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By the early nineteenth century, the 'madwoman' had become a prominent cultural figure, featuring in fine art, literature, and stage works, and became a particular fascination for Italian operatic composers, librettists and audiences alike. Sir Walter Scott's The Bride of Lammermoor (1819), and its successive Italian operatic adaptations (1829-1835), thus fanned the flames of this obsession. While interest in the archetypal madwoman continued to grow culturally, so too did proliferation of, and the reading publics' interest in descriptions and images of madness in medical literature and its popular dissemination. This interdisciplinary thesis compares the cultural and operatic representation of female madness to pertinent, popular nineteenth-century medical literature. It will comparatively analyse the representation of female madness in historical descriptions (mostly of hysteria, insanity and monomania) with Sir Walter Scott's novel The Bride of Lammermoor (1819) and its Italian operatic adaptations: Le nozze di Lammermoor (Paris, 1829) by composer Michele Carafa and librettist Giuseppe Luigi Balocchi; La fidanzata di Lammermoor (Trieste, 1831) by Luigi Rieschi and Calisto Bassi; La fidanzata di Lammermoor (Padua, 1834) by Alberto Mazzucato and Pietro Beltrame, and Lucia di Lammermoor (Naples, 1835) by Gaetano Donizetti and Salvadore Cammarano. Most previous studies on nineteenth-century Italian opera, and Lucia di Lammermoor specifically, have focussed on the musical representation of madness, and do not consider medical literature of the period. This project thus aims to remedy this position by combining the study of literature, theatre and opera, of detailed libretto and score study, with the analysis of medical texts and photographic iconographies on madness. In doing so, it aims to determine to what extent Italian operatic mad scenes - in embodying social and cultural ideas on madness - reflected and propagated popular medical ideas in the nineteenth century; and how far the visual representation of madness within opera and popular culture reciprocally influenced that in popular medical literature and photography. In short, I aim to use these cultural products and medical literature to sensitively elucidate the popular notions surrounding female madness in the early modern period and nineteenth century.

Whilst traditional definitions of savant syndrome assumed an association between intellectual impairment and talent in atypical populations, reports of outstanding talents in intellectually high functioning individuals with Autism Spectrum Disorders (ASD) highlighted limitations in these early definitions and led to a reconsideration of the syndrome. This redefinition raised interesting questions about how talented high functioning individuals with ASD might differ from those with the same diagnosis but without outstanding talents. Motivated by early and more recent theoretical models of savant syndrome, the studies described in this thesis investigated the clinical and cognitive correlates of savant syndrome in a comparison of age and intelligence matched children with ASD who did or did not possess outstanding skills. In the clinical assessment phase of testing, participants with outstanding skills, validated across a number of domains, together with groups of ASD and typically developing (TD) control participants completed tests of symptom severity, sensory abnormality and obsessionality. The results from these assessments failed to reveal a significant difference on measures of symptom severity between the ASD groups, although the savants appeared to be less impaired in the domain of creativity. There was also a trend for savants to be less impaired in sensory domains, and this was particularly marked in visual and auditory filtering which may be important for savant skills. The two ASD groups did not differ on the numbers of obsessions reported, although savant obsessions tended to be more focussed on functional domains (e.g. crafts and numbers) than the obsessions reported for non-savants. Both ASD groups showed marked obsessional tendencies in comparison to TD controls. The cognitive test battery probed concentration, intelligence, cognitive style and pattern perception in the two groups. This revealed superior concentration, pattern perception and performance on several measures of intelligence and local processing in the savant group. However, a logistic regression analysis carried out on the tests that distinguished savants and non-savants in the group comparison studies, showed that measures of concentration and working memory were most powerful in predicting savant status. It was therefore concluded that whilst new theoretical accounts of savant syndrome, highlighting superior pattern processing abilities, provide an advance on earlier theories, they underestimate the importance of working memory and therefore merit further revision.

Chronic ulcers are a major healthcare problem characterised by ineffectual healing and infection. Xanthine oxidoreductase (XOR, EC 1.1.3.22), incorporated into a dressing or graft may provide enhanced healing and antibacterial activity. XOR is a complex molybdoflavoprotein with broad substrate specificity, and in aerobic conditions, generates superoxide (0₂̇⁻) and hydrogen peroxide (H₂O₂) through purine catabolism. Low levels of these species from XOR are known to enhance the proliferation of many mammalian cells including human dermal fibroblasts, essential for the healing process (Murrell et al, 1990). XOR also generates nitric oxide (̇NO) from physiological levels of nitrite, optimally at low pH in anoxic conditions (cf the conditions prevailing in a chronic ulcer). Nitric oxide contributes to healing in general by increasing perfusion, stimulating angiogenesis and killing bacteria. Chronic wounds are known to harbour a range of anaerobic and facultative bacteria, many of which are detrimental to wound healing. It has been shown that the simultaneous generation of 0₂̇⁻ and ̇NO by XOR in low oxygen, results in the rapid production of peroxynitrite (ONOO⁻), a very much more potent bactericidal species than 0₂̇⁻, ̇NO or H₂O₂. Experiments were performed to characterise the effects of XOR activities on factors pertinent to healing to test the hypothesis that XOR incorporated into a dressing or dermograft will facilitate ulcer healing. Superoxide generation by xanthine oxidase (XO) was characterised, and shown to vary in biological media commonly used for the growth of either fibroblasts or bacteria in the laboratory setting. In support of existing research, superoxide generation by XO in low oxygen (1%) was reduced when compared with air. Nevertheless, peroxynitrite generation was also observed in low oxygen (1%). This thesis supports previous research showing that XO enhances the proliferation of adult human dermal fibroblasts (HDF) using standard culture conditions in air. In the presence of 21% oxygen (air), high levels of XO (10-50mU ml⁻¹) were shown to be cytotoxic to adult fibroblasts whereas lower levels appeared to increase DNA synthesis suggesting enhanced proliferation (lmUml⁻¹). This thesis also extends these findings showing a similar effect on neonatal HDF. The novel findings in this thesis are that at low oxygen tension (p0₂ below 5%) the growth of adult HDF is not adversely affected in the presence of high XO concentrations (5-50mU ml⁻¹ XO); in fact, HDF appear to show some evidence of enhanced proliferation under these conditions. Bacterial strains relevant to the chronic wound responded differentially to XO but showed growth inhibition at 10 and 50mU ml⁻¹ XO. Overall, these findings suggest that an XO-incorporating graft or dressing may deliver both proliferative and antimicrobial effects in a hypoxic ulcer setting.