Improving the Estimation of Military Worth of the Advanced Tactical Laser through Simulation Aggregation

Fielding High Energy Laser (HEL) weapon systems presents technological challenges as well as employment and financial challenges. The risk associated with the challenges mandates the development process include computer simulation models capable of predicting weapon system performance from the engineering level to assessing the military worth of employing HEL systems in combat scenarios. This research effort focuses on developing laser performance data at a higher fidelity engagement model and integrating the performance data into a mission level model. The propagation of the laser from the transmitting aperture to the target is modeled at the engagement level through the employment of the High Energy Laser End-to-End Operational Simulation (HELEEOS), developed by the AFIT Center for Directed Energy (CDE). The output from HELEEOS directly transfers into data lookup tables for the Extended Air Defense Simulation Model (EADSIM). The EADSIM simulations asses the combat performance of a proposed new HEL weapon, the Advanced Tactical Laser (ATL), in a well-defined mission level scenario based on HEL Joint Technology Office (JTO) requirements for future HEL systems. EADSIM is a mission level simulation model included in the Air Force Analytical Tool Kit. Specifically the research explores the development of the necessary information requirements for HELEEOS and EADSIM to accurately model ATL effects and evaluates challenges related to modeling HEL engagements in EADSIM. Results include discussion on EADSIM HEL weapons modeling capabilities, recommendations on general mission level characteristics that should be modeled, and appropriate measures of performance for campaign-level modeling

Multiparticle States and the Hadron Spectrum on the Lattice

The Clebsch-Gordan decomposition is calculated for direct products of the irreducible representations of the cubic space group. These results are used to identify multiparticle states which appear in the hadron spectrum on the lattice. Consideration of the cubic space group indicates how combinations of both zero momentum and non-zero momentum multiparticle states contribute to the spectrum.Comment: v2) Little groups for lattice momenta corrected. Includes a more consistent labeling scheme. (13 pages

In situ gelling drug delivery systems for topical drug delivery

© 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY licence. https://creativecommons.org/licenses/by/4.0/In situ gelling formulations are drug delivery systems which typically exist in a liquid form at room temperature and change into gel state after application to the body in response to various stimuli such as changes in temperature, pH and ionic composition. Their biomedical application can further be improved by incorporating drug nanoparticles into in situ gelling systems in order to prolong drug release, reduce dosing frequency and improve therapeutic outcomes of patients, developing highly functional but challenging dosage forms. The composition of in situ gelling formulations influence factors relating to performance such as their syringeability, rheology, drug release profile and drug bioavailability at target sites, amongst other factors. The inclusion of mucoadhesive polymeric constituents into in situ gelling formulations has also been explored to ensure that the therapeutic agents are retained at target site for extended period of time. This review article will discuss traditional techniques (water bath-based vial inversion and viscometry) as well as advanced methodology (rheometry, differential scanning calorimetry, Small Angle Neutron Scattering, Small Angle X-ray Scattering, etc.) for evaluating in situ gel forming systems for topical drug delivery. The clinical properties of in situ gelling systems that have been studied for potential biomedical applications over the last ten years will be reviewed to highlight current knowledge in the performance of these systems. Formulation issues that have slowed the translation of some promising drug formulations from the research laboratory to the clinic will also be detailed.Peer reviewe

The Swallowing Characteristics of Thickeners, Jellies and Yoghurt Observed Using an In Vitro Model

© The Author(s) 2019 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Drinks and foods may be thickened to improve swallowing safety for dysphagia patients, but the resultant consistencies are not always palatable. Characterising alternative appetising foods is an important task. The study aims to characterise the in vitro swallowing behaviour of specifically formulated thickened dysphagia fluids containing xanthan gum and/or starch with standard jellies and yoghurt using a validated mechanical model, the “Cambridge Throat”. Observing from the side, the model throat can follow an experimental oral transit time (in vitro-OTT) and a bolus length (BL) at the juncture of the pharynx and larynx, to assess the velocity and cohesion of bolus flow. Our results showed that higher thickener concentration produced longer in vitro-OTT and shorter BL. At high concentration (spoon-thick), fluids thickened with starch-based thickener showed significantly longer in vitro-OTT than when xanthan gum-based thickener was used (84.5 s ± 34.5 s and 5.5 s ± 1.6 s, respectively, p < 0.05). In contrast, at low concentration (nectar-like), fluids containing xanthan gum-based thickener demonstrated shorter BL than those of starch-based thickener (6.4 mm ± 0.5 mm and 8.2 mm ± 0.8 mm, respectively, p < 0.05). The jellies and yoghurt had comparable in vitro-OTT and BL to thickeners at high concentrations (honey-like and spoon-thick), indicating similar swallowing characteristics. The in vitro results showed correlation with published in vivo data though the limitations of applying the in vitro swallowing test for dysphagia studies were noted. These findings contribute useful information for designing new thickening agents and selecting alternative and palatable safe-to-swallow foods.Peer reviewe

Mucoadhesion and mucosa-mimetic materials - a mini-review

Mucoadhesion describes an attractive interaction between dosage form and mucosal membrane. The evaluation of mucoadhesive excipients often requires the use of ex vivo mucosal tissues taken from laboratory animals. These can be difficult to source, highly heterogeneous, and require the use of animal products. Thus, from both a user-convenience and ethical point-of-view, it is desirable to produce a synthetic alternative to these tissues - a mucosa-mimetic material. In this mini-review, the use of alternative materials to test the performance of mucoadhesives is reviewed and discussed. There is a surprising prevalence of the use of mucosa-mimics in the literature, which hitherto has not been compiled and compared.Peer reviewe

Optimising poly(lactic-co-glycolic acid) microparticle fabrication using a Taguchi orthogonal array design-of-experiment approach

© 2019 Mensah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The objective of this study was to identify, understand and generate a Taguchi orthogonal array model for the formation of 10–50 μm microparticles with applications in topical/ocular controlled drug delivery. Poly(lactic-co-glycolic acid) (PLGA) microparticles were fabricated by the single emulsion oil-in-water method and the particle size was characterized using laser diffraction and scanning electronic microscopy (SEM). Sequential Taguchi L 12 and L 18 orthogonal array (OA) designs were employed to study the influence of ten and eight parameters, respectively, on microparticle size (response). The first optimization step using the L 12 design showed that all parameters significantly influenced the particle size of the prepared PLGA microparticles with exception of the concentration of poly(vinyl alcohol) (PVA) in the hardening bath. The smallest mean particle size obtained from the L 12 design was 54.39 μm. A subsequent L 18 design showed that the molecular weight of PLGA does not significantly affect the particle size. An experimental run comprising of defined parameters including molecular weight of PLGA (89 kDa), concentration of PLGA (20% w/v), concentration of PVA in the emulsion (0.8% w/v), solvent type (ethyl acetate), organic/aqeuous phase ratio (1:1 v/v), vortexing speed (9), vortexing duration (60 seconds), concentration of PVA in hardening bath (0.8% w/v), stirring speed of hardening bath (1200 rpm) and solvent evaporation duration (24 hours) resulted in the lowest mean particle size of 23.51 μm which was predicted and confirmed by the L 18 array. A comparable size was demonstrated during the fabrication of BSA-incorporated microparticles. Taguchi OA design proved to be a valuable tool in determining the combination of process parameters that can provide the optimal condition for microparticle formulation. Taguchi OA design can be used to correctly predict the size of microparticles fabricated by the single emulsion process and can therefore, ultimately, save time and costs during the manufacturing process of drug delivery formulations by minimising experimental runs.Peer reviewedFinal Published versio

Exotic Meson Decay Widths using Lattice QCD

A decay width calculation for a hybrid exotic meson h, with JPC=1-+, is presented for the channel h->pi+a1. This quenched lattice QCD simulation employs Luescher's finite box method. Operators coupling to the h and pi+a1 states are used at various levels of smearing and fuzzing, and at four quark masses. Eigenvalues of the corresponding correlation matrices yield energy spectra that determine scattering phase shifts for a discrete set of relative pi+a1 momenta. Although the phase shift data is sparse, fits to a Breit-Wigner model are attempted, resulting in a decay width of about 60 MeV when averaged over two lattice sizes.Comment: 9 pages, 8 figures, RevTex4, minor change to Fig.

Polymers exhibiting lower critical solution temperatures as a route to thermoreversible gelators for healthcare

Funding Information: M.T.C. acknowledges support from the EPSRC (EP/T00813X/1). The University of Hertfordshire are thanked for funding the research project of P.H. Publisher Copyright: © 2020 The Authors. Advanced Functional Materials published by Wiley-VCH GmbHThe ability to trigger changes to material properties with external stimuli, so-called “smart” behavior, has enabled novel technologies for a wide range of healthcare applications. Response to small changes in temperature is particularly attractive, where material transformations may be triggered by contact with the human body. Thermoreversible gelators are materials where warming triggers reversible phase change from low viscosity polymer solution to a gel state. These systems can be generated by the exploitation of macromolecules with lower critical solution temperatures included in their architectures. The resultant materials are attractive for topical and mucosal drug delivery, as well as for injectables. In addition, the materials are attractive for tissue engineering and 3D printing. The fundamental science underpinning these systems is described, along with progress in each class of material and their applications. Significant opportunities exist in the fundamental understanding of how polymer chemistry and nanoscience describe the performance of these systems and guide the rational design of novel systems. Furthermore, barriers to translating technologies must be addressed, for example, rigorous toxicological evaluation is rarely conducted. As such, applications remain tied to narrow fields, and advancements will be made where the existing knowledge in these areas may be applied to novel problems of science.Peer reviewe

Poly(N-isopropyl acrylamide) – poly(ethylene glycol) – poly(N-isopropyl acrylamide) as a thermoreversible gelator for topical administration

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported licence: https://creativecommons.org/licenses/by-nc/3.0/.Poly(N-isopropyl acrylamide) – block– poly(ethylene glycol) – block– poly(N-isopropyl acrylamide) is known to exhibit a thermally-induced solution-to-gel transition in water, which may be exploited for biomedical applications. This “thermoreversible gelator” has great potential for application in topical drug delivery to the surfaces of the body such as the skin, eye, and vagina, but this has not yet been evaluated. This study evaluates PNIPAM98-PEG122-PNIPAM98 as a thermoreversible gelator for vaginal drug delivery, for the first time evaluating the effect of polymer concentration on gelation, studying rheological parameters relevant to topicals, measuring dissolution rates, stability and the phenomemon of mucoadhesion. Two drugs relevant to vaginal administration, progesterone and tenofovir disoproxil fumarate are investigated for use in the thermoreversible gelators, studying both hydrophobic and hydrophilic drug solubilisation and release. Throughout the study, comparison is made with poloxamer 407, the most commonly studied thermoreversible gelator. PNIPAM98-PEG122-PNIPAM98 exhibits several advantages for topical drug delivery, having low viscosity at room temperature to allow easy application, then exhibiting a gelation just below body temperature to form a viscous gel which is resistant to dissolution and relatively mucoadhesive. Drug release is highly dependent on temperature, with elevation to body temperature resulting in a dramatic retardation of progesterone release, which may be used in future medicines to provide sustained delivery of hydrophobic xenobiotics.Peer reviewedFinal Accepted Versio

Measurement of Plasmodium falciparum transmission intensity using serological cohort data from Indonesian schoolchildren.

BACKGROUND: As malaria transmission intensity approaches zero, measuring it becomes progressively more difficult and inefficient because parasite-positive individuals are hard to detect. This situation may arise shortly before achieving local elimination, or during surveillance post-elimination to prevent reintroduction. Antibody responses against the parasite last longer than the infections themselves. This "footprint" of infection may thus be used for assessing transmission intensity. A statistical approach is presented for measuring the seroconversion rate (SCR), a correlate of the force of infection, from individual-level longitudinal data on antibody titres in an area of low Plasmodium falciparum transmission. METHODS: Blood samples were collected from 160 Indonesian schoolchildren every month for six months. Titres of antibodies against AMA-1 and MSP-1(19) antigens of P. falciparum were measured using ELISA. The distribution of antibody titres among seronegative and -positive individuals, respectively, was estimated by comparing the titres from the study data (a mixture of both seropositive and -negative individuals) with titres from a (unexposed) negative control group of Indonesian individuals. Two Markov-Chain models for the transition of individuals between serological states were fitted to individual anti-PfAMA-1 or anti-PfMSP-1 titre time series using Bayesian Markov-Chain-Monte-Carlo (MCMC). This yielded estimates of SCR as well as of the duration of seropositivity. RESULTS: A posterior median SCR of 0.02 (Pf AMA-1) and 0.09 (PfMSP-1) person(-1) year(-1) was estimated, with credible intervals ranging from 1E-4 to 0.2 person(-1) year(-1). This level of transmission intensity is at the lower range of what can reliably be measured with the present study size. A Bayesian test for seroconversion of an individual between two observations is presented and used to identify the subjects who have most likely experienced an infection. Furthermore, the theoretical limits of measuring transmission intensity, and how these depend on duration and size of a study as well as on transmission intensity itself, is illustrated. CONCLUSIONS: This analysis shows that it is possible to measure SCR's from individual-level longitudinal data on antibody titres. In addition, individual seroconversion events can be identified, which can be useful in assessing interruption of transmission. Analyses of further serological datasets using the present method are required to improve and validate it. This includes measurement of the duration of antibody responses, how it depends on host age or cumulative exposure, or on the particular antigen used