Preferred antiretroviral drugs for the next decade of scale up

Global commitments aim to provide antiretroviral therapy (ART) to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer-term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings

Mesures d'air ambiant en conditions de trafic : évolution des COV sur 3 ans

International audienceInfluence of traffic emission on air quality in European cities has widely been studied. Nevertheless, measurement campaigns are usually limited. We present here a set of VOC measurements which has been collected during 5 to 6 campaigns each year over three years. Ambient air is sampled outside vehicles, inside the traffic. Evolution of the concentrations both in urban and rural air over the 3 years are discussed, compound by compound, and compared to data from literature. Influence of traffic on concentrations is obvious. The major fînding is that the concentrations of pollutants related to traffic have been decreasing between 2003 and 2005, specially in urban atmospheres, and in a lesser way, in rural areas.L'influence des émissions liées au trafic automobile sur la qualité de l'air a largement été étudiée. Cependant, les campagnes de mesures sont généralement limitées, dans la durée et le nombre de composés étudiés. Nous présentons ici les résultats d'un ensemble de campagnes réalisées sur une durée de 3 ans, sur plusieurs composés organiques volatils. Le prélèvement est réalisé à l'extérieur de véhicules en roulage, dans la Région Parisienne, en milieux urbain et semi-rural. L'évolution des concentrations au cours du temps est discutée, et les teneurs sont comparées aux données de la littérature. Le fait marquant est la diminution très importante entre 2003 et 2005 des teneurs pour une majorité des polluants, surtout en milieu urbain, et dans une moindre mesure en milieu rural. La diminution de la teneur en benzène des essences, ainsi que l'amélioration des moteurs et le développement des pots catalytiques, explique largement cette tendance

Formation and structure of slightly anionically charged nanoemulsions obtained by the phase inversion concentration (PIC) method

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.While nanoemulsions (10–200 nm) are not thermodynamically stable systems they can exhibit quite long term stability. In this paper oil/surfactant mixtures, containing diethylhexyl carbonate/phenoxyethanol/parabens as oil and polyglyceryl-4 laurate/dilauryl citrate as surfactant, form nanoemulsions simply by dilution with water, i.e. by means of the phase inversion concentration (PIC) method. In order to study this highly interesting phenomenon an investigation at constant oil-to-surfactant (O/S) ratio was done by means of viscosity, conductivity, and UV/Vis-transmittance measurements. This phase study as a function of the dilution by water shows that at an intermediate water content a two-phase system of bicontinuous structure is formed, which exhibits a very pronounced viscosity and conductivity maximum shortly before the homogeneous nanoemulsion phase is reached. In the same region SANS shows a high degree of ordering of this bicontinuous structure. SANS and cryo-TEM investigations of the nanoemulsion regime show an increasing average size with dilution and, more interestingly, the presence of two populations with different average particle sizes around 10–15 nm and 25–40 nm. The relative proportion of each population depends on the amount of added water, leading to an average growth of the particle size with increasing dilution

A new subunit vaccine based on nucleoprotein nanoparticles confers partial clinical and virological protection in calves against bovine respiratory syncytial virus

Human and bovine respiratory syncytial viruses (HRSV and BRSV) are two closely related, worldwide prevalent viruses that are the leading cause of severe airway disease in children and calves, respectively. Efficacy of commercial bovine vaccines needs improvement and no human vaccine is licensed yet. We reported that nasal vaccination with the HRSV nucleoprotein produced as recombinant ringshaped nanoparticles (NSRS) protects mice against a viral challenge with HRSV. The aim of this work was to evaluate this new vaccine that uses a conserved viral antigen, in calves, natural hosts for BRSV. Calves, free of colostral or natural anti-BRSV antibodies, were vaccinated with NSRS either intramuscularly, or both intramuscularly and intranasally using MontanideTM ISA71 and IMS4132 as adjuvants and challenged with BRSV. All vaccinated calves developed anti-N antibodies in blood and nasal secretions and N-specific cellular immunity in local lymph nodes. Clinical monitoring post-challenge demonstrated moderate respiratory pathology with local lung tissue consolidations for the non vaccinated calves that were significantly reduced in the vaccinated calves. Vaccinated calves had lower viral loads than the nonvaccinated control calves. Thus NSRS vaccination in calves provided cross-protective immunity against BRSV infection without adverse inflammatory reaction

Polar Smectic Films

We report on a new experimental procedure for forming and studying polar smectic liquid crystal films. A free standing smectic film is put in contact with a liquid drop, so that the film has one liquid crystal/liquid interface and one liquid crystal/air interface. This polar environment results in changes in the textures observed in the film, including a boojum texture and a previously unobserved spiral texture in which the winding direction of the spiral reverses at a finite radius from its center. Some aspects of these textures are explained by the presence of a Ksb term in the bulk elastic free energy density that favors a combination of splay and bend deformations.Comment: 4 pages, REVTeX, 3 figures, submitted to PR

Simulating causal collapse models

We present simulations of causal dynamical collapse models of field theories on a 1+1 null lattice. We use our simulations to compare and contrast two possible interpretations of the models, one in which the field values are real and the other in which the state vector is real. We suggest that a procedure of coarse graining and renormalising the fundamental field can overcome its noisiness and argue that this coarse grained renormalised field will show interesting structure if the state vector does on the coarse grained scale.Comment: 18 pages, 8 fugures, LaTeX, Reference added, discussion of probability distribution of labellings correcte

Development of liquid chromatography methods coupled to mass spectrometry for the analysis of substances with a wide variety of polarity in meconium.

International audienceMeconium is the first fecal excretion of newborns. This complex accumulative matrix allows assessing the exposure of the fetus to xenobiotics during the last 6 months of pregnancy. To determine the eventual effect of fetal exposure to micropollutants in this matrix, robust and sensitive analytical methods must be developed. This article describes the method development of liquid chromatography methods coupled to triple quadrupole mass spectrometry for relevant pollutants. The 28 selected target compounds had different physico-chemical properties from very polar (glyphosate) to non-polar molecules (pyrethroids). Tests were performed with three different types of columns: reversed phase, ion exchange and HILIC. As a unique method could not be determined for the simultaneous analysis of all compounds, three columns were selected and suitable chromatographic methods were optimized. Similar results were noticed for the separation of the target compounds dissolved in either meconium extract or solvent for reversed phase and ion exchange columns. However, for HILIC, the matrix had a significant influence on the peak shape and robustness of the method. Finally, the analytical methods were applied to “real” meconium samples

Rescue of a severe mouse model for spinal muscular atrophy by U7 snRNA-mediated splicing modulation

In spinal muscular atrophy (SMA), the leading genetic cause of early childhood death, the survival motor neuron 1 gene (SMN1) is deleted or inactivated. The nearly identical SMN2 gene has a silent mutation that impairs the utilization of exon 7 and the production of functional protein. It has been hypothesized that therapies boosting SMN2 exon 7 inclusion might prevent or cure SMA. Exon 7 inclusion can be stimulated in cell culture by oligonucleotides or intracellularly expressed RNAs, but evidence for an in vivo improvement of SMA symptoms is lacking. Here, we unambiguously confirm the above hypothesis by showing that a bifunctional U7 snRNA that stimulates exon 7 inclusion, when introduced by germline transgenesis, can efficiently complement the most severe mouse SMA model. These results are significant for the development of a somatic SMA therapy, but may also provide new means to study pathophysiological aspects of this devastating diseas