Trouvaille: A Conversation About the Proofs of Maurice Blanchot’s L’Entretien Infini at Houghton Library

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Real-time COVID-19 hospital admissions forecasting with leading indicators and ensemble methods in England

Hospitalisations from COVID-19 with Omicron sub-lineages have put a sustained pressure on the English healthcare system. Understanding the expected healthcare demand enables more effective and timely planning from public health. We collect syndromic surveillance sources, which include online search data, NHS 111 telephonic and online triages. Incorporating this data we explore generalised additive models, generalised linear mixed-models, penalised generalised linear models and model ensemble methods to forecast over a two-week forecast horizon at an NHS Trust level. Furthermore, we showcase how model combinations improve forecast scoring through a mean ensemble, weighted ensemble, and ensemble by regression. Validated over multiple Omicron waves, at different spatial scales, we show that leading indicators can improve performance of forecasting models, particularly at epidemic changepoints. Using a variety of scoring rules, we show that ensemble approaches outperformed all individual models, providing higher performance at a 21-day window than the corresponding individual models at 14-days. We introduce a modelling structure used by public health officials in England in 2022 to inform NHS healthcare strategy and policy decision making. This paper explores the significance of ensemble methods to improve forecasting performance and how novel syndromic surveillance can be practically applied in epidemic forecasting

Interstitial lung disease in the elderly

Background Despite the relationship between idiopathic pulmonary fibrosis (IPF) and advancing age, little is known about the epidemiology of interstitial lung disease (ILD) in the elderly. We describe the diagnoses, clinical characteristics, and outcomes of patients who were elderly at the time of ILD diagnosis. Methods Among subjects from a prospective cohort study of ILD, elderly was defined as age ≥ 70 years. Diagnoses were derived from a multidisciplinary review. Differences between elderly and nonelderly groups were determined using the χ2 test and analysis of variance. Results Of the 327 subjects enrolled, 80 (24%) were elderly. The majority of elderly subjects were white men. The most common diagnoses were unclassifiable ILD (45%), IPF (34%), connective tissue disease (CTD)-ILD (11%), and hypersensitivity pneumonitis (8%). Most elderly subjects (74%) with unclassifiable ILD had an imaging pattern inconsistent with usual interstitial pneumonia (UIP). There were no significant differences in pulmonary function or 3-year mortality between nonelderly and elderly subjects combined or in a subgroup analysis of those with IPF. Conclusions Although IPF was the single most common diagnosis, the majority of elderly subjects had non-IPF ILD. Our findings highlight the need for every patient with new-onset ILD, regardless of age, to be surveyed for exposures and findings of CTD. Unclassifiable ILD was common among the elderly, but for most, the radiographic pattern was inconsistent with UIP. Although the effect of ILD may be more pronounced in the elderly due to reduced global functionality, ILD was not more severe or aggressive in this group

Inhibitors of Foot and Mouth Disease Virus Targeting a Novel Pocket of the RNA-Dependent RNA Polymerase

Foot-and-Mouth Disease Virus (FMDV) is a picornavirus that infects cloven-hoofed animals and leads to severe losses in livestock production. In the case of an FMD outbreak, emergency vaccination requires at least 7 days to trigger an effective immune response. There are currently no approved inhibitors for the treatment or prevention of FMDV infections.Using a luciferase-based assay we screened a library of compounds and identified seven novel inhibitors of 3Dpol, the RNA-dependent RNA polymerase of FMDV. The compounds inhibited specifically 3Dpol (IC(50)s from 2-17 µM) and not other viral or bacterial polymerases. Enzyme kinetic studies on the inhibition mechanism by compounds 5D9 and 7F8 showed that they are non-competitive inhibitors with respect to NTP and nucleic acid substrates. Molecular modeling and docking studies into the 3Dpol structure revealed an inhibitor binding pocket proximal to, but distinct from the 3Dpol catalytic site. Residues surrounding this pocket are conserved among all 60 FMDV subtypes. Site directed mutagenesis of two residues located at either side of the pocket caused distinct resistance to the compounds, demonstrating that they indeed bind at this site. Several compounds inhibited viral replication with 5D9 suppressing virus production in FMDV-infected cells with EC(50) = 12 µM and EC(90) = 20 µM).We identified several non-competitive inhibitors of FMDV 3Dpol that target a novel binding pocket, which can be used for future structure-based drug design studies. Such studies can lead to the discovery of even more potent antivirals that could provide alternative or supplementary options to contain future outbreaks of FMD

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

Exposure to ambient particulate matter is associated with accelerated functional decline in idiopathic pulmonary fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis (IPF), a progressive disease with an unknown pathogenesis, may be due in part to an abnormal response to injurious stimuli by alveolar epithelial cells. Air pollution and particulate inhalation of matter evoke a wide variety of pulmonary and systemic inflammatory diseases. We therefore hypothesized that increased average ambient particulate matter (PM) concentrations would be associated with an accelerated rate of decline in FVC in IPF. METHODS: We identified a cohort of subjects seen at a single university referral center from 2007 to 2013. Average concentrations of particulate matter < 10 and < 2.5 μg/m3 (PM10 and PM2.5, respectively) were assigned to each patient based on geocoded residential addresses. A linear multivariable mixed-effects model determined the association between the rate of decline in FVC and average PM concentration, controlling for baseline FVC at first measurement and other covariates. RESULTS: One hundred thirty-five subjects were included in the final analysis after exclusion of subjects missing repeated spirometry measurements and those for whom exposure data were not available. There was a significant association between PM10 levels and the rate of decline in FVC during the study period, with each μg/m3 increase in PM10 corresponding with an additional 46 cc/y decline in FVC (P = .008). CONCLUSIONS: Ambient air pollution, as measured by average PM10 concentration, is associated with an increase in the rate of decline of FVC in IPF, suggesting a potential mechanistic role for air pollution in the progression of disease

Submarine volcanic morphology of the western Galapagos based on EM300 bathymetry and MR1 side-scan sonar

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 8 (2007): Q03010, doi:10.1029/2006GC001464.A compilation of high-resolution EM300 multibeam bathymetric and existing MR1 side-scan sonar data was used to investigate the volcanic morphology of the flanks of the western Galápagos Islands. The data portray an assortment of constructional volcanic features on the shallow to deep submarine flanks of Fernandina, Isabela, and Santiago Islands, including rift zones and groups of cones that are considered to be the primary elements in constructing the archipelagic apron. Ten submarine rift zones were mapped, ranging in length from 5 to 20 km, comparable in length to western Canary Island rift zones but significantly shorter than Hawaiian submarine rift zones. A detailed analysis of the northwestern Fernandina submarine rift, including calculated magnetization from a surface-towed magnetic study, suggests that the most recent volcanism has focused at the shallow end of the rift. Small submarine volcanic cones with various morphologies (e.g., pointed, cratered, and occasionally breached) are common in the submarine western Galápagos both on rift zones and on the island flanks where no rifts are present. At depths greater than ∼3000 m, large lava flow fields in regions of low bathymetric relief have been previously identified as a common seafloor feature in the western Galápagos by Geist et al. (2006); however, their source(s) remained enigmatic. The new EM300 data show that a number of the deep lava flows originate from small cones along the mid-lower portion of the NW submarine rift of Fernandina, suggesting that the deep flows owe their origin, at least in part, to submarine rift zone volcanism.Data collected on TN188 was funded by NSF grant OCE0326148 and NOAA grant NA04OAR460009 to S.M.W. Support for data collected on previous multibeam and MR1 cruises was provided by NSF grants OCE9811504 and OCE0002461 (D.J.F.)

Crystal Structure of Legionella DotD: Insights into the Relationship between Type IVB and Type II/III Secretion Systems

The Dot/Icm type IVB secretion system (T4BSS) is a pivotal determinant of Legionella pneumophila pathogenesis. L. pneumophila translocate more than 100 effector proteins into host cytoplasm using Dot/Icm T4BSS, modulating host cellular functions to establish a replicative niche within host cells. The T4BSS core complex spanning the inner and outer membranes is thought to be made up of at least five proteins: DotC, DotD, DotF, DotG and DotH. DotH is the outer membrane protein; its targeting depends on lipoproteins DotC and DotD. However, the core complex structure and assembly mechanism are still unknown. Here, we report the crystal structure of DotD at 2.0 Å resolution. The structure of DotD is distinct from that of VirB7, the outer membrane lipoprotein of the type IVA secretion system. In contrast, the C-terminal domain of DotD is remarkably similar to the N-terminal subdomain of secretins, the integral outer membrane proteins that form substrate conduits for the type II and the type III secretion systems (T2SS and T3SS). A short β-segment in the otherwise disordered N-terminal region, located on the hydrophobic cleft of the C-terminal domain, is essential for outer membrane targeting of DotH and Dot/Icm T4BSS core complex formation. These findings uncover an intriguing link between T4BSS and T2SS/T3SS

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