78 research outputs found

    PrĂ©caritĂ©s en France : ÉlĂ©ments d’analyse auprĂšs de deux populations masculines d’outsiders

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    La prĂ©caritĂ© se conjugue au pluriel. Deux populations masculines (jeune Ă  la rue et ĂągĂ©e en rĂ©sidence) sont analysĂ©es sous l’angle de leurs processus identitaires, leurs consommations addictives et leurs rapports au travail. Cette sociologie des Outsiders combine les acquis d’Elias et de Becker pour tenter de mieux comprendre les situations prĂ©caires et leurs dynamiques individuelles et collectives.Precariousness is plural. Of no fixed abode young and older men are analyzed about identity process, addictions and sense of work. Outsiders’ sociology articulate Elias and Becker theories to analyze precariousness situations, individual or collective trends

    PrĂ©caritĂ©s en France : ÉlĂ©ments d’analyse auprĂšs de deux populations masculines d’outsiders

    Get PDF
    La prĂ©caritĂ© se conjugue au pluriel. Deux populations masculines (jeune Ă  la rue et ĂągĂ©e en rĂ©sidence) sont analysĂ©es sous l’angle de leurs processus identitaires, leurs consommations addictives et leurs rapports au travail. Cette sociologie des Outsiders combine les acquis d’Elias et de Becker pour tenter de mieux comprendre les situations prĂ©caires et leurs dynamiques individuelles et collectives.Precariousness is plural. Of no fixed abode young and older men are analyzed about identity process, addictions and sense of work. Outsiders’ sociology articulate Elias and Becker theories to analyze precariousness situations, individual or collective trends

    Dynamic study of blood-brain barrier closure after its disruption using ultrasound: a quantitative analysis.

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    International audienceDelivery of therapeutic or diagnostic agents to the brain is majorly hindered by the blood-brain barrier (BBB). Recently, many studies have demonstrated local and transient disruption of the BBB using low power ultrasound sonication combined with intravascular microbubbles. However, BBB opening and closure mechanisms are poorly understood, especially the maximum gap that may be safely generated between endothelial cells and the duration of opening of the BBB. Here, we studied BBB opening and closure under magnetic resonance (MR) guidance in a rat model. First, MR contrast agents (CA) of different hydrodynamic diameters (1 to 65 nm) were employed to estimate the largest molecular size permissible across the cerebral tissues. Second, to estimate the duration of the BBB opening, the CA were injected at various times post-BBB disruption (12 minutes to 24 hours). A T(1) mapping strategy was developed to assess CA concentration at the ultrasound (US) focal point. Based on our experimental data and BBB closure modeling, a calibration curve was obtained to compute the half closure time as a function of CA hydrodynamic diameter. These findings and the model provide an invaluable basis for optimal design and delivery of nanoparticles to the brain

    Amphiphilic block copolymers enhance the cellular uptake of DNA molecules through a facilitated plasma membrane transport

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    Amphiphilic block copolymers have been developed recently for their efficient, in vivo transfection activities in various tissues. Surprisingly, we observed that amphiphilic block copolymers such as LutrolÂź do not allow the transfection of cultured cells in vitro, suggesting that the cell environment is strongly involved in their mechanism of action. In an in vitro model mimicking the in vivo situation we showed that pre-treatment of cells with LutrolÂź, prior to their incubation with DNA molecules in the presence of cationic lipid, resulted in higher levels of reporter gene expression. We also showed that this improvement in transfection efficiency associated with the presence of LutrolÂź was observed irrespective of the plasmid promoter. Considering the various steps that could be improved by LutrolÂź, we concluded that the nucleic acids molecule internalization step is the most important barrier affected by LutrolÂź. Microscopic examination of transfected cells pre-treated with LutrolÂź confirmed that more plasmid DNA copies were internalized. Absence of cationic lipid did not impair LutrolÂź-mediated DNA internalization, but critically impaired endosomal escape. Our results strongly suggest that in vivo, LutrolÂź improves transfection by a physicochemical mechanism, leading to cellular uptake enhancement through a direct delivery into the cytoplasm, and not via endosomal pathways

    Recommendations and guidelines from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 1 -- In vivo small-animal imaging

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    The value of in vivo preclinical diffusion MRI (dMRI) is substantial. Small-animal dMRI has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. Many of the influential works in this field were first performed in small animals or ex vivo samples. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be answered using the data. This work aims to serve as a reference, presenting selected recommendations and guidelines from the diffusion community, on best practices for preclinical dMRI of in vivo animals. In each section, we also highlight areas for which no guidelines exist (and why), and where future work should focus. We first describe the value that small animal imaging adds to the field of dMRI, followed by general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in animal species and disease models and discuss how they are appropriate for different studies. We then give guidelines for in vivo acquisition protocols, including decisions on hardware, animal preparation, imaging sequences and data processing, including pre-processing, model-fitting, and tractography. Finally, we provide an online resource which lists publicly available preclinical dMRI datasets and software packages, to promote responsible and reproducible research. An overarching goal herein is to enhance the rigor and reproducibility of small animal dMRI acquisitions and analyses, and thereby advance biomedical knowledge.Comment: 69 pages, 6 figures, 1 tabl

    Daily magnesium fluxes regulate cellular timekeeping and energy balance

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    Circadian clocks are fundamental to the biology of most eukaryotes, coordinating behaviour and physiology to resonate with the environmental cycle of day and night through complex networks of clock-controlled genes1, 2, 3. A fundamental knowledge gap exists, however, between circadian gene expression cycles and the biochemical mechanisms that ultimately facilitate circadian regulation of cell biology4, 5. Here we report circadian rhythms in the intracellular concentration of magnesium ions, [Mg2+]i, which act as a cell-autonomous timekeeping component to determine key clock properties both in a human cell line and in a unicellular alga that diverged from each other more than 1 billion years ago6. Given the essential role of Mg2+ as a cofactor for ATP, a functional consequence of [Mg2+]i oscillations is dynamic regulation of cellular energy expenditure over the daily cycle. Mechanistically, we find that these rhythms provide bilateral feedback linking rhythmic metabolism to clock-controlled gene expression. The global regulation of nucleotide triphosphate turnover by intracellular Mg2+ availability has potential to impact upon many of the cell’s more than 600 MgATP-dependent enzymes7 and every cellular system where MgNTP hydrolysis becomes rate limiting. Indeed, we find that circadian control of translation by mTOR8 is regulated through [Mg2+]i oscillations. It will now be important to identify which additional biological processes are subject to this form of regulation in tissues of multicellular organisms such as plants and humans, in the context of health and disease

    CMS physics technical design report : Addendum on high density QCD with heavy ions

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    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

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    Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≀ 18 years: 69, 48, 23; 85%), older adults (≄ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men
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