Reviews

Where the Shadows Lie: A Jungian Interpretation of Tolkien\u27s The Lord of the Rings. Pia Skogemann. Reviewed by Edith L. Crowe. Finding Oz: How L. Frank Baum Discovered the Great American Story. Evan I. Schwartz. Reviewed by Richard Tuerk. Out of My Bone: The Letters of Joy Davidman. Ed. Don W. King. Reviewed by Joe R. Christopher. Collected Poems. Mervyn Peake, edited with an introduction by R.W. Maslen. Reviewed by David Bratman. C.S. Lewis on the Final Frontier: Science and the Supernatural in the Space Trilogy. Sanford Schwartz. Reviewed by Joe R. Christopher. Death and Fantasy: Essays on Philip Pullman, C.S. Lewis, George MacDonald, And R.L. Stevenson. William Gray. Reviewed by David D. Oberhelman. Stephen R. Donaldson and the Modern Epic Vision. Christine Barkley; Series editors Donald E. Palumbo and C. W. Sullivan III. Jefferson. Reviewed by Kim Coleman Healy. The Fantastic Horizon: Essays and Reviews. Darrell Schweitzer. Reviewed by David Bratman

Reviews

Lilith in a New Light: Essays on the George Macdonald Fantasy Novel. Ed. Lucas H. Harriman. Reviewed by William Gray. Black & White Ogre Country: The Lost Tales of Hilary Tolkien. Edited by Angela Gardner. Illustrated by Jef Murray. Reviewed by Glen GoodKnight. C.S. Lewis and the Search for Rational Religion. John Beversluis. Reviewed by Donald T. Williams. Faith and Choice in the Works of Joss Whedon. K.. Dale Koontz. Reviewed by Amy H. Sturgis. Fritz Leiber, Critical Essays. Ed. Benjamin Szumskyj. Reviewed by Darrell Schweitzer. Myth and Magic: Art according to the Inklings. Eduardo Segura and Thomas Honegger. Reviewed by Jason Fisher. From Narnia to a Space Odyssey: The War of Ideas between Arthur C. Clarke And C. S. Lewis. Ed., and with introduction, by Ryder W. Miller. Reviewed by Joe R. Christopher. The Mirror Crack\u27d: Fear and Horror in JRR Tolkien\u27s Major Works. Ed. Lynn Forest-Hill. Reviewed by Edith L. Crowe. Arda Reconstructed: The Creation of the Published Silmarillion. Douglas Charles Kane. Reviewed by Jason Fisher. Night Operation. Owen Barfield. Reviewed by David Bratman. Eager Spring. Owen Barfield. Reviewed by David Bratman

Australia\u27s health 1994 : the fourth biennial report of the Australian Institute of Health and Welfare

Australia\u27s Health is the most comprehensive and authoritative source of national information on health in Australia. Australia\u27s Health is published mid-year in even-numbered years and provides national statistics and related information that form a record of health status, service provision and expenditure in Australia

A Centennial Retrospective on Charles Williams

Edited transcript of a panel discussion (including audience contributions) at the 17th Mythopoeic Society Conference

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

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

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

Miner slams Hill decision: Atheist PM

PRS