The relationship between recalled self-esteem as a child and current levels of professional burnout among Anglican clergy in England

This study links and tests three strands of theory concerned with explaining individual differences in levels of professional burnout in general and among religious professionals in particular. These three strands concern the significance of current self-esteem, recalled self-esteem as a child, and personality. Data were provided by a sample of 1,278 male stipendiary parochial clergy working in the Church of England who completed the modified Maslach Burnout Inventory (specially designed for use among clergy), and the short-form Revised Eysenck Personality Questionnaire (designed to measure the personality dimensions of extraversion, neuroticism and psychoticism), together with a semantic differential index of recalled self-esteem as a child. The bivariate correlation coefficients demonstrated significant associations between more positive self-esteem as a child and lower levels of professional burnout (higher personal accomplishment, lower emotional exhaustion and lower depersonalisation). The bivariate correlation coefficients also demonstrated significant associations between personality and professional burnout. Multiple regression analyses, however, demonstrated that the association between recalled self-esteem as a child and professional burnout largely disappeared after controlling for the personality variables. The conclusion is drawn that knowledge about the personality profile of clergy functions as a more secure predictor of susceptibility to professional burnout than knowledge about recalled self-esteem as a child

Working out abjection in the Panapompom bêche-de-mer fishery: Race, economic change and the future in Papua New Guinea

This is the accepted version of the following article: Rollason, W. (2010), Working out abjection in the Panapompom bêche-de-mer fishery: Race, economic change and the future in Papua New Guinea. The Australian Journal of Anthropology, 21: 149–170. doi: 10.1111/j.1757-6547.2010.00076.x, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/j.1757-6547.2010.00076.x/abstract.This is a paper about how men from Panapompom, an island in Milne Bay Province of Papua New Guinea (PNG), understand how they relate to white people and imagine the future. Until recently, men from Panapompom understood themselves to be engaged in a project of ‘development’, in which they would become more and more similar to white people. This was a desirable future. However, changes in the way Panapompom men work for money have resulted in a very different imagination of the future—one in which Panapompom people are not getting whiter, but blacker, and hence more and more excluded from the lives to which they aspire. Men now dive for bêche-de-mer, work which they regard as being particularly hard and dangerous. Diving has profound effects on the skin, blackening and hardening it, leading Panapompom men to liken themselves to the machines that create the wealth that white people use. These ‘mechanising’ effects that diving has on the black body lead men to see white people as the sole beneficiaries of the bêche-de-mer industry, and black people as mere tools or extensions. For bêche-de-mer divers, value and desired forms of life are lodged in Australia, Europe or America, while they find themselves excluded from this future by their growing blackness.ESR

Toca 511 gene transfer and treatment with the prodrug, 5-fluorocytosine, promotes durable antitumor immunity in a mouse glioma model.

BackgroundToca 511 (vocimagene amiretrorepvec) is a retroviral replicating vector encoding an optimized yeast cytosine deaminase (CD). Tumor-selective expression of CD converts the prodrug, 5-fluorocytosine (5-FC), into the active chemotherapeutic, 5-fluorouracil (5-FU). This therapeutic approach is being tested in a randomized phase II/III trial in recurrent glioblastoma and anaplastic astrocytoma (NCT0241416). The aim of this study was to identify the immune cell subsets contributing to antitumor immune responses following treatment with 5-FC in Toca 511-expressing gliomas in a syngeneic mouse model.MethodsFlow cytometry was utilized to monitor and characterize the immune cell infiltrate in subcutaneous Tu-2449 gliomas in B6C3F1 mice treated with Toca 511 and 5-FC.ResultsTumor-bearing animals treated with Toca 511 and 5-FC display alterations in immune cell populations within the tumor that result in antitumor immune protection. Attenuated immune subsets were exclusive to immunosuppressive cells of myeloid origin. Depletion of immunosuppressive cells temporally preceded a second event which included expansion of T cells which were polarized away from Th2 and Th17 in the CD4+ T cell compartment with concomitant expansion of interferon gamma-expressing CD8+ T cells. Immune alterations correlated with clearance of Tu-2449 subcutaneous tumors and T cell-dependent protection from future tumor challenge.ConclusionsTreatment with Toca 511 and 5-FC has a concentrated effect at the site of the tumor which causes direct tumor cell death and alterations in immune cell infiltrate, resulting in a tumor microenvironment that is more permissive to establishment of a T cell mediated antitumor immune response

Algorithmic Randomness and Capacity of Closed Sets

We investigate the connection between measure, capacity and algorithmic randomness for the space of closed sets. For any computable measure m, a computable capacity T may be defined by letting T(Q) be the measure of the family of closed sets K which have nonempty intersection with Q. We prove an effective version of Choquet's capacity theorem by showing that every computable capacity may be obtained from a computable measure in this way. We establish conditions on the measure m that characterize when the capacity of an m-random closed set equals zero. This includes new results in classical probability theory as well as results for algorithmic randomness. For certain computable measures, we construct effectively closed sets with positive capacity and with Lebesgue measure zero. We show that for computable measures, a real q is upper semi-computable if and only if there is an effectively closed set with capacity q

Retroviral replicating vector-mediated gene therapy achieves long-term control of tumor recurrence and leads to durable anticancer immunity.

BackgroundProdrug-activator gene therapy with Toca 511, a tumor-selective retroviral replicating vector (RRV) encoding yeast cytosine deaminase, is being evaluated in recurrent high-grade glioma patients. Nonlytic retroviral infection leads to permanent integration of RRV into the cancer cell genome, converting infected cancer cell and progeny into stable vector producer cells, enabling ongoing transduction and viral persistence within tumors. Cytosine deaminase in infected tumor cells converts the antifungal prodrug 5-fluorocytosine into the anticancer drug 5-fluorouracil, mediating local tumor destruction without significant systemic adverse effects.MethodsHere we investigated mechanisms underlying the therapeutic efficacy of this approach in orthotopic brain tumor models, employing both human glioma xenografts in immunodeficient hosts and syngeneic murine gliomas in immunocompetent hosts.ResultsIn both models, a single injection of replicating vector followed by prodrug administration achieved long-term survival benefit. In the immunodeficient model, tumors recurred repeatedly, but bioluminescence imaging of tumors enabled tailored scheduling of multicycle prodrug administration, continued control of disease burden, and long-term survival. In the immunocompetent model, complete loss of tumor signal was observed after only 1-2 cycles of prodrug, followed by long-term survival without recurrence for >300 days despite discontinuation of prodrug. Long-term survivors rejected challenge with uninfected glioma cells, indicating immunological responses against native tumor antigens, and immune cell depletion showed a critical role for CD4+ T cells.ConclusionThese results support dual mechanisms of action contributing to the efficacy of RRV-mediated prodrug-activator gene therapy: long-term tumor control by prodrug conversion-mediated cytoreduction, and induction of antitumor immunity

Radiosensitization of gliomas by intracellular generation of 5-fluorouracil potentiates prodrug activator gene therapy with a retroviral replicating vector.

A tumor-selective non-lytic retroviral replicating vector (RRV), Toca 511, and an extended-release formulation of 5-fluorocytosine (5-FC), Toca FC, are currently being evaluated in clinical trials in patients with recurrent high-grade glioma (NCT01156584, NCT01470794 and NCT01985256). Tumor-selective propagation of this RRV enables highly efficient transduction of glioma cells with cytosine deaminase (CD), which serves as a prodrug activator for conversion of the anti-fungal prodrug 5-FC to the anti-cancer drug 5-fluorouracil (5-FU) directly within the infected cells. We investigated whether, in addition to its direct cytotoxic effects, 5-FU generated intracellularly by RRV-mediated CD/5-FC prodrug activator gene therapy could also act as a radiosensitizing agent. Efficient transduction by RRV and expression of CD were confirmed in the highly aggressive, radioresistant human glioblastoma cell line U87EGFRvIII and its parental cell line U87MG (U87). RRV-transduced cells showed significant radiosensitization even after transient exposure to 5-FC. This was confirmed both in vitro by a clonogenic colony survival assay and in vivo by bioluminescence imaging analysis. These results provide a convincing rationale for development of tumor-targeted radiosensitization strategies utilizing the tumor-selective replicative capability of RRV, and incorporation of radiation therapy into future clinical trials evaluating Toca 511 and Toca FC in brain tumor patients

Building a Better Racetrack

We find IIb compactifications on Calabi-Yau orientifolds in which all Kahler moduli are stabilized, along lines suggested by Kachru, Kallosh, Linde and Trivedi.Comment: 47 pages, 1 figure, harvmac (v2: added references, minor comments, v3: improved discussion of metastability and explicit flux vacua

Hypermoduli Stabilization, Flux Attractors, and Generating Functions

We study stabilization of hypermoduli with emphasis on the effects of generalized fluxes. We find a class of no-scale vacua described by ISD conditions even in the presence of geometric flux. The associated flux attractor equations can be integrated by a generating function with the property that the hypermoduli are determined by a simple extremization principle. We work out several orbifold examples where all vector moduli and many hypermoduli are stabilized, with VEVs given explicitly in terms of fluxes.Comment: 45 pages, no figures; Version submitted to JHE