Thiolation of NHC-boranes: influence of the substitution at boron

International audienceSeveral N-Heterocyclic Carbene (NHC)-boryl sulfides with B-substituents were prepared. The added steric hindrance leads to much improved selectivities as only the NHC-boryl mono-sulfides were obtained. The B-substituted NHC-boranes are also conducive to more selective S to N NHC-boryl shift, provided that the NHC used is not too sterically demanding

Apport de l'hydrogéochimie pour la caractérisation des mouvements gravitaires

National audienceLes travaux menés depuis plus d'une dizaine d'années sur différents massifs instables ont montré les potentialités des observations hydrogéochimiques (suivi à long-terme et expérimentations) pour une meilleure compréhension du comportement hydro-mécanique des instabilités de versant et potentiellement l'identification de précurseurs de la rupture ou d'accélération

A Guide to Best Practice in Sensory Analysis of Pharmaceutical Formulations

It is well established that treatment regime compliance is linked to the acceptability of a pharmaceutical formulation, and hence also to therapeutic outcomes. To that end, acceptability must be assessed during the development of all pharmaceutical products and especially for those intended for paediatric patients. Although acceptability is a multifaceted concept, poor sensory characteristics often contribute to poor patient acceptability. In particular, poor taste is often cited as a major reason for many patients, especially children, to refuse to take their medicine. It is thus important to understand and, as far as possible, optimise the sensory characteristics and, in particular, the taste/flavour/mouthfeel of the formulation throughout the development of the product. Sensory analysis has been widely practiced, providing objective data concerning the sensory aspects of food and cosmetic products. In this paper, we present proposals concerning how the well-established principles of sensory analysis can best be applied to pharmaceutical product development, allowing objective, scientifically valid, sensory data to be obtained safely. We briefly discuss methodologies that may be helpful in reducing the number of samples that may need to be assessed by human volunteers. However, it is only possible to be sure whether or not the sensory characteristics of a pharmaceutical product are non-aversive to potential users by undertaking sensory assessments in human volunteers. Testing is also required during formulation assessment and to ensure that the sensory characteristics remain acceptable throughout the product shelf life. We provide a risk assessment procedure to aid developers to define where studies are low risk, the results of a survey of European regulators on their views concerning such studies, and detailed guidance concerning the types of sensory studies that can be undertaken at each phase of product development, along with guidance about the practicalities of performing such sensory studies. We hope that this guidance will also lead to the development of internationally agreed standards between industry and regulators concerning how these aspects should be measured and assessed throughout the development process and when writing and evaluating regulatory submissions. Finally, we hope that the guidance herein will help formulators as they seek to develop better medicines for all patients and, in particular, paediatric patients

How informality can address emerging issues: Making the most of the G7

The G7 should address new, unprecedented and highly disruptive issues that characterise our complex world, rather than well‐understood international problems that fit into existing categories. We argue that the G7 can do this by playing to its strengths – informality and like‐mindedness in particular – in addressing emerging and transversal issues such as Artificial Intelligence (AI) and cryptocurrencies

In vitro studies and preliminary in vivo evaluation of silicified concentrated collagen hydrogels

Hybrid and nanocomposite silicacollagen materials derived from concentrated collagen hydrogels were evaluated in vitro and in vivo to establish their potentialities for biological dressings. Silicification significantly improved the mechanical and thermal stability of the collagen network within the hybrid systems. Nanocomposites were found to favor the metabolic activity of immobilized human dermal fibroblastswhile decreasing the hydrogel contraction. Cell adhesion experiments suggested that in vitro cell behavior was dictated by mechanical properties and surface structure of the scaffold. First-to-date in vivo implantation of bulk hydrogels in subcutaneous sites of rats was performed over the vascular inflammatory period. These materials were colonized and vascularized without inducing strong inflammatory response. These data raise reasonable hope for the future application of silicacollagen biomaterials as biological dressings.Fil: Desimone, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Hélary, Christophe. Université Pierre et Marie Curie; FranciaFil: Quignard, Sandrine. Université Pierre et Marie Curie; FranciaFil: Rietveld, Ivo B. Universite de Paris; FranciaFil: Bataille, Clement. Université de Versailles Saint-quentin-en-yvelines.; FranciaFil: Copello, Guillermo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Mosser, Gervaise. Université Pierre et Marie Curie; FranciaFil: Giraud Guille, Marie-Madeleine. Université Pierre et Marie Curie; FranciaFil: Livage, Jacques. Université Pierre et Marie Curie; FranciaFil: Meddahi Pellé, Anne. Université de Versailles Saint-quentin-en-yvelines.; FranciaFil: Coradin, Thibaud. Université Pierre et Marie Curie; Franci

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

A multi-model CMIP6-PMIP4 study of Arctic sea ice at 127 ka: sea ice data compilation and model differences

The Last Interglacial period (LIG) is a period with increased summer insolation at high northern latitudes, which results in strong changes in the terrestrial and marine cryosphere. Understanding the mechanisms for this response via climate modelling and comparing the models' representation of climate reconstructions is one of the objectives set up by the Paleoclimate Modelling Intercomparison Project for its contribution to the sixth phase of the Coupled Model Intercomparison Project. Here we analyse the results from 16 climate models in terms of Arctic sea ice. The multi-model mean reduction in minimum sea ice area from the pre industrial period (PI) to the LIG reaches 50 % (multi-model mean LIG area is 3.20×106 km2, compared to 6.46×106 km2 for the PI). On the other hand, there is little change for the maximum sea ice area (which is 15–16×106 km2 for both the PI and the LIG. To evaluate the model results we synthesise LIG sea ice data from marine cores collected in the Arctic Ocean, Nordic Seas and northern North Atlantic. The reconstructions for the northern North Atlantic show year-round ice-free conditions, and most models yield results in agreement with these reconstructions. Model–data disagreement appear for the sites in the Nordic Seas close to Greenland and at the edge of the Arctic Ocean. The northernmost site with good chronology, for which a sea ice concentration larger than 75 % is reconstructed even in summer, discriminates those models which simulate too little sea ice. However, the remaining models appear to simulate too much sea ice over the two sites south of the northernmost one, for which the reconstructed sea ice cover is seasonal. Hence models either underestimate or overestimate sea ice cover for the LIG, and their bias does not appear to be related to their bias for the pre-industrial period. Drivers for the inter-model differences are different phasing of the up and down short-wave anomalies over the Arctic Ocean, which are associated with differences in model albedo; possible cloud property differences, in terms of optical depth; and LIG ocean circulation changes which occur for some, but not all, LIG simulations. Finally, we note that inter-comparisons between the LIG simulations and simulations for future climate with moderate (1 % yr−1) CO2 increase show a relationship between LIG sea ice and sea ice simulated under CO2 increase around the years of doubling CO2. The LIG may therefore yield insight into likely 21st century Arctic sea ice changes using these LIG simulations

Invisible inhabitants of city wastelands : discreet and uncertain shelters in vacant lots and derelict spaces along motorways around Paris

Les terrains vagues et les délaissés autoroutiers ont, en tant que friches, une existence temporaire mais chronique en ville. Ce sont des espaces dits vacants qui, de l’extérieur, semblent abandonnés, inoccupés, et parfois impénétrables. Pourtant, ils comportent souvent des abris, des tentes ou des cabanes, peu ou pas du tout visibles depuis les espaces urbains qui les entourent. À partir d’une ethnographie de ces situations discrètes, précaires et instables, cette thèse en anthropologie appréhende, de l’intérieur et sous l’angle de l’habiter, des terrains en friche localisés en petite couronne parisienne. Qu’est-ce que raconte l’effacement des abris sur la « présence-au-monde » et le rapport à la ville de leurs habitantes et habitants ? En quoi cet effacement donne-t-il à comprendre ce qui constitue une certaine habitabilité des terrains en friche ? En quoi cette habitabilité se distingue-t-elle, et même se confronte-t-elle, à l’appropriation ? Effacement des abris, « présence-au-monde » et rapport à la ville montrent que, sans être les seuls, ces terrains en friche – en apparence inutiles, clôturés, indéterminés, inappropriés pour se loger, voire s’abriter – sont, au sein de la ville déterminée, planifiée et contrôlée, indispensables à celles et ceux qui, français ou étrangers, de pays tiers ou européens, migrants ou immigrés, séjournant depuis peu ou de longue date en ville, n’ont pas d’espace propre et ne sont pas protégés par la société, la Ville et/ou l’État.Vacant lots and derelict spaces along motorways, insofar as they are wastelands, have a temporary but chronic existence in the city. These wastelands may appear, from the outside, to be abandoned, unoccupied, and sometimes impenetrable. However, they often include shelters, tents or huts, little or not at all visible from the urban spaces that surround them. Based on an ethnography of these discrete, precarious and unstable situations, this doctoral dissertation in anthropology examines from within and through the lens of dwelling, wastelands located in the inner suburbs of Paris. What does the effacement of shelters tell about the "being-in-the-world" and the relationship to the city of their inhabitants? How does this visual disappearance make it possible to understand what constitutes a certain habitability of wasteland? How does this habitability differ from, and even how does it confront, appropriation? Effacement of shelters, “being-in-the-world”, and relationship to the city show that, among other things, these wasteland - seemingly useless, fenced, indeterminate, unsuitable as housing or shelter - are, within the determined, planned and controlled city, essential for those who, French or foreign, from Europe or otherwise, migrants or immigrants, staying for a short time or for a long time in the city, do not have their own space and are not protected by society, the City or the State