A novel preference-informed complementary trial (PICT) design for clinical trial research influenced by strong patient preferences

Background: Patients and their families often have preferences for medical care that relate to wider considerations beyond the clinical effectiveness of the proposed interventions. Traditionally, these preferences have not been adequately considered in research. Research questions where patients and families have strong preferences may not be appropriate for traditional randomized controlled trials (RCTs) due to threats to internal and external validity, as there may be high levels of drop-out and non-adherence or recruitment of a sample that is not representative of the treatment population. Several preference-informed designs have been developed to address problems with traditional RCTs, but these designs have their own limitations and may not be suitable for many research questions where strong preferences and opinions are present. Methods: In this paper, we propose a novel and innovative preference-informed complementary trial (PICT) design which addresses key weaknesses with both traditional RCTs and available preference-informed designs. In the PICT design, complementary trials would be operated within a single study, and patients and/or families would be given the opportunity to choose between a trial with all treatment options available and a trial with treatment options that exclude the option which is subject to strong preferences. This approach would allow those with strong preferences to take part in research and would improve external validity through recruiting more representative populations and internal validity. Here we discuss the strengths and limitations of the PICT design and considerations for analysis and present a motivating example for the design based on the use of opioids for pain management for children with musculoskeletal injuries. Conclusions: PICTs provide a novel and innovative design for clinical trials with more than two arms, which can address problems with existing preference-informed trial designs and enhance the ability of researchers to reflect shared decision-making in research as well as improving the validity of trials of topics with strong preferences

CNN color demosaicking generalizes for any CFA

A convolutional neural network is trained in auto/heteroassociative mode for reconstructing RGB components from a randomly mosaicked color image. The trained network was shown to perform equally well when images are sampled periodically or with a different random mosaic. Therefore, this model is able to generalize on every type of color filter array. We attribute this property of universal demosaicking to the network learning the statistical structure of color images independently of the mosaic pattern arrangement

Magnetophoresis Assisted Capillary Assembly of Cobalt Nanorods: A New Source of Permanent Magnets for MEMS

International audienceThis paper presents the fabrication of high-performance micro-magnets for the electromagnetic transduction of MEMS. The fabrication method relies on the use of nickel microstructures electroplated onto silicon substrates to control the capillary assembly of cobalt nanorods via magnetophoresis under an external magnetic field. The resulting sub-millimeter size permanent magnets with thicknesses of up to 150 µm produce a stray field of 30 mT at a distance of 100 µm. We demonstrate that this magnetic induction is sufficient to actuate a silicon microcantilever by means of the Lorentz force and that the MEMS resonance frequency can adequately be measured using integrated piezoresistances. This novel room-temperature synthesis approach is foreseen to facilitate the integration of high-performance magnets into MEMS

Development Of Micro-Magnets For The Electromagnetic Transduction Of MEMS

International audienceThis paper presents a new class of high-performance permanent micro-magnets based on the controlled assembly of cobalt nanorods for the electromagnetic transduction of MEMS. Micromagnets are fabricated using a low temperature fabrication process that yields a dense material exhibiting high coercive field and remanence to saturation magnetization ratio. The cartography of the magnetic induction produced by the sub-millimeter size magnets was obtained using a scanning Hall effect micro-probe microscope. Silicon microcantilevers placed in the vicinity of these magnets were successfully actuated using the Lorentz force with low currents. The good signal to noise ratio measured at resonance demonstrates the potentiality of these nanostructured micro-magnets

Optimization of a vibrating MEMS electromagnetic energy harvester using simulations

International audienceNowadays, wireless sensor networks (WSN) are becoming essential in our daily life. However, a major constraint concerns the energy power supply. Indeed, batteries need to be recharged or replaced often which implies a limited lifetime for WSN nodes. One alternative consists in harvesting mechanical energy from surrounding vibrations of the environment. Using finite element simulations, we report here a complete guideline to optimize a MEMS electromagnetic energy harvester consisting of an in-plane vibrating silicon frame supporting an array of micromagnets that faces a static 2D micro-coil. The dimensioning of the magnet array and the specific design of the coil are addressed, considering patterned 50 µm thick NdFeB films with out of plane magnetization. The optimization of the electromechanical coupling which allows to efficiently convert the energy results from a trade-off between the high magnetic flux gradients produced by the micromagnets and the maximum number of turns of the facing coil

Mise à l’écart et embarras dans l’enquête en sciences sociales

Retour réflexif sur l’enquête et les conditions concrètes du travail de production scientifique lorsque l’inconfort ou la déstabilisation éthique et émotionnelle heurte le sens de la justice et de la justesse. La rupture épistémologique ne passe plus alors uniquement par la mise à distance mais par l’objectivation des réactions sensorielles devenant un levier pour la production de connaissances. Reflexive return on the investigation and the conditions of scientific production work when ethical and emotional discomfort or destabilization offends the sense of justice and accuracy. The epistemological rupture no longer only involves distance but also the objectification of sensory reactions, which become a lever for the production of knowledge. Retroalimentación reflexiva sobre la investigación y las condiciones del trabajo de producción científica cuando la incomodidad ética y emocional o la desestabilización ofenden el sentido de justicia y exactitud. La ruptura epistemológica ya no sólo implica la distancia, sino también la objetivación de las reacciones sensoriales, que se convierten en una palanca para la producción de conocimiento

Hybrid Ni–Co–Ni Structures Prepared by Magnetophoresis as Efficient Permanent Magnets for Integration into Microelectromechanical Systems

International audienceThe direct integration of performant permanent magnets (PMs) within miniaturized circuits remains both a scientific and a technological challenge. Magnetophoresis-driven capillary assembly of hard magnetic nanoparticles is a promising approach to fabricate 3D rare-earth-free PMs. However, this process implies the use of soft magnetic blocks to generate the magnetic field gradients required to localize the assembly directly onto silicon substrates. The impact of these soft elements onto the overall magnetic properties is evaluated using Co nanorods as hard material and 150 μm–thick Ni blocks. As expected, the presence of Ni softens the overall properties of the hybrid magnet obtained, but PM properties are preserved for reduced Ni volumes. Magnetic induction as high as 19 mT at a distance of 200 μm is generated by the hybrid Ni–Co–Ni structures, allowing for the electromagnetic actuation of a microelectromechanical resonant senso

Magnetophoresis-Assisted Capillary Assembly: A Versatile Approach for Fabricating Tailored 3D Magnetic Supercrystals

International audienceThe fabrication and integration of sub-millimeter magnetic materials into predefined circuits is of major importance for the realization of portable devices designed for telecommunications, automotive, biomedical, and space applications but remains highly challenging. We report here a versatile approach for the fabrication and direct integration of nanostructured magnetic materials of controlled shaped at specific locations onto silicon substrates. The magnetophoresis-assisted capillary assembly of magnetic nanoparticles, either spherical or anisotropic, leads to the fabrication of high-performance Co-based permanent magnets and Fe-based supercrystals. Integrated sub-millimeter magnets as well as millimeter self-standing magnets exhibiting magnetic properties competing with NdFeB-based composites were obtained through this cost- and time-efficient process. The proof-of-concept of electromagnetic actuation of a micro-electromechanical system cantilever by means of these supercrystals highlights their potentiality as efficient integrated magnetic materials within nomadic devices

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old