Comparison of temporal evolution of computed tomography imaging features in COVID-19 and influenza infections in a multicenter cohort study

Purpose To compare temporal evolution of imaging features of coronavirus disease 2019 (COVID-19) and influenza in computed tomography and evaluate their predictive value for distinction. Methods In this retrospective, multicenter study 179 CT examinations of 52 COVID-19 and 44 influenza critically ill patients were included. Lung involvement, main pattern (ground glass opacity, crazy paving, consolidation) and additional lung and chest findings were evaluated by two independent observers. Additional findings and clinical data were compared patient-wise. A decision tree analysis was performed to identify imaging features with predictive value in distinguishing both entities. Results In contrast to influenza patients, lung involvement remains high in COVID-19 patients > 14 days after the diagnosis. The predominant pattern in COVID-19 evolves from ground glass at the beginning to consolidation in later disease. In influenza there is more consolidation at the beginning and overall less ground glass opacity (p = 0.002). Decision tree analysis yielded the following: Earlier in disease course, pleural effusion is a typical feature of influenza (p = 0.007) whereas ground glass opacities indicate COVID-19 (p = 0.04). In later disease, particularly more lung involvement (p < 0.001), but also less pleural (p = 0.005) and pericardial (p = 0.003) effusion favor COVID-19 over influenza. Regardless of time point, less lung involvement (p < 0.001), tree-in-bud (p = 0.002) and pericardial effusion (p = 0.01) make influenza more likely than COVID-19. Conclusions This study identified differences in temporal evolution of imaging features between COVID-19 and influenza. These findings may help to distinguish both diseases in critically ill patients when laboratory findings are delayed or inconclusive

A first update on mapping the human genetic architecture of COVID-19

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3D Printing of Sacrificial Templates for Hierarchical Porous Materials

Porosity is an essential structural feature in natural materials, such as wood and bone, where it enables vital tasks from impact absorption to nutrient transport and fracture resistance. Likewise, pores are also key for a broad application range of synthetic materials. Due to their light weight, tunable density and adjustable surface area, porous materials are indispensable for construction, catalysis and tissue engineering. The technical relevance of porosity has consequently boosted theoretical and experimental research on porous and cellular materials to improve the understanding and control of the fundamental material properties and functionalities thereof. In parallel, emerging additive manufacturing (AM) technologies have facilitated the realization of highly optimized architectures. In spite of these advancements, reliable predictions of the performance of macroscopic, porous materials as well as the direct AM of unconventional materials such as magnesium are still challenging. In this thesis, we developed three highly versatile manufacturing platforms to shape a remarkable range of materials and gain profound insights into the mechanical properties of porous materials. Photo-curable, particle-stabilized emulsions for vat photopolymerization (VP) were first prepared to study the influence of hierarchical porosity on the strength and stiffness of cellular architectures. The selective illumination of each emulsion layer during the VP process successively created controlled open lattice structures at the centimeter length scale. In addition to such macroscale porosity, the emulsion droplets served as soft templates to generate pores at the microscale within each photo-polymerized layer. The mechanical properties of the resulting hierarchical porous lattice structures can be tuned over several orders of magnitude and clearly demonstrated the benefit of hierarchy for bending-dominated architectures. Apart from this fundamental analysis, the advantage of particles to stabilize the emulsion goes beyond the prevention of coalescence during printing. Thermal debinding and sintering of the printed composites generated highly porous silica while maintaining the macroscopic lattice geometry. While the emulsion-based resins can in principle be extended to other particle chemistries, the pre-requisites defined by vat photopolymerization may not always be easy to fulfil. To address this challenge, solid salt (NaCl) particles have been widely applied as solid templates in a lot of different matrix chemistries. However, the resulting pore architecture has so far been limited to random geometries. Our second manufacturing platform aims at combining the ease of salt leaching with the shaping possibilities of AM, thus making complex architectures available for a wide range of materials. Paste-like inks were rheologically engineered by the controlled addition of a surfactant and solvent to comply with boundary conditions of direct ink writing, and printed into grid-like NaCl templates with pore sizes down to 0.3 mm. As a proof of concept, we illustrate the templating potential of the NaCl structures by infiltrating them with magnesium (Mg). Due to its highly oxidative nature and high vapor pressure, Mg is very challenging to print by direct additive manufacturing processes. In contrast, the indirect additive manufacturing approach via printed and sintered NaCl templates resulted in complex-shaped magnesium scaffolds with well-controlled, ordered porosity. The bespoke control of pore architecture is key to predict the mechanical properties and enable controlled resorption of such scaffolds by the human body. Direct Ink Writing (DIW) is a great tool to print unconventional materials, but the high compositional flexibility of this extrusion-based technique comes at the cost of resolution and shape complexity. In a third project we therefore extended our NaCl templating system beyond DIW towards masked stereolithography (MSLA) to create NaCl templates with outstanding shape complexity and surface properties. The illumination conditions and composition of a photo-curable resin with 65 wt% NaCl particles were tuned to maximize the printing resolution. Moreover, a systematic investigation of the resin formulation was performed to gain insights into the mechanisms leading to cracking of printed objects during the process. We found that the formation of a load-bearing network of salt particles is essential to prevent cracking during thermal removal of the resin diluent. To underline the versatile applications of this technology, crack-free salt molds were subsequently infiltrated and leached from illustrative material examples, including aluminum, silicone and chocolate. Overall, this thesis sheds light on the importance of hierarchy in porous materials and proposes novel template-based manufacturing platforms to generate cellular materials with exquisite architecture from a vast range of chemistries

3D Printing of Salt as a Template for Magnesium with Structured Porosity

ISSN:0935-9648ISSN:1521-409

Hierarchical porous materials made by stereolithographic printing of photo-curable emulsions

Porous materials are relevant for a broad range of technologies from catalysis and filtration, to tissue engineering and lightweight structures. Controlling the porosity of these materials over multiple length scales often leads to enticing new functionalities and higher efficiency but has been limited by manufacturing challenges and the poor understanding of the properties of hierarchical structures. Here, we report an experimental platform for the design and manufacturing of hierarchical porous materials via the stereolithographic printing of stable photo-curable Pickering emulsions. In the printing process, the micron-sized droplets of the emulsified resins work as soft templates for the incorporation of microscale porosity within sequentially photo-polymerized layers. The light patterns used to polymerize each layer on the building stage further generate controlled pores with bespoke three-dimensional geometries at the millimetre scale. Using this combined fabrication approach, we create architectured lattices with mechanical properties tuneable over several orders of magnitude and large complex-shaped inorganic objects with unprecedented porous designs.ISSN:2045-232

3D Printed Scaffolds for Monolithic Aerogel Photocatalysts with Complex Geometries

Monolithic aerogels composed of crystalline nanoparticles enable photocatalysis in three dimensions, but they suffer from low mechanical stability and it is difficult to produce them with complex geometries. Here, an approach to control the geometry of the photocatalysts to optimize their photocatalytic performance by introducing carefully designed 3D printed polymeric scaffolds into the aerogel monoliths is reported. This allows to systematically study and improve fundamental parameters in gas phase photocatalysis, such as the gas flow through and the ultraviolet light penetration into the aerogel and to customize its geometric shape to a continuous gas flow reactor. Using photocatalytic methanol reforming as a model reaction, it is shown that the optimization of these parameters leads to an increase of the hydrogen production rate by a factor of three from 400 to 1200 µmol g−1 h−1. The rigid scaffolds also enhance the mechanical stability of the aerogels, lowering the number of rejects during synthesis and facilitating handling during operation. The combination of nanoparticle-based aerogels with 3D printed polymeric scaffolds opens up new opportunities to tailor the geometry of the photocatalysts for the photocatalytic reaction and for the reactor to maximize overall performance without necessarily changing the material composition.ISSN:1613-6810ISSN:1613-682

A 3D-Printed Assemblable Bespoke Scaffold as a Versatile Microcryogel Carrier for Site-Specific Regenerative Medicine

Advances in additive manufacturing have led to diverse patient-specific implant designs utilizing computed tomography, but this requires intensive work and financial implications. Here, Digital Light Processing is used to fabricate a hive-structured assemblable bespoke scaffold (HIVE). HIVE can be manually assembled in any shape/size with ease, so a surgeon can create a scaffold that will best fit a defect before implantation. Simultaneously, it can have site-specific treatments by working as a carrier filled with microcryogels (MC) incorporating different biological factors in different pockets of HIVE. After characterization, possible site-specific applications are investigated by utilizing HIVE as a versatile carrier with incorporated treatments such as growth factors (GF), bioceramic, or cells. HIVE as a GF-carrier shows a controlled release of bone morphogenetic protein/vascular endothelial growth factor (BMP/VEGF) and induced osteogenesis/angiogenesis from human mesenchymal stem cells (hMSC)/human umbilical vein endothelial cells (HUVECs). Furthermore, as a bioceramic-carrier, HIVE demonstrates enhanced mineralization and osteogenesis, and as a HUVEC carrier, it upregulates both osteogenic and angiogenic gene expression of hMSCs. HIVE with different combinations of MCs yields a distinct local effect and successful cell migration is confirmed within assembled HIVEs. Finally, an in vivo rat subcutaneous implantation demonstrates site-specific osteogenesis and angiogenesis.ISSN:0935-9648ISSN:1521-409

3D Printed Scaffolds for Monolithic Aerogel Photocatalysts with Complex Geometries

Monolithic aerogels composed of crystalline nanoparticles enable photocatalysis in three dimensions, but they suffer from low mechanical stability and it is difficult to produce them with complex geometries. Here, an approach to control the geometry of the photocatalysts to optimize their photocatalytic performance by introducing carefully designed 3D printed polymeric scaffolds into the aerogel monoliths is reported. This allows to systematically study and improve fundamental parameters in gas phase photocatalysis, such as the gas flow through and the ultraviolet light penetration into the aerogel and to customize its geometric shape to a continuous gas flow reactor. Using photocatalytic methanol reforming as a model reaction, it is shown that the optimization of these parameters leads to an increase of the hydrogen production rate by a factor of three from 400 to 1200 µmol g−1 h−1. The rigid scaffolds also enhance the mechanical stability of the aerogels, lowering the number of rejects during synthesis and facilitating handling during operation. The combination of nanoparticle-based aerogels with 3D printed polymeric scaffolds opens up new opportunities to tailor the geometry of the photocatalysts for the photocatalytic reaction and for the reactor to maximize overall performance without necessarily changing the material composition.Aerospace Manufacturing Technologie

Light-Based Printing of Leachable Salt Molds for Facile Shaping of Complex Structures

3D printing is a powerful manufacturing technology for shaping materials into complex structures. While the palette of printable materials continues to expand, the rheological and chemical requisites for printing are not always easy to fulfill. Here, a universal manufacturing platform is reported for shaping materials into intricate geometries without the need for their printability, but instead using light-based printed salt structures as leachable molds. The salt structures are printed using photocurable resins loaded with NaCl particles. The printing, debinding, and sintering steps involved in the process are systematically investigated to identify ink formulations enabling the preparation of crack-free salt templates. The experiments reveal that the formation of a load-bearing network of salt particles is essential to prevent cracking of the mold during the process. By infiltrating the sintered salt molds and leaching the template in water, complex-shaped architectures are created from diverse compositions such as biomedical silicone, chocolate, light metals, degradable elastomers, and fiber composites, thus demonstrating the universal, cost-effective, and sustainable nature of this new manufacturing platform.Aerospace Manufacturing Technologie

Solvent-Free Three-Dimensional Printing of Biodegradable Elastomers Using Liquid Macrophotoinitiators

Vat photopolymerization 3D printing provides new opportunities for the fabrication of tissue scaffolds and medical devices. However, for the manufacturing of biodegradable elastomers, it usually requires the use of organic solvents to dissolve the solid photoinitators and achieve low resin viscosity, making this process environmentally unfriendly and not optimal for biomedical applications. Here, we report solvent-free 3D printing of biodegradable elastomers by digital light processing with well-defined photoinitiator-polymer conjugates. Being in liquid state at room temperature, the macrophotoinitiators enabled high-quality 3D printing in the absence of any organic solvents that are usually used in digital light 3D printing. This allowed the systematic investigation of structure-property relationships of 3D-printed biodegradable elastomers without the interference from reactive diluents. The developed macrophotoinitiators were compatible with various photopolymers and could be applied for solvent-free fabrication of biodegradable shape-memory devices. This work offers new perspectives for the solvent-free additive manufacturing of bioresorbable medical implants and other functional devices. Aerospace Manufacturing TechnologiesTeam DeSchutte