The Unruly Womb in Early Modern English Drama: Plotting Women\u27s Biology on the Stage

This study provides an accessible, informative and entertaining introduction to women’s sexual health as presented on the early modern stage, and how dramatists coded for it. Beginning with the rise of green sickness (the disease of virgins) from its earliest reference in drama in the 1560s, Ursula Potter traces a continuing fascination with the womb by dramatists through to the oxymoron of the chaste sex debate in the 1640s. She illuminates how playwrights both satirized and perpetuated the notion of the womb’s insatiable appetite.https://scholarworks.wmich.edu/mip_ltsd/1002/thumbnail.jp

Pedagogy and Parenting in English Drama, 1560-1610: Flogging Schoolmasters and Cockering Mothers

In this thesis I examine the representation of parents and schoolmasters and the conflicts between them in vernacular drama in Reformation England. This was a period of growth in public schooling and a time when numerous treatises on education and childrearing were in circulation in England. Prevailing pedagogical theory privileged the schoolmaster's authority over that of the parents, and set paternal authority over that of the mother. It sought to limit maternal power to the domestic sphere and the infant years, yet the drama examined here suggests that mothers, not fathers, were usually the parent in control of their children's education. The conflicts inherent in these oppositions are played out in drama dealing with schooling and childrearing; each of the works examined here participates in and contributes to public debate over school education and parenting practices in early modern England. The thesis conducts a close textual and contextual analysis of the representation of schoolmasters and parents and of parent-school relations in seven English plays. A variety of dramatic genres is represented: public drama (Love's Labour's Lost, Patient Grissill, The Winter's Tale), school drama (Nice Wanton, July and Julian, The Disobedient Child), and private royal entertainment (The Lady of May). The plays are explicated in terms of the Tudor school culture and the negotiation of authority between fathers, mothers and schoolmasters. The thesis draws extensively on sixteenth-century school dialogues and vulgaria and on education treatises, which were available in English in Tudor England, in particular the writings of Erasmus, Vives, Ascham, Mulcaster, Elyot, Brinsley and Becon. School records provide information on school conditions and curricula, the duties and qualities of schoolmasters and the role of schools in civic and public performances. The thesis addresses issues of gender, childrearing, public education and parental and pedagogical authority in the second half of the sixteenth and early seventeenth centuries

Pedagogy and Parenting in English Drama, 1560-1610: Flogging Schoolmasters and Cockering Mothers

In this thesis I examine the representation of parents and schoolmasters and the conflicts between them in vernacular drama in Reformation England. This was a period of growth in public schooling and a time when numerous treatises on education and childrearing were in circulation in England. Prevailing pedagogical theory privileged the schoolmaster's authority over that of the parents, and set paternal authority over that of the mother. It sought to limit maternal power to the domestic sphere and the infant years, yet the drama examined here suggests that mothers, not fathers, were usually the parent in control of their children's education. The conflicts inherent in these oppositions are played out in drama dealing with schooling and childrearing; each of the works examined here participates in and contributes to public debate over school education and parenting practices in early modern England. The thesis conducts a close textual and contextual analysis of the representation of schoolmasters and parents and of parent-school relations in seven English plays. A variety of dramatic genres is represented: public drama (Love's Labour's Lost, Patient Grissill, The Winter's Tale), school drama (Nice Wanton, July and Julian, The Disobedient Child), and private royal entertainment (The Lady of May). The plays are explicated in terms of the Tudor school culture and the negotiation of authority between fathers, mothers and schoolmasters. The thesis draws extensively on sixteenth-century school dialogues and vulgaria and on education treatises, which were available in English in Tudor England, in particular the writings of Erasmus, Vives, Ascham, Mulcaster, Elyot, Brinsley and Becon. School records provide information on school conditions and curricula, the duties and qualities of schoolmasters and the role of schools in civic and public performances. The thesis addresses issues of gender, childrearing, public education and parental and pedagogical authority in the second half of the sixteenth and early seventeenth centuries

Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery : Combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds

Objectives: To examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes. Methods: Health Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA inception cohorts in routine care; Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network from 1986 to 2012. The incidence of major and intermediate orthopaedic surgical episodes over 25 years was collected from national data sets. Disease activity was categorised by mean disease activity score (DAS28) annually between years 1 and 5; remission (RDAS≤2.6), low (LDAS>2.6-3.2), low-moderate (LMDAS≥3.2-4.19), high-moderate (HMDAS 4.2-5.1) and high (HDAS>5.1). Results: Data from 2045 patients were analysed. Patients in RDAS showed no HAQ progression over 5 years, whereas there was a significant relationship between rising DAS28 category and HAQ at 1 year, and the rate of HAQ progression between years 1 and 5. During 27 986 person-years follow-up, 392 intermediate and 591 major surgeries were observed. Compared with the RDAS category, there was a significantly increased cumulative incidence of intermediate surgery in HDAS (OR 2.59 CI 1.49 to 4.52) and HMDAS (OR 1.8 CI 1.05 to 3.11) categories, and for major surgery in HDAS (OR 2.48 CI 1.5 to 4.11), HMDAS (OR 2.16 CI 1.32 to 3.52) and LMDAS (OR 2.07 CI 1.28 to 3.33) categories. There was no significant difference in HAQ progression or orthopaedic episodes between RDAS and LDAS categories. Conclusions: There is an association between disease activity and both poor function and long-term orthopaedic episodes. This illustrates the far from benign consequences of persistent moderate disease activity, and supports European League Against Rheumatism treat to target recommendations to secure low disease activity or remission in all patients.Peer reviewedFinal Published versio

Photorhabdus adhesion modification protein (Pam) binds extracellular polysaccharide and alters bacterial attachment

Background Photorhabdus are Gram-negative nematode-symbiotic and insect-pathogenic bacteria. The species Photorhabdus asymbiotica is able to infect humans as well as insects. We investigated the secreted proteome of a clinical isolate of P. asymbiotica at different temperatures in order to identify proteins relevant to the infection of the two different hosts. Results A comparison of the proteins secreted by a clinical isolate of P. asymbiotica at simulated insect (28°C) and human (37°C) temperatures led to the identification of a small and highly abundant protein, designated Pam, that is only secreted at the lower temperature. The pam gene is present in all Photorhabdus strains tested and shows a high level of conservation across the whole genus, suggesting it is both ancestral to the genus and probably important to the biology of the bacterium. The Pam protein shows limited sequence similarity to the 13.6 kDa component of a binary toxin of Bacillus thuringiensis. Nevertheless, injection or feeding of heterologously produced Pam showed no insecticidal activity to either Galleria mellonella or Manduca sexta larvae. In bacterial colonies, Pam is associated with an extracellular polysaccharide (EPS)-like matrix, and modifies the ability of wild-type cells to attach to an artificial surface. Interestingly, Surface Plasmon Resonance (SPR) binding studies revealed that the Pam protein itself has adhesive properties. Although Pam is produced throughout insect infection, genetic knockout does not affect either insect virulence or the ability of P. luminescens to form a symbiotic association with its host nematode, Heterorhabditis bacteriophora. Conclusions We studied a highly abundant protein, Pam, which is secreted in a temperature-dependent manner in P. asymbiotica. Our findings indicate that Pam plays an important role in enhancing surface attachment in insect blood. Its association with exopolysaccharide suggests it may exert its effect through mediation of EPS properties. Despite its abundance and conservation in the genus, we find no evidence for a role of Pam in either virulence or symbiosis

Uncertainties and controversies in axillary management of patients with breast cancer

The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register

Staphylococcus aureus Keratinocyte Invasion Is Dependent upon Multiple High-Affinity Fibronectin-Binding Repeats within FnBPA

Staphylococcus aureus is a commensal organism and a frequent cause of skin and soft tissue infections, which can progress to serious invasive disease. This bacterium uses its fibronectin binding proteins (FnBPs) to invade host cells and it has been hypothesised that this provides a protected niche from host antimicrobial defences, allows access to deeper tissues and provides a reservoir for persistent or recurring infections. FnBPs contain multiple tandem fibronectin-binding repeats (FnBRs) which bind fibronectin with varying affinity but it is unclear what selects for this configuration. Since both colonisation and skin infection are dependent upon the interaction of S. aureus with keratinocytes we hypothesised that this might select for FnBP function and thus composition of the FnBR region. Initial experiments revealed that S. aureus attachment to keratinocytes is rapid but does not require FnBRs. By contrast, invasion of keratinocytes was dependent upon the FnBR region and occurred via similar cellular processes to those described for endothelial cells. Despite this, keratinocyte invasion was relatively inefficient and appeared to include a lag phase, most likely due to very weak expression of α5β1 integrins. Molecular dissection of the role of the FnBR region revealed that efficient invasion of keratinocytes was dependent on the presence of at least three high-affinity (but not low-affinity) FnBRs. Over-expression of a single high-affinity or three low-affinity repeats promoted invasion but not to the same levels as S. aureus expressing an FnBPA variant containing three high-affinity repeats. In summary, invasion of keratinocytes by S. aureus requires multiple high-affinity FnBRs within FnBPA, and given the importance of the interaction between these cell types and S. aureus for both colonisation and infection, may have provided the selective pressure for the multiple binding repeats within FnBPA

Longer and better lives for patients with atrial fibrillation:the 9th AFNET/EHRA consensus conference

Aims: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Methods and results: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. Conclusions: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group