American Grief: The AIDS Quilt and Texts of Witness

Along with fiction written from the perspective of heterosexual men caring for dying gay male friends and mothers caring for a child, this essay looks at the NAMES Project AIDS Memorial Quilt as the best known and originary AIDS text of witness, especially in the United States. The Quilt reflects the development of the concern with AIDS from being primarily that of gay men, drug users, and their companions, to a concern that belongs also to a more mainstream audience. Changing perceptions of and attitudes towards the Quilt are reflected in the fiction under analysis here. "American Grief" thus traces the development of the reading audience for fiction and other narratives about AIDS from being a primarily gay audience to a mainstream one. In this respect, it also examines the literary strategies evident in The Way We Write Now (1995), one of the first anthologies of AIDS literature. The discussion considers how AIDS literature intended for a mainstream reading public is often cast as pedagogical, thus assuming that it has something to teach its readers, rather than containing something with which they can identify. In texts by Louis Begley and Dennis McFarland this is apparent in relationships based on watching, rather than on intervention or participation or identification. Finally, the essay considers AIDS fiction by Alice Elliott Dark and Alice Hoffman that focuses on families in which one member is ill with AIDS, in terms of Jessica Benjamin's concept of intersubjectivity

Cartographies of identities : resistance, diaspora, and trans-cultural dialogue in the works of Arab British and Arab American women writers

The purpose of this thesis is to compare the works of contemporary Arab British and Arab American women novelists with a view toward delineating a poetics of the more nascent Arab British literature. I argue that there is a tendency among Arab British women novelists to foreground and advocate trans-cultural dialogue and cross-ethnic identification strategies in a more pronounced approach than their Arab American counterparts who tend, in turn, to employ literary strategies to resist stereotypes and misconceptions about Arab communities in American popular culture. I argue that these differences result from two diverse racialized Arab immigration and settlement patterns on both sides of the Atlantic. Chapter One looks at how Arab British novelist Fadia Faqir's My Name is Salma and Arab American novelist Diana Abu-Jaber's Arabian Jazz define Arabness differently in the light of the precarious position Arabs occupy in ethnic and racial discourses in Britain and in the United States. Chapter Two examines how Arab British women writers Ahdaf Soueif and Leila Aboulela valorize trans-cultural and cross-ethnic dialogues and alliances in their novels The Map of Love and Minaret respectively through engaging with the two (interlocking) strands of feminism in the Arab world: secular and Islamic feminisms. In Chapter Three, I demonstrate how the two novels of Arab American women writers Diana Abu-Jaber's Crescent and Laila Halaby's West of the Jordan explore the contradictions of Arab American communities from within and employ strategies of intertextuality and storytelling to subvert stereotypes about Arabs. As this study is interested in exploring the historical and socio-political contexts in which Arab women writers on both sides of the Atlantic produce their work, the conclusion investigates how the two sets of authors have represented, from an Arab perspective, the events of 9/11 and the ensuing war on terror in their novels.EThOS - Electronic Theses Online ServiceUniversity of JordanGBUnited Kingdo

Rapid microbiological screening for tuberculosis in HIV-positive patients on the first day of acute hospital admission by systematic testing of urine samples using Xpert MTB/RIF: a prospective cohort in South Africa

Abstract Background Autopsy studies of HIV/AIDS-related hospital deaths in sub-Saharan Africa reveal frequent failure of pre-mortem diagnosis of tuberculosis (TB), which is found in 34–64 % of adult cadavers. We determined the overall prevalence and predictors of TB among consecutive unselected HIV-positive adults requiring acute hospital admission and the comparative diagnostic yield obtained by screening urine and sputum samples obtained on day 1 of admission with Xpert MTB/RIF (Xpert). Methods To determine overall TB prevalence accurately, comprehensive clinical sampling (sputum, urine, blood plus other relevant samples) was done and TB was defined by detection of Mycobacterium tuberculosis in any sample using Xpert and/or mycobacterial liquid culture. To evaluate a rapid screening strategy, we compared the diagnostic yield of Xpert testing sputum samples and urine samples obtained with assistance from a respiratory study nurse in the first 24 h of admission. Results Unselected HIV-positive acute adult new medical admissions (n = 427) who were not receiving TB treatment were enrolled irrespective of clinical presentation or symptom profile. From 2,391 cultures and Xpert tests done (mean, 5.6 tests/patient) on 1,745 samples (mean, 4.1 samples/patient), TB was diagnosed in 139 patients (median CD4 cell count, 80 cells/μL). TB prevalence was very high (32.6 %; 95 % CI, 28.1–37.2 %; 139/427). However, patient symptoms and risk factors were poorly predictive for TB. Overall, ≥1 non-respiratory sample(s) tested positive in 115/139 (83 %) of all TB cases, including positive blood cultures in 41/139 (29.5 %) of TB cases. In the first 24 h of admission, sputum (spot and/or induced samples) and urine were obtainable from 37.0 % and 99.5 % of patients, respectively (P <0.001). From these, the proportions of total TB cases (n = 139) that were diagnosed by Xpert testing sputum, urine or both sputum and urine combined within the first 24 h were 39/139 (28.1 %), 89/139 (64.0 %) and 108/139 (77.7 %) cases, respectively (P <0.001). Conclusions The very high prevalence of active TB and its non-specific presentation strongly suggest the need for routine microbiological screening for TB in all HIV-positive medical admissions in high-burden settings. The incremental diagnostic yield from Xpert testing urine was very high and this strategy might be used to rapidly screen new admissions, especially if sputum is difficult to obtain

Childhood brain tumors: A review of strategies to translate CNS drug delivery to clinical trials

Brain tumors account for over 20% of childhood cancers and are the biggest cancer killer in children and young adults. Several initiatives over the past 40 years have tried to identify more effective drug treatments, but with very limited success. This is largely due to the bloodâ brain barrier, which restricts the entry of many drugs into the brain. In this review, we describe the main techniques that are being developed to enhance brain tumor drug delivery and explore the preclinical brain tumor models that are essential for translational development of these techniques. We also identify existing approved drugs that, if coupled with an efficient delivery method, could have potential as brain tumor treatments. Bringing this information together is part of a funded initiative to highlight drug delivery as a research strategy to overcome the current challenges for children diagnosed with brain tumors

Highlights of children with Cancer UK’s workshop on drug delivery in paediatric brain tumours

The first Workshop on Drug Delivery in Paediatric Brain Tumours was hosted in London by the charity Children with Cancer UK. The goals of the workshop were to break down the barriers to treating central nervous system (CNS) tumours in children, leading to new collaborations and further innovations in this under-represented and emotive field. These barriers include the physical delivery challenges presented by the blood–brain barrier, the underpinning reasons for the intractability of CNS cancers, and the practical difficulties of delivering cancer treatment to the brains of children. Novel techniques for overcoming these problems were discussed, new models brought forth, and experiences compared

Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to alpha-aminoadipic semialdehyde dehydrogenase deficiency

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of α-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE-ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine-restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine-reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re-evaluate and update the two previously published recommendations for diagnosis, treatment, and follow-up of patients with PDE-ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus-based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE-ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE-ALDH7A1 are provided. This article is protected by copyright. All rights reserved

Real-Time MRI Guidance for Reproducible Hyperosmolar Opening of the Blood-Brain Barrier in Mice

The blood-brain barrier (BBB) prevents effective delivery of most therapeutic agents to the brain. Intra-arterial (IA) infusion of hyperosmotic mannitol has been widely used to open the BBB and improve parenchymal targeting, but the extent of BBB disruption has varied widely with therapeutic outcomes often being unpredictable. In this work, we show that real-time MRI can enable fine-tuning of the infusion rate to adjust and predict effective and local brain perfusion in mice, and thereby can be allowed for achieving the targeted and localized BBB opening (BBBO). Both the reproducibility and safety are validated by MRI and histology. The reliable and reproducible BBBO we developed in mice will allow cost-effective studies on the biology of the BBB and drug delivery to the brain. In addition, the IA route for BBBO also permits subsequent IA delivery of a specific drug during the same procedure and obtains high targeting efficiency of the therapeutic agent in the targeted tissue, which has great potential for future clinical translation in neuro-oncology, regenerative medicine and other neurological applications

Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials

Brain and spinal tumors affect 1 in 1000 people by 25 years of age, and have diverse histological, biological, anatomical and dissemination characteristics. A mortality of 30–40% means the majority are cured, although two-thirds have life-long disability, linked to accumulated brain injury that is acquired prior to diagnosis, and after surgery or chemo-radiotherapy. Only four drugs have been licensed globally for brain tumors in 40 years and only one for children. Most new cancer drugs in clinical trials do not cross the blood–brain barrier (BBB). Techniques to enhance brain tumor drug delivery are explored in this review, and cover those that augment penetration of the BBB, and those that bypass the BBB. Developing appropriate delivery techniques could improve patient outcomes by ensuring efficacious drug exposure to tumors (including those that are drug-resistant), reducing systemic toxicities and targeting leptomeningeal metastases. Together, this drug delivery strategy seeks to enhance the efficacy of new drugs and enable re-evaluation of existing drugs that might have previously failed because of inadequate delivery. A literature review of repurposed drugs is reported, and a range of preclinical brain tumor models available for translational development are explored