Exile Vol. XXXIX No. 1

Title Page by Ellen Gurley \u2793 i Epigraph by Ezra Poind ii Table of Contents iii-iv Remaining a Soldier by Kristin Kruse \u2793 1-2 Vietnam War Memorial by Brooke MacKaye 3 We both ride in back by Chris Macaluso \u2793 4 Artwork by Jamie Oliver \u2794 5 Liberal Dirge #1 by Charis Brummitt \u2796 6-7 Artwork (anonymous) 7 Two ex-lovers and a dirty glass door by Chris Macaluso \u2793 8 The Salt of the Air by Kristen Padden \u2793 9-12 Artwork (anonymous) 13 Artwork by Ellen Gurley \u2793 14 Sun-Child by Jen Rudgers \u2796 15 Crazy Horse by Kevin Nix \u2794 16 The Fall of the Western Field by Rich Croft \u2793 17 In the Closet by Beth Widmaier \u2795 18 Winter Strawberries by Katy Rudder \u2793 19 Still Life (anonymous) 19 For This and Much Beyond This Poem by Matt Wanat \u2795 20-21 Artwork by Peggy Ryan \u2793 22 The Cycle Repeats: Apathy by Ishak Kang \u2793 23 The Judge by Ellen Gurley \u2793 24 Pear Colored by Erin Dempsey \u2793 25-26 4-Square by Trey Dunham \u2794 27 Artwork by Jamie Oliver \u2794 28 Ink & Heroine by Rich Croft \u2793 29 Figments by Craig Bowers \u2793 30-31 Malfi Coast (anonymous) 31 Suzanne (anonymous) 32 Hey Stella by Carey Chistie \u2795 33 Turning Leaves by Erin Lott \u2796 34-35 Reclining Nude (anonymous) 35 Blazon by Matt Wanat \u2795 36-37 Artwork by Holly Aikens \u2793 38 Awake by A. Fair \u2796 39 Dell the Barber by Kevin Nix \u2795 40 Artwork by Holly Aikens \u2793 40 Tree House by Katy Rudder \u2793 41-46 Jailbait by Ellison J. Stind \u2795 47 Mother by Charis Brummitt \u2796 48-49 Artwork by Bess Hammer \u2795 49 Private Origami by Trey Dunham \u2794 50 Among the Tendrils of Sleep by J. Trevett Allen \u2795 51 Poet of the Unforgiven by Carey Christie \u2795 52 Stuntman Steve by Andrew Zobay \u2793 53 sculpture by Lily Streett \u2794 53 Wonderings of an Adopted Son by Andy Heckert \u2793 54-55 Artwork by Holly Aikens \u2793 55 Odd Binge by C. N. Polumbus \u2793 56-57 Artwork by Holly Aikens \u2793 57 Artwork by Peggy Ryan \u2793; untitled by Jennifer Wendell \u2794 (superimposed) 58 Shadows of Pearl by Travis Brady \u2793 59-60 October/Rt. 161 by Annette Gallagher 61 Artwork by Jamie Oliver \u2794 61 The Influx by Craig Bowers \u2793 62 Artwork by Michael Norpell \u2794 63 editorial board 64 Editorial decision is shared equally among the Editorial Board. -64 Cover: Jamie Oliver -64 NOTE: With the exeption of Malfi Coast , all artwork listed as anonymous in the published table of contents appears to be signed by Ellen Gurley. 37th Yea

Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

In addition to lowering low density lipoprotein-cholesterol (LDL-C), statin therapy also raises high density lipoprotein-cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation

Exile Vol. XL No. 2

38th Year Title Page by Carrie Horner \u2797 i Epigraph by Ezra Pound ii Table of Contents iii-iv Remembering Sundays by Allison Lemieux \u2795 1 Untitled by James Oliver \u2794 2 \u2778 Beige Chevy Malibu by Craig J. McDonough \u2794 3-4 Brushtown Road by Lelei Jennings \u2795 5 In Memoriam: River Phoenix, 1970-93 by Kirstin Rogers \u2794 6 Untitled by Kira Pollack \u2794 7 Checkmate by Kevin Nix \u2794 8 Anywhere in Ohio by Jen Hanysh \u2795 9 Untitled by Nicky Taylor \u2794 10 Under Your Influence by Katherine Anne Campo \u2794 11 Tulips by Tricia B. Swearingen \u2794 12 Untitled by Keith Chapman \u2795 12 December Storm by Erin Lott \u2796 13-19 On Meeting Phil Levine After a Reading at Denison University April 6, 1993 by Christopher Harnish \u2794 20 The 422 Bypass by Joel Husenits \u2795 21 Untitled by Ken Tyburski \u2794 22 Shakespeare\u27s Foreskin by Carey Christie \u2795 23 The Thaw by Chris Iven \u2794 24 The Rockbridge County Fair by Morgan Roper \u2794 25 Let it Drop Through by Carey Christie \u2795 26-27 Aladdin\u27s by Paul Rinkes \u2794 28-29 Untitled by Aileen Jones \u2794 30 The Tango by Hope Layne Morgan \u2794 31 Icarus by Carey Christine \u2795 32-33 fad by Jeremy Aufrance \u2795 34 Untitled by James Oliver \u2794 35 Desert Villanelle by Christopher Harnish \u2794 36 The Skull by Nicky Taylor \u2794 37 Rodeo Bar by Carl Jeffrey Boon \u2796 38 I, Mordred by Carey Christie \u2795 39-43 Between Centuries by Leslie Dana Wells \u2794 44-45 Untitled by Carrie Horner \u2797 45 Untitled by Alex Emmons \u2796 46 Coleridge\u27s Curse by Allison Lemieux \u2795 47 Untitled by Jenny Baker \u2794 48 five by Jeremy Aufrance \u2795 49 Untitled by James Oliver \u2794 50 Lobster Boy by Kirstin Rogers \u2794 51 Fire on the Mountain by Christopher Harnish \u2794 52-53 Yosemite by Morgan Roper \u2794 54 Untitled by Carrie Horner \u2797 54 Untitled by Ken Tyburski \u2794 55 Sleepless Nights Fades to Credits by Allison Lemieux \u2794 56 Dancing Days by Julie McDonald \u2794 57 Immobile by Adrienne Fair \u2796 58-59 Untitled by Kira Pollack \u2794 60 Dorm Fire by Lisa Marie Antonille \u2795 Untitled by Carrie Horner \u2797 61 The Book by Matt Wanat \u2795 62-63 Distance by Carl Jeffrey Boon \u2796 64 Untitled by Jenny Baker \u2794 65 Cover by Ken Tyburski \u2794 Editorial decision is shared equally among the Editorial Board. -6

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

The challenges of genome-wide interaction studies: Lessons to learn from the analysis of HDL blood levels

Genome-wide association studies (GWAS) have revealed 74 single nucleotide polymorphisms (SNPs) associated with high-density lipoprotein cholesterol (HDL) blood levels. This study is, to our knowledge, the first genome-wide interaction study (GWIS) to identify SNP6SNP interactions associated with HDL levels. We performed a GWIS in the Rotterdam Study (RS) cohort I (RS-I) using the GLIDE tool which leverages the massively parallel computing power of Graphics Processing Units (GPUs) to perform linear regression on all genome-wide pairs of SNPs. By performing a meta-analysis together with Rotterdam Study cohorts II and III (RS-II and RS-III), we were able to filter 181 interaction terms with a p-value, 1 · 1028 that replicated in the two independent cohorts. We were not able to replicate any of these interaction term in the AGES, ARIC, CHS, ERF, FHS and NFBC-66 cohorts (Ntotal = 30, 011) when adjusting for multiple testing. Our GWIS resulted in the consistent finding of a possible interaction between rs774801 in ARMC8 (ENSG00000114098) and rs12442098 in SPATA8 (ENSG00000185594) being associated with HDL levels. However, p-values do not reach the preset Bonferroni correction of the p-values. Our study suggest that even for highly genetically determined traits such as HDL the sample sizes needed to detect SNP6SNP interactions are large and the 2-step filtering approaches do not yield a solution. Here we present our analysis plan and our reservations concerning GWIS

Multi-Ethnic Analysis of Lipid-Associated Loci: The NHLBI CARe Project

Background: Whereas it is well established that plasma lipid levels have substantial heritability within populations, it remains unclear how many of the genetic determinants reported in previous studies (largely performed in European American cohorts) are relevant in different ethnicities. Methodology/Principal Findings: We tested a set of $\sim$50,000 polymorphisms from $\sim$2,000 candidate genes and genetic loci from genome-wide association studies (GWAS) for association with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) in 25,000 European Americans and 9,000 African Americans in the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe). We replicated associations for a number of genes in one or both ethnicities and identified a novel lipid-associated variant in a locus harboring ICAM1. We compared the architecture of genetic loci associated with lipids in both African Americans and European Americans and found that the same genes were relevant across ethnic groups but the specific associated variants at each gene often differed. Conclusions/Significance: We identify or provide further evidence for a number of genetic determinants of plasma lipid levels through population association studies. In many loci the determinants appear to differ substantially between African Americans and European Americans

Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations

Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) $(p = 8.8×10^{−7} and p = 1.5×10^{−6}$ respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels $(p = 13.5×10^{−12})$. The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report

Determinants of Depressive Symptoms at 1 Year Following ICU Discharge in Survivors of $ 7 Days of Mechanical Ventilation : Results From the RECOVER Program, a Secondary Analysis of a Prospective Multicenter Cohort Study

Abstract : Background: Moderate to severe depressive symptoms occur in up to one-third of patients at 1 year following ICU discharge, negatively affecting patient outcomes. This study evaluated patient and caregiver factors associated with the development of these symptoms. Methods: This study used the Rehabilitation and Recovery in Patients after Critical Illness and Their Family Caregivers (RECOVER) Program (Phase 1) cohort of 391 patients from 10 medical/surgical university-affiliated ICUs across Canada. We determined the association between patient depressive symptoms (captured by using the Beck Depression Inventory II [BDI-II]), patient characteristics (age, sex, socioeconomic status, Charlson score, and ICU length of stay [LOS]), functional independence measure (FIM) motor subscale score, and caregiver characteristics (Caregiver Assistance Scale and Center for Epidemiologic Studies-Depression Scale) by using linear mixed models at time points 3, 6, and 12 months. Results: BDI-II data were available for 246 patients. Median age at ICU admission was 56 years (interquartile range, 45-65 years), 143 (58%) were male, and median ICU LOS was 19 days (interquartile range, 13-32 days). During the 12-month follow-up, 67 of 246 (27.2%) patients had a BDI-II score ≥ 20, indicating moderate to severe depressive symptoms. Mixed models showed worse depressive symptoms in patients with lower FIM motor subscale scores (1.1 BDI-II points per 10 FIM points), lower income status (by 3.7 BDI-II points; P = .007), and incomplete secondary education (by 3.8 BDI-II points; P = .009); a curvilinear relation with age (P = .001) was also reported, with highest BDI-II at ages 45 to 50 years. No associations were found between patient BDI-II and comorbidities (P = .92), sex (P = .25), ICU LOS (P = .51), or caregiver variables (Caregiver Assistance Scale [P = .28] and Center for Epidemiologic Studies Depression Scale [P = .74]). Conclusions: Increased functional dependence, lower income, and lower education are associated with increased severity of post-ICU depressive symptoms, whereas age has a curvilinear relation with symptom severity. Knowledge of risk factors may inform surveillance and targeted mental health follow-up. Early mobilization and rehabilitation aiming to improve function may serve to modify mood disorders

Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.METHODS AND RESULTS: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p&lt;1×10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p&lt;5×10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment.CONCLUSIONS: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.</p