No Slip-Shod Muse: A Performance Analysis of Some of Susanna Centlivre's Plays

In 1982, Richard C. Frushell urged the necessity for a critical study of Susanna Centlivre's plays. Since then, only a handful of books and articles briefly discuss herand many attempt wrongly to force her into various critical models. Drawing on performativity models, my reading of several Centlivre plays (Love's Contrivance, The Gamester, The Basset-Table and A Bold Stroke for a Wife) asks the question, "What was it like to see these plays in performance?" Occupying somewhat uneasy ground between literature and theatre studies, I borrow useful tools from both, to create what might be styled a New Historicist Dramaturgy. I urge a re-examination of the period 1708-28. The standard reading of theatre of the period is that it was static. This "dry spell" of English theatre, most critics agree, was filled with stock characters and predictable plot lines. But it is during this so-called "dry spell" that Centlivre refines her stagecraft, and convinces cautious managers to bank on her work, providing evidence that playwrights of the period were subtly experimenting. The previous trend in scholarship of this cautious and paranoid era of theatre history has been to shy away from examining the plays in any depth, and fall back on pigeonholing them. But why were the playwrights turning out the work that they did? What is truly representative of the period? Continued examination may stop us from calling the period a "dry spell." For that purpose, examining some of Centlivre's early work encourages us to avoid the tendency to study only a few playwrights of the period, and to avoid the trap of focusing on biography rather than text. I propose a different kind of aesthetic, stemming from my interest in the text as precursor to performance. Some of these works may not seem fertile ground for theorists, but discarding them on that basis fails to take into account their original purpose: to entertain

-Catenin Binds to the Activation Function 2 Region of the Androgen Receptor and Modulates the Effects of the N-Terminal Domain and TIF2 on Ligand-Dependent Transcription

β-Catenin is a multifunctional molecule that is activated by signaling through WNT receptors. β-Catenin can also enhance the transcriptional activity of some steroid hormone receptors such as the androgen receptor and retinoic acid receptor α. Androgens can affect nuclear translocation of β-catenin and influence its subcellular distribution. Using mammalian two-hybrid binding assays, analysis of reporter gene transcription, and coimmunoprecipitation, we now show that β-catenin binds to the androgen receptor ligand-binding domain (LBD) and modulates the transcriptional effects of TIF2 and the androgen receptor N-terminal domain (NTD). In functional assays, β-catenin bound to androgen receptor only in the presence of ligand agonists, not antagonists. β-Catenin binding to the androgen receptor LBD was independent of and cooperative with the androgen receptor NTD and the p160 coactivator TIF2, both of which bind to the activation function 2 (AF-2) region of the androgen receptor. Different mutations of androgen receptor helix 3 amino acids disrupted binding of androgen receptor NTD and β-catenin. β-Catenin, androgen receptor NTD, and TIF2 binding to the androgen receptor LBD were affected similarly by a subset of helix 12 mutations, but disruption of two sites on helix 12 affected only binding of β-catenin and not of TIF2 or the androgen receptor NTD. Mutational disruption of each of five LXXLL peptide motifs in the β-catenin armadillo repeats did not disrupt either binding to androgen receptor or transcriptional coactivation. ICAT, an inhibitor of T-cell factor 4 (TCF-4), and E-cadherin binding to β-catenin also blocked binding of the androgen receptor LBD. We also demonstrated cross talk between the WNT and androgen receptor signaling pathways because excess androgen receptor could interfere with WNT signaling and excess TCF-4 inhibited the interaction of β-catenin and androgen receptor. Taken together, the data show that β-catenin can bind to the androgen receptor LBD and modulate the effects of the androgen receptor NTD and TIF2 on transcription

A systematic review of mental disorder, suicide, and deliberate self harm in lesbian, gay and bisexual people

Background: Lesbian, gay and bisexual (LGB) people may be at higher risk of mental disorders than heterosexual people.Method: We conducted a systematic review and meta-analysis of the prevalence of mental disorder, substance misuse, suicide, suicidal ideation and deliberate self harm in LGB people. We searched Medline, Embase, PsycInfo, Cinahl, the Cochrane Library Database, the Web of Knowledge, the Applied Social Sciences Index and Abstracts, the International Bibliography of the Social Sciences, Sociological Abstracts, the Campbell Collaboration and grey literature databases for articles published January 1966 to April 2005. We also used Google and Google Scholar and contacted authors where necessary. We searched all terms related to homosexual, lesbian and bisexual people and all terms related to mental disorders, suicide, and deliberate self harm. We included papers on population based studies which contained concurrent heterosexual comparison groups and valid definition of sexual orientation and mental health outcomes.Results: Of 13706 papers identified, 476 were initially selected and 28 (25 studies) met inclusion criteria. Only one study met all our four quality criteria and seven met three of these criteria. Data was extracted on 214,344 heterosexual and 11,971 non heterosexual people. Meta-analyses revealed a two fold excess in suicide attempts in lesbian, gay and bisexual people [ pooled risk ratio for lifetime risk 2.47 (CI 1.87, 3.28)]. The risk for depression and anxiety disorders (over a period of 12 months or a lifetime) on meta-analyses were at least 1.5 times higher in lesbian, gay and bisexual people (RR range 1.54-2.58) and alcohol and other substance dependence over 12 months was also 1.5 times higher (RR range 1.51-4.00). Results were similar in both sexes but meta analyses revealed that lesbian and bisexual women were particularly at risk of substance dependence (alcohol 12 months: RR 4.00, CI 2.85, 5.61; drug dependence: RR 3.50, CI 1.87, 6.53; any substance use disorder RR 3.42, CI 1.97-5.92), while lifetime prevalence of suicide attempt was especially high in gay and bisexual men (RR 4.28, CI 2.32, 7.88).Conclusion: LGB people are at higher risk of mental disorder, suicidal ideation, substance misuse, and deliberate self harm than heterosexual people

Ideações e tentativas de suicídio em adolescentes com práticas sexuais hetero e homoeróticas

Esta pesquisa, que teve como população-alvo adolescentes com idade entre 12 e 20 anos, residentes em três municípios do interior Paulista, buscou conhecer as associações entre orientação sexual e ideações e tentativas de suicídio. Corroborando com as pesquisas internacionais, evidenciou-se que os não heterossexuais têm mais chances de pensarem e tentarem suicídio, comparativamente aos heterossexuais. Todavia, encontrou-se que, dentre o grupo de adolescentes que se assumiram não heterossexuais, os que estão mais vulneráveis são aqueles que se autodefiniram bissexuais e "outros", os quais constituem o grupo de pessoas menos assumidas, dentre os não heterossexuais. Do mesmo modo, constatou-se que os respondentes apresentam diversas opiniões e valores homofóbicos, sexistas e heterocentrados, o que revela ser o espaço escolar, onde se encontram esses jovens não heterossexuais, bastante carregado de posicionamentos discursivos discriminatórios. Conclui-se que a questão do suicídio é uma problemática de saúde pública e que a população de jovens não heterossexuais necessita de abordagens específicas para a prevenção e de atenção relativas a essa conduta.This survey, which had as the target population adolescents aged between 12 and 20 years living in three municipalities in São Paulo, sought to investigate the associations between sexual orientation and ideation and suicide attempts. Confirming international research findings, it is showed that non-heterosexuals are more likely to attempt and think about suicide, compared to heterosexuals. However, we found that among the group of teenagers who assumed to be non-heterosexuals, the most vulnerable are those who define themselves as bisexual and "other", which constitute the group of people less assumed, among non-heterosexuals. Similarly, it was found that the respondents have different homophobic, sexist and heterocentric opinions and values, which turn out to be the school environment, where these young non-heterosexual study, loaded with enough discriminatory discursive positions. We conclude that the issue of suicide is a public health problem and that the population of young non-heterosexual needs specific approaches for prevention and care in respect to this conduct

Dual diagnosis clients' treatment satisfaction - a systematic review

Background: The aim of this systematic review is to synthesize existing evidence about treatment satisfaction among clients with substance misuse and mental health co-morbidity (dual diagnoses, DD). Methods: We examined satisfaction with treatment received, variations in satisfaction levels by type of treatment intervention and by diagnosis (i.e. DD clients vs. single diagnosis clients), and the influence of factors other than treatment type on satisfaction. Peer-reviewed studies published in English since 1970 were identified by searching electronic databases using pre-defined search strings. Results: Across the 27 studies that met inclusion criteria, high average satisfaction scores were found. In most studies, integrated DD treatment yielded greater client satisfaction than standard treatment without explicit DD focus. In standard treatment without DD focus, DD clients tended to be less satisfied than single diagnosis clients. Whilst the evidence base on client and treatment variables related to satisfaction is small, it suggested client demographics and symptom severity to be unrelated to treatment satisfaction. However, satisfaction tended to be linked to other treatment process and outcome variables. Findings are limited in that many studies had very small sample sizes, did not use validated satisfaction instruments and may not have controlled for potential confounders. A framework for further research in this important area is discussed. Conclusions: High satisfaction levels with current treatment provision, especially among those in integrated treatment, should enhance therapeutic optimism among practitioners dealing with DD clients

Vision 20/20: Molecular-guided surgical oncology based upon tumor metabolism or immunologic phenotype: Technological pathways for point of care imaging and intervention

Surgical guidance with fluorescence has been demonstrated in individual clinical trials for decades, but the scientific and commercial conditions exist today for a dramatic increase in clinical value. In the past decade, increased use of indocyanine green based visualization of vascular flow, biliary function, and tissue perfusion has spawned a robust growth in commercial systems that have near-infrared emission imaging and video display capabilities. This recent history combined with major preclinical innovations in fluorescent-labeled molecular probes, has the potential for a shift in surgical practice toward resection guidance based upon molecular information in addition to conventional visual and palpable cues. Most surgical subspecialties already have treatment management decisions partially based upon the immunohistochemical phenotype of the cancer, as assessed from molecular pathology of the biopsy tissue. This phenotyping can inform the surgical resection process by spatial mapping of these features. Further integration of the diagnostic and therapeutic value of tumor metabolism sensing molecules or immune binding agents directly into the surgical process can help this field mature. Maximal value to the patient would come from identifying the spatial patterns of molecular expression in vivo that are well known to exist. However, as each molecular agent is advanced into trials, the performance of the imaging system can have a critical impact on the success. For example, use of pre-existing commercial imaging systems are not well suited to image receptor targeted fluorophores because of the lower concentrations expected, requiring orders of magnitude more sensitivity. Additionally the imaging system needs the appropriate dynamic range and image processing features to view molecular probes or therapeutics that may have nonspecific uptake or pharmacokinetic issues which lead to limitations in contrast. Imaging systems need to be chosen based upon objective performance criteria, and issues around calibration, validation, and interpretation need to be established before a clinical trial starts. Finally, as early phase trials become more established, the costs associated with failures can be crippling to the field, and so judicious use of phase 0 trials with microdose levels of agents is one viable paradigm to help the field advance, but this places high sensitivity requirements on the imaging systems used. Molecular-guided surgery has truly transformative potential, and several key challenges are outlined here with the goal of seeing efficient advancement with ideal choices. The focus of this vision 20/20 paper is on the technological aspects that are needed to be paired with these agents