Large Injections Research Articles

A robust reduction in near-surface wind speed after volcanic eruptions: Implications for wind energy generation.

Near-surface wind speed (NSWS), a determinant of wind energy, is influenced by both natural and anthropogenic factors. However, the specific impacts of volcanic eruptions on NSWS, remain unexplored. Our simulations spanning the last millennium reveal a consistent 2-year global NSWS reduction following 10 major historical eruptions. This equates to an NSWS decrease of approximately two inter-annual standard deviations from AD 851 to 1849. This reduction is linked to the weakening of subtropical descending air and a decrease in downward momentum flux, triggered by volcanic aerosol forcing. The 1815 Tambora eruption, one of the most powerful in recent history, led to a ∼9.2% reduction in global wind power density in the subsequent 2 years. Our research fills a knowledge gap, establishes a theoretical foundation for empirical studies, and highlights the potential wind energy risks linked to large atmospheric aerosol injections, including volcanic eruptions, nuclear warfare, and climate intervention.

Spurious radiated power signal following massive material injections in JET and the effect of neutral gas pressure on resistive bolometers.

Massive material injections in the JET tokamak have been observed to substantially affect resistive bolometer measurements, resulting in a spurious radiated power signal proportional to the quantity injected and reaching up to 8MW. These bolometers are calibrated and designed to operate in near vacuum but certain scenarios requiring large gas injections can push the neutral pressure past nominal values. This study demonstrates that the bolometry measurement can be affected at neutral pressures above 0.1Pa following injections with standard gas valves, shattered pellet injections, and particularly massive gas injections. The power measurement of resistive bolometers is based on the temperature difference between a measurement sensor exposed to radiation and a shielded reference sensor. We employ a thermal conductivity model to demonstrate that the conduction through the gas and the distinct geometries between the sensors can affect their cooling efficiency. This additional cooling pathway, coupled with the Joule heating from the applied voltage causes the equilibrium temperatures of the sensors to diverge. Being the very basis of the measure, this temperature difference induces a signal that is erroneously interpreted as radiated power. Experiments show large discrepancies in the response to neutral pressure among bolometer channels, attributed to variations in channel physical parameters. Nonetheless, the modeled total radiated power reproduces the experimental measurements within an order of magnitude, affirming the sensitivity of resistive bolometers to neutral pressure and gas species.

Nonlinear Tissue Permeability Drives Tissue Pressure and Injection Distribution: A Computational Investigation of Subcutaneous Injections.

There is a significant opportunity to expand the understanding of subcutaneous injection mechanics with an aim to increase injectable volume while controlling tissue strain and associated subject pain. Computational modeling can evaluate the mechanics of subcutaneous injections as a supplement to experimental, animal and clinical studies. The objectives of this study are to (1) develop a computational model for subcutaneous injection in tissue, (2) investigate the influence anisotropic tissue permeability has on bolus formation, and (3) explore the effects that injection flow rate and viscosity have on injection flow and tissue strain. Poroelastic models with subsurface flow were implemented in finite element software (COMSOL, ABAQUS). Pore pressure and injectate distribution showed excellent agreement with experimental results when evaluated at multiple injection rates (20 ml/hr, 120 ml/hr and 360 ml/hr). Including the anisotropy of tissue permeability causes the injectate to preferentially spread horizontally, similar to experimentally observed bolus distributions. Cases are presented to provide additional insight into injection mechanics, including variations on the delivery rate, the injection volume, viscosity and the thickness of the subcutaneous layer. The results support the use of computational modeling as a valid tool for understanding tissue strains and injectate distributions for large volume injections.

On the Impact of Renewable Generation on the Sicilian Power System in Near-Future Scenarios: A Case Study

This paper was conceived to investigate some central issues related to the upheaval of current energy scenarios in Sicily. New power connection lines that are about to be built in the Mediterranean area, planned with a view to a constantly increasing renewable generation, encourage the carrying out of analyses on how the Sicilian electric power system will be able to make itself ready to support large power injections, especially due to new renewables plants that will be established in the region soon. This study, carried out in close collaboration with the Italian TSO Terna S.p.A and the University of Palermo, defines what the impacts of new renewable power plants will be on the Sicilian power transmission grid under intact and non-intact grid conditions. This study consists of steady-state simulations carried out using WinCreso® in two energy scenarios estimated for the years 2024 and 2027, based on real connection requests by producers to Terna, and allows one to go beyond the studies conducted so far on a 2030 basis through the precise identification of network nodes or lines in difficulty. Finally, as well as presenting an interesting case study due to Sicily’s strategic position in the Mediterranean Sea, this article proposes a methodological approach that can easily be adopted in other contexts and by other TSOs to analyze similar situations.

Vulvar migration of injected polyacrylamide hydrogel following breast augmentation: a case report and literature review

BackgroundVulvar migration is a rare complication of filler injection for breast augmentation, generally presenting as repeated pain and fever. We will report a case of woman with polyacrylamide hydrogel breast injection develops vulvar abscess.Case presentationA woman with a history of polyacrylamide hydrogel breast injection was noted to have vulvar abscess due to migration of filler materials. Filler removal surgery and vacuum sealing drainage was performed for this patient. The patient was discharged from the hospital with no further complications. After a review of pertinent literature, only four previous case reports are found. Local inflammatory response, infection, large volume injections, inframammary fold destruction, hematogenous or lymphatic migrate, trauma, gravity and external pressure could play essential parts in the migration of injected filler.ConclusionPolyacrylamide hydrogel migration poses a worldwide challenge, necessitating personalized solutions. Our case study underscores the importance of comprehensive examinations for individuals with a history of filler breast injection when suspecting vulvar filler migration.

Asset-Based Microfinance for Microenterprises: Evidence from Pakistan

We run a field experiment offering graduated microcredit clients the opportunity to finance a business asset worth four times their usual borrowing limit. We implement this using a hire-purchase contract; our control group is offered a zero interest loan at the usual borrowing limit. We find large, significant, and persistent effects: treated microenterprise owners run larger businesses with higher profits; consequently, household consumption increases, particularly on food and children’s education. A dynamic structural model with nonconvex capital adjustment costs rationalizes our results and allows counterfactual analysis; this highlights the potential for welfare improvements through large capital injections that are financially sustainable. (JEL C93, D22, G21, G32, L25, O14, O16)

The superior colliculus projection upon the macaque inferior olive.

Saccade accommodation is a productive model for exploring the role of the cerebellum in behavioral plasticity. In this model, the target is moved during the saccade, gradually inducing a change in the saccade vector as the animal adapts. The climbing fiber pathway from the inferior olive provides a visual error signal generated by the superior colliculus that is believed to be crucial for cerebellar adaptation. However, the primate tecto-olivary pathway has only been explored using large injections of the central portion of the superior colliculus. To provide a more detailed picture, we have made injections of anterograde tracers into various regions of the macaque superior colliculus. As shown previously, large central injections primarily label a dense terminal field within the C subdivision at caudal end of the contralateral medial inferior olive. Several, previously unobserved, sites of sparse terminal labeling were noted: bilaterally in the dorsal cap of Kooy and ipsilaterally in theC subdivision of the medial inferior olive. Small, physiologically directed, injections into the rostral, small saccade portion of the superior colliculus produced terminal fields in the same regions of the medial inferior olive, but with decreased density. Small injections of the caudal superior colliculus, where large amplitude gaze changes are encoded, again labeled a terminal field located in the same areas. The lack of a topographic pattern within the main tecto-olivary projection suggests that either the precise vector of the visual error is not transmitted to the vermis, or that encoding of this error is via non-topographic means.

Технологические инновации и применение искусственного интеллекта в развитии мирохозяйственных процессов: опыт стран БРИКС

The aim of the study is to analyze technological innovation in the field of artificial intelligence in the global economy with a focus on the experience of the BRICS countries. In the course of the study, the authors set the following objectives: to assess the impact of AI implementation on the economic and social growth of these countries; the positions of the BRICS countries in the world rankings in the field of artificial intelligence (Global AI Index and Stanford AI Index); and the participation of the BRICS countries in the application of generative AI. The results of the study have allowed to assess the impact of technological innovation and application of artificial intelligence on the economic and social growth of the BRICS countries as positive, especially on China, which has realized significant progress in the field of artificial intelligence over the past 10 years, as well as on India’s breakthrough over the past 2 years in the use of generative AI. China, based on sound long-term strategic planning and large financial injections, is already breaking into a leading position in the world 5 years after adopting the fundamental “Next Generation Artificial Intelligence Development Plan” in 2017. In 2021, Chinese researchers ranked first in the world in terms of cited publications in Q1 peer-reviewed scientific journals (top 25 % of journals). Chinese tech giants are recording a sharp rise in AI publications in 2022, outpacing university researchers on the index. Since 2021, India has significantly increased its position in the leading AI ratings and is becoming a world leader in the application of generative AI. The analysis of the level of development of AI technologies in the BRICS countries conducted within the framework of this article shows that, having all the necessary resources for the successful implementation of AI technologies, in the near future the BRICS countries are planning to apply AI technologies on a larger scale in medicine, education, finance and agriculture, which will significantly improve the economic performance of the state.

Ferrostatin-1-loaded thermosensitive nanodelivery system for noise-induced hearing loss treatment

Hearing loss is one of the most difficult sensory disorders to treat because of complicated anatomical and physiological barriers, which result in systemic administration, making it difficult to achieve effective drug concentrations in the inner ear. We recently found that the ferroptosis inhibitor ferrostatin-1 (Fer-1) can alleviate noise-induced hearing loss but large doses and multiple injections are required. Here, a novel Fer-1-loaded thermosensitive nanodelivery system was constructed by combining the advantages of chitosan (CS) and poly(d,l-lactide-co-glycolide acid) (PLGA) nanoparticles (NPs). β-Glycerophosphate disodium (β-GP) was added to the gel to make it temperature-sensitive. This thermosensitive nanodelivery system could be injected into the middle ear, change into a semisolid phase, and stick to the middle ear mucosa. In vivo experiments indicate that the gel prolonged retention for at least 7 d, causing little inflammatory response. In addition, the injection of the gel caused a temporary increase in the hearing threshold, but mice returned to normal hearing within 3 d. Finally, we demonstrated that this Fer-1-loaded thermosensitive nanodelivery system could alleviate noise-induced hearing loss (NIHL) by reducing the loss of outer hair cells (OHCs), inner hair cell (IHC) ribbon synapses, and auditory nerve fibers (ANFs) in a mouse model. Our results demonstrate that intratympanic injection of the Fer-1-loaded thermosensitive nanodelivery system is a safe and effective way to attenuate NIHL, providing a new idea for the treatment of NIHL.

The nuclei of the lateral lemniscus: unexpected players in the descending auditory pathway.

In the mammalian auditory pathway, the nuclei of the lateral lemniscus (NLL) are thought to be exclusively involved in the bottom-up transmission of auditory information. However, our repeated observation of numerous NLL neurons labeled after injection of retrograde tracers into the superior olivary complex (SOC) led us to systematically investigate with retrograde tracers the descending projections from the NLL to the SOC of the rat. We performed large injections of FluoroGold into the SOC to determine NLL contributions to descending projections, and focal injections of biotinylated dextran amine (BDA) to pinpoint the specific nuclei of the SOC innervated by each NLL. The SOC is innervated by thousands of neurons distributed across four nuclei or regions associated with the lateral lemniscus: the ipsilateral ventral and intermediate nuclei of the lateral lemniscus (VNLL and INLL); the medial paralemniscal region (PL) of both sides; and the ipsilateral semilunar nucleus (SLN), a previously unrecognized nucleus that wraps around the INLL dorsally, medially, and caudally and consists of small, flat neurons. In some experiments, at least 30% of neurons in the VNLL and INLL were retrogradely labeled. All nuclei of the SOC, except the medial and lateral superior olives, are innervated by abundant lemniscal neurons, and each SOC nucleus receives a unique combination of lemniscal inputs. The primary target of the projections from the VNLL is the ventral nucleus of the trapezoid body (VNTB), followed by the superior paraolivary nucleus (SPON), and the medial nucleus of the trapezoid body (MNTB). The INLL selectively innervates the VNTB. The PL innervates dorsal periolivary regions bilaterally. The SLN preferentially innervates the MNTB and may provide the first identified non-calyceal excitatory input to MNTB neurons. Our novel findings have strong implications for understanding acoustic information processing in the initial stages of the auditory pathway. Based on the proportion of lemniscal neurons involved in all the projections described, the NLL should be considered major players in the descending auditory pathway.

Characterization of large volume subcutaneous injections using computed tomography imaging and simultaneous pressure measurements

Many commercially available biologics, previously delivered only intravenously, are being re-formulated for subcutaneous delivery to improve patient access and compliance. However, due to inherent solubility limitations, large volume injections (more than 2 mL) are typically required. Different strategies are being explored to improve the tolerability of such injections, including the co-formulation with hyaluronidase and/or implementing different needle designs. While there have been separate reports of measuring injection forces and using imaging to track injection delivery and tissue response, there is no current set of methods to simultaneously characterize the injection delivery (bleb) and measure injection pressures. In this study we describe the development of Computed Tomography imaging methods in minipigs to characterize the morphology of the bleb following injection, along with inline pressure measurements to assess subcutaneous pressure during injection using two different injection volumes, 4.5 mL and 9 mL. We show that these parameters change with injection volume, and that inclusion of hyaluronidase in the injection increases bleb dispersion and reduces skin distention while also lowering the injection pressure. This method will likely be a valuable tool for assessing and comparing different injection delivery methods and formulations.

A thermal–kinetic subgrid model for supernova feedback in simulations of galaxy formation

ABSTRACT We present a subgrid model for supernova feedback designed for cosmological simulations of galaxy formation that may include a cold interstellar medium (ISM). The model uses thermal and kinetic channels of energy injection, which are built upon the stochastic kinetic and thermal models for stellar feedback used in the owls and eagle simulations, respectively. In the thermal channel, the energy is distributed statistically isotropically and injected stochastically in large amounts per event, which minimizes spurious radiative energy losses. In the kinetic channel, we inject the energy in small portions by kicking gas particles in pairs in opposite directions. The implementation of kinetic feedback is designed to conserve energy, linear and angular momentum, and is statistically isotropic. To test the model, we run simulations of isolated Milky Way-mass and dwarf galaxies, in which the gas is allowed to cool down to 10 K. Using the thermal and kinetic channels together, we obtain smooth star formation histories and powerful galactic winds with realistic mass loading factors. Furthermore, the model produces spatially resolved star formation rates (SFRs) and velocity dispersions that are in agreement with observations. We vary the numerical resolution by several orders of magnitude and find excellent convergence of the global SFRs and wind mass loading. We show that large thermal energy injections generate a hot phase of the ISM and modulate the star formation by ejecting gas from the disc, while the low-energy kicks increase the turbulent velocity dispersion in the neutral ISM, which in turn helps suppress star formation.

A detailed evaluation of the advantages and limitations of online RP-LC×HILIC compared to HILIC×RP-LC for phenolic analysis

The combination of hydrophilic interaction chromatography (HILIC) and reversed-phase liquid chromatography (RP-LC) has proved effective in the LC × LC analysis of polyphenols due to the high degree of orthogonality associated with these separation modes for various classes of phenolic compounds. However, despite the growing number of such applications, HILIC is almost exclusively used as the first dimension (1D) separation mode, and RP-LC in the second dimension (2D). This is somewhat surprising in light of the potential advantages of swapping these separation modes. In this contribution, we present a detailed evaluation of the potential of online RP-LC × HILIC-MS for the analysis of phenolic compounds, comparing the performance of this system to the more established HILIC × RP-LC-MS configuration.Method development was performed using a predictive optimisation program, and fixed solvent modulation was employed to combat the solvent incompatibility between HILIC and RP-LC mobile phases. Red wine, rooibos tea, Protea and chestnut phenolic extracts containing a large diversity of phenolic compound classes were analysed by both HILIC × RP-LC- and RP-LC × HILIC-MS in order to compare the separation performance.Overall, the kinetic performance of HILIC × RP-LC was found to be clearly superior, with higher peak capacities and better resolution obtained for the majority of samples compared to RP-LC × HILIC analyses using similar column dimensions. Dilution of the 1D solvent combined with large volume injections proved insufficient to focus especially phenolic acids in the 2D HILIC separation, which resulted in severe 2D peak distortion for these compounds, and negatively impacted on method performance. On the other hand, a noteworthy improvement in the sensitivity of RP-LC × HILIC-MS analyses was observed due to higher ESI-MS response for the 2D HILIC mobile phase and greater sample loading capacity of the 1D RP-LC column, brought on by the high solubility of phenolic samples in aqueous solutions. As a result, a significantly higher number of compounds were detected in the RP-LC × HILIC-MS separations. These findings point to the potential advantage of RP-LC × HILIC as a complementary configuration to HILIC × RP-LC for phenolic analysis.

A study on the design of an in silico self-amplifying mRNA vaccine against Nipah virus using immunoinformatics

The scientific community continues to be impressed with RNA-based vaccines with great efficacy, quick synthesis and speed-to-market. The traditional vaccine may require large doses or repeat injections to achieve an expression for protection against the virus; the self-amplifying mRNA vaccine addresses this limitation. Therefore, a thorough examination of the most antigenic component of the Nipah virus was carried out to design the coding sequence of an antigen, which will provoke a virus-specific immune response. After that, we predicted and evaluated epitopes from NiV G-protein. We employed 8 HTL, 2 CTL and 3 B-cell epitopes. The study of structural compatibility was done by performing docking between HLA alleles and epitopes to get insights into the immune response of epitopes. The entire peptide coding sequence of an antigen was linked using a linker to design the structure of the vaccine. Physicochemical parameters of the designed vaccine constructs were assessed using a protparam server. Later, the vaccine sequence was converted into cDNA. We inserted a gene-expressing replicase at the start of a coding sequence for self-amplification. Next, to formulate the final version of vaccine signal sequences were added. Based on these findings, this mRNA vaccine appears to be a promising option against the Nipah virus. Communicated by Ramaswamy H. Sarma

Modeling large-volume subcutaneous injection of monoclonal antibodies with anisotropic porohyperelastic models and data-driven tissue layer geometries

Subcutaneous injection of therapeutic monoclonal antibodies (mAbs) has become one of the fastest-growing fields in the pharmaceutical industry. The transport and mechanical processes behind large volume injections are poorly understood. Here, we leverage a large-deformation poroelastic model to study high-dose, high-speed subcutaneous injection. We account for the anisotropy of subcutaneous tissue using of a fibril-reinforced porohyperelastic model. We also incorporate the multi-layer structure of the skin tissue, generating data-driven geometrical models of the tissue layers using histological data. We analyze the impact of handheld autoinjectors on the injection dynamics for different patient forces. Our simulations show the importance of considering the large deformation approach to model large injection volumes. This work opens opportunities to better understand the mechanics and transport processes that occur in large-volume subcutaneous injections of mAbs.

Breathless through Time: Oxygen and Animals across Earth's History.

AbstractOxygen levels in the atmosphere and ocean have changed dramatically over Earth history, with major impacts on marine life. Because the early part of Earth's history lacked both atmospheric oxygen and animals, a persistent co-evolutionary narrative has developed linking oxygen change with changes in animal diversity. Although it was long believed that oxygen rose to essentially modern levels around the Cambrian period, a more muted increase is now believed likely. Thus, if oxygen increase facilitated the Cambrian explosion, it did so by crossing critical ecological thresholds at low O2. Atmospheric oxygen likely remained at low or moderate levels through the early Paleozoic era, and this likely contributed to high metazoan extinction rates until oxygen finally rose to modern levels in the later Paleozoic. After this point, ocean deoxygenation (and marine mass extinctions) is increasingly linked to large igneous province eruptions-massive volcanic carbon inputs to the Earth system that caused global warming, ocean acidification, and oxygen loss. Although the timescales of these ancient events limit their utility as exact analogs for modern anthropogenic global change, the clear message from the geologic record is that large and rapid CO2 injections into the Earth system consistently cause the same deadly trio of stressors that are observed today. The next frontier in understanding the impact of oxygen changes (or, more broadly, temperature-dependent hypoxia) in deep time requires approaches from ecophysiology that will help conservation biologists better calibrate the response of the biosphere at large taxonomic, spatial, and temporal scales.

Dynamical perturbation of the stratosphere by a pyrocumulonimbus injection of carbonaceous aerosols

Abstract. The Pacific Northwest Pyrocumulonimbus Event (PNE) took place in British Columbia during the evening and nighttime hours between 12 and 13 August 2017. Several pyroconvective clouds erupted on this occasion, and released in the upper troposphere and lower stratosphere unprecedented amounts of carbonaceous aerosols (300 ktn). Only a few years later, an even larger pyrocumulonimbus (pyroCb) injection took place over Australia. This event, named “the Australian New Year (ANY) event”, injected up to 1100 ktn of aerosol between 29 December 2019 and 4 January 2020. Such large injections of carbonaceous aerosol modify the stratospheric radiative budgets, locally perturbing stratospheric temperatures and winds. In this study, we use the Goddard Earth Observing System Chemistry Climate Model (GEOS CCM) to study the perturbations on the stratospheric meteorology induced by an aerosol injection of the magnitude of the PNE. Our simulations include the radiative interactions of aerosols, so that their impact on temperatures and winds are explicitly simulated. We show how the presence of the carbonaceous aerosols from the pyroCb causes the formation and maintenance of a synoptic-scale stratospheric anticyclone. We follow this disturbance considering the potential vorticity anomaly and the brown carbon aerosol loading and we describe its dynamical and thermodynamical structure and its evolution in time. The analysis presented here shows that the simulated anticyclone undergoes daily expansion–compression cycles governed by the radiative heating, which are directly related to the vertical motion of the plume, and that the aerosol radiative heating is essential in maintaining the anticyclone itself.

KNa1.1 gain-of-function preferentially dampens excitability of murine parvalbumin-positive interneurons

KCNT1 encodes the sodium-activated potassium channel KNa1.1, expressed preferentially in the frontal cortex, hippocampus, cerebellum, and brainstem. Pathogenic missense variants in KCNT1 are associated with intractable epilepsy, namely epilepsy of infancy with migrating focal seizures (EIMFS), and sleep-related hypermotor epilepsy (SHE). In vitro studies of pathogenic KCNT1 variants support predominantly a gain-of-function molecular mechanism, but how these variants behave in a neuron or ultimately drive formation of an epileptogenic circuit is an important and timely question. Using CRISPR/Cas9 gene editing, we introduced a gain-of-function variant into the endogenous mouse Kcnt1 gene. Compared to wild-type (WT) littermates, heterozygous and homozygous knock-in mice displayed greater seizure susceptibility to the chemoconvulsants kainate and pentylenetetrazole (PTZ), but not to flurothyl. Using acute slice electrophysiology in heterozygous and homozygous Kcnt1 knock-in and WT littermates, we demonstrated that CA1 hippocampal pyramidal neurons exhibit greater amplitude of miniature inhibitory postsynaptic currents in mutant mice with no difference in frequency, suggesting greater inhibitory tone associated with the Kcnt1 mutation. To address alterations in GABAergic signaling, we bred Kcnt1 knock-in mice to a parvalbumin-tdTomato reporter line, and found that parvalbumin-expressing (PV+) interneurons failed to fire repetitively with large amplitude current injections and were more prone to depolarization block. These alterations in firing can be recapitulated by direct application of the KNa1.1 channel activator loxapine in WT but are occluded in knock-in littermates, supporting a direct channel gain-of-function mechanism. Taken together, these results suggest that KNa1.1 gain-of-function dampens interneuron excitability to a greater extent than it impacts pyramidal neuron excitability, driving seizure susceptibility in a mouse model of KCNT1-associated epilepsy.

A Magnetic-Sensing-Based Wide-Bandwidth Grid Impedance Measurement Technique With Small Perturbation Injection

Grid impedance is an important parameter in the impedance-based stability analysis method for analyzing the interaction between the power electronic inverters and the power grid. However, the existing measurement technique is deteriorated by narrow-bandwidth sensors, large perturbation injections, and inaccurate response components extraction based on the fast Fourier transform (FFT) algorithm. To overcome these problems, a magnetic-sensing-based wide-bandwidth grid impedance measurement technique with a small perturbation injection is proposed in this article. A novel impedance extraction algorithm based on the quadrature delay estimator (QDE) is developed to overcome the spectral leakages and frequency aliasing effect of the existing FFT-based impedance extraction algorithm. The proposed grid impedance measurement technique is implemented on a digitally controlled inverter system, and its effectiveness is verified through the experimental results.

Advances in Large Volume Subcutaneous Injections: A Pilot Tolerability Study of an Innovative Needle-Free Injection Platform.

Many medical conditions require chronic treatment with subcutaneous injectable biologics often exceeding 1.0 mL. However, subcutaneous administration of volumes of 2.0 mL or greater using a standard needle and syringe or auto-injector proves challenging, and patients often must administer two separate injections to achieve their full dose or endure injection times in excess of 10 s if using a mechanical autoinjector. In addition, needle-based injections often cause patient anxiety and discomfort. In this article, we describe an approach to meet these needs with a needle-free medication delivery device capable of rapidly delivering up to 2.0 mL with minimal discomfort. A pilot study was conducted with this needle-free injection system to evaluate the delivery of a 2.0 mL volume in human subjects. The results demonstrated that injections of up to 2.0 mL were well tolerated and often preferred over two separate 1.0 mL injections using the needle-free injection system.