Soft Deployable Structures via Core-Shell Inflatables.

Deployable structures capable of significant geometric reconfigurations are ubiquitous in nature. While engineering contraptions typically comprise articulated rigid elements, soft structures that experience material growth for deployment mostly remain the handiwork of biology, e.g., when winged insects deploy their wings during metamorphosis. Here we perform experiments and develop formal models to rationalize the previously unexplored physics of soft deployable structures using core-shell inflatables. We first derive a Maxwell construction to model the expansion of a hyperelastic cylindrical core constrained by a rigid shell. Based on these results, we identify a strategy to obtain synchronized deployment in soft networks. We then show that a single actuated element behaves as an elastic beam with a pressure-dependent bending stiffness which allows us to model complex deployed networks and demonstrate the ability to reconfigure their final shape. Finally, we generalize our results to obtain three-dimensional elastic gridshells, demonstrating our approach's applicability to assemble complex structures using core-shell inflatables as building blocks. Our results leverage material and geometric nonlinearities to create a low-energy pathway to growth and reconfiguration for soft deployable structures.

Ensembles of data-efficient vision transformers as a new paradigm for automated classification in ecology.

Monitoring biodiversity is paramount to manage and protect natural resources. Collecting images of organisms over large temporal or spatial scales is a promising practice to monitor the biodiversity of natural ecosystems, providing large amounts of data with minimal interference with the environment. Deep learning models are currently used to automate classification of organisms into taxonomic units. However, imprecision in these classifiers introduces a measurement noise that is difficult to control and can significantly hinder the analysis and interpretation of data. We overcome this limitation through ensembles of Data-efficient image Transformers (DeiTs), which not only are easy to train and implement, but also significantly outperform the previous state of the art (SOTA). We validate our results on ten ecological imaging datasets of diverse origin, ranging from plankton to birds. On all the datasets, we achieve a new SOTA, with a reduction of the error with respect to the previous SOTA ranging from 29.35% to 100.00%, and often achieving performances very close to perfect classification. Ensembles of DeiTs perform better not because of superior single-model performances but rather due to smaller overlaps in the predictions by independent models and lower top-1 probabilities. This increases the benefit of ensembling, especially when using geometric averages to combine individual learners. While we only test our approach on biodiversity image datasets, our approach is generic and can be applied to any kind of images.

Instability mediated self-templating of drop crystals.

The breakup of liquid threads into droplets is prevalent in engineering and natural settings. While drop formation in these systems has a long-standing history, existing studies typically consider axisymmetric systems. Conversely, the physics at play when multiple threads are involved and the interaction of a thread with a symmetry breaking boundary remain unexplored. Here, we show that the breakup of closely spaced liquid threads sequentially printed in an immiscible bath locks into crystal-like lattices of droplets. We rationalize the hydrodynamics at the origin of this previously unknown phenomenon. We leverage this knowledge to tune the lattice pattern via the control of injection flow rate and nozzle translation speed, thereby overcoming the limitations in structural versatility typically seen in existing fluid manipulations paradigms. We further demonstrate that these drop crystals have the ability to self-correct and propose a simple mechanism to describe the convergence toward a uniform pattern of drops.

Formation of Pixelated Elastic Films via Capillary Suction of Curable Elastomers in Templated Hele-Shaw Cells.

Natural materials are highly organized, frequently possessing intricate and sophisticated hierarchical structures from which superior properties emerge. In the wake of biomimicry, there is a growing interest in designing architected materials in the laboratory as such structures could enable myriad functionalities in engineering. Yet, their fabrication remains challenging despite recent progress in additive manufacturing. In particular, soft materials are typically poorly suited to form the requisite structures consisting of regular geometries. Here, a new frugal methodology is reported to fabricate pixelated soft materials. This approach is conceptually analogous to the watershed transform used in image analysis and allows the passive assembly of complex geometries through the capillary-mediated flow of curable elastomers in confined geometries. Emerging from sources distributed across a Hele-Shaw cell consisting of two parallel flat plates separated by an infinitesimally small gap, these flows eventually meet at the "dividing lines" thereby forming Voronoi tesselations. After curing is complete, these structures turn into composite elastic sheets. Rationalizing the fluid mechanics at play allows the structural geometry of the newly formed sheets to be tailored and thereby their local material properties to be tuned.

IFCT-1502 CLINIVO: real-world evidence of long-term survival with nivolumab in a nationwide cohort of patients with advanced non-small-cell lung cancer.

BACKGROUND: Immunotherapy using inhibitors targeting immune checkpoint programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) is currently the standard of care in patients with advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We carried out a nationwide cohort retrospective study of consecutive patients with advanced, refractory NSCLC who received nivolumab as second to later lines of treatment as part of the expanded access program. Key objectives were to assess the efficacy and safety of nivolumab and the efficacy of first post-nivolumab treatment. RESULTS: Nine hundred and two patients were enrolled: 317 (35%) with squamous cell carcinoma and 585 (65%) with non-squamous cell carcinoma. Median age was 64 years; there were 630 (70%) men, 795 (88%) smokers, 723 (81%) patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0/1, 197 (22%) patients with brain metastases, and 212 (27%) with liver metastases. Best response was partial response for 16.2% and stable disease (SD) for 30.5%. Progression-free survival and overall survival (OS) rates at 2, 3, and 5 years were 8% and 25%, 6% and 16%, and 4% and 10%, respectively. At multivariate analysis, ECOG PS ≥2 [hazard ratio (HR) = 2.13, 95% confidence interval (95% CI) 1.78-2.55, P < 0.001], squamous histology (HR = 1.17, 95% CI 1.01-1.36, P = 0.04), and presence of central nervous system metastases (HR = 1.29, 95% CI 1.08-1.54, P = 0.005) were significantly associated with lower OS. Four hundred and ninety-two patients received at least one treatment after discontinuation of nivolumab, consisting of systemic therapies in 450 (91%). Radiation therapy was delivered to 118 (24%) patients. CONCLUSION: The CLINIVO cohort represents the largest real-world evidence cohort with the use of immune checkpoint inhibitor in advanced, metastatic NSCLC after failure of first-line chemotherapy, with long-term follow-up and analysis of subsequent therapies. Our data confirm the efficacy of nivolumab in a cohort larger than that reported in landmark clinical trials and identify prognostic factors, which reinforces the need for accurate selection of patients for treatment with immune checkpoint inhibitors. Our data indicate that oligoprogression is frequent after nivolumab exposure and provide a unique insight into the long-term survival.

Bubble casting soft robotics.

Inspired by living organisms, soft robots are developed from intrinsically compliant materials, enabling continuous motions that mimic animal and vegetal movement1. In soft robots, the canonical hinges and bolts are replaced by elastomers assembled into actuators programmed to change shape following the application of stimuli, for example pneumatic inflation2-5. The morphing information is typically directly embedded within the shape of these actuators, whose assembly is facilitated by recent advances in rapid prototyping techniques6-11. Yet, these manufacturing processes have limitations in scalability, design flexibility and robustness. Here we demonstrate a new all-in-one methodology for the fabrication and the programming of soft machines. Instead of relying on the assembly of individual parts, our approach harnesses interfacial flows in elastomers that progressively cure to robustly produce monolithic pneumatic actuators whose shape can easily be tailored to suit applications ranging from artificial muscles to grippers. We rationalize the fluid mechanics at play in the assembly of our actuators and model their subsequent morphing. We leverage this quantitative knowledge to program these soft machines and produce complex functionalities, for example sequential motion obtained from a monotonic stimulus. We expect that the flexibility, robustness and predictive nature of our methodology will accelerate the proliferation of soft robotics by enabling the assembly of complex actuators, for example long, tortuous or vascular structures, thereby paving the way towards new functionalities stemming from geometric and material nonlinearities.

Drops on the Underside of a Slightly Inclined Wet Substrate Move Too Fast to Grow.

Pendant drops suspended on the underside of a wet substrate are known to accumulate fluid from the surrounding thin liquid film, a process that often results in dripping. The growth of such drops is hastened by their ability to translate over an otherwise uniform horizontal film. Here we show that this scenario is surprisingly reversed when the substrate is slightly tilted (≈2°); drops become too fast to grow and shrink over the course of their motion. Combining experiments and numerical simulations, we rationalize the transition between the conventional growth regime and the previously unknown decay regime we report. Using an analytical treatment of the Landau-Levich meniscus that connects the drop to the film, we quantitatively predict the drop dynamics in the two flow regimes and the value of the critical inclination angle where the transition between them occurs.

Revealing x-ray and gamma ray temporal and spectral similarities in the GRB 190829A afterglow.

Gamma-ray bursts (GRBs), which are bright flashes of gamma rays from extragalactic sources followed by fading afterglow emission, are associated with stellar core collapse events. We report the detection of very-high-energy (VHE) gamma rays from the afterglow of GRB 190829A, between 4 and 56 hours after the trigger, using the High Energy Stereoscopic System (H.E.S.S.). The low luminosity and redshift of GRB 190829A reduce both internal and external absorption, allowing determination of its intrinsic energy spectrum. Between energies of 0.18 and 3.3 tera-electron volts, this spectrum is described by a power law with photon index of 2.07 ± 0.09, similar to the x-ray spectrum. The x-ray and VHE gamma-ray light curves also show similar decay profiles. These similar characteristics in the x-ray and gamma-ray bands challenge GRB afterglow emission scenarios.

3D printed furosemide and sildenafil tablets: Innovative production and quality control.

Three-dimensional (3D) printing of pharmaceuticals has the potential to revolutionise personalised medicine but is as yet largely unexplored. A proof-of-concept study of a novel heated, piston-driven semi-solid extrusion 3D printer was performed by producing furosemide and sildenafil tablets for paediatric patients. The average weight of the tablets was 141.1 mg (RSD 1.26%). The acceptance values of the content uniformity were 4.2-10.6 (concentration RSD 0.41-0.63%), 4.8-8.9 (concentration RSD 0.76-0.97%) and 6.6-9.2 (concentration RSD 0.94-1.44%) for furosemide 2 mg, 10 mg and sildenafil 4 mg, respectively. The dissolution rate limiting step was the dissolving and eroding of the tablet matrix and showed an immediate release. The tablets complied to the requirements of the European Pharmacopoeia (EP) for uniformity of mass (EP 2.9.5), content uniformity (EP 2.9.40) and conventional release (EP 2.9.3). While they complied, not all of these quality tests for tablets might be suitable for 3D printed tablets due to the layering of the tablets and the small batch production. To assess adequate layer adhesion adjusted friability (EP 2.9.7) and resistance to crushing (EP 2.9.8) tests are proposed.

Elastic amplification of the Rayleigh-Taylor instability in solidifying melts.

The concomitant mechanical deformation and solidification of melts are relevant to a broad range of phenomena. Examples include the preparation of cotton candy, the atomization of metals, the manufacture of glass fibers, and the formation of elongated structures in volcanic eruptions known as Pele's hair. Usually, solid-like deformations during solidification are neglected as the melt is much more malleable in its initial liquid-like form. Here we demonstrate how elastic deformations in the midst of solidification, i.e., while the melt responds as a very soft solid ([Formula: see text] Pa), can lead to the formation of previously unknown periodic structures. Namely, we generate an array of droplets on a thin layer of liquid elastomer melt coated on the outside of a rotating cylinder through the Rayleigh-Taylor instability. Then, as the melt cures and goes through its gelation point, the rotation speed is increased and the drops stretch into hairs. The ongoing solidification eventually hardens the material, permanently "freezing" these elastic deformations into a patterned solid. Using experiments, simulation, and theory, we demonstrate that the formation of our two-step patterns can be rationalized when combining the tools from fluid mechanics, elasticity, and statistics. Our study therefore provides a framework to analyze multistep pattern formation processes and harness them to assemble complex materials.

[Update on precursors of vulvar carcinoma]. / Lésions vulvaires précancéreuses : mise au point.

Vulvar carcinomas represent 4% of all gynaecological cancers with 838 new cases in France in 2018. The precursor lesions of vulvar carcinomas are differentiated vulvar intraepithelial lesion (dVIN) in a context of lichen sclerosus and vulvar high-grade squamous intraepithelial lesion (HSIL) link to human papillomavirus (HPV) infection. Three typical clinical forms of HSIL are described: the Bowenoid papulosis, the Bowen's disease and the confluent VIN. Histopathology cannot differentiate effectively these two types of lesions. P16 and P53 immunostaining are valuable tools to respectively assess HPV infection and divide different types of dVIN. However, P53 immunostaining is still lacking sensibility to detect dVIN. First line therapies are medical treatment excluding the cases with a doubt of invasion. The gold standard treatment for dVIN and vulvar HSIL are respectively topical corticosteroids and imiquimod. Primary prevention for vulvar HSIL and dVIN are respectively HPV vaccination and early treatment of lichen sclerosus. Destructive therapy can be used in case of medical treatment failure such as CO2 laser, cryotherapy, dynamic phototherapy. Surgical indications should be carefully assessed between the risk of recurrence, the spread of the lesions, the aesthetic and functional aspect. Surgical procedures consist in either superficial vulvectomy or radical vulvectomy with or without flap reconstruction. Recurrence rate after surgery is around 20%.

Hyaluronic Acid: Redefining Its Role.

The discovery of several unexpected complex biological roles of hyaluronic acid (HA) has promoted new research impetus for biologists and, the clinical interest in several fields of medicine, such as ophthalmology, articular pathologies, cutaneous repair, skin remodeling, vascular prosthesis, adipose tissue engineering, nerve reconstruction and cancer therapy. In addition, the great potential of HA in medicine has stimulated the interest of pharmaceutical companies which, by means of new technologies can produce HA and several new derivatives in order to increase both the residence time in a variety of human tissues and the anti-inflammatory properties. Minor chemical modifications of the molecule, such as the esterification with benzyl alcohol (Hyaff-11® biomaterials), have made possible the production of water-insoluble polymers that have been manufactured in various forms: membranes, gauzes, nonwoven meshes, gels, tubes. All these biomaterials are used as wound-covering, anti-adhesive devices and as scaffolds for tissue engineering, such as epidermis, dermis, micro-vascularized skin, cartilage and bone. In this review, the essential biological functions of HA and the applications of its derivatives for pharmaceutical and tissue regeneration purposes are reviewed.

Marangoni flows drive the alignment of fibrillar cell-laden hydrogels.

When a sessile droplet containing a solute in a volatile solvent evaporates, flow in the droplet can transport and assemble solute particles into complex patterns. Transport in evaporating sessile droplets has largely been examined in solvents that undergo complete evaporation. Here, we demonstrate that flow in evaporating aqueous sessile droplets containing type I collagen-a self-assembling polymer-can be harnessed to engineer hydrated networks of aligned collagen fibers. We find that Marangoni flows direct collagen fiber assembly over millimeter-scale areas in a manner that depends on the rate of self-assembly, the relative humidity of the surrounding environment, and the geometry of the droplet. Skeletal muscle cells that are incorporated into and cultured within these evaporating droplets collectively orient and subsequently differentiate into myotubes in response to aligned networks of collagen. Our findings demonstrate a simple, tunable, and high-throughput approach to engineer aligned fibrillar hydrogels and cell-laden biomimetic materials.

Printing on liquid elastomers.

In recent years the research community has paid significant attention to geometrically engineered materials. These materials derive their unique properties from their structure rather than their chemistry alone. Despite their success in the laboratory, the assembly of such soft functional materials remains an outstanding challenge. Here, we propose a robust fluid-mediated route for the rapid fabrication of soft elastomers architected with liquid inclusions. Our approach consists of depositing water drops at the surface of an immiscible liquid elastomer bath. As the elastomer cures, the drops are encapsulated in the polymer and impart shape and function to the newly formed elastic matrix. Using the framework of fluid mechanics, we show how this type of composite material can be tailored.

Curvature Regularization near Contacts with Stretched Elastic Tubes.

Inserting a rigid object into a soft elastic tube produces conformal contact between the two, resulting in contact lines. The curvature of the tube walls near these contact lines is often large and is typically regularized by the finite bending rigidity of the tube. Here, it is demonstrated using experiments and a Föppl-von Kármán-like theory that a second, independent, mechanism of curvature regularization occurs when the tube is axially stretched. In contrast with the effects of finite bending rigidity, the radius of curvature obtained increases with the applied stretching force and decreases with sheet thickness. The dependence of the curvature on a suitably rescaled stretching force is found to be universal, independent of the shape of the intruder, and results from an interplay between the longitudinal stresses due to the applied stretch and hoop stresses characteristic of curved geometry. These results suggest that curvature measurements can be used to infer the mechanical properties of stretched tubular structures.

A very-high-energy component deep in the γ-ray burst afterglow.

Gamma-ray bursts (GRBs) are brief flashes of γ-rays and are considered to be the most energetic explosive phenomena in the Universe1. The emission from GRBs comprises a short (typically tens of seconds) and bright prompt emission, followed by a much longer afterglow phase. During the afterglow phase, the shocked outflow-produced by the interaction between the ejected matter and the circumburst medium-slows down, and a gradual decrease in brightness is observed2. GRBs typically emit most of their energy via γ-rays with energies in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with energies of tens of gigaelectronvolts have been detected by space-based instruments3. However, the origins of such high-energy (above one gigaelectronvolt) photons and the presence of very-high-energy (more than 100 gigaelectronvolts) emission have remained elusive4. Here we report observations of very-high-energy emission in the bright GRB 180720B deep in the GRB afterglow-ten hours after the end of the prompt emission phase, when the X-ray flux had already decayed by four orders of magnitude. Two possible explanations exist for the observed radiation: inverse Compton emission and synchrotron emission of ultrarelativistic electrons. Our observations show that the energy fluxes in the X-ray and γ-ray range and their photon indices remain comparable to each other throughout the afterglow. This discovery places distinct constraints on the GRB environment for both emission mechanisms, with the inverse Compton explanation alleviating the particle energy requirements for the emission observed at late times. The late timing of this detection has consequences for the future observations of GRBs at the highest energies.

An unbounded approach to microfluidics using the Rayleigh-Plateau instability of viscous threads directly drawn in a bath.

We study the droplet-forming instability of a thin jet extruded from a nozzle moving horizontally below the surface of an isoviscous immiscible fluid bath. While this interfacial instability is a classic problem in fluid mechanics, it has never been studied in the context of the deposition of a thread into a reservoir, an open-sky version of microfluidics. As the nozzle translates through the reservoir, drops may form at the nozzle (dripping) or further downstream (jetting). We first focus on rectilinear printing paths and derive a scaling law to rationalize the transition between dripping and jetting. We then leverage the flexibility of our system and study the dynamics of breakup when printing sinusoidal paths. We unravel a methodology to control both the size of the drops formed by the instability and the distance that separates them.