Novel applications of long-established histochemical techniques to study nanoparticle-cell interactions at transmission electron microscopy

Alcian blue staining has been used to visualise nanoparticles at transmission electron microscop

Alcian blue staining to study nanoparticle-cell interactions at transmission electron microscopy

Alcian blue staining has been used to visualise nanoparticles at transmission electron microscop

Alcian blue staining to track the intracellular fate of hyaluronic-acid-based nanoparticles at transmission electron microscopy

The main step in the assessment of nanomaterial safety and suitability for biomedical use is the location and the dynamic tracking of nanoparticles (NPs) inside cells or tissues. To precisely investigate the uptake mechanisms and intracellular fate of NPs, transmission electron microscopy is the technique of choice; however, the detection of NPs may sometimes be problematic. In fact, while NPs containing strongly electron dense (e.g. metal) components do not require specific detection methods at the ultrastructural level, organic NPs are hardly detectable in the intracellular enviromnent due to their intrinsic moderate electron density. In this study, the critical-electrolyte-concentration Alcian Blue method set up by Schofield et at in 1975 was applied to track hyaluronic-acid-based NPs in muscle cells in vitro. This long-established histochemical method proved to be a powerful tool allowing to identify not only whole NPs while entering cells and moving into the cytoplasm, but also their remnants following lysosomal degradation and extrusion

The interaction of two surface vortices near a topographic slope in a stratified ocean

We study the influence of bottom topography on the interaction of two identical vortices in a two-layer, quasi-geostrophic model. The two vortices have piecewise-uniform potential vorticity, and are lying in the upper layer of the model. The topography is a smooth bottom slope. For two cyclones, topography modifies the merger critical distance and the merger efficiency: the topographic wave and vortices can advect the two cyclones along the shelf when they are initially far from it, or towards the shelf when they are initially closer to it. They can also advect the two cyclones towards each other, and thus favour merger. The topographic wave and vortices exert a deformation on these cyclones, which filament. Regimes of partial vortex merger or of vortex splitting are then observed. The interaction of the vorticity poles in the two layers are analysed to explain the evolution of the two upper layer cyclones. For taller topography, two new regimes appear: vortex drift and splitting, and filamentation and asymmetric merger. They are due to the hetonic coupling of lower layer vorticity with the upper vortices, or to the strong shear that the former exert on the latter. The interaction of two anticyclones shows regimes of co-rotation or merger, but specifically, it leads to the drift of the two vortices away from the slope, via a hetonic coupling with opposite signed vorticity in the lower layer. This vorticity originates in the breaking of the topographic wave. The analysis of passive tracer evolution confirms the inshore or offshore drift of the fluid, the formation of tracer fronts along filaments and its mixing in regions of vortex merger. The trajectories of particles indicates how the fluid initially in the vortices is finally partitioned.Publisher PDFPeer reviewe

Hyaluronic acid-based nanocomplexes as an innovative therapeutic tool to treat myotonic dystrophy

Hyaluronic acid-based nanocomplexes have been synthesized and tested as an innovative therapeutic tool to treat myotonic dystroph

A low-cost system for indoor motion tracking of unmanned aerial vehicles

International audienceThis paper presents development and performance analysis of an indoor low-cost motion tracking system for miniature Unmanned Aerial Vehicles. The proposed system is based on infrared markers embedded on the vehicle, the positions of which are captured in real time by Wiimote infrared cameras. Using at least two of these cameras, vehicle 3D position and orientation can be determined. Implementation of system hardware architecture developed as student research project in academic environment is discussed with its own limitations. Estimation method is presented. System performance analysis is also proposed, addressing optimization of detection area, accuracy and dispersion of measurements, and robustness with respect to outliers and hardware parameters. Experimental results are provided to illustrate system performance and to demonstrate satisfaction of imposed strict constraints for reliable motion tracking of a miniature UAV

Vortex merger near a topographic slope in a homogeneous rotating fluid

This work is a contribution to the PHYSINDIEN research program. It was supported by CNRS-RFBR contract PRC 1069/16-55-150001.The effect of a bottom slope on the merger of two identical Rankine vortices is investigated in a two dimensional, quasi-geostrophic, incompressible fluid. When two cyclones initially lie parallel to the slope, and more than two vortex diameters away from the slope, the critical merger distance is unchanged. When the cyclones are closer to the slope, they can merge at larger distances, but they lose more mass into filaments, thus weakening the efficiency of merger. Several effects account for this: the topographic Rossby wave advects the cyclones, reduces their mutual distance and deforms them. This along shelf wave breaks into filaments and into secondary vortices which shear out the initial cyclones. The global motion of fluid towards the shallow domain and the erosion of the two cyclones are confirmed by the evolution of particles seeded both in the cyclone sand near the topographic slope. The addition of tracer to the flow indicates that diffusion is ballistic at early times. For two anticyclones, merger is also facilitated because one vortex is ejected offshore towards the other, via coupling with a topographic cyclone. Again two anticyclones can merge at large distance but they are eroded in the process. Finally, for taller topographies, the critical merger distance is again increased and the topographic influence can scatter or completely erode one of the two initial cyclones. Conclusions are drawn on possible improvements of the model configuration for an application to the ocean.PostprintPeer reviewe

Effectiveness of electronic guideline-based implementation systems in ambulatory care settings - a systematic review

<p>Abstract</p> <p>Background</p> <p>Electronic guideline-based decision support systems have been suggested to successfully deliver the knowledge embedded in clinical practice guidelines. A number of studies have already shown positive findings for decision support systems such as drug-dosing systems and computer-generated reminder systems for preventive care services.</p> <p>Methods</p> <p>A systematic literature search (1990 to December 2008) of the English literature indexed in the Medline database, Embase, the Cochrane Central Register of Controlled Trials, and CRD (DARE, HTA and NHS EED databases) was conducted to identify evaluation studies of electronic multi-step guideline implementation systems in ambulatory care settings. Important inclusion criterions were the multidimensionality of the guideline (the guideline needed to consist of several aspects or steps) and real-time interaction with the system during consultation. Clinical decision support systems such as one-time reminders for preventive care for which positive findings were shown in earlier reviews were excluded. Two comparisons were considered: electronic multidimensional guidelines versus usual care (comparison one) and electronic multidimensional guidelines versus other guideline implementation methods (comparison two).</p> <p>Results</p> <p>Twenty-seven publications were selected for analysis in this systematic review. Most designs were cluster randomized controlled trials investigating process outcomes more than patient outcomes. With success defined as at least 50% of the outcome variables being significant, none of the studies were successful in improving patient outcomes. Only seven of seventeen studies that investigated process outcomes showed improvements in process of care variables compared with the usual care group (comparison one). No incremental effect of the electronic implementation over the distribution of paper versions of the guideline was found, neither for the patient outcomes nor for the process outcomes (comparison two).</p> <p>Conclusions</p> <p>There is little evidence at the moment for the effectiveness of an increasingly used and commercialised instrument such as electronic multidimensional guidelines. After more than a decade of development of numerous electronic systems, research on the most effective implementation strategy for this kind of guideline-based decision support systems is still lacking. This conclusion implies a considerable risk towards inappropriate investments in ineffective implementation interventions and in suboptimal care.</p

BMC Med

BACKGROUND: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). METHODS: We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype. RESULTS: 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. CONCLUSIONS: Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates

Managing formalization to increase global team effectiveness and meaningfulness of work in multinational organizations

Global teams may help to integrate across locations, and yet, with formalized rules and procedures, responsiveness to those locations’ effectiveness, and the team members’ experiences of work as meaningful may suffer. We employ a mixed-methods approach to understand how the level and content of formalization can be managed to resolve these tensions in multinationals. In a sample of global teams from a large mining and resources organization operating across 44 countries, interviews, observations, and a quantitative 2-wave survey revealed a great deal of variability between teams in how formalization processes were enacted. Only those formalization processes that promoted knowledge sharing were instrumental in improving team effectiveness. Implementing rules and procedures in the set-up of the teams and projects, rather than during interactions, and utilizing protocols to help establish the global team as a source of identity increased this knowledge sharing. Finally, we found members’ personal need for structure moderated the effect of team formalization on how meaningful individuals found their work within the team. These findings have significant implications for theory and practice in multinational organizations