Computational Modeling of Fluid Flow and Intra-Ocular Pressure following Glaucoma Surgery

Background Glaucoma surgery is the most effective means for lowering intraocular pressure by providing a new route for fluid to exit the eye. This new pathway is through the sclera of the eye into sub-conjunctival tissue, where a fluid filled bleb typically forms under the conjunctiva. The long-term success of the procedure relies on the capacity of the sub-conjunctival tissue to absorb the excess fluid presented to it, without generating excessive scar tissue during tissue remodeling that will shut-down fluid flow. The role of inflammatory factors that promote scarring are well researched yet little is known regarding the impact of physical forces on the healing response. Methodology To help elucidate the interplay of physical factors controlling the distribution and absorption of aqueous humor in sub-conjunctival tissue, and tissue remodeling, we have developed a computational model of fluid production in the eye and removal via the trabecular/uveoscleral pathways and the surgical pathway. This surgical pathway is then linked to a porous media computational model of a fluid bleb positioned within the sub-conjunctival tissue. The computational analysis is centered on typical functioning bleb geometry found in a human eye following glaucoma surgery. A parametric study is conducted of changes in fluid absorption by the sub-conjunctival blood vessels, changes in hydraulic conductivity due to scarring, and changes in bleb size and shape, and eye outflow facility. Conclusions This study is motivated by the fact that some blebs are known to have ‘successful’ characteristics that are generally described by clinicians as being low, diffuse and large without the formation of a distinct sub-conjunctival encapsulation. The model predictions are shown to accord with clinical observations in a number of key ways, specifically the variation of intra-ocular pressure with bleb size and shape and the correspondence between sites of predicted maximum interstitial fluid pressure and key features observed in blebs, which gives validity to the model described here. This model should contribute to a more complete explanation of the physical processes behind successful bleb characteristics and provide a new basis for clinically grading blebs

Effect of heteroatom and functionalitysubstitution on the oxidation potential of cyclicnitroxide radicals: role of electrostatics inelectrochemistry†

The oxidation potential of a test set of 21 nitroxide radicals, including a number of novel compounds, has been studied experimentally in acetonitrile and correlated with theoretical calculations. It was found that both Hammett constants (σp) of the substituents on the nitroxide radicals and hyperfine splitting constants of the respective nitrogen atoms (αN) were well correlated to their experimental oxidation potentials. Theoretical calculations, carried out at the G3(MP2,CC)(+)//M06-2X/6-31+G(d,p) level of theory with PCM solvation corrections, were shown to reproduce experiments to within a mean absolute deviation of 33 mV, with a maximum deviation of 64 mV. The oxidation potentials of the nitroxides examined varied over 400 mV, depending on ring size and substitution. This considerable variation can be rationalised by the ability of various substituents to electrostatically stabilize the oxidised oxoammonium cation. Importantly, this can be quantified by a simple predictive relationship involving the distance scaled dipole and quadrupole moments of the analogous cyclohexyl ring. This highlights the often-overlooked role of through-space electrostatic substituent effects, even in formally neutral compounds.Z. J. thanks the financial support from the ARC Future Fellowship and the award of Foundation Research Excellent Award (FREA) from the University of Queensland. M. J. M. acknowledges financial support from the ARC Discovery grant. This work was performed in part at the Queensland node of the Australian National Fabrication Facility, a company established under the National Collaborative Research Infrastructure Strategy to provide nano and microfabrication facilities for Australia’s researchers. M. L. C. acknowledges financial support from ARC Centre of Excellence for Electromaterials Science and generous allocations on the National Facility of the Australian National Computational Infrastructure

Incentives and monitoring: impact on the financial and non-financial orientation of capital budgeting

Purpose While investment decisions may be financial decisions, there is a growing recognition that they are also often non-financially based decisions. The purpose of this study is to report findings focused on the project selection stage of capital budgeting, which has the objectives of exploring for: the relative degree of emphasis decision makers attach to a financial and non-financial orientation in capital budgeting; and the role, if any, that two agency theory variables have on the relative degree of emphasis: a personal incentive for project go-ahead and monitoring of project outcomes through a post-audit

Roadmap for In-Space Propulsion Technology

NASA has created a roadmap for the development of advanced in-space propulsion technologies for the NASA Office of the Chief Technologist (OCT). This roadmap was drafted by a team of subject matter experts from within the Agency and then independently evaluated, integrated and prioritized by a National Research Council (NRC) panel. The roadmap describes a portfolio of in-space propulsion technologies that could meet future space science and exploration needs, and shows their traceability to potential future missions. Mission applications range from small satellites and robotic deep space exploration to space stations and human missions to Mars. Development of technologies within the area of in-space propulsion will result in technical solutions with improvements in thrust, specific impulse (Isp), power, specific mass (or specific power), volume, system mass, system complexity, operational complexity, commonality with other spacecraft systems, manufacturability, durability, and of course, cost. These types of improvements will yield decreased transit times, increased payload mass, safer spacecraft, and decreased costs. In some instances, development of technologies within this area will result in mission-enabling breakthroughs that will revolutionize space exploration. There is no single propulsion technology that will benefit all missions or mission types. The requirements for in-space propulsion vary widely according to their intended application. This paper provides an updated summary of the In-Space Propulsion Systems technology area roadmap incorporating the recommendations of the NRC

In-Space Chemical Propulsion Systems Roadmap

In-space propulsion begins where the launch vehicle upper stage leaves off, performing the functions of primary propulsion, reaction control, station keeping, precision pointing, and orbital maneuvering. The main engines used in space provide the primary propulsive force for orbit transfer, planetary trajectories and extra planetary landing and ascent. The reaction control and orbital maneuvering systems provide the propulsive force for orbit maintenance, position control, station keeping, and spacecraft attitude control. Advanced in-space propulsion technologies will enable much more effective exploration of our Solar System and will permit mission designers to plan missions to "fly anytime, anywhere, and complete a host of science objectives at the destinations" with greater reliability and safety. With wide range of possible missions and candidate propulsion technologies, the question of which technologies are "best" for future missions is a difficult one. A portfolio of propulsion technologies should be developed to provide optimum solutions for a diverse set of missions and destinations. A large fraction of the rocket engines in use today are chemical rockets; that is, they obtain the energy needed to generate thrust by chemical reactions to create a hot gas that is expanded to produce thrust. A significant limitation of chemical propulsion is that it has a relatively low specific impulse (Is, or thrust per mass flow rate of propellant). A significant improvement (>30%) in Is can be obtained by using cryogenic propellants, such as liquid oxygen and liquid hydrogen, for example. Historically, these propellants have not been applied beyond upper stages

Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature

Funding Information: Financial support. This work was supported by the European Union’s Horizon 2020 Program under grants (848196 DIAMONDS, 668303 PERFORM, 279185 EUCLIDS, Prof Levin), by the Imperial Biomedical Research Centre (BRC) of the National Institute for Health Research (NIHR), grants (206508/Z/17/Z and MRF-160-0008-ELP-KAFO-C0801 to Dr Kaforou) from the Wellcome Trust and the Medical Research Foundation, a grant (215214/Z/19/Z to Dr Jackson) from the Wellcome Trust, a grant (R61HD105590-01 PreVAIL kIds to Dr. Burns) from the National Institutes of Health, and grants (WDPI_G28062 and WDPI_P89720 to Drs Herberg and Georgiou) from the Community Jameel Imperial College COVID-19 Excellence Fund and the Rosetrees Trust. This work has been supported by the Imperial Confidence in Concept Scheme, funded by MRC Confidence in Concept, Wellcome Trust Institutional Strategic Support Fund, NIHR Imperial BRC, and Rosetrees Trust (to Rodriguez-Manzano and Kaforou). Publisher Copyright: © 2023 The Author(s). Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.Background: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections. Methods: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39). Results: In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV. Conclusions: MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.Peer reviewe

Technology Area Roadmap for In-Space Propulsion Technologies

The exponential increase of launch system size.and cost.with delta-V makes missions that require large total impulse cost prohibitive. Led by NASA fs Marshall Space Flight Center, a team from government, industry, and academia has developed a flight demonstration mission concept of an integrated electrodynamic (ED) tethered satellite system called PROPEL: \Propulsion using Electrodynamics.. The PROPEL Mission is focused on demonstrating a versatile configuration of an ED tether to overcome the limitations of the rocket equation, enable new classes of missions currently unaffordable or infeasible, and significantly advance the Technology Readiness Level (TRL) to an operational level. We are also focused on establishing a far deeper understanding of critical processes and technologies to be able to scale and improve tether systems in the future. Here, we provide an overview of the proposed PROPEL mission. One of the critical processes for efficient ED tether operation is the ability to inject current to and collect current from the ionosphere. Because the PROPEL mission is planned to have both boost and deboost capability using a single tether, the tether current must be capable of flowing in both directions and at levels well over 1 A. Given the greater mobility of electrons over that of ions, this generally requires that both ends of the ED tether system can both collect and emit electrons. For example, hollow cathode plasma contactors (HCPCs) generally are viewed as state-of-the-art and high TRL devices; however, for ED tether applications important questions remain of how efficiently they can operate as both electron collectors and emitters. Other technologies will be highlighted that are being investigated as possible alternatives to the HCPC such as Solex that generates a plasma cloud from a solid material (Teflon) and electron emission (only) technologies such as cold-cathode electron field emission or photo-electron beam generation (PEBG) technique

Sustaining a new model of acute stroke care : A mixed-method process evaluation of the Melbourne Mobile Stroke Unit

Background Internationally, Mobile Stroke Unit (MSU) ambulances have changed pre-hospital acute stroke care delivery. MSU clinical and cost-effectiveness studies are emerging, but little is known about important factors for achieving sustainability of this innovative model of care. Methods Mixed-methods study from the Melbourne MSU (operational since November 2017) process evaluation. Participant purposive sampling included clinical, operational and executive/management representatives from Ambulance Victoria (AV) (emergency medical service provider), the MSU clinical team, and receiving hospitals. Sustainability was defined as ongoing MSU operations, including MSU workforce and future model considerations. Theoretically-based on-line survey with Unified Theory of Acceptance and Use of Technology (UTAUT), Self Determination Theory (SDT, Intrinsic Motivation), and open-text questions targeting barriers and benefits was administered (June-September 2019). Individual/group interviews were conducted, eliciting improvement suggestions and requirements for ongoing use. Descriptive and regression analyses (quantitative data) and directed content and thematic analysis (open text and interview data) were conducted. Results There were 135 surveys completed. Identifying that the MSU was beneficial to daily work (β = 0.61), not experiencing pressure/tension about working on the MSU (β = 0.17) and thinking they did well working within the team model (β = 0.17) were significantly associated with wanting to continue working within the MSU model [R2 = 0.76; F(15, 60) = 12.76, P < .001]. Experiences varied between those on the MSU team and those working with the MSU. Advantages were identified for patients (better, faster care) and clinicians (interdisciplinary learning). Disadvantages included challenges integrating into established systems, and establishing working relationships. Themes identified from 35 interviews were MSU team composition, MSU vehicle design and layout, personnel recruitment and rostering, communication improvements between organisations, telemedicine options, MSU operations and dispatch specificity. Conclusion Important factors affecting the sustainability of the MSU model of stroke care emerged. A cohesive team approach, with identifiable benefits and good communication between participating organisations is important for clinical and operational sustainability

Gangliosides Block Aggregatibacter Actinomycetemcomitans Leukotoxin (LtxA)-Mediated Hemolysis

Aggregatibacter actinomycetemcomitans is an oral pathogen and etiologic agent of localized aggressive periodontitis. The bacterium is also a cardiovascular pathogen causing infective endocarditis. A. actinomycetemcomitans produces leukotoxin (LtxA), an important virulence factor that targets white blood cells (WBCs) and plays a role in immune evasion during disease. The functional receptor for LtxA on WBCs is leukocyte function antigen-1 (LFA-1), a β-2 integrin that is modified with N-linked carbohydrates. Interaction between toxin and receptor leads to cell death. We recently discovered that LtxA can also lyse red blood cells (RBCs) and hemolysis may be important for pathogenesis of A. actinomycetemcomitans. In this study, we further investigated how LtxA might recognize and lyse RBCs. We found that, in contrast to a related toxin, E. coli α-hemolysin, LtxA does not recognize glycophorin on RBCs. However, gangliosides were able to completely block LtxA-mediated hemolysis. Furthermore, LtxA did not show a preference for any individual ganglioside. LtxA also bound to ganglioside-rich C6 rat glioma cells, but did not kill them. Interaction between LtxA and C6 cells could be blocked by gangliosides with no apparent specificity. Gangliosides were only partially effective at preventing LtxA-mediated cytotoxicity of WBCs, and the effect was only observed when a high ratio of ganglioside:LtxA was used over a short incubation period. Based on the results presented here, we suggest that because of the similarity between N-linked sugars on LFA-1 and the structures of gangliosides, LtxA may have acquired the ability to lyse RBCs