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Direct and precise monitoring of intracranial physiology holds immense importance in delineating injuries, prognostication and averting disease1. Wired clinical instruments that use percutaneous leads are accurate but are susceptible to infection, patient mobility constraints and potential surgical complications during removal2. Wireless implantable devices provide greater operational freedom but include issues such as limited detection range, poor degradation and difficulty in size reduction in the human body3. Here we present an injectable, bioresorbable and wireless metastructured hydrogel (metagel) sensor for ultrasonic monitoring of intracranial signals. The metagel sensors are cubes 2 × 2 × 2 mm3 in size that encompass both biodegradable and stimulus-responsive hydrogels and periodically aligned air columns with a specific acoustic reflection spectrum. Implanted into intracranial space with a puncture needle, the metagel deforms in response to physiological environmental changes, causing peak frequency shifts of reflected ultrasound waves that can be wirelessly measured by an external ultrasound probe. The metagel sensor can independently detect intracranial pressure, temperature, pH and flow rate, realize a detection depth of 10 cm and almost fully degrade within 18 weeks. Animal experiments on rats and pigs indicate promising multiparametric sensing performances on a par with conventional non-resorbable wired clinical benchmarks.
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Implantes Absorvíveis , Encéfalo , Hidrogéis , Monitorização Fisiológica , Ondas Ultrassônicas , Tecnologia sem Fio , Animais , Masculino , Ratos , Encéfalo/fisiologia , Hidrogéis/química , Concentração de Íons de Hidrogênio , Injeções/instrumentação , Pressão Intracraniana , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Ratos Sprague-Dawley , Porco Miniatura , Temperatura , Fatores de Tempo , Tecnologia sem Fio/instrumentaçãoRESUMO
Nonhealing diabetic wounds are predominantly attributed to the inhibition of angiogenesis, re-epithelialization, and extracellular matrix (ECM) synthesis caused by hypoxia. Although oxygen therapy has demonstrated efficacy in promoting healing, its therapeutic impact remains suboptimal due to unsustainable oxygenation. Here, this work proposes an oxygen-releasing hydrogel patch embedded with polyethylene glycol-modified calcium peroxide microparticles, which sustainably releases oxygen for 7 days without requiring any supplementary conditions. The released oxygen effectively promotes cell migration and angiogenesis under hypoxic conditions as validated in vitro. The in vivo tests in diabetic mice models show that the sustainably released oxygen significantly facilitates the synthesis of ECM, induces angiogenesis, and decreases the expression of inflammatory cytokines, achieving a diabetic wound healing rate of 84.2% on day 7, outperforming the existing oxygen-releasing approaches. Moreover, the proposed hydrogel patch is designed with porous, soft, antibacterial, biodegradable, and storage stability for 15 days. The proposed hydrogel patch is expected to be promising in clinics treating diabetic wounds.
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Diabetes Mellitus Experimental , Hidrogéis , Oxigênio , Peróxidos , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Oxigênio/química , Peróxidos/química , Peróxidos/farmacologia , Humanos , Polietilenoglicóis/química , Neovascularização Fisiológica/efeitos dos fármacos , Masculino , Células Endoteliais da Veia Umbilical Humana , Movimento Celular/efeitos dos fármacosRESUMO
Cerebral aneurysms and brain tumors are leading life-threatening diseases worldwide. By deliberately occluding the target lesion to reduce the blood supply, embolization has been widely used clinically to treat cerebral aneurysms and brain tumors. Conventional embolization is usually performed by threading a catheter through blood vessels to the target lesion, which is often limited by the poor steerability of the catheter in complex neurovascular networks, especially in submillimeter regions. Here, we propose magnetic soft microfiberbots with high steerability, reliable maneuverability, and multimodal shape reconfigurability to perform robotic embolization in submillimeter regions via a remote, untethered, and magnetically controllable manner. Magnetic soft microfiberbots were fabricated by thermal drawing magnetic soft composite into microfibers, followed by magnetizing and molding procedures to endow a helical magnetic polarity. By controlling magnetic fields, magnetic soft microfiberbots exhibit reversible elongated/aggregated shape morphing and helical propulsion in flow conditions, allowing for controllable navigation through complex vasculature and robotic embolization in submillimeter regions. We performed in vitro embolization of aneurysm and tumor in neurovascular phantoms and in vivo embolization of a rabbit femoral artery model under real-time fluoroscopy. These studies demonstrate the potential clinical value of our work, paving the way for a robotic embolization scheme in robotic settings.
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Neoplasias Encefálicas , Aneurisma Intracraniano , Procedimentos Cirúrgicos Robóticos , Robótica , Animais , Coelhos , Procedimentos Cirúrgicos Robóticos/métodos , Aneurisma Intracraniano/terapia , Fenômenos MagnéticosRESUMO
Bioadhesive hydrogels offer unprecedented opportunities in hemostatic agents and tissue sealing; however, the application of existing bioadhesive hydrogels through narrow spaces to achieve strong adhesion in fluid-rich physiological environments is challenged either by undesired indiscriminate adhesion or weak wet tissue adhesion. Here, a laparoscopically compatible asymmetric adhesive hydrogel (aAH) composed of sprayable adhesive hydrogel powders and injectable anti-adhesive glue is proposed for hemostasis and to seal the bloody tissues in a non-pressing way, allowing for preventing postoperative adhesion. The powders can seed on the irregular bloody wound to rapidly absorb interfacial fluid, crosslink, and form an adhesive hydrogel to hemostatic seal (blood clotting time and tissue sealing in 10 s, ≈200 mm Hg of burst pressure in sealed porcine tissues). The aAH can be simply formed by crosslinking the upper powder with injectable glue to prevent postoperative adhesion (adhesive strength as low as 1 kPa). The aAH outperforms commercial hemostatic agents and sealants in the sealing of bleeding organs in live rats, demonstrating superior anti-adhesive efficiency. Further, the hemostatic seamless sealing by aAH succeeds in shortening the time of warm ischemia, decreasing the blood loss, and reducing the possibility of rebleeding in the porcine laparoscopic partial nephrectomy model.
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Materiais Biocompatíveis , Hemostáticos , Ratos , Suínos , Animais , Aderências Teciduais/prevenção & controle , Hidrogéis/farmacologia , Hemostáticos/farmacologia , Hemostasia , HemorragiaRESUMO
Introduction: Electromagnetically controlled small-scale robots show great potential in precise diagnosis, targeted delivery, and minimally invasive surgery. The automatic navigation of such robots could reduce human intervention, as well as the risk and difficulty of surgery. However, it is challenging to build a precise kinematics model for automatic robotic control because the controlling process is affected by various delays and complex environments. Method: Here, we propose a learning-based intelligent trajectory planning strategy for automatic navigation of magnetic robots without kinematics modeling. The Long Short-Term Memory (LSTM) neural network is employed to establish a global mapping relationship between the current sequence in the electromagnetic actuation system and the trajectory coordinates. Result: We manually control the robot to move on a curved path 50 times to form the training database to train the LSTM network. The trained LSTM network is validated to output the current sequence for automatically controlling the magnetic robot to move on the same curved path and the tortuous and branched new paths in simulated vascular tracks. Discussion: The proposed trajectory planning strategy is expected to impact the clinical applications of robots.
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In situ bioprinting is promising for developing scaffolds directly on defect models in operating rooms, which provides a new strategy for in situ tissue regeneration. However, due to the limitation of existing in situ biofabrication technologies including printing depth and suitable bioinks, bioprinting scaffolds in deep dermal or extremity injuries remains a grand challenge. Here, we present an in vivo scaffold fabrication approach by minimally invasive bioprinting electroactive hydrogel scaffolds to promote in situ tissue regeneration. The minimally invasive bioprinting system consists of a ferromagnetic soft catheter robot for extrusion, a digital laparoscope for in situ monitoring, and a Veress needle for establishing a pneumoperitoneum. After 3D reconstruction of the defects with computed tomography, electroactive hydrogel scaffolds are printed within partial liver resection of live rats, and in situ tissue regeneration is achieved by promoting the proliferation, migration, and differentiation of cells and maintaining liver function in vivo.
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Natural hearing which means hearing naturally like normal people is critical for patients with hearing loss to participate in life. Cochlear implants have enabled numerous severe hearing loss patients to hear voice functionally, while cochlear implant users can hardly distinguish different tones or appreciate music subject to the absence of rate coding and insufficient frequency channels. Here a bioinspired soft elastic metamaterial that reproduces the shape and key functions of the human cochlea is reported. Inspired by human cochlea, the metamaterials are designed to possess graded microstructures with high effective refractive index distributed on a spiral shape to implement position-related frequency demultiplexing, passive sound enhancements of 10 times, and high-speed parallel processing of 168-channel sound/piezoelectric signals. Besides, it is demonstrated that natural hearing artificial cochlea has fine frequency resolution up to 30 Hz, a wide audible range from 150-12 000 Hz, and a considerable output voltage that can activate the auditory pathway in mice. This work blazes a promising trail for reconstruction of natural hearing in patients with severe hearing loss.
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Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva , Humanos , Animais , Camundongos , Audição , Surdez/reabilitação , Surdez/cirurgiaRESUMO
A robust neural interface with intimate electrical coupling between neural electrodes and neural tissues is critical for stable chronic neuromodulation. The development of bioadhesive hydrogel neural electrodes is a potential approach for tightly fixing the neural electrodes on the epineurium surface to construct a robust neural interface. Herein, we construct a photopatternable, antifouling, conductive (â¼6 S cm-1), bioadhesive (interfacial toughness â¼100 J m-2), soft, and elastic (â¼290% strain, Young's modulus of 7.25 kPa) hydrogel to establish a robust neural interface for bioelectronics. The UV-sensitive zwitterionic monomer can facilitate the formation of an electrostatic-assembled conductive polymer PEDOT:PSS network, and it can be further photo-cross-linked into elastic polymer network. Such a semi-interpenetrating network endows the hydrogel electrodes with good conductivity. Especially, the photopatternable feature enables the facile microfabrication processes of multifunctional hydrogel (MH) interface with a characteristic size of 50 µm. The MH neural electrodes, which show improved performance of impedance, charge storage capacity, and charge injection capability, can produce effective electrical stimulation with high current density (1 mA cm-2) at ultralow voltages (±25 mV). The MH interface could realize high-efficient electrical communication at the chronic neural interface for stable recording and stimulation of a sciatic nerve in the rat model.
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Electron transport layers (ETLs) are important components of high-performance all-inorganic perovskite nanocrystals light-emitting diodes (PNCs-LED). Herein, atomic layer deposition (ALD) of inorganic ZnO layer is combined to the organic 1,3,5-Tris(1-phenyl-1H-benzimidazol-2-yl)benzene (TPBi) to form dual ETLs to enhance both the efficiency and stability of PNCs-LED simultaneously. Optimization of ZnO thickness suggested that 10 cycles ALD yields the best performance of the devices. The external quantum efficiency of the device reaches to 7.21% with a low turn-on voltage (2.4 V). Impressively, the dual ETL PNCs-LED realizes maximumT50lifetime of 761 h at the initial luminance of 100 nit, which is one of the top lifetimes among PNCs-LEDs up to now. The improved performance of dual ETL PNCs-LED is mainly due to the improved charge transport balance with favorable energy level matching. These findings present a promising strategy to modify the function layer via ALD to achieve both highly efficient and stable PNCs-LED.
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Shape-memory polymers (SMPs) have gradually emerged in the mechanism and biomedical fields and facilitate the upgrading of industrial mechanisms and the breakthrough of technical bottlenecks. However, most of the SMPs are infeasible in harsh environments, such as aerospace, due to the low glass transition temperature. There are still some works that remain in creating truly portable or non-contacting actuators that can match the performances and functions of traditional metal structures. Polyether-ether-ketone (PEEK) with a high glass transition temperature of 143 °C is endowed with outstanding high-temperature resistance and radiation-resistant properties and shape memory behavior. Thus, we explore the shape-memory properties and actuation performances of high-temperature PEEK in bending behaviors. The shape-recovery ratio, actuation speed and force under different programming conditions and structure parameters are summarized to complete the actuation capacities. Meanwhile, a metallic ball transported by shape-memory PEEK and deployed drag sail with thermo-responsive composite joints were shown to verify the potential in aerospace.
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The poor contractility of the detrusor muscle in underactive bladders (UABs) fails to increase the pressure inside the UAB, leading to strenuous and incomplete urination. However, existing therapeutic strategies by modulating/repairing detrusor muscles, e.g., neurostimulation and regenerative medicine, still have low efficacy and/or adverse effects. Here, we present an implantable magnetic soft robotic bladder (MRB) that can directly apply mechanical compression to the UAB to assist urination. Composed of a biocompatible elastomer composite with optimized magnetic domains, the MRB enables on-demand contraction of the UAB when actuated by magnetic fields. A representative MRB for a UAB in a porcine model is demonstrated, and MRB-assisted urination is validated by in situ computed tomography imaging after 14-day implantation. The urodynamic tests show a series of successful urination with a high pressure increase and fast urine flow. Our work paves the way for developing MRB to assist urination for humans with UABs.
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Color vision deficiency (CVD) is a common ocular disorder affecting more than 300 million people on the earth. Although no clinical cure for the disorder currently exists, some specialized color filtering glasses/lenses based on dyes, metasurfaces, or nanocomposites have been employed for CVD management. However, as CVD patients usually diversify in their classification and severity, none of the current lenses provides a customized correction for various CVD patients, resulting in undesirable correction effects. Here, we present an inverse-designed approach for the precise correction of CVD. The wavelength shift of a patient's abnormal cone photoreceptors was measured to inversely design the best blocking wavelength and blocking rate of the lens. Then the customized aid lenses were fabricated using silica-coated gold nanoparticles with appropriate sizes and concentrations, verified by the simulated color vision and human tests. This study demonstrates the potential of the inverse-designed aid lenses in precise color filtering and customized CVD management.
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Doenças Cardiovasculares , Defeitos da Visão Cromática , Nanopartículas Metálicas , Nanocompostos , Cor , Defeitos da Visão Cromática/terapia , Ouro , Humanos , Nanopartículas Metálicas/uso terapêuticoRESUMO
Vibrations, which widely exist throughout the world, could be a nearly endless and locally obtained green energy source. It has been a long-standing challenge to efficiently utilize dispersed vibration energy, especially within the high-frequency range, since the amplitudes of high-frequency vibrations in local parts of objects are relatively weak. Here, for the first time, we propose a soft and disordered hyperuniform elastic metamaterial (DHEM), achieving a remarkable concentration of vibrations in broad frequency bands by a maximum enhancement factor of â¼4000 at 1930 Hz. The DHEM, with rational sizes from â¼1 cm to â¼1000 cm, covers a broad range of frequencies from â¼10 Hz to â¼10 kHz, which are emitted by many vibration sources including domestic appliances, factories and transportation systems, for example. Moreover, the performance of the soft DHEM under deformation is validated, enabling conformal attachments on uneven objects. Our findings lay the groundwork for reducing traditional energy consumption by recovering some of the energy dissipated by devices in the working world.
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In vivo bioprinting has recently emerged as a direct fabrication technique to create artificial tissues and medical devices on target sites within the body, enabling advanced clinical strategies. However, existing in vivo bioprinting methods are often limited to applications near the skin or require open surgery for printing on internal organs. Here, we report a ferromagnetic soft catheter robot (FSCR) system capable of in situ computer-controlled bioprinting in a minimally invasive manner based on magnetic actuation. The FSCR is designed by dispersing ferromagnetic particles in a fiber-reinforced polymer matrix. This design results in stable ink extrusion and allows for printing various materials with different rheological properties and functionalities. A superimposed magnetic field drives the FSCR to achieve digitally controlled printing with high accuracy. We demonstrate printing multiple patterns on planar surfaces, and considering the non-planar surface of natural organs, we then develop an in situ printing strategy for curved surfaces and demonstrate minimally invasive in vivo bioprinting of hydrogels in a rat model. Our catheter robot will permit intelligent and minimally invasive bio-fabrication.
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Bioimpressão , Catéteres , Imãs/química , Robótica , Animais , Linhagem Celular , Elasticidade , Condutividade Elétrica , Humanos , Hidrogéis/química , Fígado/diagnóstico por imagem , Ratos Sprague-Dawley , Suínos , Tomografia Computadorizada por Raios X , ViscosidadeRESUMO
Black phase CsPbI3 perovskites have emerged as one of the most promising materials for use in optoelectronic devices due to their remarkable properties. However, black phase CsPbI3 usually possesses poor stability and involves a phase change process, resulting in an undesired orthorhombic (δ) yellow phase. Here, the enhanced stability of CsPbI3 nanocrystals is achieved by incorporating the Cu2+ ion into the CsPbI3 lattice under mild conditions. In particular, the Cu2+-doped CsPbI3 film can maintain red luminescence for 35 days in air while the undoped ones transformed into the nonluminescent yellow phase in several days. Furthermore, first-principles calculations verified that the enhanced stability is ascribed to the increased formation energy due to the successful doping of Cu2+ in CsPbI3. Benefiting from such an effective doping strategy, the as-prepared Cu2+-doped CsPbI3 as an emitting layer shows much better performance compared with that of the undoped counterpart. The turn-on voltage of the Cu2+-doped quantum-dot light-emitting diode (QLED) (1.6 V) is significantly reduced compared with that of the pristine QLED (3.8 V). In addition, the luminance of the Cu2+-doped QLED can reach 1270 cd/m2, which is more than twice that of the pristine CsPbI3 QLED (542 cd/m2). The device performance is believed to be further improved by optimizing the purification process and device structure, shedding light on future applications.
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Structural color has been particularly attractive as it provides a highly promising approach for next-generation color printing. Plasmonic nanostructures have been intensively investigated for color printing, while suffering from intrinsic loss that degrades the quality of the coloration. Dielectric materials have emerged as an alternative because of their high refractive index that enables highly confined optical modes within the nanostructure at the diffraction limit. Here, we demonstrate an all-dielectric nanoring metasurface for coloration. By harnessing the intrinsic nanoring structure design, vivid structural color has been achieved in the visible range. The color gamut is expected to occupy 115% of the standard color space (sRGB) on the chromaticity diagram of the International Commission on Illumination (CIE) 1931 in theory. Our structure can be applied to various complex devices and materials and find potential applications such as displays, information, and art works.
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The adhesion of soft connective tissues (tendons, ligaments, and cartilages) on bones in many animals can maintain high toughness (â½800 J m-2) over millions of cycles of mechanical loads. Such fatigue-resistant adhesion has not been achieved between synthetic hydrogels and engineering materials, but is highly desirable for diverse applications such as artificial cartilages and tendons, robust antifouling coatings, and hydrogel robots. Inspired by the nanostructured interfaces between tendons/ligaments/cartilages and bones, we report that bonding ordered nanocrystalline domains of synthetic hydrogels on engineering materials can give a fatigue-resistant adhesion with an interfacial fatigue threshold of 800 J m-2, because the fatigue-crack propagation at the interface requires a higher energy to fracture the ordered nanostructures than amorphous polymer chains. Our method enables fatigue-resistant hydrogel coatings on diverse engineering materials with complex geometries. We further demonstrate that the fatigue-resistant hydrogel coatings exhibit low friction and low wear against natural cartilages.
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Cartilagem/fisiologia , Hidrogéis/química , Teste de Materiais , Tíbia/fisiologia , Engenharia Tecidual/métodos , Animais , Adesão Celular/fisiologia , Galinhas , Modelos Moleculares , Propriedades de SuperfícieRESUMO
Mental fatigue, characterized by subjective feelings of "tiredness" and "lack of energy", can degrade individual performance in a variety of situations, for example, in motor vehicle driving or while performing surgery. Thus, a method for nonintrusive monitoring of mental fatigue status is urgently needed. Recent research shows that physiological signal-based fatigue-classification methods using wearable electronics can be sufficiently accurate; by contrast, rigid, bulky devices constrain the behavior of those wearing them, potentially interfering with test signals. Recently, wearable electronics, such as epidermal electronics systems (EES) and electronic tattoos (E-tattoos), have been developed to meet the requirements for the comfortable measurement of various physiological signals. However, comfortable, effective, and nonintrusive monitoring of mental fatigue levels remains to be fulfilled. In this work, an EES is established to simultaneously detect multiple physiological signals in a comfortable and nonintrusive way. Machine-learning algorithms are employed to determine the mental fatigue levels and a predictive accuracy of up to 89% is achieved based on six different kinds of physiological features using decision tree algorithms. Furthermore, EES with the trained predictive model are applied to monitor in situ human mental fatigue levels when doing several routine research jobs, as well as the effect of relaxation methods in relieving fatigue.
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Algoritmos , Aprendizado de Máquina , Eletrônica , Humanos , Fadiga Mental/diagnóstico , Monitorização FisiológicaRESUMO
Efficiently identifying optical structures with desired functionalities, referred to as inverse design, can dramatically accelerate the invention of new photonic devices, and this is especially useful in the design of large scale integrated photonic chips. Structural color with high-resolution, high-saturation, and low-loss holds great promise in image display, data storage and information security. However, the inverse design of structural color remains an open challenge, and this impedes practical application. Here, we propose an inverse design strategy for structural color using machine learning (ML) technologies. The supervised learning (SL) models are trained with the geometries and colors of dielectric arrays to capture accurate geometry-color relationships, and these are then applied to a reinforcement learning (RL) algorithm in order to find the optical structural geometries for the desired color. Our work succeeds in finding simple and accurate models to describe geometry-color relationships, which significantly improves the efficiency of the design. This strategy provides a systematic method to directly encode generic functionality into a set of structures and geometries, paving the way for the inverse design of functional photonic devices.
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Slippery and hydrophilic surfaces find critical applications in areas as diverse as biomedical devices, microfluidics, antifouling, and underwater robots. Existing methods to achieve such surfaces rely mostly on grafting hydrophilic polymer brushes or coating hydrogel layers, but these methods suffer from several limitations. Grafted polymer brushes are prone to damage and do not provide sufficient mechanical compliance due to their nanometer-scale thickness. Hydrogel coatings are applicable only for relatively simple geometries, precluding their use for the surfaces with complex geometries and features. Here, a new method is proposed to interpenetrate hydrophilic polymers into the surface of diverse polymers with arbitrary shapes to form naturally integrated "hydrogel skins." The hydrogel skins exhibit tissue-like softness (Young's modulus ≈ 30 kPa), have uniform and tunable thickness in the range of 5-25 µm, and can withstand prolonged shearing forces with no measurable damage. The hydrogel skins also provide superior low-friction, antifouling, and ionically conductive surfaces to the polymer substrates without compromising their original mechanical properties and geometry. Applications of the hydrogel skins on inner and outer surfaces of various practical polymer devices including medical tubing, Foley catheters, cardiac pacemaker leads, and soft robots on massive scales are further demonstrated.