134 research outputs found
Gender, Sexuality and the Law School: (Re)thinking Blackstone’s Tower with Queer and Feminist Theory
This article will focus on exploring gender and sexuality within the law school. Largely silent from Twining’s ‘grand tour’, these two areas are now key parts of the law school landscape, having become firmly established as key elements of law school discourse and legal scholarship in the years since Blackstone’s Tower was published. The Blackstone’s Tower of Twining’s imagination was, Twining suggested, ‘holding up a mirror to a familiar world’, and it was a world that made only passing reference to gender and no reference to sexuality. Feminism is mentioned twice in 244 pages, whilst queer—still emergent within legal scholarship in 1994—is not referenced at all. A once radical and vital text can perhaps appear antiquated to today’s readers. Yet, this should not be regarded as a criticism of the text but rather a reflection of how the law school and legal scholarship has transformed since 1994. Whether in the number of gender and/or sexuality and law courses that now permeate through the UK law school, or the extraordinary growth first of feminist scholarship and more recently queer scholarship, the law school has been profoundly impacted by socio-legal shifts in gender and sexuality research. This is scholarship that does not merely serve as ‘another’ theory or an addendum to jurisprudence, for these theories have offered the ability to reshape the very architecture of the law school and to re-imagine Blackstone’s Tower for what it is and what it can be. This article seeks to explore that journey and offer a glimpse of future possibilities
Queer Histories and the Politics of Policing, Emma K Russell [Routledge, 2020, 162pp, £120 (hardback)]
Book Review - Queer Histories and the Politics of Policing, Emma K Russell [Routledge, 2020, 162pp, £120 (hardback)
(Re)regulating Gay Sex in Viral Times: COVID-19 and the Impersonal Intimacy of the Glory Hole
COVID-19 has transformed the way we live our lives, and sex has been a significant element of that transformation. Gay male sex in the UK has faced the most significant (re)criminalisation and (re)regulation in living memory with intimacy outside of the heteronormative framework of domestic coupledom at best discouraged and, at worst, made into a criminal offence. This criminalisation provides a temporal praxis in which gay men experience sex in the shadows once more, an echo of a historic legal and cultural regulation of desire. This history also provides a space for experiencing forms of impersonal intimacy and queer desire in a way that is arguably well-suited for viral times, namely the glory hole. These historic partitions and apertures – connecting gay men across legal and cultural boundaries of desire and affirmed through modes of anonymous and promiscuous sex – may once again provide a queer way to experience intimacy as impersonal. This article explores this potential and situates the glory hole as a cultural and legal site of this tension between the intimate and the impersonal, as well as considering how it is being recast as commercial artefact and performance space during these viral times
Bareback sex in the age of preventative medication : rethinking the 'harms' of HIV transmission
The experiences of People living with HIV have been transformed over recent years. Advances in medical science have made the virus a manageable chronic condition, while eliminating the risk of onward transmission for those with access to treatment, something referred to as TasP (treatment as prevention) or U=U (undetectable equals untransmissible). More recently, the availability of PrEP (pre-exposure prophylaxis), alongside PEP (post-exposure prophylaxis), through the NHS has created the conditions for condomless sexual encounters to take place without the fear of HIV transmission associated with previous decades. Despite this, the criminal law has continued to frame HIV in terms of personal responsibility and bodily autonomy within the dominant narratives of danger, disease, and out-dated science. Doctrinal law has failed to keep pace with social and scientific change. Therefore, in this article, we provide a re-examination of the criminal issues relating to HIV transmission within this new landscape, arguing that it necessitates a shift in attitude, policy and doctrine. We specifically argue that HIV transmission does not meet the appropriate harm threshold to constitute GBH and that if criminal law is ultimately about preventing or regulating harm, the ongoing criminalisation of HIV transmission is counter to that aim
Sequential screening for lung cancer in a high-risk group: randomised controlled trial: LungSEARCH: a randomised controlled trial of Surveillance using sputum and imaging for the EARly detection of lung Cancer in a High-risk group.
BACKGROUND: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. METHODS: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). RESULTS: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. CONCLUSIONS: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening
A dominant gain-of-function mutation in universal tyrosine kinase <i>SRC </i>causes thrombocytopenia, myelofibrosis, bleeding, and bone pathologies
The Src family kinase (SFK)member SRC is amajor target in drug development because it is activated in many human cancers, yet deleterious SRC germline mutations have not been reported. We used genome sequencing and Human Phenotype Ontology patient coding to identify a gain-of-function mutation in SRC causing thrombocytopenia, myelofibrosis, bleeding, and bone pathologies in nine cases. Modeling of the E527K substitution predicts loss of SRC's self-inhibitory capacity, whichwe confirmedwith in vitro studies showing increased SRC kinase activity and enhanced Tyr419 phosphorylation in COS-7 cells overexpressing E527K SRC. The active form of SRC predominates in patients' platelets, resulting in enhanced overall tyrosine phosphorylation. Patientswith myelofibrosis have hypercellular bone marrow with trilineage dysplasia, and their stem cells grown in vitro form more myeloid and megakaryocyte (MK) colonies than control cells. These MKs generate platelets that are dysmorphic, low in number, highly variable in size, and have a paucity of a-granules. Overactive SRC in patient-derived MKs causes a reduction in proplatelet formation, which can be rescued by SRC kinase inhibition. Stem cells transduced with lentiviral E527K SRC formMKs with a similar defect and enhanced tyrosine phosphorylation levels. Patient-derived and E527K-transduced MKs show Y419 SRC- positive stained podosomes that induce altered actin organization. Expression of mutated src in zebrafish recapitulates patients' blood and bone phenotypes. Similar studies of platelets andMKs may reveal the mechanism underlying the severe bleeding frequently observed in cancer patients treated with next-generation SFK inhibitors. © 2016 by the American Association for the Advancement of Science; all rights reserved
A gain-of-function variant in <i>DIAPH1 </i>causes dominant macrothrombocytopenia and hearing loss
Macrothrombocytopenia (MTP) is a heterogeneous group of disorders characterized by enlarged and reduced numbers of circulating platelets, sometimes resulting in abnormal bleeding. In most MTP, this phenotype arises because of altered regulation of platelet formation from megakaryocytes (MK). We report the identification of DIAPH1, which encodes the Rho-effector diaphanous-related formin 1 (DIAPH1), as a candidate gene for MTP using exome sequencing, ontological phenotyping and similarity regression. We describe two unrelated pedigrees with MTP and sensorineural hearing loss that segregate with a DIAPH1 p.R1213* variant predicting partial truncation of the DIAPH1 diaphanous autoregulatory domain. The R1213* variant was associated with reduced proplatelet formation from cultured MKs, cell clustering and abnormal cortical filamentous actin. Similarly, in platelets there was increased filamentous actin and stable microtubules, indicating constitutive activation of DIAPH1. Over-expression of DIAPH1 R1213* in cells reproduced the cytoskeletal alterations found in platelets. Our description of a novel disorder of platelet formation and hearing loss extends the repertoire of DIAPH1-related disease and provides new insights into the autoregulation of DIAPH1 activity
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The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance
In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.</p
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