21 research outputs found

    Exile Vol. III No. 1

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    The Dreamer by Jesse Matlack 8-11 And Now a Response by John Kenower 12-16 Two Scenes from a Play by Robert Whitlatch 17-21 The Urgency of the Situation by Jim Gallant 22-23 James Branch Cabell by Robert Canary 24-29 Was Rasselt Im Stroh by Carol Dugle 30-31 Three Stops for an Artist by Nicos Stangos 32-36 POETRY Of Darkness by Burnell Chaney 16 Wolf in Sheep\u27s Clothing by Ellen Moore 21 Fresh Snow OR The Stars Have Fallen by Thomas Turnbull 29 When I Left Home by Yoko Kuyama 37 Standing Under a Tall Bare Tree by Yoko Kuyama 38 I Have Been Alone Too Long by Ellen Moore 40 Dirge: For Myself by Ellen Moore 40 In this issue the editors of EXILE are proud to publish Three Stops for an Artist by Nicos Stangos. This story has been awarded the semi-annual Denison Book Store - EXILE Creative Writing Prize

    Exile Vol. VI No. 2

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    EDITORIAL 4-5 Clearing in the Forest (woodcut) by Raymond Berger 6 Haiku (poems) by Jean Ludwig 7 Four in Another Punchbowl (story) 8-15 Untitled (etching) by Patricia Wagenhals 16 Staggering Sky (poem) by Robert Canary 16 Song (poem) by Christine Condit 17 Quadrangle (poem) by James Gallant 18-19 P Stands for Pole (story) by Lee Cullen 20-30 The Beachcomber (poem) by William Bennett 31 Harvest in Kansas (poem) by James Gallant 32 Awarded the semi-annual EXILE-Denison Bookstore Writing Prize: P Stands for Pole by Lee Cullen 20-3

    Exile Vol. V No. 2

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    EDITORIAL 4-6 Jamais (poem) by Iris Carroll 6 The Minister\u27s Narcissus by Julia Santucci 7-18 DRAWING by Anne Irgens 12 Solitude (poem) by Christine Condit 18 Island Lady\u27s Bill-Green Sky (poem) by Robert Wehling 19 Looking for Enchantment (poem) by Dennis Trudell 19 Silence (woodcut) by Carol Wilson 20 Saturday Night (story) by Ed Grimm 21-25 On Unemployment (poem) by William Bennett 25 Atlas (poem) by Bob Canary 26 A Psychology of Confrontation (essay) by Barbara Haupt 27-35 Urban (woodcut) by Carol Wilson 36 The Way They Make Guys (story) by Dennis Trudell 37-38 This story [ The Minister\u27s Narcissus ] by Julia Santucci has been awarded the semi-annual EXILE-Denison Bookstore creative writing prize. (pg 18

    Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

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    The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514

    The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor.

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    The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families

    Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry

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    Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635-0.677) in African and 0.844 (95% CI = 0.840-0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67-2.00) and 2.19 (95% CI = 2.14-2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659-0.700 and AUC = 0.845, 95% CI = 0.841-0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87-2.26 and OR = 2.21, 95% CI = 2.16-2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping

    Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.

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    Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10-180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset
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