Exile Vol. XLII No. 1

40th Year Title Page by Sakura Yamamoto \u2797 i Epigraph by Ezra Pound ii Table of Contents iii / Untitled (artwork) by Gretchen Hambly \u2796 iv Breughel Again, Brussels by Adrienne Fair \u2796 1 for play with whitman by alex e blazer \u2797 4 Saeta Sunday by Carl Boon \u2796 5 An Abbreviated Life by Mike Westmoreland 6 Anthem of Governor\u27s Bay by Jamey Hein \u2796 7-10 Time is everywhere, yet nowhere (artwork) by Susanne Ducker \u2796 11 Crosses by Liz Bolyard \u2796 12 Raccoons at the Cats\u27 Food by Jennifer Rudgers \u2796 13-14 Father Federico by Trish Klei \u2797 15 Dream Poem I by Colin Bossen \u2798 16 Virgin Mary in Kentucky by Amy Ard \u2796 17 the jig is up by alex e blazer \u2797 18-20 Visiting Uncle Ernie by Liz Bolyard \u2796 21-22 A Capuchin Monk by Linda Fuller-Smith 23 Sunday, October 15, 1995 by Carl Boon \u2796 24 Old Man and the Marriage Party by Trish Klei \u2797 25 Untitled (artwork) by Gretchen Hambly \u2796 26 Cowboy Up by J. Murdoch Be Matheson \u2796 27-34 Fragments by Colin Bossen \u2798 35 meditation (artwork) by alex e blazer \u2797 36 Palazzo Rezzonico by Linda Fuller-Smith 37 A Poem About The Photographic Imprint I Would Leave If A Nuclear Bomb Hit Nearby As I Took Out The Trash One Night by Trish Klei \u2797 38 The Crazies I\u27ve Called by Julie Johnston \u2796 39-46 Contributors\u27 Notes 47-48 Editorial Board 49 Editorial decisions are shared equally among the Editorial Board. -49 Cover art by alex emmons -4

Exile Vol. XLI

39th Year Cover Art by Elisa Gargarelle \u2795 (quote from J.D. Salinger\u27s Catcher in the Rye) untitled by Aileen Jones \u2797 i Girl by Colin Bossen \u2798 1 sun by Alex Blazer \u2796 2 Shifting by Alex Blazer \u2796 2 The Fish by Sarah Ramsey \u2795 3 New Woman by Lisa Stillman \u2795 4 Why by Lelei Jennings \u2795 5 Camel Cafe by Jeremy Aufrance \u2795 5 Jenny by Lizzy Loud \u2795 6 Beautiful Dreamer by Melissa Bostrom \u2796 7 Rising by Lizzy Loud \u2795 12 Pinsetter by Jeremy Aufrance \u2795 13 A Greater Distance by Jeff Boon \u2795 14 Shiho by Jeff Boon \u2795 15 Sub-stance by Alex Blazer \u2796 15 Sisters by Gretchen Hambley \u2796 16 Anne Sexton by Allison Lemieux \u2796 17 The Holy Grail... by Ed Shim \u2795 17 untitled by Liz Bolyard \u2796 18 23 by Keith Chapman \u2795 18 Bang, Zoom! by Victoria Lyall \u2796 19 Gabe and Me by Heather Trabert \u2797 20 Tornado Summer by Liz Bolyard \u2796 21 Nude by Elise Gargarella \u2795 21 Why I can\u27t tell short stories by Colin Bossen \u2798 22 america by Lynn Tramonte \u2798 24 Upon Being Asked... by Matt Makman \u2796 24 Being Azra by Lynn Tramonte \u2798 25 Mystic Truths by Adrienne Binni \u2795 27 King\u27s Court by Elisha Gargarella \u2795 27 Incense by Erin Lott \u2796 28 Sunday Morning... by Lisa Stillman \u2795 33 untitled by Elisa Gargarella \u2795 33 Quien no ha visto... by Adrienne Binni \u2795 34 The Space Between Us by Allison Lemieux \u2795 35 searching for the Bermuda... by Victoria Lyall \u2796 35 untitled by Man Chhoa \u2796 36 The Hunted by J. Murdoch Matheson \u2796 37 Editorial decisions are shared equally among the editorial board. -4

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

IFITM3 restricts the morbidity and mortality associated with influenza

The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses1, 2, 3, 4, 5, 6, 7. Both the magnitude and breadth of the IFITM proteins’ in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model8, we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 ‘Spanish’ influenza9, 10. Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and human

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Some Aspects of the Whole Plant Physiology of Selected Short Stature Wheat Cultivars

Since their initial release in 1961 short stature wheats of Norin 10 origin have, by virtue of their grain yield potential, made a dramatic impact on wheat breeding programmes in every country where the crop is produced. In an attempt to define the physiological components concerned in this enhanced grain yield potential, some aspects of whole plant physiology of some Norin 10 derivatives were examined and compared with a standard height Australian cultivar of the Gabo type. The research programme incorporated a study of - a) Morphogenetic changes associated with physiological development, on the basis of the whole plant. b) Analysis of morphological and physiological characteristics of the growth cycle of the plant. c) Plant parameters affected by nitrogen fertilizer in two field environments