The University of Queensland Alambra Archaeological Mission (UQAAM) conducted a program of geophysical survey and archaeological excavation over four seasons from 2012 to 2016. This program has allowed this study to compile a large array of geophysical data, which has been tested against actual excavation results. By integrating the two forms of archaeological investigation, the UQAAM has been able to identify geophysical 'signatures' diagnostic and indicative of internal architectural features relating to the Cypriot Prehistoric Bronze Age (c2400-1750BC). This is the first time internal features have been identified using these techniques on a Middle Bronze Age site in Cyprus. The program has also identified two, and possibly four, areas of domestic settlement. This has yielded results that are of considerable value to cultural heritage managers of the site, which is experiencing development pressures. While identifying several constraints with the geophysical survey for the Prehistoric Bronze Age in Cyprus, the program has demonstrated the efficacy of a combined geophysical survey and excavation approach to sites of the Early-Middle Bronze Age period.

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The "width" of the mind is an important topic in contemporary philosophical psychology. Support for active externalism derives from theoretical, engineering, and observational perspectives. Given the history of psychology, psychopathology is notable in its absence from the list of avenues of support for the idea that some cognitive processes extend beyond the physical bounds of the organism in question. The current project is to defend the possibility, plausibility, and desirability of externalist psychopathology. Doing so both adds to the case for externalism and suggests ways of improving our study of cognitive dysfunction. I establish the possibility of externalist psychopathology through the development of models of wide cognitive processing, and, by implication, failure of such processing, from the work of S.L. Hurley and Robert Wilson. The plausibility of wide conceptualization and explanation of cognitive disorders is shown through an examination of apraxia, disorders of learned, skilled movements. The desirability of externalist psychopathology is suggested through a look at theoretical and therapeutic virtues, again drawing on Wilson's work.

P.F. Strawson's work on moral responsibility is well-known. However, an important implication of the landmark "Freedom and Resentment" has gone unnoticed. Specifically, a natural development of Strawson's position is that we should understand being morally responsible as having externalistically construed pragmatic criteria, not individualistically construed psychological ones. This runs counter to the contemporary ways of studying moral responsibility. I show the deficiencies of such contemporary work in relation to Strawson by critically examining the positions of John Martin Fischer and Mark Ravizza, R. Jay Wallace, and Philip Pettit for problems due to individualistic assumptions.What I call the individualist assumption in the philosophy of psychology is the assumption that whatever we find it significant to name -whatever patterns of feeling and behavior we find salient enough to use in explanations of ourselves and othersmust also pick out complex events, states, or processes with respect to some theory of the functioning of individual organisms (for example, neurophysiology) (Scheman, 1996).

CYP3A4 and CYP4A5 share specificity for a wide range of xenobiotics with the CYP3 subfamily collectively involved in the biotransformation of approximately 30% of all drugs. CYP3A4/5 mRNA transcripts have been reported in the skin, yet knowledge of their protein expression and function is lacking. In this study, we observed gene and protein expression of CYP3A4/5 in both human skin and tissue-engineered skin equivalents (TESEs), and enzyme activity was detected using the model substrate benzyl-Omethyl-cyanocoumarin. Mass spectrometric analysis of TESE lysates following testosterone application revealed a time-dependent increase in metabolite production, confirming the functional expression of these enzymes in skin. K E Y W O R D Sepithelium, steroids, three-dimensional tissue models, toxicity, xenobiotic metabolism | BACKGROUNDCytochrome P450 (CYP450) enzymes are a superfamily of haemoproteins that metabolize a multitude of endogenous and xenobiotic molecules and are essential to maintain homoeostasis. [1,2] As the most highly expressed xenobiotic enzymes in the liver, they are responsible for the majority of phase I reactions, metabolizing between 70%and 80% of all drugs. [3,4] The CYP3 subfamily of the CYP450 enzymes, comprising of CYP3A4, CYP3A5, CYP3A7 and CYP3A43, are collectively involved in the metabolism of over a third of these drugs.[4]CYP3A4, the most abundantly expressed isoform in the liver, [5] has a large active site that enables its interaction with a wide range of structurally diverse compounds and permits metabolism of such molecules and drugs as hormones (testosterone, oestrogen), anticancer drugs (paclitaxel, tamoxifen) and antifungal agents (ketoconazole) amongst others. [4,6] CYP3A5 shares 85% amino acid sequence homology with CYP3A4 and displays similar substrate specificity. [7] Gene expression of CYP3A4 and CYP3A5 has been detected in skin and tissue-engineered skin equivalents (TESEs) by genomic analysis in some studies [8,9,S1,S2] but not others, [S3] and to date, protein expression has not been detected. [S4,S5] Given the use of skin as a drug delivery route, it is extremely important to determine functional expression of CYP3A4/5. Moreover, the increasing use of TESE as an alternative to animal testing for drug irritation and sensitivity assays has led to their proposed use in drug-induced toxicity assays. However, data on functional xenobiotic enzyme activity in these models are lacking and urgently required. | QUESTIONS ADDRESSEDThe relative gene and protein expression of CYP3A4 and CYP3A5 in human skin in comparison with liver remains unclear. It is also unknown whether the expression is localized to the dermis or epidermisThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.