to-trial dynamics however remains largely elusive to current data analysis approaches. A range of strategies have been proposed in modalities such as electro-encephalography but gaining a fundamental insight into latent sources of trial-to-trial variability in neural recordings is still a major challenge. In this paper, we present a proof-of-concept study to the analysis of trial-to-trial variability dynamics founded on non-autonomous dynamical systems. At this initial stage, we evaluate the capacity of a simple statistic based on the behaviour of trajectories in classification settings, the trajectory coherence, in order to identify trial-to-trial dynamics. First, we derive the conditions leading to observable changes in datasets generated by a compact dynamical system (the Duffing equation). This canonical system plays the role of a ubiquitous model of non-stationary supervised classification problems. Second, we estimate the coherence of class-trajectories in empirically reconstructed space of system states. We show how this analysis can discern variations attributable to non-autonomous deterministic processes from stochastic fluctuations. The analyses are benchmarked using simulated and two different real datasets which have been shown to exhibit attractor dynamics. As an illustrative example, we focused on the analysis of the rat's frontal cortex ensemble dynamics during a decision-making task. Results suggest that, in line with recent hypotheses, rather than internal noise, it is the deterministic trend which most likely underlies the observed trial-to-trial variability. Thus, the empirical tool developed within this study potentially allows us to infer the source of variability in in-vivo neural recordings

Nutrients limitation of primary productivity in the Southeast Pacific (BIOSOPE cruise)

Revue sans Comité de lectureInternational audienceIron is an essential nutrient involved in a variety of biological processes in the ocean, including photosynthesis, respiration and nitrogen fixation. Atmospheric deposition of aerosols is recognized as the main source of iron for the surface ocean. In high nutrient, low chlorophyll areas, it is now clearly established that iron limits phytoplankton productivity but its biogeochemical role in low nutrient, low chlorophyll environments has been poorly studied. We investigated this question in the unexplored southeast Pacific, arguably the most oligotrophic area of the global ocean. Situated far from any continental aerosol source, the atmospheric iron flux to this province is amongst the lowest of the world ocean. Here we report that, despite low dissolved iron concentrations (~0.1 nmol l-1) measured across the whole gyre (3 stations situated in the center, the western and the eastern edge), photosynthesis and primary productivity are only limited by iron availability at the border of the gyre, but not in the center. The seasonal stability of the gyre has apparently allowed for the development of populations acclimated to these extreme oligotrophic conditions. Moreover, despite clear evidence of nitrogen limitation in the central gyre, we were unable to measure nitrogen fixation in our experiments, even after iron and/or phosphate additions, and cyanobacterial nifH gene abundances were extremely low compared to the North Pacific Gyre. The South Pacific gyre is therefore unique with respect to the physiological status of its phytoplankton populations

Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing

Objectives It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. Methods This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. Results Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. Conclusions Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based AR

Groups without cultured representatives dominate eukaryotic picophytoplankton in the oligotrophic South East Pacific Ocean

Background: Photosynthetic picoeukaryotes (PPE) with a cell size less than 3 µm play a critical role in oceanic primary production. In recent years, the composition of marine picoeukaryote communities has been intensively investigated by molecular approaches, but their photosynthetic fraction remains poorly characterized. This is largely because the classical approach that relies on constructing 18S rRNA gene clone libraries from filtered seawater samples using universal eukaryotic primers is heavily biased toward heterotrophs, especially alveolates and stramenopiles, despite the fact that autotrophic cells in general outnumber heterotrophic ones in the euphotic zone. Methodology/Principal Findings: In order to better assess the composition of the eukaryotic picophytoplankton in the South East Pacific Ocean, encompassing the most oligotrophic oceanic regions on earth, we used a novel approach based on flow cytometry sorting followed by construction of 18S rRNA gene clone libraries. This strategy dramatically increased the recovery of sequences from putative autotrophic groups. The composition of the PPE community appeared highly variable both vertically down the water column and horizontally across the South East Pacific Ocean. In the central gyre, uncultivated lineages dominated: a recently discovered clade of Prasinophyceae (IX), clades of marine Chrysophyceae and Haptophyta, the latter division containing a potentially new class besides Prymnesiophyceae and Pavlophyceae. In contrast, on the edge of the gyre and in the coastal Chilean upwelling, groups with cultivated representatives (Prasinophyceae clade VII and Mamiellales) dominated. Conclusions/Significance: Our data demonstrate that a very large fraction of the eukaryotic picophytoplankton still escapes cultivation. The use of flow cytometry sorting should prove very useful to better characterize specific plankton populations by molecular approaches such as gene cloning or metagenomics, and also to obtain into culture strains representative of these novel groups

Under pressure:Mechanochemical effects on structure and ion conduction in the sodium-ion solid electrolyte Na₃PS₄

10.1021/jacs.0c06668Journal of the American Chemical Society1424318422-1843