Sex workers perspectives on strategies to reduce sexual exploitation and HIV risk: a qualitative study in Tijuana, Mexico.

Globally, female sex workers are a population at greatly elevated risk of HIV infection, and the reasons for and context of sex industry involvement have key implications for HIV risk and prevention. Evidence suggests that experiences of sexual exploitation (i.e., forced/coerced sex exchange) contribute to health-related harms. However, public health interventions that address HIV vulnerability and sexual exploitation are lacking. Therefore, the objective of this study was to elicit recommendations for interventions to prevent sexual exploitation and reduce HIV risk from current female sex workers with a history of sexual exploitation or youth sex work. From 2010-2011, we conducted in-depth interviews with sex workers (n = 31) in Tijuana, Mexico who reported having previously experienced sexual exploitation or youth sex work. Participants recommended that interventions aim to (1) reduce susceptibility to sexual exploitation by providing social support and peer-based education; (2) mitigate harms by improving access to HIV prevention resources and psychological support, and reducing gender-based violence; and (3) provide opportunities to exit the sex industry via vocational supports and improved access to effective drug treatment. Structural interventions incorporating these strategies are recommended to reduce susceptibility to sexual exploitation and enhance capacities to prevent HIV infection among marginalized women and girls in Mexico and across international settings

Topology, Quantum Gravity and Particle Physics

It is argued that quantum gravity has an interpretation as a topological field theory provided a certain constraint from the path intergral measure is respected. The constraint forces us to couple gauge and matter fields to gravity for space - time dimensions different from 3. We then discuss possible models which may be relevant to our universe.Comment: 18 pages, LaTeX. Replaced version corrects typos and has additional reference

Las nuevas relaciones entre la psiquiatría y la atención primaria: Experiencia británica.

Se describe aquí un importante y reciente desarrollo en el campo de la psiquiatría comunitaria en Gran Bretaña: las relaciones entre la atención psiquiátrica y la atención primaria de salud. Presentando un acercamiento a la atención psiquiátrica comunitaria que puede ser complementaria a los que recientemente se están desarrollando en Españ

Las nuevas relaciones entre la psiquiatría y la atención primaria: Experiencia británica.

Se describe aquí un importante y reciente desarrollo en el campo de la psiquiatría comunitaria en Gran Bretaña: las relaciones entre la atención psiquiátrica y la atención primaria de salud. Presentando un acercamiento a la atención psiquiátrica comunitaria que puede ser complementaria a los que recientemente se están desarrollando en Españ

BLACK HOLE MULTIPLETS AND SPONTANEOUS BREAKING OF LOCAL SUPERSYMMETRY

We classify states saturating a double or a single supersymmetric positivity bound of a four-dimensional N=4 supersymmetry. The massive four-dimensional double-bound states (Bogomolny states) are shown to form a light-like representation of ten-dimensional supersymmetry. The single-bound states form a massive representation (centrino multiplet) of a four-dimensional supersymmetry. The first component of the centrino multiplet is identified with extreme black holes with regular horizon which have one quarter of unbroken supersymmetry. The centrino multiplet includes a massive spin 3/2 state, the centrino, as a highest spin state. Existence of massive black hole supermultiplets may affect the massless sector of the theory. Assuming that gluino condensate is formed one can study its properties. The bilinear combination of covariantly constant Killing spinors supplies the possible form for a gluino condensate. The condensate has null properties, does not introduce a cosmological constant, and may lead to a spontaneous breaking of local supersymmetry. This suggests that centrino may provide a consistent super-Higgs mechanism.Comment: 15 pages, LaTe

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

P08.36 Radioresistance of glioblastoma stem-like cells is associated with DNA replication stress, which is a promising therapeutic target

Introduction: The inevitability of tumour recurrence in glioblastoma (GBM) patients despite multi-modality treatment consisting of surgery, radiotherapy and chemotherapy, is reflected by a median survival of only 14 months. Tumour recurrence is thought to be driven by a small population of glioblastoma stem-like cells (GSCs) that are resistant to conventional therapies. DNA damage response (DDR) pathways have been shown to be up-regulated in GSCs and implicated in radioresistance and treatment failure. However the precise cause of enhanced DDR signalling in GSCs and the extent to which these signalling networks contribute to therapy resistance remains elusive. The objectives of this study were to investigate the underlying cause of DDR upregulation and treatment resistance in GSCs with a view to identifying novel and promising therapeutic targets. Materials and Methods: A panel of primary patient derived GBM cell lines cultured under conditions to enrich for or deplete the tumour stem cell population (GSC vs bulk respectively) were utilised in order to investigate enhanced GSC DDR under basal conditions and in response to ionising radiation. Confirmatory studies were also performed in cells sorted for the putative GSC marker CD133. The effects of a panel of small molecule DDR inhibitor agents on cell survival in GSC and bulk cells were quantified. Results: GSCs exhibited higher levels of total and activated DDR targets ATR, CHK1, ATM and PARP1 under basal conditions and were radioresistant compared to paired bulk populations. This was not due to increased levels of reactive oxygen species (ROS). Instead, we show that RPA is significantly higher in replicating GSCs and confirm by DNA fibre assays that GSCs and CD133+ cells have increased numbers of stalled replication forks, fewer new origins and slower DNA replication compared to bulk or CD133- populations, demonstrating for the first time that replication stress (RS) is a hallmark of GSCs. We identify increased expression of long neural genes as a likely mechanism for RS and DNA double strand breaks (DSBs) in GSCs and show that their radioresistance is reversed by dual inhibition of key RS and DDR proteins ATR and PARP. Conclusions: This study demonstrates the novel finding that replication stress is a hallmark of GSCs and resonates with recently published studies in neural progenitor cells showing that RS preferentially induces DNA DSB in long neural genes. Taken together, we implicate RS as a driver of enhanced DDR in GSCs and identify novel therapeutics with potential to improve clinical outcomes by overcoming the radioresistance of GB