Silicon (Si) is regarded as the most promising anode material for high‐energy lithium‐ion batteries (LIBs) due to its high theoretical capacity, and low working potential. However, the large volume variation during the continuous lithiation/delithiation processes easily leads to structural damage and serious side reactions. To overcome the resultant rapid specific capacity decay, the nanocrystallization and compound strategies are proposed to construct hierarchically assembled structures with different morphologies and functions, which develop novel energy storage devices at nano/micro scale. The introduction of assembly strategies in the preparation process of silicon‐based materials can integrate the advantages of both nanoscale and microstructures, which significantly enhance the comprehensive performance of the prepared silicon‐based assemblies. Unfortunately, the summary and understanding of assembly are still lacking. In this review, the understanding of assembly is deepened in terms of driving forces, methods, influencing factors and advantages. The recent research progress of silicon‐based assembled anodes and the mechanism of the functional advantages for assembled structures are reviewed from the aspects of spatial confinement, layered construction, fasciculate structure assembly, superparticles, and interconnected assembly strategies. Various feasible strategies for structural assembly and performance improvement are pointed out. Finally, the challenges and integrated improvement strategies for assembled silicon‐based anodes are summarized. This review outlines the latest progress of silicon‐based assembled anodes from the aspects of assembly strategies, emphasizing the mechanism of the functional advantages for assembled structures. These summaries further deepen the understanding of the assembly mechanism and provide the systematic theoretical basis for the construction of superior silicon‐based anodes. Graphite is the most common commercial anode material for lithium‐ion batteries, while the limited theoretical capacity (372 mA h g–1) cannot meet the mileage required for energy devices. Silicon, attributed to the low working potential (0.5 V vs Li/Li+), high theoretical capacity (4200 mA h g–1) and the natural abundance, has become one of the most promising anode materials to replace graphite for high energy lithium‐ion batteries. However, the born defects of silicon anodes, including inferior electrical conductivity, sluggish lithium‐ion diffusion coefficient and serious volume expansion (>300%) during lithium insertion and extraction, easily increase electrode internal stress which will result in pulverization of electrode and the formation of unstable solid electrolyte interfaces (SEI) film, leading to rapid capacity decay  form a stable hierarchical architecture with regular geometric appearance based on the interaction of non‐covalent bonds. The assembly can significantly enhance the comprehensive properties of the material compared with the primary structural units, thus the assembly strategy is widely used in the fields of optoelectronics, biological medicine, catalysis, energy storage and so on. As an anode material for lithium‐ion batteries, the assembled micron‐scale material has a lower interfacial area compared with the nanoparticles, which can effectively reduce the interparticle resistance at the nano‐size and mitigate the risk of side effects, thereby improving the energy density of the lithium‐ion battery. Moreover, under the same mass loading, the micron‐scale assembly can obtain a higher tap density, which makes the electrode thickness thinner and the electron transfer pathway shorter and increases the volumetric specific capacity of the whole cell. Therefore, the assembly of silicon‐based nanomaterials can integrate the advantages of both nanomaterials and microstructures for the development of novel energy storage devices, which is an important strategy for the construction of silicon anode materials for lithium‐ion batteries with high energy density and excellent electrochemical properties.To effectively achieve the goal of high energy density for composite electrodes, a strategy has been proposed for assembling silicon‐based nanomaterials into micron‐sized hierarchical structures.24 Ass However, there is still a lack of a summary of silicon‐based assembled anodes, which fails to provide a better understanding of the assembly process. This review systematically summarizes the recent research advances in utilizing assembly strategies to address a series of challenges caused by the enormous volume variation and inferior electrical conductivity of silicon electrodes, emphasizing the advantages of silicon‐based assembled structures in the electrochemistry of lithium‐ion batteries. The driving forces, methods, influencing factors, and characteristics of the assembly process are also discussed to deepen the understanding of the assembled mechanism, and it is found that various assembly processes manipulated through interactions show surprising universality and great potential. Finally, the current challenges and development prospects of silicon‐based assembled anodes for lithium‐ion batteries are summarized.The research focus of high‐performance silicon‐based anodes mainly tends to be the construction of hierarchical complex structures, and the introduction of assembly strategies is crucial for the fabrication of high‐performance silicon‐based structures with different morphologies and functions. In recent years, there has been more and more research on silicon‐based assembled anodes for improving the performance of batteries.49 How2The assembly behavior of basic structural units is mainly realized based on the interaction force of non‐covalent bonds. Various materials can be synthesized as assemblies with different forms and functions, depending on the characteristics of the basic structural unit, such as the morphology, shape, potential and functional groups on the surface, and the final structure with the lowest free energy after assembly. In this section, the driving force, methods and influencing factors for assembly, and the advantages of the assembled structure as the anode of lithium‐ion battery are discussed in detail.2.1 Among them, electrostatic drive, a common non‐covalent interaction form, can be divided into attractive force and repulsive force according to the difference in the charges of particles. The electrostatic repulsion of components with the same charge can prevent agglomeration between components. On the contrary, electrostatic attraction can directly assemble components with opposite charges. For example, cationic‐modified colloidal metal‐organic frameworks (MOFs) were assembled onto negatively charged carbon‐based substrates driven by electrostatic attraction to form yolk‐shelled microcages. The proposed assembly strategy driven by electrostatic force has greatly expanded the application of MOFs, and the different types of MOFs , Zn‐ZIF‐8, and Zr‐UiO‐66) can be successfully assembled on the surface of carbon cloth and carbon paper , but a kind of synergistic effect with holistic and complex.57 Amor Figure .[59]3C2) nanosheets through van der Waals forces, which favor the reduction of the free energy of the system and form a nano heterostructures. Van der Waals forces can also cooperate with other forces for the self‐assembly of nanorods through side‐by‐side, face‐to‐face, and end‐to‐end, respectively. Van der Waals forces, distinct from the electrostatic forces, bring nanocomponents to assemble together in an attractive force form, which requires the suitable solvents and ligands to achieve directional assembly with different dimensions. It also demonstrated the universality and large‐scale production of van der Waals force‐driven strategy.Van der Waals forces, another common non‐covalent interaction form, has also been widely used in the assembly strategy. For instance, nanowires and nanorods are uniformly and controllably assembled on the 2D MXene  spherical micelles) (SV) and hard (silica nanoparticles) nanoparticles, which induced the preparation of colloidal assemblies with controlled valence characteristic via the hydrogen bonding between the pyridine groups in the poly(2‐vinylpyridine) (P2VP) micellar corona and the surface hydroxyl groups of silica nanoparticles. A series of colloidal assemblies with different saturated valence states and multidimensions  chains, two‐dimensional (2D) networks, three‐dimensional (3D) blocks, etc.) were synthesized by adjusting the relative size and feeding ratio of the two particles, which could achieve the dynamic regulation for the valence state  were embedded into 3D honeycomb macro‐micro‐mesoporous carbon via a simple and cost‐effective aqueous evaporation‐induced assembly process. Of course, there are many influencing factors in the synthesis process of this method that need to be finely controlled, including surfactants, volatile components, precursor types, relative humidity, etc.The assembly technology usually takes advantage of the characteristics of the initial structural unit, or modified functional groups on the surface of the initial structural unit, forming the hierarchical structure with a certain order based on certain rules. A series of mature preparation methods for assembled structure have been developed, including solvent evaporation induced assembly, microemulsion method, template‐assisted assembly method, chemical vapor deposition, electrospinning technique, etc.68 Amo2 superstructure with single‐crystal walls, bouquet‐posy‐like topologies, and radially oriented mesochannels, which consists of 1 spherical core and 12 symmetric satellite hemispheres  with unique chirality through a lamellar micelle spiral self‐assembly method using block copolymer as the soft template  can also be synthesized by a dual‐templates assembly method, in which the macroporous silica inverse opal is employed as the hard template and amphiphilic triblock copolymer Pluronic F127 is employed as the soft template , assisting the assembly of various particles in the appropriate active site arrangement.78 It e Figure .[80] Cho et al. proposed a strategy that the silicon nanolayer and pyrolytic carbon were uniformly wrapped on the graphite substrate via the two‐step CVD process, which solved the problem of side reactions caused by structural failure. Moreover, this strategy resulted in uniform and dense coatings that could be precisely controlled for efficient assembly of building blocks. Compared with the CVD strategy, the assembly via the electrospinning strategy was much cheaper and more controllable.Chemical vapor deposition (CVD) is the process of depositing vaporous substances on the gas phase or gas‐solid interface. The CVD strategy is widely used in various fields, due to its ability that effectively and finely control the structure of the final product by adjusting the precursor source, deposition temperature, and reaction rate. A nitrogen‐doped carbon layer was coated on the silicon nanoparticles by the CVD method, which maximized the stress release in the lithiated silicon and effectively relieved the volume expansion of the silicon nanoparticles during the (de)lithiation process.14 Cho A high‐density corn‐like Co3O4/graphene assembly material was fabricated by in situ thermal treatment self‐assembly method. A polymer composite with fully exfoliated and highly aligned MOF nanosheets was prepared via layer‐by‐layer assembly. All the self‐assembly methods mentioned above can effectively realize the controllable self‐assembly of materials.In addition to assembly method mentioned above, guided by a site‐selective liquid bridging interaction, the unique patch‐like particles assemble by heteroepitaxial growth into MOF‐based supra‐framework or supra‐colloidal with unprecedented precision.83 A h Chemical modification with organic molecules is considered to be a very important prerequisite for the realization of particle assembly. The organic molecules wrapped in the outer layer of the substrate play the dual roles of stabilizing particles and providing inter‐particle interactions. Through the interaction between these organic molecules, nanoparticles can be easily chemically assembly into aggregates with new structures.The control of the assembly process relates to various influencing factors, mainly including the concentration, size, physicochemical properties of self‐assembled units, types of solvents and surface additives, evaporation rate, temperature, and the surface physical and chemical properties of the substrate.89 Che2.3 After assembling molecules or nanoparticles into 1D, 2D, or 3D structures, the novel overall synergistic characteristics can be obtained. The structure of assembled molecules is highly versatile and can be designed by controlling the interactions between the original particles according to the required properties. The introduction of assembly technology into lithium‐ion batteries will greatly improve and expand various electrochemical properties. On the one hand, after the assembly of nano‐materials, the composite of various conductive substances creates abundant active sites, and improves the electrical contact between the loose particles, further improving the conductivity of the material and promoting the rapid transmission of electrons. Gao et al. have optimized the self‐assembly of SnO2 with MOF and graphene and prepared a unique structural configuration with abundant accessible electroactive sites for lithium ions storage, which shortened the ion transport pathways and exhibited superior electronic conductivity. Compared with monodisperse materials, the assembly structures exhibit higher electrochemical activity, faster charge transfer kinetics, and lithium ions diffusion.The excellent properties of nanoscale assembly can be regulated by simple manipulation or adjusting scale and geometric appearance. Therefore, the research of controllable functional nano‐assembly is one of the focuses of nanotechnology development at present and even for a long time in the future. For instance, uniformly sized hedgehog particles assembled from polydisperse nanoparticles have been successfully synthesized, thereby obtaining a series of assemblies such as nanorods, nanorods aggregates, hedgehog particles and low‐corrugation particles by controllably adjusting the reaction temperature, times, solvent, etc.90 Aft At the same time, the assembly can also reduce the resistance caused by the nano‐scale loose particles, and its porous structure can effectively alleviate the volume expansion during the charging and discharging process. Compared with loose nanoparticles, the assembly can achieve a lower interfacial area, effectively inhibit the excessive growth of SEI, reduce the risk of side reactions, and further improve the energy density of the lithium‐ion battery. Here, the assembly (Mn3O4@CNT/TiO2) of Mn3O4 nanoparticles with a stretchable 3D Hoberman spherical carbon nanotube (CNT) network not only takes advantage of the carbon nanotube materials to achieve highly conductive and enhances the reaction kinetics of Mn3O4 through electron density enhancement effect, but also introduces internal void space to adapt to the volume expansion of Mn3O4 during lithium insertion and extraction and maintains a stable outer surface of the material. The extra coating of the ultra‐thin and uniform TiO2 shell on Mn3O4@CNT/TiO2 can effectively limit the generation of SEI and improve stability. As an anode material for lithium‐ion batteries, the Mn3O4@CNT/TiO2 exhibits excellent rate capability, better cycling stability and a commercial‐level areal capacity. Other than that, the graphene‐wrapped porous Fe3O4/N‐doped C frameworks were successfully synthesized to keep structural integrity while preventing the direct contact between the active material and the electrolyte and reducing the formation of unstable SEI layer. The hierarchical porous structure can not only adapt to the volume change during cycling but also promote the penetration of the electrolyte.On the other hand, the assembled nanomaterials have higher tap density, thinner electrode and shorter electron transport pathway under the same mass loading, resulting in a higher volumetric specific capacity.98 At 3 In this section, the silicon‐based assemblies will be briefly summarized and discussed, from the perspective of the methodologies and functions.The combination of the nanoscale of silicon with features such as hollow porosity can be an effective way to solve the volume expansion of silicon anodes. However, the large specific surface area and high porosity caused by the porous structures lead to the low tap density and volumetric energy density of a single nano‐silicon structure. There are many research show that the silicon‐based assembly and even super‐structures can effectively solve the challenges of tap density and volumetric energy density. Whereas, the long‐term cycling stability of electrodes is still restricted by many factors, such as the unavoidable side reactions of the exposed silicon assembly in the electrolyte leading to the uncontrollable growth of the SEI film on material surface, and the low intrinsic electron and ionic conductivity of single silicon material, which seriously hinder its practical application. In recent years, these limitations have been effectively overcome by designing silicon‐based assembly with different hierarchical structures, such as the adoption of the surface and interface engineering, composite of single silicon with other materials, construction of different structures, doping of elements and other strategies, to further obtain silicon‐based composite assemblies with high energy density and long cycle life.104 In3.1 The spatially nanoconfined assembly strategy can effectively resolve the agglomeration and instability of silicon‐based units by encapsulating silicon nanoparticles into fixed confined spaces to form independent structures. The silicon nanoparticles were isolated through the external nanoconfined framework, which suppresses the excessive reaction between silicon and the electrolyte, and facilitates the formation of a stable and uniform SEI film, improving the performance of the battery. At the same time, the external nanoconfined framework can relieve the mechanical stress caused by the repeated lithium insertion and extraction of the silicon‐assembled electrode to a certain extent, and minimize the volume expansion.The large volume variation of silicon is inevitable during the repeated lithiation and delithiation process. To achieve the required high energy density, the volume change of silicon would become more serious when the electrodes with high mass loading. The nanocrystallization strategy of silicon units can effectively alleviate the volume expansion and pulverization of particles, but consequent instability and agglomeration have become a new problem. Furthermore, the large exposure of nano‐silicon particles would exacerbate the excessive reaction of the silicon particles with the electrolyte to form an unstable SEI film, resulting in lower Coulombic efficiency and rapid capacity decaying.107 Th However, this disordered amorphous carbon coating could not accommodate the interfacial stress caused by the large volume fluctuation and finally breakages over subsequent cycling, thus failing to deliver an ideal cycling life for batteries. Therefore, a robust interfacial microporous confined carbon coating system was designed on the surface of silicon nanoparticles, which can accommodate the volume variation of silicon nanoparticles without providing void space. Alternatively, a multicomponent‐coating can be introduced to improve the stability of silica‐based materials. Based on the TiO2 with high mechanical stability, a dual‐shell coating structure was used to encapsulate the silicon‐based materials (SiOx@TiO2@C) to relieve the mechanical stress during the lithiation/delithiation process . Moreover, CNTs acted as conductive “highway” to provide fast lithium‐ion and electron transport for the outer double shell and the inner silicon yolks, which improved the overall tap density and conductivity. Besides the yolk‐shell structure, a porous‐core framework could also be introduced to provide sufficient space for the volume expansion of silicon and avoid pulverization of particles (Si p‐NS@TNSs)  Figure .[118 The dense and robust silicon coating could resist high pressures of over 100 MPa, which remained barely broken after the calendaring procedure and exhibited an impressive volume capacity of 2041 mA h cm–3. The graphene cage with excellent mechanical strength and flexibility combined with the internal void space of the micro‐silicon cluster, which promoted the silicon nanoparticles to expand within the graphene cage while maintaining interfacial stability and structural integrity during cycling. Another strategy, the integration of dense structural engineering and dually encapsulated silicon structure, was proposed and successfully synthesized a 3D high‐density Ti3C2Tx MXene and graphene double‐encapsulated silicon monolith structure (HD‐Si@Ti3C2Tx@G) to ensure mechanical stability while achieving an ultrahigh volumetric capacity of 5206 mA h cm−3 and gravimetric capacity of 2892 mA h g–1 for lithium‐ion batteries  and high density (1.6 g cm–3). The dual‐encapsulated confined strategy greatly improved the utilization rate of the silicon anode and ensured the stability of the electrode structure and propitious electrolyte penetration, exhibiting superior long‐term cycling stability.Although the reserved hollow space design can accommodate the enormous volume change of the silicon anode during lithium insertion and extraction processes, the reserved space may exceed the demand for volume expansion, resulting in a series of problems with structural collapse and poor mechanical stability during the electrode calendaring process, which thus sacrifices the capacity and energy density of silicon‐based anodes. In response to this, wang et al. had fabricated a pressure‐resistant silicon structure by constructing a compact silicon shell coating on the porous secondary microparticles, which were microsilicon clusters composed of many silicon nanoparticles by a bottom‐up microemulsion method, followed by assembled to form a graphene‐encapsulated silicon‐shell‐protected silicon hollow structure.119 Th The confined double carbon structure tightly encapsulated silicon particles significantly reduced the absolute stress and strain during repeated cycling, and demonstrated high‐capacity retention of 80% and a fast charge‐discharge capability of 12 min. In addition to being able to conduct electricity quickly, the carbon skeleton assembly also maintained structural integrity after extremely long‐term cycling. Herein, a Si/C microsphere inspired by the structure of watermelon fruit was reported  the carbon‐coated nano‐silicon particles alleviated the tremendous volume variation, ii) the internal void space accommodated the volume expansion of nano‐silicon, iii) the confined graphite framework inhibited the aggregation of the nano‐silicon particles, iv) the whole confined carbon shell effectively prevented the exposure of nano‐silicon under high‐pressure density. The secondary assembly of nano‐silicon particles effectively increased the tap density by 220% relative to loose silicon nanoparticles, which was of great significance for the commercial application of high‐energy‐density battery electrode materials. In addition, graphite as a lubricant allowed the composite electrodes to endure high mechanical pressure during calendaring without rupture during electrode calendaring  with unique zero‐strain property and high lithium storage capacity  silicon was embedded into a robust matrix to also effectively address the structural stability issues of porous frameworks, thereby exhibiting good cycling performance (capacity retention of ≈91% after 2875 cycles) and calendar life (97.6% for 365 days).The nanocrystallization strategy of silicon units can effectively alleviate the volume expansion and pulverization of silicon particles during the repeated lithiation and delithiation process. The critical particle size (150 nm) of silicon units plays an important role in maintaining structural stability, according to the previous literature. The cracking and fracture behavior of silicon nanoparticles exhibits a strong size dependence upon the first lithiation: particle size below 150 nm, the particles neither cracked nor fractured during the first lithiation; above 150 nm, the particles initially formed cracks and then fractured due to lithiation expansion.125 Thy Figure .[1263.2 Moreover, the gap of the layered structures can not only adapt to the mechanical stress accompanying the insertion and extraction of lithium ions, effectively relieve the volume expansion of the silicon‐based electrodes, but also significantly hinder the agglomeration of silicon particles and promote the stable and efficient cycling of lithium‐ion batteries. Generally, there are two main strategies for layered silicon‐based assembly: silicon‐based particles or nanowires are directly assembled with 2D materials; silicon‐based thin films or nanosheets with 2D structures are directly assembled with other materials. For example, a nitrogen‐rich carbon/silicon composite with a graphene‐like structure was synthesized based on the electrostatic interaction between the carboxyl group and amino groups, which improved the electronic conductivity and effectively buffered the volume change of silicon nanoparticles during repeated cycling. Similarly, a sandwich‐like Si/Ti3C2Tx MXene composite was prepared by uniformly decorating silicon nanoparticles on loosely multilayered Ti3C2Tx with accordion‐like structure. The defects on the loosely multilayered Ti3C2Tx MXene flakes were conducive to the interfacial assembly of silicon nanoparticles with flakes, forming a 3D electronic transfer pathway, which promoted electron transport during cycling. In addition, combining with the inherent large surface area and good flexibility of MXene nanosheets, the larger interlayer distance of accordion‐like structured MXenes might be conducive to the flexible intercalation of Si‐based materials, providing an elastic buffer to accommodate the volume variation of silicon electrodes during lithiation.To overcome the low electrical conductivity and large volume variation of silicon electrodes, layered silicon‐based assemblies are designed by introducing highly conductive 2D structural materials. 2D structural materials with the high specific surface area can greatly shorten the pathways of electron transport and lithium‐ion diffusion, which achieve rapid insertion and extraction of lithium ions, reducing polarization and improving rate performance.132 Mo However, the exposed silicon elements between the layers may lead to the formation of unstable SEI films upon direct contact with the electrolyte, reducing the cycling efficiency and resulting in rapid capacity fading. To solve this problem, SiO2 nanoparticles could also be firmly anchored on the flexible MXene layers using the bonding effect and then synthesized SiO2/MXene microspheres by a spray drying method, which effectively reduced the specific surface area, relieved the side reactions and improved the Coulombic efficiency, thereby improving the structural stability during the long‐term cycling. However, this strategy cannot significantly address the defects of exposed silicon particles. Therefore, a new strategy has been proposed, which is to encapsulate the silicon particles with conductive carbon and metal to suppress the excessive contact between the particle silicon and the electrolyte, and then assemble the layered structure. Conductive metallic shell and carbon shell could not only improve the conductivity and corresponding mechanical stress of the whole electrode, but also acted as a shelter to effectively prevent excessive contact between silicon and electrolyte, and alleviated the abnormal growth of SEI films. Additionally, the layered structure loading with evenly distributed silicon nanoparticles eliminated collisions between silicon nanoparticles during cycling, providing a buffer space for volume expansion. 2D layered materials can be used as a composite substrate or a 3D scaffold to be assembled with silicon to design and synthesize a series of 3D Si/C assembly materials. The constructed layered structure combines the structural features of both micro‐scale building blocks and nano‐scale assemblies, thus can significantly improve the charge transport‐ability, strain accommodation, and structural stability after assembly. In order to better alleviate the intrinsic defects of Si electrodes, a unique SiOC material with tunable chemical component, optimistic reversible capacity, multiple synthetic routes, and small volume expansion was selected to fabricate a 3D lamellar SiOC@C/graphene assembly with porous microstructure via electrostatic self‐assembly process and hydrothermal reaction. The SiOC was composed of amorphous SiOxC4‐x tetrahedral units and disordered free carbon nanoclusters, which randomly distributed in the amorphous network and was difficult to form a consecutive conductive system, resulting in poor electrical conductivity. Thus, the graphene supporter, disordered free carbon nanoclusters in SiOC and the carbon layer on the surface of SiOC were synergistically assembled into a multi‐dimensional interconnected conductive system to avoid the aforementioned defects. The multidimensional conductive structure and the robust structure synergistically enhanced the electrical conductivity and promoted the rapid ion transport capability, exhibiting excellent rate capability as the anode electrode of lithium‐ion batteries, further enhancing the potential applications of SiOC. To overcome the drawbacks caused by this disordered distribution of carbon network distribution, Yang's group synthesized a new porous SiOC nanocomposite anode with a carbon matrix homogeneously distribution at the atomic scale to provide an excellent conductive network. And then, the porous SiOC nanospheres were encapsulated into a 2D conductive graphene film via boron doping induced self‐assembly, which reduced the interparticle resistance of nanospheres. The lamellate graphene skeleton structure released the volume change stress of SiOC, facilitated electrons and ions transfer pathways and improved the rate capability of the assembled anode, and also inhibited continuous growth of the SEI film to ensure interface stability during cycling.The strategy that low‐dimensional silicon elements were embedded into 2D materials to construct a layered assembly structure can effectively alleviate the volume expansion of Si‐based electrodes while improving the conductivity.137 Ho A class of MXene/Si@SiOx@C sandwich superstructure  with high mechanical strength Figure .[1493.3 Silicon particles with good dispersibility are assembled with 1D carbon nanotubes under the electrostatic driving force to form fasciculate structures, or fasciculate fibers by electrospinning, both of which provide fast radial electron transfer paths and exhibit high‐rates capability and high electrical conductivity. However, the silicon particles assembled on carbon nanotubes are still unavoidably exposed in the electrolyte, likewise, there is not enough space within the fasciculate fibers to accommodate the volume expansion. Combined with the advantages of spatial confinement, carbon nanofibers are fabricated by encapsulating silicon nanoparticles with cavities, which allow the volume change of silicon nanoparticles, significantly improving the structural stability during cycling. Another strategy is to coat a silicon oxide/carbon hybrid layer on the surface of the silicon‐based building block, which is deposited onto a carbon nanotube to construct a three‐layer coaxial nanotube (SiO2/C@SiO2@CNT). Among them, the CNTs acted as a supporting framework and the outermost carbon layer served as double‐layer buffer media, which could buffer the mechanical stress caused by the volume variation and serve as a conductive matrix to provide excellent electronic conductivity for the material. The void spaces within the CNTs offered a swift and efficient route for the rapid transportation of electrolytes, and the synergistic effect and specific structure of the material modules endowed excellent cycling stability for the electrode.Silicon‐based materials are introduced into the highly conductive 1D carbon materials to assemble fasciculate structures, which can provide a proposed radial short‐distance transport path for electrons and lithium ions, realizing rapid insertion and extraction of lithium ions and enhancing the rate capability of the assembled electrodes. Moreover, the abundant void space inside the fasciculate structure can accommodate the volume variation of silicon‐based particles.150 Si The carbon fiber shell wrapped with silicon could effectively suppress the excessive contact between silicon particles and electrolyte, and the void space between the internal silicon particles can also buffer the volume expansion during cycling, endowing the electrode with an excellent initial capacity of 1384 mA h g–1 and outstanding cycle life (99% capacity retention after 300 cycles). However, the physical contact points among internal silicon particles or individual fibers are often insufficient, easily leading to high electrode contact resistance and prolonging charge transfer pathways through electrodes, which will impede its energy storage properties such as rate capability and power density. Therefore, the carbon conductive network can be introduced into the fasciculate fibers to improve the conductivity and stability of the electrode, Wu et al. encapsulated Si nanoparticles in a honeycomb‐like carbon framework and further wrapped by an interconnected cobweb‐like carbon‐shell network containing multi‐walled carbon nanotubes to prepare silicon/interconnected hollow carbon composite fibers with a hierarchical core‐shell structure. The interconnected carbon networks with high mechanical strength not only provided more access sites for electron transfer to improve the transport capacity of ions and electrons, but also effectively inhibited the penetration of electrolytes. Moreover, the honeycomb‐like pores inside the porous carbon framework effectively accommodated the volume expansion of silicon, resulting in the silicon‐based fiber electrode demonstrating excellent rate performance and cycling stability, and the original morphology and structure could still be maintained after 100 cycles.To ensure the structural integrity of silicon electrodes in practical applications, a relatively low amount of silicon has to be used to alleviate the structural damage caused by volume expansion. Whereas, such a low silicon content seriously weakens the capacity advantage of the silicon‐based materials at the electrode level, which cannot reach the commercial level and seriously hinders the practical application of silicon‐based electrodes. On the premise of ensuring the structural stability, the electrode capacity was improved by increasing the silicon content in the material, and the coaxial fibers with a core‐shell structure (silicon content of ≈50 wt%) were synthesized by a dual nozzle electrospinning technique.156 Th The topological microscrolls formed by the rolling of cellulose nanosheets effectively confined the silicon nanoparticles in carbon nanotubes/carbon cages, which achieved an unprecedented silicon loading of 92%. The twining helical carbon nanotubes/carbon cage structure could stably support the uniformly dispersed silicon nanoparticles and form abundant voids to provide sufficient buffer space, which was beneficial to relieve the expansion pressure of the silicon particles. The binder‐free and free‐standing flexible electrode assembled from this microscroll exhibited an extremely high specific capacity of 2704 mA h g–1 and unparalleled cycling stability, maintaining a capacity of 2056 mA h g–1 after 300 cycles. This green and scalable synthesis method provided an efficient route for the commercial application of silicon anodes in lithium‐ion batteries.Another interesting strategy was proposed by Wang et al. A novel Si@CNT/C ultralong topological microscroll (lengths > 100 µm) was synthesized by assembling Si‐anchored bundled CNTs onto cellulose nanosheets, followed by a freeze‐drying process to realize topological microscroll wrapping of cellulose nanosheets bunched Si@CNT Figure .[1593.4 “Superparticle” is considered to be an ordered nano/microstructure formed from the self‐assembly of molecules and nanoscale building blocks under certain synergistic effects. For example, a carbon superstructure with rigid skeleton was synthesized by “rivet” links, reducing the adsorption energy, meliorating charge density distribution, enabling the high accessibility of interior protophilic sites, achieving efficient ion diffusion with a lower energy barrier, and providing the ultra‐stable charge storage and fast proton‐coupled dynamics. Based on a novel inverse microemulsion template strategy, a truly 3D ordered plasmonic colloidosomes  with the hierarchical pore structure  effectively prevented fracture, and the carbon framework served as both a mechanical backbone and an electron transport highway. The carbon encapsulation of entire secondary particles confined the SEI to the outer surface of microspheres instead of individual particles, which reduced the area that can be permeated by electrolyte and achieved a high Coulomb efficiency (99.87%), and reserved sufficient space for expansion/contraction following (de)lithiation. Benefiting from the space‐efficient packing inside the secondary silica particles, the tap density (0.53 g cm–2) was significantly higher than that of the randomly packed primary silica particles (0.15 g cm–2), exhibiting a higher volumetric capacity (1270 mA h cm–3). The unique structure endowed excellent cycling stability of batteries, maintaining 97% of the capacity after 1000 cycles.To alleviate the electrical contact loss and particle fracture that are considered to be the main factors for the Si capacity decay, a 3D binder‐free and free‐standing type anode electrode paper was well‐designed. A 3D interconnected nitrogen‐carbon network connected with hollow carbon nanospheres with uniformly distributed silicon nanodots (SHCM/NCF) to improve the structural stability and electrical conductivity of silicon‐based assembled anodes.165 The Figure  was desi Shi and co‐workers established a finite element model for cross‐scale simulating the stress evolution of self‐assembled functional structures, and skillfully designed a scalable self‐assembled hierarchical Si@TiO2@C (SA‐SiTC) , thus ensuring the long‐cycle stability of the electrode (842.6 mA h g−1 after 1000 cycles). More importantly, this self‐assembled structure with higher tap density exhibited a high volumetric capacity of 1174 mA h cm–3, and the outward tensile stress of internal Si and the specific capacity was 0.51× and 2.33× that of individual particles after 500 cycles, respectively, and remained integrity of the morphology during (de)lithiation. Therefore, the mechanical strength of the material is as essential as the electrochemical performance of the electrode, and both play an important role in the actual production process of the battery. For this purpose, a unique hierarchical carbon‐nanotube@silicon@carbon (CNT@Si@C) microsphere was designed and synthesized to fully tolerate the industrial calendaring process for electrode manufacturing, with extraordinary mechanical strength that could withstand a pressure of 200 MPa without breakdown, and exhibit only ≈40% particle expansion upon full lithiation.Mechanical tensile stress with different degrees is generated during the lithiation process, which may destroy similar porous and hollow structures, resulting in poor mechanical properties and structural collapse of the electrodes. Therefore, mechanical tensile stress is required to be effectively controlled to maintain the electrode structure stability and excellent electrochemical performance. At present, the most common solution to control tensile stress is to coat the surface of the materials to maintain the mechanical stability of the structure.167 Sh) Figure  based on The subsequently assembled silicene flowers/graphene (SF@G) materials with microsized hydrangea flower‐like structure composed of many interconnected nanoplates , thereby realizing the rapid ions and electrons transport from and to silicon.170 Ths Figure . Based o3.52@C and other superstructures, which effectively solve the defects of low conductivity, low tap density, large volume expansion, and low thermodynamic stability. However, there are weak interactions between the building blocks inside the superstructures prepared by the vast majority of strategies, even just a simple stacking of building blocks induced by various driving forces through steps such as coating, spray drying and CVD, etc., which may bring about structural damage and affect the overall structural stability of the electrode, resulting in a sharp capacity decay and unstable cycling performance. By introducing an interconnected assembly strategy, a connection module is constructed between the building blocks to achieve a substantial connection, thereby improving the interfacial stability of the assembly. For example, Shi et al. proposed an interfacial assembly strategy with “nucleation‐assembly‐dissolution‐growth”, and assembled nanosheet structured Li2Ti3O7 on the surface of Si nanoparticles (Si@Li2Ti3O7) to improve the lithium ions diffusion capacity. As shown in Figure 2Ti3O7 particles to form a hierarchical Si@Li2Ti3O7/C microcluster (H‐SiLC), showing excellent cycle stability. Although this nanosheet connection module can promote the interfacial contact between the primitives, it still fails to provide a robust connection. To solve this problem, a novel boron doping‐induced interconnection assembly (BDIIA) method was proposed. Porous SiOC nanospheres with carbon matrix homogeneously distribution at the atomic scale were induced by boric acid to construct robust boron‐doped SiOC interconnect assemblies (B‐SiOC)  Figure , which c4Figures To construct silicon‐based anodes for lithium‐ion batteries with high energy density and excellent electrochemical performance, novel energy storage devices with different morphologies and functions can be prepared by assembly strategies based on traditional materials science and chemical reaction engineering. The behavior of assembly is mainly realized based on the interaction force of non‐covalent bonds, as an effective strategy to optimize the performance of silicon‐based anode, which is of great significance for the electrochemical performance of lithium‐ion batteries systems. When the silicon‐based assembly is used as the anode electrode of the lithium‐ion battery, the energy storage and conversion function of the electrode can be better improved: 1) high bulk density endows the electrode with excellent volumetric specific capacity; 2) the close‐packed assembly framework can not only effectively shorten the transfer pathways of electrons and ions and improve the reaction kinetics of the system, but also reduce the interparticle resistance of the nanosphere and improve the overall energy density of the lithium‐ion battery; 3) low electrode interfacial area can avoid side reactions with the electrolyte, thereby obtaining higher Coulombic efficiency; 4) the strong hierarchical structure that can always maintain structural integrity during cycling, which is conducive to stable, fast, and high‐capacity lithium storage performance. More importantly, the assembly of silicon‐based anodes is highly versatile and diverse. This review highlighted the construction methods, various driving forces, influencing factors and functions of the assembly. In addition, the latest research progress of silicon‐based assembled anodes is systematically summarized according to different assembly strategies. The electrochemical performance, assembly methods, and main characteristics of silicon‐based assembly anodes for the reported various silicon‐based assembled anodes are summarized in The silicon‐based assembled structure has great potential in making significant contributions to constructing silicon anodes for lithium‐ion batteries with high energy density and excellent electrochemical performance. However, the assembly strategy is not a panacea, and its application in the battery field is still in its infancy. Considering all practical aspects, there are still many challenges to be overcome in silicon‐based assembled anodes. Therefore, the following prospects are proposed for the future development of silicon‐based assembled anodes for the lithium‐ion battery: 1) Although the assembly of silicon‐based anode materials can effectively improve the electrochemical performance, the corresponding process is relatively complicated and the cost is high, which inevitably limits its large‐scale practical production. Therefore, a simple and cost‐effective assembly process should be advocated. 2) The structural evolution of complex structures during repeated charging and discharging is critical to their actual performance, and the working conditions of most electrodes are far from the operating environments of actual equipment, so new characterization techniques need to be introduced to overcome such limitations. The introduction of in situ characterization during the exploration can not only provide the structural variation of silicon‐based assemblies but also offer valuable guidance for the construction process. 3) The assembly process is difficult to be completely and precisely controlled, which is a technical bottleneck of designing and fabricating the assembly with ideal function and morphology, so the assembly technology with high controllability is urgently needed. It is advocated to clarify the interface properties and reaction mechanisms of various silicon‐based structures, to achieve targeted assembly and integration of different assembly structures. Assembly, as a tool capable of precisely controlling the interfacial chemical structure, is considered to play a crucial role in constructing novel energy storage devices and improving electrochemical performance. It is hoped that the great potential of assembly structure can be fully realized in future research on the science and technology of advanced materials.The authors declare no conflict of interest.


What is the topic of this review?More than half of all pregnancies in the UK are exposed to adversity linked to increased problems in pregnancy for mothers and adverse outcomes for their children, but we do not know the mechanism(s) underpinning these relationships.What advances does it highlight?Studies in mice prove that placental endocrine insufficiency driven by genetic manipulation of imprinted genes in the offspring can concurrently drive fetal growth restriction, alterations in maternal caregiving and aberrant behaviour in wild‐type offspring exposed to an adverse environment. This suggests that placental endocrine insufficiency might contribute to the co‐morbidity of low birth weight, maternal depression and neurodevelopmental disorders observed in human populations.Prenatal adversity, which is estimated to impact more than half of all pregnancies in the UK, compromises fetal growth and increases the chances of stillbirth, prematurity and infant mortality. Beyond these immediate and highly visible problems, infants that survive carry the invisible burden of increased risk of some of the most common and pervasive diseases that impact human populations. In utero exposure to depression and anxiety is one adversity that has been linked to these poorer outcomes, suggesting that maternal mood disorders drive the outcomes. However, recent studies in animal models suggest that both the maternal mood disorders and the detrimental outcomes for children could be the result of the same underlying placental pathology. In these studies, genetically wild‐type rodent mothers exposed to placental endocrine insufficiency engaged in less pup‐focused behaviours and less self‐care. Genetically wild‐type rodent offspring raised in this abnormal environment exhibited increased anxiety‐like behaviours, with male offspring additionally exhibiting deficits in cognition and atypical social behaviour, with some evidence of depressive‐like symptoms. This work establishes experimentally that placental endocrine insufficiency alone is sufficient to drive atypical behaviour in both mothers and their offspring. Although there are some data to suggest that this phenomenon is relevant to human pregnancy, considerably more work is required. A recent survey in the UK reported that 27.4% of pregnant women were overweight, 18.3% obese and 3.3% severely obese at their first booking appointment, which takes place in the first trimester of pregnancy  the decidua, which is the maternally derived compartment formed from remodelling of the uterine wall; (2) the fetally derived junctional zone, which is the endocrine compartment composed of spongiotrophoblast and glycogen cells; and (3) the fetally derived labyrinth, which is the transport region, composed of a two‐layer syncitiotrophoblast covering the fetal capillaries     resulted in a significant loss of both spongiotrophoblast and glycogen cells   were highly effective in the nest‐building task, performing even better that the control dams exposed to normal levels of placental hormones. However, these dams neglected both their pups and themselves during this task. Effectively, in the disturbed situation (nest‐building task) the dams exposed to higher levels of placental hormones in pregnancy prioritized caring for their pups and self‐care, whereas those exposed to lower levels of hormones prioritized rebuilding their nests. As an important point, dams exposed to higher levels of placental hormones continued to prioritize caring for their pups even when their pups were replaced by fully wild‐type foster pups, proving experimentally that their enhanced nurturing behaviour was programmed during pregnancy.4Peg3 is a paternally expressed imprinted gene originally made famous for its role in directly influencing maternal behaviour, with mutant dams neglecting their pups  and half were genetically wild‐type but raised in the same adverse environment (which we refer to as non‐transgenic). These offspring were studied concurrently alongside fully wild‐type litters raised by wild‐type dams as environmental controls (Harrison et al., In order to distinguish between the direct effect of genetically elevated In addition to quantifying the behavioural consequences of placental endocrine insufficiency in this model, we also undertook a molecular approach by applying RNA sequencing analysis to four key brain regions, namely the adult hypothalamus, hippocampus, amygdala and ventral striatum. This analysis revealed striking differences in the transcriptional signatures between the groups. Of particular interest, we identified changes in gene expression unique to the transgenic animals in the hypothalamus and amygdala, which are brain regions that develop predominantly prenatally, when there are significant deficits in the placental spongiotrophoblast compartment (Tunster et al., Other studies have identified specific hormones dependent on the placenta for their synthesis that play key roles in fetal brain development (Bonnin et al., 6Phlda2, Cdkn1c, Ascl2 and Peg3 alters the composition of the mouse placental endocrine compartment. Several other imprinted genes might function in a similar manner as positive and negative regulators of placental endocrine function (R. M. John, Our studies in mice demonstrate formally that defective placental development impacting the production of placental hormones can concurrently drive low birth weight and alterations in the behaviour of both mothers and their offspring. There are many scenarios that can lead to defects in the placental endocrine lineages in mice. We have shown that, individually, genetic alteration to the imprinted genes Cdkn1c occur in utero when dams are fed low‐protein diets during pregnancy (Van de Pette et al., Phlda2 (Eaton et al., Imprinted genes are of particular interest in this respect because they are known to respond epigenetically to prenatal adversities. For example, loss of silencing and hypomethylation of the paternal allele of These experiments in animal models provide support to the idea that adversity in pregnancy programs changes to the offspring by inducing placental endocrine insufficiency. This idea does not exclude alterations to the fetal epigenome, as demonstrated formally to occur in response to a maternal low‐protein diet (Van de Pette et al., 7Numerous epidemiological studies have reported on the co‐morbidity of maternal mood disorders, low birth weight and behavioural disorders in children including depression, anxiety, attention deficit hyperactivity disorder and conduct disorders (Lautarescu et al., We have demonstrated that placental endocrine insufficiency can cause low birth weight (Salas et al., PEG3 is lower in pregnancies where mothers are clinically depressed or self‐report report higher symptoms of depression (Janssen et al., There is some indirect evidence to suggest that this alternative mechanism is relevant to human pregnancy. For example, placental expression of It is likely that there are several routes by which adversity in pregnancy might drive placental endocrine insufficiency. The important point is that the outcomes will be common owing to the fundamental importance of placental lactogen for both maternal and fetal health. Previous research has focused primarily on the passive role of the placenta as a barrier protecting the fetal brain from damaging exposures. Our studies, and those of other groups, identify a more active role for the placenta in determining maternal and fetal brain health. Focused studies are now required to establish whether the influences of placental hormones on maternal and offspring behaviour demonstrated in experimental models have validity in human populations.None declared.


Deficits in motivation are present early in the course of psychotic disorders. However, growing data have highlighted important heterogeneity in motivation among individuals with psychosis, suggesting that this variable may not be a unitary concept. Outside of the psychosis literature, research on self‐determination theory has identified three motivational orientations that guide the initiation and regulation of behaviour: autonomous, controlled and impersonal. Thus, our study goal is to investigate the longitudinal course of motivational orientations among individuals participating in a specialized clinical service for individuals with first‐episode psychosis .Forty‐one individuals with first‐episode psychosis participating in CSC completed assessments of motivation orientations at enrolment and after 6 months of care.Whereas there were no changes in controlled or impersonal orientations over the first 6‐months of care, individuals with first‐episode psychosis reported an increase in autonomous orientations. Moreover, while individuals with first‐episode psychosis reported lower autonomous orientations at enrolment as compared to individuals without psychosis, after 6 months of care, ratings of autonomous orientations among individuals with first‐episode psychosis were equivalent to those of individuals without psychosis.Although the results should be interpreted cautiously given the uncontrolled study design, the results suggest that the benefits of participation in early intervention services for psychosis may extend to improvements in motivation. The results of this study could offer further insight into whether (and what aspects of) motivation orientations change over the course of treatment in such specialized clinical services.22.1Forty‐one individuals participating in care at the Early Psychosis Intervention Center . This scale is comprised of 17 vignettes describing social or achievement situations that are followed by three different interpretations of the situation that map onto autonomous, controlled and impersonal motivational orientations, respectively. Participants rate the likelihood that they would make each of the three interpretations in these situations on a 1 to 7 scale with higher scores indicating a greater likelihood to make the interpretation. Score on the GCOS have been found to be associated with other measures of motivational processes both within and outside of the psychosis literature . Breitborde et al.  for all analyses ranged from 0.11 to 0.48 and never reached levels that would be considered problematic with regard to the accuracy of parameter estimates  that represents a clinically‐meaningful difference in GCOS scores  or impersonal orientations . Compared to quasi‐normative GCOS data, individuals with FEP reported lower autonomy  and greater impersonal  orientations. There was no statistically significant difference in controlled orientation scores for individuals with FEP as compared to the quasi‐normative data . Follow‐up equivalence analyses using LEAD revealed that the symmetrical null hypothesis of equivalence would be rejected at α=0.05 in situations in which the value of δ<0.27. This value of δ represents a 7% difference from the quasi‐normative values–a percentage difference much smaller than that commonly used for δ in bioequivalence research . Thus,these data are consistent with the conclusion of statistical equivalence.GCOS scores at baseline and after 6 months of treatment are reported in Table 3.2t = 2.38; P = .04; dav = 0.29). Post‐hoc probing did not indicate that this increase was moderated by diagnosis , duration of illness or utilization of specific interventions during the first 6 months of care. Moreover, there was no statistically significant difference between six‐month autonomous orientation scores for individuals with FEP as compared to quasi‐normative data for individuals with no known psychotic disorder . Follow‐up equivalence analyses revealed that the symmetrical null hypothesis of non‐equivalence would be rejected at α = .05 in situations in which the value of δ ≤ 0.18. This value of δ represents a 3% difference from the quasi‐normative values—a percentage difference much smaller than that commonly used for δ in bioequivalence research  or impersonal orientations  among participants during the first 6 months of EPICENTER treatment. Similar to baseline data, participants with FEP continued to report greater impersonal orientations  and statistically equivalent controlled orientations  as compared to quasi‐normative values for individuals with no known psychotic disorder.There was no statistically significant change in the controlled  lower autonomous orientations, (b) greater impersonal orientations; and (c) statistically equivalent controlled orientations as compared to individuals without psychosis. Although there were no longitudinal changes in controlled or impersonal orientations, individuals with FEP reported an increase in autonomous orientations over their first 6 months of care at EPICENTER such that their 6‐month scores were statistically equivalent to quasi‐normative GCOS data for individuals with no known psychotic disorder.In total, these data have several important implications with regard to our understanding of motivation among individuals with FEP. First, data with regard to controlled orientations suggests that the appeal of extrinsic reinforcers may remain intact among individuals with FEP—suggesting that external reinforcers may remain key drivers of motivation for these individuals. Specialized treatment programs for individuals with FEP may benefit from incorporation of opportunities for extrinsic reinforcers within their clinical setting to facilitate increased engagement in care and to promote improved clinical outcomes  possesses similar psychometric properties to the original GCOS and is adapted to present vignettes that may be more relevant to individuals with serious mental illness (Cooper et al., Within the rapid international expansion of specialized clinical services for individuals with FEP, there is growing recognition of the importance of incorporating strategies to facilitate increased motivation among individuals with FEP (Moe et al., Dr Breitborde and Dr Moe have received salary support from IMHR to support the launch of a specialized clinic for individuals with first‐episode psychosis.


Marine microbial communities are extremely complex and diverse. The number of locally coexisting species often vastly exceeds the number of identifiable niches, and taxonomic composition often appears decoupled from local environmental conditions. This is contrary to the view that environmental conditions should select for a few locally well‐adapted species. Here we use an individual‐based eco‐evolutionary model to show that virtually unlimited taxonomic diversity can be supported in highly evolving assemblages, even in the absence of niche separation. With a steady stream of heritable changes to phenotype, competitive exclusion may be weakened, allowing sustained coexistence of nearly neutral phenotypes with highly divergent lineages. This behaviour is robust even to abrupt environmental perturbations that might be expected to cause strong selection pressure and an associated loss of diversity. We, therefore, suggest that rapid evolution and individual‐level variability are key drivers of species coexistence and maintenance of microbial biodiversity. Here we use an individual‐based eco‐evolutionary model in which taxonomic diversity emerges as a consequence of evolutionary history. Using this model we are able to show that virtually unlimited genetic divergence can be emerge through convergent evolution in highly abundant and rapidly evolving assemblages, even in the absence of niche separation. Instead, the community is resolved at the individual level, with species and populations treated as emergent properties based on genetic rather than phenotypic distance. To achieve this, we take an established eco‐evolutionary model . The eco‐evolutionary responses to these changes again reflect the findings of Beckmann et al.  and (f), we introduce more realistic  changes, adding a 0.5°C per year warming (from the end of year 5) to the experiments with a constant temperature (e) and an annual cycle (f). In the absence of the seasonal cycle, this warming trend had almost no effect on the pattern of coalescence (panel e). However, when introduced to a simulation with a seasonal cycle, the warming trend led to a markedly more rapid loss of diversity. This likely occurs as yearly increases in temperature favour species adapted to the warmest part of the annual cycle over those adapted to the coldest temperatures.Perspectives on microbial life in the ocean are increasingly shaped by the vast amounts of molecular information made available by modern sequencing techniques  coexistence can be understood from two perspectives. From a phenotypic perspective, the ecological components of the model point to dominance by a single ‘optimal’ phenotype under constant environmental conditions Figure . HoweverThese results are driven by a mutation‐selection balance that requires a dependable and relatively high rate of heritable trait changes. Following  presents a fairly large target for beneficial changes. It remains to be seen what patterns of coalescence will emerge in a model where evolutionary changes occur in multiple traits simultaneously. In a much larger multidimensional trait space, beneficial changes are likely to occur much less predictably, potentially shifting the system towards harder selective sweeps and stronger competitive exclusion.27Prochlorococcus cells currently alive in the ocean, or even the estimated effective population size of 1013 in a well‐mixed parcel of sea water (Kashtan et al., These caveats notwithstanding, rapid evolution allows neutrality to emerge through a process of convergent and imperfect evolution and we see the sustained coexistence of phenotypically similar but genetically distinct lineages. This is a defining characteristic of functional redundancy (Louca et al., Prochlorococcus, this is much longer than required to explain the observed (Kashtan et al., Despite the inclusion of selection and environmental variability, our comparisons to the neutral model of coalescence suggest that hard selective sweeps are only likely to occur in the model under extremely rapid environmental changes that seem unlikely to occur over large spatial scales in a well‐mixed ocean. Several of our simulations remain consistent with a strictly neutral theory (Halley & Iwasa, Our findings suggest that rapid evolution likely plays a key role in the coexistence of phenotypically similar but genetically distinct species in microbial communities, with functional redundancy emerging through convergent evolution. Nonetheless, our simulations remain highly idealized, in particular neglecting to account for dispersal and mixing of communities in a three‐dimensional environment. Further work is therefore required to explore the significance of soft selective sweeps in a metacommunity context.BAW designed the study and performed the research, BAW and SC wrote the manuscript.https://publons.com/publon/10.1111/ele.14061.The peer review history for this article is available at


Inulin and oligofructose are classes of prebiotics belonging to a group of nondigestible carbohydrates referred to as inulin‐type fructans. While short‐chain fructooligosaccharides are enzymatically synthesized from the hydrolysis and transglycosylation of sucrose. Inulin‐type fructans and short‐chain fructooligosaccharides act as carbon sources for selective pathways supporting digestive health including altering the composition of the gut microbiota along with improving transit time. Due to their physicochemical properties, inulin‐type fructans and short‐chain fructooligosaccharides have been widely used in the food industry as partial replacements for both fat and sugar. Yet, levels of replacement need to be carefully considered as it may result in changes to physical and sensory properties that could be detected by consumers. Furthermore, it has been reported depending on the processing parameters used during production that inulin‐type fructans and short‐chain fructooligosaccharides may or may not undergo structural alterations. Therefore, this paper reviews the role of inulin‐type fructans and short‐chain fructooligosaccharides within the food industry as fat and sugar replacers and texture modifiers, their impact on final sensory properties, and to what degree processing parameters are likely to impact their functional properties. Inulin‐type fructans and short‐chain fructooligosaccharides are becoming and increasingly common ingredient used in the food industry as fat and sugar replacers and texture modifiers. Yet careful consideration must be given to the type and quantity of fructans used in replacement of fat and sugar in order product integrity while maintaining product quality. If required, inulin may undergo enzymatic hydrolysis to alter the DP resulting in the production of OF  having the potential to reduce energy intake by 65%–75% compared to digestible carbohydrates  and scFOS are highly soluble at around 80%  linkages of ITF and scFOS can be degraded by acid hydrolysis resulting in the production of OF and fructose leading to a reduction in nutritional properties . This suggests that the degradation of fructans could be minimized by employing LC‐ITF (DP > 10) during the production of bread.The rate of hydrolysis of ITF/scFOS appears to be somewhat dependent on the type of yeast used during production, with commercial and wild bread/beer strains tending to show a higher degree of fructan degradation compared to low‐/noninvertase‐producing yeasts . Yet, the low‐fat ice cream containing 4% ITF recorded similar sensory scores compared to the full‐fat control. Additionally, both  with ITF (DP > 20) at 2%, 3%, and 4% on the physicochemical properties and sensory attributes of low‐fat ice cream were investigated by . Furthermore, when fat was reduced and replaced with 1%, 2%, and 3% ITF, no statistical differences in body and texture scores were found, however, only the low‐fat yogurt with 1% inulin concentration could match the whole‐milk yogurt in terms of consistency. These results are similar to those documented by  and therefore better gel‐forming properties . Yet, significant differences in batter viscosity and decline in cake height were detected along with alterations in sensory attributes, including increased hardness and chewiness values as the replacement of fat with ITF increased to 100% (p < .05).In sponge cakes and muffins, the replacement of fat with ITF has been investigated extensively . While the addition of scFOS in nonfat‐reduced sausages reduced hardness, chewiness, and gumminess, the fat‐reduced scFOS‐supplemented sausages were able to match the non‐scFOS fat reduced control sausages in terms of textural properties. More interestingly, in terms of sensory characteristics, both nonfat‐ and fat‐reduced and scFOS‐supplemented sausages scored higher in terms of juiciness, but lower in terms of tenderness (p < .05). No other differences were detected with the scFOS‐supplemented sausages being considered acceptable by the panelists.Furthermore, another study  glycosidic linkages Capuano, . Yet, thSeveral attempts have been undertaken to replace sugar with fructans in fruit juices. Klewicki  exposed However, it could be argued that these conditions do not directly reflect those used in modern fruit juice production. The same authors also reported that under less extreme processing conditions, similar to those used in the food industry , 80% of scFOS was retained during the pasteurization of a milk–peach–mango drink: a finding mirroring those of  also induces the degradation of fructans . Adding to this, Farzanmehr and Abbasi .The replacement of sucrose in cakes with OF was investigated by Rodriguez‐Garcia et al.  ranging From this, it could be inferred that the degree to which textural and sensory characteristics are affected is highly dependent on the level of sucrose/fructan replacement. On this basis, Rodriguez‐Garcia et al.  suggest p < .05). This leads to a less homogenous cake structure and greater perceived levels of mouth coating and dryness. While the same authors noted in biscuits produced using lower DP inulin (Orafti® HSI) as a sugar replacer that final biscuits were softer and less crunchy compared to full‐sugar control.Another contributing factor is the DP of inulin used during production, with Tsatsaragkou et al.  documentIn addition to the level of sucrose/fructans, replacement, and DP of fructans used during production, variations in results may have also occurred due to differences in ingredient composition, with a key difference being the initial level of fat used in production. In this regard, Rodriguez‐Garcia et al.  noted inThis suggests that it may be possible to produce an acceptable sponge cake while reducing both fat and sugar simultaneously, but further work in this area is still required in order to optimize product formulation.5The textural aspect of food is an extremely critical factor regarding consumer acceptance (Tomadoni et al., One way to improve and maintain the texture of reduced‐fat and sugar food is via the use of viscosity modifiers and hydrocolloids including xanthan, guar, and gellan gum (Saha & Bhattacharya, As the addition of ITF increases beyond 10%, changes in product rheology become increasingly apparent with the formation of an extremely thick solid‐like gel (Karimi et al., One of the most promising applications of ITF to modify product rheology is the production of milk‐based dairy desserts. Tarrega et al.  supplemeA finding confirmed by both Gonzalez‐Tomas et al.  and TorrThe differences in the level of thickness detected between whole‐ and skimmed‐milk dairy‐based desserts made with ITFs are complex and dependent on the amount of initial fat present and the type of ITF used in production (Gonzalez‐Tomas et al., The perceived level of roughness is also dependent on the rate of shear and thermal production methods used. At low shear, the lower level of disruption to the matrices allows the formation of larger crystals and aggregate clusters to occur (Bayarri et al., 6It is clear from this review that both ITF and scFOS can act successfully as both fat and sugar replacer as well as a viscosity modifier in several different food products ranging from ice cream to bread, cake, shortbread biscuits, fruit juices, and meat. Yet, the degree to which fat and sugar can be successfully replaced with ITF and scFOS is highly dependent on the product formulation and the methods used during production. Therefore, future work should focus on refining both processing parameters and product formulation to optimize the level of supplementation to ensure consumer quality is met. Furthermore, while several studies have suggested that degradation of ITF and scFOS can occur during production, it remains unclear whether these alterations are substantial enough to alter their prebiotic efficacy, and thus should also be the focus of future work.Peter Jackson would like to thank Prof Bob Rastall and Dr Anisha Wijeyesekera for their support and feedback in writing this manuscript.None to declare.


Policymakers face difficult choices over which health interventions to publicly finance. We developed an approach to health benefits package design that accommodates explicit tradeoffs between improvements in health and provision of financial risk protection (FRP). We designed a mathematical optimization model to balance gains in health and FRP across candidate interventions when publicly financed. The optimal subset of interventions selected for inclusion was determined with bi‐criterion integer programming conditional on a budget constraint. The optimal set of interventions to publicly finance in a health benefits package varied according to whether the objective for optimization was population health benefits or FRP. When both objectives were considered jointly, the resulting optimal essential benefits package depended on the weights placed on the two objectives. In the Sustainable Development Goals era, smart spending toward universal health coverage is essential. Mathematical optimization provides a quantitative framework for policymakers to design health policies and select interventions that jointly prioritize multiple objectives with explicit financial constraints. But whaOne economic evaluation approach that is commonly used to determine the efficient allocation of resources within the health sector is cost‐effectiveness analysis (CEA) . We focus on two major health system objectives, improving population health and FRP , assessed in comparison to a counterfactual in which that candidate intervention was excluded. Next, we applied constrained optimization to determine the optimal mix of candidate interventions given an objective  and budget constraint .As an illustration, we apply our optimization model to the case study of Ethiopia, a low‐income country in sub‐Saharan Africa with diverse epidemiologic needs. Ethiopia‐specific parameters were derived from the following sources: population estimates from the United Nations Population Division World Population Prospects  for the World Bank's low‐income country grouping  that acts on disease incidence was calculated as:Ei,x is the effectiveness of intervention i on incidence of disease x, Ai,x is the share of disease x addressable (in the population) by intervention i, CFRx is the case fatality ratio (CFR) of disease x, and Ix is baseline incidence of disease x. When an intervention directly modified mortality risks, the number of deaths averted was calculated based on the intervention impact on the current mortality burden, Dx (rather than incidence Ix):Ei,x is instead the treatment effectiveness of intervention i on deaths attributable to disease x, and Dx is baseline disease‐related mortality.Intervention health impact was modeled in two ways: via reduced disease incidence (directly or through risk factor control), and via reduced disease‐related fatality risks. In both instances, we quantified impact in terms of the number of deaths averted from an intervention coverage increase. Focusing on mortality outcomes undervalues diseases with high morbidity relative to mortality  but was implemented for simplicity and due to data availability. The reduction in expected deaths from a coverage change  and in the future (through the treatment of diabetes complications). For ease of exposition, we considered a “steady state” system in which coverage increases have immediate health and financial benefits. We also considered a scenario with benefit and cost consequence time lags based on the natural history of each disease for a cohort of present‐day individuals. Where delayed effects were relevant, we binned interventions into either short‐, medium‐, or long‐term categories with time delays for the health and FRP benefits of 5, 10, and 20 years, respectively (and with immediate costs). Rotavirus vaccination in newborns is one example of a short‐term delayed intervention; screening and control of hypertension in 50–69 year‐olds is categorized as a medium‐term delayed intervention; and human papillomavirus vaccination of 12‐year‐old females is the only intervention categorized in the 20‐year delay category Table .Inclusion of an intervention in the benefits package was assumed to produce FRP  through two channels. First, we assumed that inclusion of services in the package eliminated all OOP direct medical costs associated with those services. We considered OOP direct medical costs only, which is consistent with the computations of CHE estimates routinely provided by WHO and the World Bank  of a household's per capita total consumption expenditures (yh). We used the threshold of 10% of per capita household consumption in our main analysis, and included a sensitivity analysis with a threshold of 25% . δHi are the covered households, and POPi,x is the target population for each intervention .We quantified the FRP benefits in terms of CHE cases averted when each intervention is publicly financed through a benefits package, compared to a counterfactual in which that intervention is excluded. Health expenditures were deemed “catastrophic” when direct household OOP health expenditures would exceed a pre‐defined threshold  were counted as CHE cases averted if the baseline OOP expenditures (now waived) for the service constituted expenditures above the 10% threshold of consumption expenditures. Since we assumed inclusion of an intervention eliminates all OOP expenditures, we counted all the associated expected CHE cases as CHE cases averted when the intervention is publicly financed. When relevant, secondary FRP benefits were estimated as decreased demand for downstream care:i indexes the intervention under consideration for benefit package inclusion and j indexes downstream care relevant to the same disease class x.For health interventions that target multiple disease categories , the ensemble Per intervention, estimates of deaths averted and CHE cases averted were computed including upper and lower bound estimates based on uncertainty available for the treatment effect and the disease burden . We conducted scenario analyses to estimate optimistic and pessimistic outcomes (see section 14 “Scenario cases” in Supporting Information i) to fund each intervention was estimated as the intervention unit cost times the new treatment population . All intervention unit costs and OOP costs are summarized in Tables We approximated the distribution of household consumption expenditures per capita using a gamma distribution where scale and shape parameters are a function of the per person total household expenditures and Gini coefficient for Ethiopia  or CHE cases averted . Second, we also performed a bi‐criterion optimization by optimizing on one objective, Obji1, and incorporating the second objective, Obji2, as a constraint. For instance, if we maximized deaths averted, we included an additional constraint that CHE cases averted exceeded a given constant K. By varying K, a Pareto efficiency frontier was generated. When K equals 0, the outcome is at least as good as the single objective optimization of Obji1. When K equals the maximum possible solution for Obji2, there is forced consistency with the single objective optimization of Obji2. In this analysis, K ranged from 0 to 115,747 for CHE cases averted and from 0 to 6010 for deaths averted. Our bi‐criterion optimization is expressed as:Zi is a binary decision variable for inclusion of intervention i , K is a positive integer that captures the increase in the second objective, B is the budgetary constraint, and TCi is the cost of including intervention i . We considered a range of constraint values (K) for the second objective that covered the entire feasible funding space to generate the Pareto efficiency frontier; and K was incrementally changed by single units of either deaths averted or CHE cases averted. The technical appendix of Karsu and Morton . All data, code, and result files are available on request.We used integer programming to identify the optimal subset of interventions to include in the benefits package under a given budgetary constraint, denoted 33.1Figure 3.2We first analyzed results at a budget constraint of 40 million USD as the total budgetary constraint of a potential benefits package (zero‐base). As context, the total health expenditures with government financing in Ethiopia was approximately 700 million USD in 2016/2017  and FRP (CHE cases averted) generally. This is illustrated by the expansion of the feasible funding space between Figure Another feature of the single‐objective optimization results is that some budget increases can lead to large incremental outcome changes. With incremental budget increases, there are instances where a high‐value intervention in one or more outcome becomes newly affordable.For example, Figure 4Mathematical optimization allows analysts to simultaneously specify multiple constraints and objectives that matter to decision‐makers. Particularly in the context of publicly financed UHC, mathematical optimization can incorporate a set of criteria and outcomes of interest. We explicitly considered here the two major health system objectives of improving population health and FRP within an optimization approach which we illustrated with a case study of Ethiopia. Our findings demonstrate substantial tradeoffs between health maximization (captured by maximizing deaths averted) and FRP maximization (captured by maximizing CHE cases averted). Multiple “optimal” benefit packages could be selected for public financing depending on the relative local policy importance given to population health compared to FRP.Essential benefit packages (EBPs) commonly cover both preventive and curative services. Preventive care has the potential to avert intensive and costly curative interventions but also requires coverage across large populations. By contrast, focusing on curative care may enhance care‐seeking and utilization for those most in need but often has high cost per patient treated. Our analysis demonstrates how mathematical modeling in tandem with optimization can formally account for service‐type tradeoffs by temporally mapping interventions and accounting for both the health and FRP benefits of each candidate intervention. However, selecting what interventions are being prioritized at different budget levels depends on numerous factors with multiple sophisticated interactions. Hence, it remains difficult to interpret here prioritization differences across distinct budget level constraints in a generalizable manner, a limitation (at this preliminary exposition stage) of this complex type of analysis.Our analysis has a number of limitations. First, in the development of our optimization model, we made several simplifying assumptions: we only considered two major objectives of health systems . We did not formally account for health disparities  or priority to the worse‐off or special disadvantaged groups. We also limited our health outcome to deaths averted omitting DALY estimation (see, e.g., Karsu & Morton, This work is grounded in a growing literature that calls for or applies mathematical optimization and operations research methods to resource allocation problems in health policy (examples include Crown et al., All authors declare no conflicts of interest.Supplementary MaterialClick here for additional data file.


The limited supply and increasing demand of group O RhD‐negative red blood cells (RBCs) have resulted in other transfusion strategies being explored by blood services that carry potential risks but may still provide an overall benefit to patients. Our aim was to analyse the potential economic benefits of prehospital transfusion (PHT) against no PHT.The impact of three PHT strategies  on quality‐adjusted‐life‐years (QALYs) of all United Kingdom trauma patients in a given year and the subset of patients considered most at risk , was modelled.For the entire cohort and the subset of patients, transfusing RhD‐negative RBCs generated the most QALYs , followed by the RhD‐positive RBCs , and no prehospital RBCs . The QALY difference between RhD‐negative and RhD‐positive policies was smaller  than RhD‐positive and no RBCs policies in QALYs term , indicating that harms from transfusing RhD‐positive RBCs are lower than harms associated with no RBC transfusion. A survival increase from PHT of 0.02% (entire cohort) and 0.7% (subset cohort) would still make the RhD‐positive strategy better in QALYs terms than no PHT.While the use of RhD‐positive RBCs carries risks, the benefits measured in QALYs are higher than if no PHT are administered, even for women of childbearing potential. Group O RhD‐positive RBCs could be considered when there is a national shortage of RhD‐negative RBCs. The difference in quality‐adjusted life‐years (QALYs) between group O RhD‐negative and O RhD‐positive red cell transfusion was much smaller than that between O RhD‐positive and no prehospital transfusion (PHT).The benefits of transfusing group O RhD‐positive red cells, measured in terms of QALYs, are substantially greater than if no prehospital transfusion is administered, even for RhD‐negative women of childbearing potential.en route to the hospital [Several observational studies have demonstrated survival benefits following the administration of red blood cells (RBCs) or low titre group O whole blood  compared to saline alone in the resuscitation of traumatic haemorrhagic patients in the prehospital environment , 2, 3. Rhospital . A recenhospital .In the prehospital setting, group O RhD‐negative RBC is transfused to avoid harms caused by the RhD‐positive blood being transfused to RhD‐negative recipients because the recipient's ABO/RhD type is known. These harms include severe haemolysis and possibly death , 8, a haHowever, the ability to provide RhD‐negative RBCs for prehospital transfusion (PHT) is constrained by donor supply. The current demand for group O RhD‐negative RBCs in England is 13% of the supply compared to the 7% frequency of group O RhD‐negative in the general population. An international study of blood centre collectors found that only 10% of their RBC distributions to hospitals were group O‐negative . TherefoIn this study, we compare the relative advantages of different policies for providing PHT, whereby the effect on the recipient's QALY was modelled in the following three scenarios: using RhD‐negative RBCs for all PHTs, using RhD‐positive RBCs for all PHTs, or not administering PHTs to injured patients.We modelled the impact of three scenarios on two groups of trauma patients: (i) a representative sample of all United Kingdom trauma patients in a given year, and (ii) the subset of patients who were RhD‐negative females of childbearing potential <50 years old (referred as FCP), by simulating the harms experienced by patients over the remainder of their lifetimes. In the case of HDFN occurrence, we also modelled its impact on the affected babies.A cohort was defined as a representative sample of patients who suffered a trauma in the United Kingdom in 1 year (5561 patients), as calculated previously . For posWe modelled the reductions in health‐related quality of life (HRQoL) following the trauma using a health economics approach to capture the QALYs associated with each transfusion scenario. To calculate QALYs associated with each transfusion scenario, we obtained the HRQoL associated with each post‐trauma outcome and modelled the number of years patients would spend in different health states to attain the QALYs experienced. HRQoL evidence was obtained by conducting a systematic literature review to find studies using EQ‐5D , SF‐36  and HUI‐Patient survives trauma without harmPatient dies following traumaPatient survives trauma but experiences HTR morbidityPatient survives trauma but dies from HTRPatient survives trauma but has a child with severe HDFN morbidityPatient survives trauma but has a child with HDFN mortalityFor each three resuscitation scenarios  and the two patient groups , we ‘allocated’ patients to six health states in each year following transfusion Figure :Patient Allocations 3–6 were only relevant when RhD‐positive blood was transfused, and the recipient was RhD‐negative. The probability of trauma survival and death was based on values obtained from two studies , 2 demonWhere a patient was predicted to have a future child with severe HDFN morbidity due to RhD‐positive RBCs during the resuscitation, we modelled a QALY impact to both the patient and child, where the impact to the patient is based on the impact to HRQoL observed for mothers of children with Cerebral Palsy, as there were no other published data on the impact of HRQoL for mothers of children with HDFN , 24, 25.We calculated the impact of PHTs/no transfusions over the whole of one cohort's lifetime and expressed this in two sets of outcome measures Figure . The firWhen RhD‐positive RBCs were transfused, we calculated the potential impact on babies born with HDFN or on those who died because of HDFN. Whereas the specific harms to patients were expressed as the QALYs attributed to patients in each health state, the harms to babies dying from HDFN or experiencing a long‐term adverse event from it were expressed as the QALYs lost, compared to if those babies had not suffered HDFN. This QALY difference was subtracted from the total QALYs experienced by the cohort. Key Modelling Assumptions made are described under Supporting information.The sensitivity analysis modified three sets of parameters to test ‘worst‐case’ scenarios: (i) HRQoL measures, (ii) probabilities of harms leading to the three risks, and (iii) trauma survival rates. Overall, five scenarios were modelled for each policy option: the main scenario, three sensitivity scenarios changing the parameter groups above individually, and one sensitivity scenario changing all parameters simultaneously.Based on survival data from studies of patients who received PHTs , 2, we cFor patients who received RhD‐positive RBCs, the same percentage would be expected to die at 24 h because both RhD‐positive and RhD‐negative RBCs were assumed to confer the same survival benefits. However, due to receipt of RhD‐positive RBCs, the model predicted that, of these survivors, there would be a small number of patients who would directly experience any anti‐D mediated adverse events. In addition, the receipt of the RhD‐positive RBCs would be expected to cause 0.13 foetal/neonatal major morbidity events and 0.18 foetal/neonatal mortality events due to HDFN caused by transfusing RhD‐positive RBCs to the female trauma patients in this cohort. These foetal/neonatal adverse events reduce the total number of QALYs among the recipients of RhD‐positive prehospital RBCs to 141,879.8, a difference of 19.2 QALYs for the entire cohort compared to recipients of prehospital RhD‐negative RBCs, with the monetization value being almost £600,000.For the group of patients who did not receive a PHT, the model predicted that there would be 1201/5561 (21.6%) deaths leading to approximately 22,600 fewer QALYs over the lifetime of the recipients in this group  compared to those who received a PHT. There were no other anti‐D mediated adverse events predicted to occur in this group, as they were not exposed to the RhD‐antigen through PHT. Using the valuation approach outlined in the Green Book , a publiOf the 5561 patients in England who received a PHT, 100 would have been FCPs who were at risk of a future pregnancy affected by HDFN . The proSensitivity analyses, given a degree of uncertainty relating to some of the key model inputs, were performed by adjusting some of these parameters Table . ChanginThe third sensitivity scenario reduced the survival benefits from 10.2% to 3% (compared to no transfusion), based on the effect of PHTs on episode mortality observed in the RePHILL trial . With loPrevious models of transfusing RhD‐positive RBCs to injured trauma patients of unknown RhD‐type have presented the risks of adverse events as probabilities of their occurrence , 13, 14.This result is driven by the survival benefits of providing PHTs, while the likelihood of RhD‐positive RBCs causing harm is comparatively very low. In our model, we assumed a survival benefit of 10.2% based on two observational studies —RhD‐posiFollowing the United Kingdom government Treasury green book  approachComparing the discounted monetized QALYs per patient between recipients of RhD‐negative RBCs and RhD‐positive RBCs, the use of RhD‐negative blood provides about £125 more value per patient than RhD‐positive blood. However, the equivalent figure for RhD‐negative FCPs is £6369, indicating that a policy of providing RhD‐negative blood for FCPs provides benefits and should be pursued where possible. Hospitals in England currently pay the same amount for RhD‐negative and RhD‐positive group O blood. However, RhD‐negative blood is in higher demand, and blood services spend additional resources to recruit and retain more RhD‐negative donors. The totality of these costs is not well described in the literature, but it seems unlikely to exceed the value of providing RhD‐negative blood to FCPs. Furthermore, it is less clear what the totality of these costs will be for the whole patient group and whether recruitment costs will outweigh patient benefits, and further research is required to understand these.This study has several limitations. First, since the model was built using data from the literature, the extent to which these findings can be generalizable depends on the generalizability of the original data. Secondly, it would have been good to have provided a projection on the effect of blood transfusion on QALYs based on the patient's injury severity; however, all studies/trials have pooled the transfusion effect for all types and injury severity, and we were not able to quantify this in QALY terms. Thirdly, this study was designed to describe the effect of PHT on the 24‐h mortality rate, as this time‐point is the most likely to be modifiable by PHT, as beyond the 24 h, the cause of death in trauma patients is typically factors other than exsanguination. Indeed, the American National Heart, Lung, and Blood Institute and Department of Defence have recently supported the development of short‐term outcomes  for adult trauma patients based on recent RCTs . In the In conclusion, this study quantified the change in QALYs based on two PHT strategies compared to not providing PHTs to injured patients. While a small number of patients were predicted to experience harm from receiving RhD‐positive RBCs, the number of QALYs gained by providing prehospital RBCs was much larger. Our data support a policy of using RhD‐negative blood for FCPs where possible. The quantification of transfusion risks and benefits prehospital in terms of QALY also enables future work to compare the allocation of group O RhD‐negative blood between different clinical settings to maximize health outcomes and to consider cost‐effectiveness.R.C. is a member of Terumo BCT's Physician Advisory Board; L.G. and M.Y. have received expenses for speaking at conferences sponsored by Terumo BCT. L.G. has received unrestricted research grants from Barkey Plasmatherm.Appendix S1. Supporting Information.Click here for additional data file.