This dissertation is an investigation into the representation of the sexed and gendered body on the English stage between the years 1570 and 1635. The parameters of the study are fully set out in the introduction, however, a summary that might prove useful to the general reader is as follows: The thesis commences with an account of the 'one-sex' anatomical model - as recently set out by Thomas Laqueur in Making Sex: Body and Gender from the Greeks to Freud (Cambridge. Mass.: Harvard University Press, 1990). It then proceeds to question the dominance of such an anatomical paradigm throughout the entire Renaissance - and, in its first chapter, sets out evidence from various medical treatises in order to outline the emergence of a contrasting 'two-sex' model of human reproductive biology. Chapter two then uses evidence from a 'two-sex' model in order to re-examine the homo-erotic implications of theatrical narratives that present (or imply) spontaneous sex changes (by means of an analysis of John Lyly's Gallathea and Shakespeare's Falstaff plays). In chapter three, attention turns to the female body in early modern English society and attempts to assess the implications of an emergent 'two-sex' model on female cultural and social agency in the period (by means of an analysis of actual female-to-male cross-dressers and the anatomical representations of the female body that were undertaken in elite cultural forms such as the Court Masque). Chapter four then turns back to the professional English transvestite stage in order to examine the strategies of recuperation of the female body that were employed in a production environment that was exclusively controlled by men (and this is undertaken by means of an analysis of Middleton and Dekker's The Roaring Girl and Beaumont and Fletcher's The Maid's Tradedy). Chapter five turns its attention to an analysis of theatre and anatomy hall architecture in order to examine the ways in which one exclusive private theatre (Christopher Beeston's Phoenix, in Drury Lane) sought to exploit an architectural accident in order to provide elite audiences with a staged representation of the processes of anatomical dissection. Finally, chapter six examines four plays by John Ford: The Witch of Edmonton, The Broken Heart, Love's Sacrifice and 'Tis Pity She's A Whore in order to examine the anatomical emblazonment of the female body in two specific Private theatres. The dissertation also contains four appendices: I) Selections from the Published Debate Between Jean Riolan and Jacques Duval Concerning the Case of Marie Le Marcis, the Hermaphrodite of Rouen II) The List of Sex Changes from Johann Schenck von Graffenberg's Observationum Medicarum Rarum (Frankfurt, 1600) III) Selections From Thomas Artus' L'Isle des Hermaphrodites IV) Selections From The Boke of Duke Huon ofBurdeux, translated by Sir John Bourchier (Lord Berners] (Wynkyn de Worde, 1534) V) Anthony Wood, Athena Oxonienses. An Exact history of all the Writers and Bishops who have had their Education in the most Ancient and Famous University ofOxford(a Biography of William Petty)

The maintenance of function in an ageing population is essential to ensure current and future health in older people. The ability to walk independently in a range of situations and environments is key to successful ageing. Age-related gait adaptations including spatial-temporal parameters, joint kinematics and kinetics have been identified to be a consequence of the ageing process. For example, reduced walking speed and increased pelvic tilt are suggestive of compensation strategies to minimise falls. The majority of research has compared young adults (20-40 yrs) to older adults (≥ 50 yrs), categorising older adults into a single group regardless of actual age. An alternative approach is to explore the effects of age on gait and functional movement characteristics within an older adult population. One-hundred and fifty-eight community-dwelling older adults, age range 55 to 86 years (65.7 ± 6.8 yrs) were recruited to create a new gait database. Three-dimensional motion analysis captured five walking tasks: normal walking (with and without force plate contact), manual dual task walking and walking with obstacle clearance (stepping onto, off and over an obstacle). Age-related adaptations to walking occurred from age 75 years by adopting a joint kinetic strategy (including reduced hip extension moment) and altering gait (including a reduced walking speed). Increasing the task complexity was associated with altered gait patterns for this older adult group including a reduction in toe-clearance during manual dual task walking (increasing the likelihood of tripping) and increased arm swing during obstacle clearance (potentially increasing stability). This work represents the creation of one of the largest databases of gait in older people including three-dimensional motion analysis for normal walking and three functional walking tasks for healthy high-functioning older adults. It has the potential to be used to identify factors that predispose older adults to falling or with previously unidentified pathological changes.

Nonmetric traits (NMTs) are often used by osteoarchaeologists in the study of human variation. Some NMTs are affected by environmental factors whereas others are genetic in origin. Such genetic variants have long been used to support the hypotheses on the history and divergence of human populations suggesting that some population groups can be genetically distinguished. However, when genetic NMTs occur in higher than expected frequency these can be interpreted as possible indicators of relatedness. This method is applied to a sample of 977 individuals from the Medieval Poulton Chapel, St. Owen’s Church and Norton Priory Collections, U.K. One hundred and twenty-six cranial and postcranial NMTs were examined to determine: 1) the prevalence, 2) whether there are significant differences between the sexes and/or by age category, 3) if there is variation in mechanical and genetic NMT frequency between the three samples and, 4) to explore possible familial relationships through hierarchal cluster analysis and burial spatial distribution. It is thought that family members are often buried near one another, suggesting that individuals sharing similar genetic NMTs would be buried within close proximity to each other. This thesis has revealed the frequency of 126 NMTs for each sample. No significant differences were reported between the sexes at Poulton Chapel whereas significant differences were noted at St. Owen’s Church and Norton Priory, especially for NMTs considered genetic in origin. For all samples, significant differences were found among the age categories. Intra-populational differences were explored between the three samples. The results of these comparisons highlight that 60 NMTs are shared between the Poulton Chapel and Norton Priory Collection, while St. Owen’s Church only shares few traits with both sites. This suggests a probable geographical north-south divide between the three sites. Finally, the hierarchal cluster analysis identified probable familial relationships for the Norton Priory sample. This is supported by the burial spatial distribution and historical documentary evidence. Unfortunately, this analysis was unsuccessful for St. Owen’s Church with limited results for the Poulton Chapel sample. Future research is required to incorporate aDNA analysis to confirm the likelihood of familial links within these sites, supporting the use of certain NMTs is the use of establishing familial relationships.

No description available.

A multiple-degree-of-freedom artificial hand has been developed at the University of Southampton with the aim of including control philosophies to form a highly functional prosthesis hand. Using electromyographic signals is an established technique for the control of a hand. In it simplest form, the signals allow for opening a hand and subsequent closing to grasp an object. This thesis describes the work carried out in the development of an electromyographic control system, with the aim to have a simple and robust method. A model of the control system was developed to differentiate grip postures using two surface electromyographic signals. A new method, moving approximate entropy was employed to investigate whether any significant patterns can be observed in the structure of the electromyographic signals. An investigation, using moving approximate entropy, on twenty healthy participants' wrist muscles (flexor carpi ulnaris and extensor carpi radialis) during wrist exion, wrist extension and cocontraction at different speeds has shown repeatable and distinct patterns at three states of contraction: start, middle and end. An analysis of the results also showed differences at different speeds of contraction. There is a low variation of the approximate entropy values between participants. This result, if used in the control of an artificial hand, would eliminate any training requirement. Other methods, mean absolute value, number of zero crossings, sample entropy, standard deviation, skewness and kurtosis have been determined from the signals. Of these features, mean absolute value and kurtosis were selected for information extraction. These three methods: moving approximate entropy, mean absolute value and kurtosis are used in the feature extraction process of the control system. A fuzzy logic system is used to classify the extracted information in discriminating the final grip posture. The results demonstrate the ability of the system to classify the information related to different grip postures.

The aim of this study was to define new quantitative parameters of dynamic Pelvic Floor Muscle (PFM) function using 2D transperineal (TP) ultrasound imaging combined with image processing methods (IPM). Ultrasound and digital vaginal data were obtained from a volunteer convenience sample of 23 continent and 9 Stress Urinary Incontinent (SUI) women recruited from the San Francisco Bay Area community, California, U.S.A. Two methods of IPM were used; speckle tracking for measuring displacement of the ano-rectal angle (ARA) and symphysis pubis (SP); and segmentation IPM for measuring displacement of the urethra. Good to excellent inter and intra observer reliability was established for processing the ultrasound images on stored audio-visual imaging files (AVI). Intraclass correlation coefficient (ICC) values: 0.61 to 0.99; 95% confidence intervals (CI) 0.08→0.84 to 0.97→0.99; standard error of measurement (SEM) 0.01to 0.25 cm. There was good agreement between measures on Bland and Altman analysis: mean difference 0.06 to -0.21 cm; 95% CI 0.02→0.45cm to -0.01→0.20cm. Validity of the IPM was confirmed with digital palpation, and furthermore indicated good sensitivity and specificity. Technical and methodological limitations of the IPM, and suggestions for future studies were discussed. Several research questions were addressed using TP ultrasound combined with IPM that enabled the dynamic evaluation of pelvic floor (PF) displacement throughout an entire manoeuvre, rather than limiting the quantification from static images at rest to the end of the manoeuvre. In this way, IPM determined unique quantitative data regarding the automatic displacement, velocity and acceleration of the ARA and urethra during a cough, Valsalva, voluntary PFM contraction, The Knack and a Transversus Abdominis contraction. During automatic events that raised intra-abdominal pressure (IAP), normal PFM function produced timely compression of the PF and additional external support to the urethra, reducing the displacement, velocity, and acceleration. In women with SUI, who have weaker urethral attachments, this shortening contraction did not occur; consequently, the urethra of women with SUI moved further and faster for a longer duration. Caution regarding the generalisability of this study is warranted due to the small number of women in the SUI group and the significant difference in parity between groups. However this non-invasive physiological measurement tool demonstrated a new way of assessing the PFM. It is envisaged that this study will provide the foundation for future studies with larger parity matched populations and eventually improve the rehabilitation of women with SUI and other PF disorders.

Within the genus Homo, we observe a decrease in mandibular robusticity and in the size of anterior and postcanine dentition, a trend that is usually referred to as reduction or gracilisation. Factors linked to diet, food processing and encephalization have been suggested to be the main drivers of this trend. Stone tools and fire would have allowed Pleistocene hominins to reduce food toughness, thus relaxing the selective pressures on the masticatory apparatus. In the Holocene, the changes in human lifestyle triggered by agriculture would have determined the reduction in human tooth size. Brain expansion may have acted as a constraint on the development of the lower jaw. In this work, a primate perspective was adopted to clarify the relative influence of adaptive and non-adaptive factors on mandibular and dental reduction in the genus Homo. The effect of diet and structural constraints (allometry and encephalization) on dental and mandibular size and robusticity were analysed. The results show that incisor size and mandibular robusticity correlate significantly with diet proxies in non-human extant catarrhines and with neurocranium shape changes in the neurocranium in Homo sapiens. In non-human African apes, the elongation of the neurocranium influences postcanine tooth size. In Homo, body size plays an important part in tooth size allometry, but not in robusticity. These results suggest that improvements in tool-based food preparation may have been a leading factor in the reduction of incisor size in hominins. Molars and premolars were probably influenced by the expansion of the neurocranium during Pleistocene, and incisor size may be constrained by neurocranium shape changes in H. sapiens. This work confirmed the importance of food processing in the trend of reduction and produced convincing evidence for the significance of structural constraints in the evolution of the hominin anatomy. These findings contribute to explain the complex evolution of the human skull.

This research explored the lived experience of becoming an Applied Sport and Exercise Scientist. To become an accredited independent practitioner within the British Association of Sport and Exercise Science neophyte practitioners are required to undertake supervised experience. A review of contemporary literature revealed a paucity of research exploring the training and development of applied practitioners within sport and exercise science. Consequently, educational learning theory provided a vehicle from which to understand and critique related literature and provide context to analytical interpretations. Van Manen’s (1990) hermeneutic phenomenological approach to human science guided the research process. This provided a middle ground between description and interpretation from which to explore participant experience. Semi-structured interviews were conducted with fifteen supervisees and nine supervisors to elucidate the lived experience of becoming an Applied Sport and Exercise Scientist. Digitally recorded data were transcribed verbatim and analysed via phenomenological thematic analysis. Template analysis was drawn upon to support the analytical process and assist in organisation of themes. To gain an in-depth understanding of participant experience the hermeneutic circle provided a means of remaining cognisant of fore-conceptions, whilst allowing original findings to emerge. A number of themes were identified from which two essential themes were derived from the essential structure of the experience; ‘Being and learning relationships are predicated upon the emotion derived from interpersonal relationships’ and ‘Mutual participation enables movement towards independence’. Establishing trust and an emotional bond provided meaning within the supervisory dyad. Active participation from both supervisee and supervisor enabled reciprocity and supervisee development. This research raises awareness for supervisees, supervisors and supervisory processes regarding the importance of interpersonal relationships within the training and development of applied practitioners. Future research is suggested to focus upon both supervisees’ and supervisors’ longitudinal experiences and their recommendation for the introduction of formal peer mentoring post accreditation.

Rett Syndrome (RTT) is an X-linked genetic disorder and a major cause of intellectual disability in girls. Mutations in the methyl-CpG binding protein 2 (MECP2) gene, are the primary cause of the disorder. Despite the dominant neurological phenotypes that characterise RTT, MECP2 is expressed ubiquitously throughout the body and a number of peripheral phenotypes such as growth retardation (reduced height and weight), skeletal deformities (scoliosis/kyphosis), reduced bone mass and low energy fractures are also common yet under-reported clinical features of the disorder. In order to explore whether MeCP2 protein deficiency results in altered structural and functional properties of bone and to test the potential reversibility of any such defects, I have conducted series of histological, imaging and biomechanical tests of bone using an accurate genetic (functional knockout) mouse model of RTT. Initial experiments using a GFP reporter mouse line demonstrated the presence of MeCP2 in bone cells and the effective silencing on the gene in functional knockout mice. Different aspects of the study were conducted in different types of bone tissues that were especially suited for individual assays. For instance, biomechanical three point bending tests were conducted in long bone (femur) whilst trabecular geometry measures were measured in spinal vertebrae. Both hemizygous Mecp2stop/y male mice in which Mecp2 is silenced in all cells and female Mecp2stop/+ mice in which Mecp2 is silenced in ~50% of cells as a consequence of random X-chromosome inactivation (XCI), revealed, lighter and smaller long bones and significant reductions in cortical bone mechanical properties (~ 39.5% reduction in stiffness, 31% reduction in ultimate load and 37% reduction in Young’s modulus respectively in Mecp2stop/y male mice; %) and material properties (microhardess reduced 12.3% in Mecp2stop/y male mice and 14% inMecp2stop/+ female mice) as compared to age wild type control mice. Micro structural analysis conducted using µCT also revealed a significant reduction in cortical (54% reduction in cortical thickness, 30% in bone volume, 20% in total area, and 38% in marrow area) and trabecular (~30% in trabecular thickness) bone parameters as compared to age matched wild-type controls MeCP2-deficent mice. Histological analysis using Sirius red staining as a marker of collagen revealed a ~25% reduction in collagen content in MeCP2 deficient mice as compared to age matched wild type controls. In experiments designed to establish the potential for reversal of MeCP2-related deficits, unsilencing of Mecp2 in adult mice by tamoxifen-induced and cre-mediated excision of a stop cassette located at the endogenous Mecp2 locus (male; Mecp2stop/y, CreER and female; Mecp2+/stop, CreER), resulted in a restoration of biomechanical properties towards the wild-type levels. Specifically, Male Mecp2stop/y, CreER mice displayed improvement in mechanical properties (stiffness 40%, ultimate load 10%, young’s modulus 61% and micro hardness 12%) and structural bone parameter (trabecular thickness 80%) as compared to Mecp2stop/y male mice. Female Mecp2+/stop, CreER, displayed a significant improvement (19%) in microhardess measures as compared to Mecp2 deficient mice. Overall, the results of my studies show that MeCP2-deficiency results in overt, but potentially reversible, alterations in the biomechanical integrity of bone and highlights the importance of targeting skeletal phenotypes in considering the development of pharmacological and gene-based therapies for Rett Syndrome.

Pulmonary arterial hypertension (PAH) is a progressive and debilitating disease characterised by increases in pulmonary vasoconstriction and excessive remodelling of the pulmonary arteries. Together, these processes lead to sustained elevations in pulmonary arterial pressure, right heart failure and eventual death if left untreated. Despite the number and variety of treatment options available, the survival rate in incident and prevalent cases of PAH remains poor. Therefore, a better understanding of the pathobiology of PAH is required to generate novel therapeutic approaches with improved efficiency in patients. In PAH there is a well described gender bias. Women are consistently reported to represent up to 75% of the total PAH population; however, the reasons for this female predominance remain unclear. Recently, estrogen has been implicated as a major risk factor, for example, elevated estrogen levels and alterations in estrogen metabolism are closely correlated with PAH development in females. The role of testosterone in PAH is currently under investigated. Effects of estrogen are mediated through two classical estrogen receptors (ER)-α and –β, or the novel G-protein-coupled estrogen receptor (GPER). Expression of all of these receptors is identified in pulmonary vasculature, including in smooth muscle and endothelial cells. The role they play in PAH pathogenesis in females is largely undetermined. Given the diverse effects of estrogen described in the pulmonary vasculature during PAH, for example, proliferative effects in pulmonary artery smooth muscle cells (PASMCs), we hypothesised that estrogen receptors play an integral role in PAH in females. To examine this, we used both translational and experimental studies to characterise ERs in PAH. Chronic hypoxic male and female mice, and mice over-expressing the serotonin transporter (SERT+ mice), which demonstrate female susceptibility, were used to investigate the effects of an ERα antagonist in vivo. GPER knockout mice were also investigated in chronic hypoxia. In situ and in vitro studies in human PASMCs with ER agonists and antagonists added clinical relevance to our findings. In addition, testosterone manipulation was investigated in male mice by castration in vivo. Immunohistochemistry, immunoblotting and qRT-PCR analysis demonstrated that ERα was increased in PASMCs and pulmonary arteries from female PAH patients and chronic hypoxic mice, respectively. On the other hand, ERβ was decreased in PAH and hypoxia. It was also observed that females expressed higher levels of ERα in PAH compared to males whereas ERβ was lower in females. PAH was assessed by measuring right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH) and pulmonary vascular remodelling and muscularisation. Chronic hypoxia induced-pulmonary hypertension (PH) was attenuated in female mice dosed with the ERα antagonist MPP, shown by marked reductions in RVSP and pulmonary vascular remodelling. Hypoxic male mice remained unaffected by MPP treatment. Spontaneous PH and chronic hypoxia induced-PH observed in female SERT+ mice were reversed by treatment with MPP. Immunoblotting and qRT-PCR analysis revealed that the possible mechanism involved in the beneficial effect of MPP in females in vivo involved restoring the dysfunctional bone morphogenetic protein receptor-2 (BMPR2) axis observed in PAH. This effect was only observed in female mice. In addition, chronic hypoxia induced- PH in male and female mice was unaffected by GPER deletion. Expression of GPER between female non-PAH controls and PAH patients was unchanged. In isolated human PASMCs estrogen induced proliferation was inhibited by MPP, but not PHTPP or G15, an ERβ and GPER antagonist, respectively. The ERα agonist, PPT stimulated proliferation of human PASMCs. Both estrogen and PPT induced proliferation was dependent on downstream PI3K/Akt and ERK MAPK activity. In males, testosterone deprivation by surgical castration had no effect on chronic-hypoxia induced PH. RVSP, RVH and pulmonary vascular remodelling were unchanged in hypoxic castrated mice relative to sham controls. Testosterone levels, assessed by enzyme linked immunosorbent assay (ELISA) demonstrated no effects of hypoxia on plasma testosterone levels. Testosterone levels were approximately halved by castration. qRT-PCR analysis showed that in mouse lung there were also no difference in expression of the androgen receptor (AR) and 5α-reducatse, the testosterone metabolising enzyme. Testosterone had no effect on proliferation of human PASMCs, although its primary metabolite, dihydrotestosterone (DHT), stimulated proliferation in a dose-dependent manner. In summary of these findings, we have identified an ERα-dependent mechanism of PAH in females, but not in males. ERα is noticeably increased in female human PASMCs from PAH patients compared to male PAH patients. Additionally, ERα activation in female human PASMCs leads to proliferation driven by PI3K/Akt and ERK MAPK activation. Treatment with an ERα antagonist attenuated the development of chronic hypoxia induced-PH in females but not males, and reversed PH in SERT+ female mice. We demonstrate that the mechanism attributed to the beneficial effect of MPP in vivo involved restoration of the dysfunctional BMPR2 signalling axis. Our results suggest that increased ERα expression may drive PAH development in females. Furthermore, we demonstrate that ERα does not play a key role in the development of hypoxia induced-PH in male mice. In addition we conclude that testosterone does not contribute to chronic hypoxic-PH observed in males. We suggest that altered local synthesis and metabolism in the lung and right ventricle may however, facilitate progression of established PAH in males and worsening survival rates. Overall, our results provide evidence for ERα in PAH development and implicate targeting ERs as a novel therapeutic target in PAH treatment.