An investigation into the influence of drug lipophilicity on the in vivo absorption profiles from subcutaneous microspheres and in situ forming depots.

Drug lipophilicity is known to have a major influence on in vivo drug absorption from intramuscularly and subcutaneously administered solutions. Indeed, chemical modification to increase drug lipophilicity is used to enable sustained drug release from solutions. In contrast to the wealth of knowledge on drug release from simple solutions, the influence of drug lipophilicity on its release from controlled release formulations, such as, microparticles and in situ forming depots, have not been systematically studied. Controlled release vehicles are designed to 'control' drug release, hence, in vitro studies show negligible influence of drug lipophilicity on release. The situation could however be different in vivo, due to interactions between the vehicle and biological tissue. We therefore investigated the influence of drug lipophilicity on its in vivo release in rats from two controlled release formulations, PLGA microparticles and in situ forming depots. Both systems exhibited a burst drug release. Subsequent to the burst release, we found that lipophilicity did not influence the rate or extent of drug absorption from the two formulations over a 10-day study period, which would imply that drug partitioning out of the depots was not the main mechanism of drug release from both formulations. This study must however be repeated with a greater number of animals to increase its power

Historic Farmsteads: Preliminary Character Statement - North East region

This document is one of eight Preliminary Character\ud Statements, which provide information on the\ud characteristics of traditional farm buildings in each\ud Region

An axisymmetric evolution code for the Einstein equations on hyperboloidal slices

We present the first stable dynamical numerical evolutions of the Einstein equations in terms of a conformally rescaled metric on hyperboloidal hypersurfaces extending to future null infinity. Axisymmetry is imposed in order to reduce the computational cost. The formulation is based on an earlier axisymmetric evolution scheme, adapted to time slices of constant mean curvature. Ideas from a previous study by Moncrief and the author are applied in order to regularize the formally singular evolution equations at future null infinity. Long-term stable and convergent evolutions of Schwarzschild spacetime are obtained, including a gravitational perturbation. The Bondi news function is evaluated at future null infinity.Comment: 21 pages, 4 figures. Minor additions, updated to agree with journal versio

Notes on the integration of numerical relativity waveforms

A primary goal of numerical relativity is to provide estimates of the wave strain, $h$, from strong gravitational wave sources, to be used in detector templates. The simulations, however, typically measure waves in terms of the Weyl curvature component, $\psi_4$. Assuming Bondi gauge, transforming to the strain $h$ reduces to integration of $\psi_4$ twice in time. Integrations performed in either the time or frequency domain, however, lead to secular non-linear drifts in the resulting strain $h$. These non-linear drifts are not explained by the two unknown integration constants which can at most result in linear drifts. We identify a number of fundamental difficulties which can arise from integrating finite length, discretely sampled and noisy data streams. These issues are an artifact of post-processing data. They are independent of the characteristics of the original simulation, such as gauge or numerical method used. We suggest, however, a simple procedure for integrating numerical waveforms in the frequency domain, which is effective at strongly reducing spurious secular non-linear drifts in the resulting strain.Comment: 23 pages, 10 figures, matches final published versio

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

A continuous process strategy has been developed for the preparation of α-thio-β chloroacrylamides, a class of highly versatile synthetic intermediates. Flow platforms to generate the α-chloroamide and α-thioamide precursors were successfully adopted, progressing from the previously employed batch chemistry, and in both instances afford a readily scalable methodology. The implementation of the key α-thio-β-chloroacrylamide casade as a continuous flow reaction on a multi-gram scale is described, while the tuneable nature of the cascade, facilitated by continuous processing, is highlighted by selective generation of established intermediates and byproducts

Can Systemic Interventions Designed to Reduce Reoffending by Youth also Reduce their Victimization?

Previous research indicates considerable overlap between populations of boys who are victimized and boys who victimize others. This study was concerned with whether a systems-focused treatment program designed to address individual and systemic risk factors associated with the perpetration of sexual and violent crimes might also be successful in reducing boys’ victimization by others. Boys adjudicated for sexual offences who received ‘treatment as usual’ (TAU; n = 335) were compared with similarly adjudicated boys who completed the treatment program (n = 200) on their histories of contact with police either as offenders or victims. Despite their higher rates of pre-intervention victimization, the treatment group were victimized less frequently post-intervention than the TAU group. Continued offending was the strongest predictor of victimization post-intervention. These findings suggest that offending and victimization share common risk factors that may be addressed simultaneously within offence-focused treatment

Insecticidal and Repellent Properties of Subtropical Plant Extracts Against Pulse Beetle, Callosobruchus chinensis

Extracts of eight plants local to Oman, namely Qarat (Acacia nilotica), Mustafal (Annona squamosa), Shereesh (Azadirachta indica), Luban (Boswellia sacra), Kheshkhash (Crotolaria juncea), Zebrot (Jatropha dhofarica) Yas, (Myrtus communis) and Suwwad (Suaeda aegyptiaca) were prepared by steeping shaded dried leaf/ seed powder of each plant in water and solvent (methanol or ethanol). The extracts were tested for their insecticidal and repellent properties against the pulse beetles, Callosobruchus chinensis. The extracts from the seeds of A. squamosa recorded l00% mortality of beetles within twenty and four hours of their exposure to methanol and ethanol extracts, respectively. The other extracts that caused high mortality were from A. nilotica, C. juncea, M. communis and S. aegzptiaca in methanol and B. sacra, J. dhofarica, S. aegptiaca and commercial neem in ethanol. Extracts of M. communis in methanol were highly repellent to the beetles compared to other extracts. Legume seeds treated with extracts of A. squamosa were not repellent, rather the beetles were attracted to them

Exploring the Choice of Decision Making Method in an Agent Based Model of Land Use Change

In agent-based models of land use/cover change (ABM/LUCC), small changes in micro-level decision-making methods used by agents may significantly affect macro-level outcomes. Yet, the implications of choosing a specific decision making model are seldom explored in ABM/LUCC studies. This paper discusses an ABM/LUCC modelling study of smallholder farming households in the Amazonian varzea in Maraj´o Island, Brazil. These agents represent the 21 households within the community of Paricatuba. Farmers in this community cultivate acai as a primary source of income, in addition to other farming and economic activities such as offsite employment. In the model, agents make annual decisions to allocate scarce land, capital and labour resources to best provide revenue for the household. Household agents have the same overall goals, resources, information, and feasible actions available to them within the simulation environment. Alternative simulations are developed in which the household agents employ one of two primary decision-making methods, either based on linear programming or decision trees. A comparison of these methods in a Monte Carlo simulation indicates that in certain scenarios, alternative decision-making methods with otherwise common objectives and environments may lead to widely divergent outcomes. The evaluation of multiple decision making methods within a common model can be used to highlight the advantages and limitations of these methods and challenge assumptions

Illustrating a new 'conceptual design pattern' for agent-based models of land use via five case studies—the MR POTATOHEAD framework

This chapter presents a "conceptual design pattern" (CDP) that represents key elements of standard ABM/LUCC models in a comprehensive logical framework and includes basic functionality and data often present in ABM/LUCC models. The CDP illustrates the key building blocks for ABM/LUCC models, creating a template to assist scholars new to the field to understand existing models and design their own models. Second, the framework facilitates direct comparison of the structure and function of existing models. We present five separately developed models within this framework (SLUDGE, SOME, FEARLUS, LUCITA, and SYPRIA), demonstrating how multiple models can be represented and compared within the same meta-structure. The exercise highlights elements common to all models, demonstrates the unique contributions of each model, reveals commonalities between models, and highlights processes associated with land-use change that are not covered by our models. The CDP as presented here is very much a work in progress, and we welcome feedback from other ABM/LUCC developers, in the hopes of ultimately developing a shared model representation that will accelerate the development of not only ABM/LUCC, but also the theory of land-use change

Taming tosyl azide: the development of a scalable continuous diazo transfer process

Heat and shock sensitive tosyl azide was generated and used on demand in a telescoped diazo transfer process. Small quantities of tosyl azide were accessed in a 'one pot' batch procedure using shelf stable, readily available reagents. For large scale diazo transfer reactions tosyl azide was generated and used in a telescoped flow process, to mitigate the risks associated with handling potentially explosive reagents on scale. The in situ formed tosyl azide was used to rapidly perform diazo transfer to a range of acceptors, including beta-ketoesters, beta-ketoamides, malonate esters and beta-ketosulfones. An effective in-line quench of sulfonyl azides was also developed, whereby a sacrificial acceptor molecule ensured complete consumption of any residual hazardous diazo transfer reagent. The telescoped diazo transfer process with in-line quenching was used to safely prepare over 21 g of an alpha-diazocarbonyl in > 98% purity without any column chromatography