Design, synthesis and in vitro degradation of a novel co-drug for the treatment of psoriasis

Psoriasis is a common, chronic and relapsing inflammatory skin disease. It affects approximately 2% of the western population and has no cure. Combination therapy for psoriasis often proves more efficacious and better tolerated than monotherapy with a single drug. Combination therapy could be administered in the form of a co-drug, where two or more therapeutic compounds active against the same condition are linked by a cleavable covalent bond. Similar to the pro-drug approach, the liberation of parent moieties post-administration, by enzymatic and/or chemical mechanisms, is a pre-requisite for effective treatment. In this study, a series of co-drugs incorporating dithranol in combination with one of several non-steroidal anti-inflammatory drugs, both useful for the treatment of psoriasis, were designed, synthesized and evaluated. An ester co-drug comprising dithranol and naproxen in a 1:1 stoichiometric ratio was determined to possess the optimal physicochemical properties for topical delivery. The co-drug was fully hydrolyzed in vitro by porcine liver esterase within four hours. When incubated with homogenized porcine skin, 9.5% of the parent compounds were liberated after 24 h, suggesting in situ esterase-mediated cleavage of the co-drug would occur within the skin. The kinetics of the reaction revealed first order kinetics, Vmax = 10.3 μM/min and Km = 65.1 μM. The co-drug contains a modified dithranol chromophore that was just 37% of the absorbance of dithranol at 375 nm and suggests reduced skin/clothes staining. Overall, these findings suggest that the dithranol-naproxen co-drug offers an attractive, novel approach for the treatment of psoriasis.

Handbook of research methods and applications in empirical finance

The objective of this book is to present the quantitative techniques that are commonly employed in empirical finance research together with real world, state of the art research examples. Each chapter is written by international experts in their fields. The unique approach is to describe a question or issue in finance and then to demonstrate the methodologies that may be used to solve it. All of the techniques described are used to address real problems rather than being presented for their own sake and the areas of application have been carefully selected so that a broad range of methodological approaches can be covered. This book is aimed primarily at doctoral researchers and academics who are engaged in conducting original empirical research in finance. In addition, the book will be useful to researchers in the financial markets and also advanced Masters-level students who are writing dissertations.

Evaluating relative impact of virtual reality system variables on architectural design comprehension and presence - A variable-centered approach using fractional factorial experiment

The relative contributions of five variables (Stereoscopy, screen size, field of view, level of realism and level of detail) of virtual reality systems on spatial comprehension and presence are evaluated here. Using a variable-centered approach instead of an object-centric view as its theoretical basis, the contributions of these five variables and their two-way interactions are estimated through a 25-1 fractional factorial experiment (screening design) of resolution V with 84 subjects. The experiment design, procedure, measures used, creation of scales and indices, results of statistical analysis, their meaning and agenda for future research are elaborated.

Acoustic scattering : high frequency boundary element methods and unified transform methods

We describe some recent advances in the numerical solution of acoustic scattering problems. A major focus of the paper is the efficient solution of high frequency scattering problems via hybrid numerical-asymptotic boundary element methods. We also make connections to the unified transform method due to A. S. Fokas and co-authors, analysing particular instances of this method, proposed by J. A. De-Santo and co-authors, for problems of acoustic scattering by diffraction gratings.

Sensory and consumer science methods used with older adults: a review of current methods and recommendations for the future

Capturing the sensory perception and preferences of older adults, whether healthy or with particular disease states, poses major methodological challenges for the sensory community. Currently a vastly under researched area, it is at the same time a vital area of research as alterations in sensory perception can affect daily dietary food choices, intake, health and wellbeing. Tailored sensory methods are needed that take into account the challenges of working with such populations including poor access leading to low patient numbers (study power), cognitive abilities, use of medications, clinical treatments and context (hospitals and care homes). The objective of this paper was to review current analytical and affective sensory methodologies used with different cohorts of healthy and frail older adults, with focus on food preference and liking. We particularly drew attention to studies concerning general ageing as well as to those considering age-related diseases that have an emphasis on malnutrition and weight loss. Pubmed and Web of Science databases were searched to 2014 for relevant articles in English. From this search 75 papers concerning sensory acuity, 41 regarding perceived intensity and 73 relating to hedonic measures were reviewed. Simpler testing methods, such as directional forced choice tests and paired preference tests need to be further explored to determine whether they lead to more reliable results and better inter-cohort comparisons. Finally, sensory quality and related quality of life for older adults suffering from dementia must be included and not ignored in our future actions.

Mediated action and sexual risk: Searching for 'culture' in discourses of homosexuality and AIDS prevention in China

This paper examines the concept of ‘culture’ and its relationship to HIV prevention. Culture is here seen as the interaction between human beings and the various ‘cultural tools’ they appropriate when taking action. Among these tools are ways of speaking which encode certain meanings, ideologies and social practices. When individuals take action with regard to AIDS, what they do is mediated through voices which they borrow strategically from their environ- ment. The textual tools that are available and the ways individuals adapt and combine them work to either limit or amplify their participation in HIV prevention. What are traditionally seen as ‘cultures’ or ‘sub-cultures’, or worse, ‘risk groups’, are, in this perspective, viewed as ‘communities of practice’, groups of individuals who share particular cultural tools and ways of using them. This conceptual framework is applied to recent discourses of homosexuality and AIDS prevention in China. An instance of ‘of� cial’ discourse in the form of an AIDS education pamphlet for ‘gays’ is analysed for the voices it contains and how these voices are strategically marshalled by the authors and mixed with other voices in ways which amplify participation in AIDS prevention for some and limit it for others. This ‘offical’ discourse is then compared to the discourse of homosexually active Chinese men recently interviewed in Beijing and Fuzhou to examine which of these of� cial voices and other voices they appropriate, and how they adapt these voices in responding to HIV.

Design, implementation and interpretation of in vitro batchculture experiments to assess enteric methane mitigation in ruminants—a review

In vitro fermentation techniques (IVFT) have been widely used to evaluate the nutritivevalue of feeds for ruminants and in the last decade to assess the effect of different nutritionalstrategies on methane (CH4) production. However, many technical factors may influencethe results obtained. The present review has been prepared by the ‘Global Network’ FACCE-JPI international research consortium to provide a critical evaluation of the main factorsthat need to be considered when designing, conducting and interpreting IVFT experimentsthat investigate nutritional strategies to mitigate CH4emission from ruminants. Given theincreasing and wide-scale use of IVFT, there is a need to critically review reports in the lit-erature and establish what criteria are essential to the establishment and implementationof in vitro techniques. Key aspects considered include: i) donor animal species and numberof animal used, ii) diet fed to donor animals, iii) collection and processing of rumen fluidas inoculum, iv) choice of substrate and incubation buffer, v) incubation procedures andCH4measurements, vi) headspace gas composition and vii) comparability of in vitro andin vivo measurements. Based on an evaluation of experimental evidence, a set of techni-cal recommendations are presented to harmonize IVFT for feed evaluation, assessment ofrumen function and CH4production.