693 research outputs found

    Safely Shooting a Quiet Woman: A Study of Patriarchy, Sexuality, Racism, and Putrefaction in John Websterā€™s Plays

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    This thesis explores the representation of sexuality in John Websterā€™s three plays, The White Devil, The Duchess of Malfi, and The Devilā€™s Law-Case. Himself a barrister, Webster writes in a mode clearly colored by his profession; Websterā€™s perspective on law, during the same period as the illustrious Sir Edward Coke, leads one to investigate how judicial structures in his plays repress female sexuality. The dialogue and its implied social context for Websterā€™s characters reveals the misogynistic and Machiavellian nature of sixteenth and seventeenth-century male-female dynamics and ultimately affords male characters a space to exert control over their female counterparts. When female characters, as a result, disrupt this relationship, Websterā€™s gentlemen respond with force; incestuous desires, violent outbursts, and sometimes madness ensue. This thesis examines how court and familial dynamics interact with conflicting erotic urges, ultimately leading to brutality and murder. Though writing from London, Websterā€™s plays all have an Italian setting; thus, the interaction between nationality and sexuality is investigated. This thesis seeks to examine the complicated role of sexuality contained within three of Websterā€™s plays

    Hands-on, Shoes-off: Multisensory Tools Enhance Family Engagement Within an Art Museum

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    Families with young children typically struggle to engage with traditional art museum environments. This research examined the impact of multisensory tools on family engagement within Mathaf: Arab Museum of Modern Art, Qatar. Sixty families with at least one child aged 0-11 were observed during two tasks. One task required participants to look at a series of paintings to select their favorite. In another task families were given a toolkit of multisensory items to facilitate interaction with a painting. A semi-structured observational method produced quantitative and qualitative data about participant engagement and intergenerational interaction. Self-rating scores of task enjoyment were also collected. Results indicated that multisensory tools enhance family engagement with museums, artworks and with each other. Results also suggested that word-based interpretation was not necessary. We consider the potential implications of these findings in relation to family programming within art museums and museums more generally

    Toxicity of cancer therapy: what the cardiologist needs to know about angiogenesis inhibitors

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    Clinical outcomes for patients with a wide range of malignancies have improved substantially over the last two decades. Tyrosine kinase inhibitors (TKIs) are potent signalling cascade inhibitors and have been responsible for significant advances in cancer therapy. By inhibiting vascular endothelial growth factor receptor (VEGFR)-mediated tumour blood vessel growth, VEGFR-TKIs have become a mainstay of treatment for a number of solid malignancies. However, the incidence of VEGFR-TKI-associated cardiovascular toxicity is substantial and previously under-recognised. Almost all patients have an acute rise in blood pressure, and the majority develop hypertension. They are associated with the development of left ventricular systolic dysfunction (LVSD), heart failure and myocardial ischaemia and can have effects on myocardial repolarisation. Attention should be given to rigorous baseline assessment of patients prior to commencing VEGFR-TKIs, with careful consideration of baseline cardiovascular risk factors. Baseline blood pressure measurement, ECG and cardiac imaging should be performed routinely. Hypertension management currently follows national guidelines, but there may be a future role forendothelin-1 antagonism in the prevention or treatment of VEGFR-TKI-associated hypertension. VEGFR-TKI-associated LVSD appears to be independent of dose and is reversible. Patients who develop LVSD and heart failure should be managed with conventional heart failure therapies, but the role of prophylactic therapy is yet to be defined. Serial monitoring of left ventricular function and QT interval require better standardisation and coordinated care. Management of these complex patients requires collaborative, cardio-oncology care to allow the true therapeutic potential from cancer treatment while minimising competing cardiovascular effects

    Complement deficiencies limit CD20 monoclonal antibody treatment efficacy in CLL

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    Monoclonal antibodies (MAbs) form a central part of chronic lymphocytic leukaemia (CLL) treatment. We therefore evaluated whether complement defects in CLL patients reduced the induction of complement-dependent cytotoxicity (CDC) by using anti-CD20 MAbs rituximab (RTX) and ofatumumab (OFA). Ofatumumab elicited higher CDC levels than RTX in all CLL samples examined, particularly in poor prognosis cohorts (11qāˆ’ and 17pāˆ’). Serum sample analyses revealed that 38.1% of patients were deficient in one or more complement components, correlating with reduced CDC responses. Although a proportion of patients with deficient complement levels initially induced high levels of CDC, on secondary challenge CDC activity in sera was significantly reduced, compared with that in normal human serum (NHS; P<0.01; n=52). In addition, a high CLL cell number contributed to rapid complement exhaustion. Supplementing CLL serum with NHS or individual complement components, particularly C2, restored CDC on secondary challenge to NHS levels (P<0.0001; n=9). In vivo studies revealed that complement components were exhausted in CLL patient sera post RTX treatment, correlating with an inability to elicit CDC. Supplementing MAb treatment with fresh-frozen plasma may therefore maintain CDC levels in CLL patients with a complement deficiency or high white blood cell count. This study has important implications for CLL patients receiving anti-CD20 MAb therapy

    Differential Hox expression in murine embryonic stem cell models of normal and malignant hematopoiesis

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    The Hox family are master transcriptional regulators of developmental processes, including hematopoiesis. The Hox regulators, caudal homeobox factors (Cdx1-4), and Meis1, along with several individual Hox proteins, are implicated in stem cell expansion during embryonic development, with gene dosage playing a significant role in the overall function of the integrated Hox network. To investigate the role of this network in normal and aberrant, early hematopoiesis, we employed an in vitro embryonic stem cell differentiation system, which recapitulates mouse developmental hematopoiesis. Expression profiles of Hox, Pbx1, and Meis1 genes were quantified at distinct stages during the hematopoietic differentiation process and compared with the effects of expressing the leukemic oncogene Tel/PDGFR;2. During normal differentiation the Hoxa cluster, Pbx1 and Meis1 predominated, with a marked reduction in the majority of Hox genes (27/39) and Meis1 occurring during hematopoietic commitment. Only the posterior Hoxa cluster genes (a9, a10, a11, and a13) maintained or increased expression at the hematopoietic colony stage. Cdx4, Meis1, and a subset of Hox genes, including a7 and a9, were differentially expressed after short-term oncogenic (Tel/PDGFR;2) induction. Whereas Hoxa4-10, b1, b2, b4, and b9 were upregulated during oncogenic driven myelomonocytic differentiation. Heterodimers between Hoxa7/Hoxa9, Meis1, and Pbx have previously been implicated in regulating target genes involved in hematopoietic stem cell (HSC) expansion and leukemic progression. These results provide direct evidence that transcriptional flux through the Hox network occurs at very early stages during hematopoietic differentiation and validates embryonic stem cell models for gaining insights into the genetic regulation of normal and malignant hematopoiesis

    The epidemiology of injuries in adult amateur rowers: A cross-sectional study

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    Objectives To investigate the prevalence, nature and factors associated with injury among adult amateur rowers. Design Retrospective cross-sectional study. Setting UK-based amateur rowing clubs. Participants 160 amateur rowers. Main outcome measures Frequency, type, location, severity and rowing-related factors associated with injury. Results Injury rate was 5.7 per 1000 sessions, with no effect of sex (Ļ‡2ā€Æ=ā€Æ0.195, Pā€Æ=ā€Æ0.659) or weight class (Ļ‡2ā€Æ=ā€Æ0.800, Pā€Æ=ā€Æ0.371). The lower-back demonstrated an epidemiological incidence proportion (IP) of 0.39 (95%CIā€Æ=ā€Æ0.33 to 0.46). The IP for water- and land-based training was 0.39 (95%CIā€Æ=ā€Æ0.31 to 0.47) and 0.57 (95%CIā€Æ=ā€Æ0.49 to 0.65), respectively. IP was highest between January and March (0.13ā€“0.15), whilst time loss was 0.49 (95%CIā€Æ=ā€Æ0.42ā€“0.57). The IP for ā€˜overuseā€™ and ā€˜traumaticā€™ injuries was 0.71 (95%CIā€Æ=ā€Æ0.65 to 0.78) and 0.22 (95%CIā€Æ=ā€Æ0.16 to 0.27), respectively. Training volume was positively associated with injury rate (rā€Æ=ā€Æ0.418, Pā€Æ<ā€Æ0.001). Conclusions Injury rates appear higher among amateur rowers with the most common injury site being the lower-back. Our results suggest several contextual factors influence injury risk including seasonal phase, training type and training volume

    A dedicated haem lyase is required for the maturation of a novel bacterial cytochrome c with unconventional covalent haem binding

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    In bacterial c-type cytochromes, the haem cofactor is covalently attached via two cysteine residues organized in a haem c-binding motif. Here, a novel octa-haem c protein, MccA, is described that contains only seven conventional haem c-binding motifs (CXXCH), in addition to several single cysteine residues and a conserved CH signature. Mass spectrometric analysis of purified MccA from Wolinella succinogenes suggests that two of the single cysteine residues are actually part of an unprecedented CX15CH sequence involved in haem c binding. Spectroscopic characterization of MccA identified an unusual high-potential haem c with a red-shifted absorption maximum, not unlike that of certain eukaryotic cytochromes c that exceptionally bind haem via only one thioether bridge. A haem lyase gene was found to be specifically required for the maturation of MccA in W. succinogenes. Equivalent haem lyase-encoding genes belonging to either the bacterial cytochrome c biogenesis system I or II are present in the vicinity of every known mccA gene suggesting a dedicated cytochrome c maturation pathway. The results necessitate reconsideration of computer-based prediction of putative haem c-binding motifs in bacterial proteomes

    Individual and situational factors affecting the movement characteristics and internal responses to Touch match-play during an international tournament

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    Purpose: To examine the influence of individual and situational factors on the movement characteristics and internal responses of players to an international Touch tournament. Methods: Using 47 International Touch players (25 men and 22 women), the associations between the movement characteristics and internal responses with individual (sprint, glycolytic test, Yo-Yo intermittent recovery test level 1 [Yo-Yo IR1], jump performance and well-being) and situational (sex, squad, position, competition day, points scored/conceded, result, and opposition rank) factors were examined using linear mixed modelling. Results: Yo-Yo IR1 distance was associated with all movement characteristics and internal responses (r =Ā āˆ’0.29 to 0.37), whilst sprint and glycolytic times only influenced mean heart rate (HRmean) (r =Ā 0.15) and high-speed distance (r =Ā 0.10), respectively. Sex influenced high-speed distance (r =Ā āˆ’0.41), whilst squad was associated with playing time and HRmean (r =Ā āˆ’0.10ā€“0.33). Other associations included: playing position with all movement characteristics (r =Ā āˆ’0.67ā€“0.81); points conceded with relative distance (r =Ā āˆ’0.14); winning with high metabolic power and session RPE (r =Ā āˆ’0.07ā€“0.09), and opposition rank with HRmean and RPE (r =Ā 0.11ā€“0.35). Conclusions: Individual and situational factors can influence the movement characteristics and internal responses to Touch and should be considered when developing the characteristics of players and interpreting responses to match-play
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