John Cheever's relationship with the American magazine marketplace, 1930 to 1964

John Cheever published over two hundred short stories in an array of small-, mid-, and large-circulation magazines between 1930 and 1981. One hundred and twenty of these stories appeared in The New Yorker. During Cheever’s career and since his death in 1982, many critics have typically analysed his short stories in isolation from the conditions of their production, lest Cheever’s subversive modernist tendencies be confused with the conservative middlebrow ethos of The New Yorker, or the populist aspect of other large-circulation magazines. Critics, including Cheever’s daughter and his most recent biographer Blake Bailey, also claim that Cheever was a financial and, ultimately, artistic victim of the magazine marketplace. Drawing on largely unpublished editorial and administrative correspondence in the New Yorker Records and editorially annotated short story typescripts in the John Cheever Literary Manuscripts collection, and using a historicised close-reading practice, this thesis examines the influence of the magazine marketplace on the short fiction that Cheever produced between 1930 and 1964. It challenges the critical consensus by arguing that Cheever did not dissociate his authorship from commerciality at any point during his career, and consistently exploited the magazine marketplace to his financial and creative advantage, whether this meant temporarily producing stories for little magazines in the early 1930s and romance stories for mainstream titles in the 1940s, or selling his New Yorker rejections to its rivals, which he did throughout his career. Cheever also developed strong working relationships with his editors at The New Yorker during the 1940s and 1950s. This thesis re-evaluates these relationships by analysing comparatively the drafts, archival materials that have hitherto been neglected by critics, and published versions of some of Cheever’s best known New Yorker stories. In so doing, this thesis demonstrates the crucial role that editorial collaboration played in Cheever’s writing process

John Cheever's relationship with the American magazine marketplace, 1930 to 1964

John Cheever published over two hundred short stories in an array of small-, mid-, and large-circulation magazines between 1930 and 1981. One hundred and twenty of these stories appeared in The New Yorker. During Cheever’s career and since his death in 1982, many critics have typically analysed his short stories in isolation from the conditions of their production, lest Cheever’s subversive modernist tendencies be confused with the conservative middlebrow ethos of The New Yorker, or the populist aspect of other large-circulation magazines. Critics, including Cheever’s daughter and his most recent biographer Blake Bailey, also claim that Cheever was a financial and, ultimately, artistic victim of the magazine marketplace. Drawing on largely unpublished editorial and administrative correspondence in the New Yorker Records and editorially annotated short story typescripts in the John Cheever Literary Manuscripts collection, and using a historicised close-reading practice, this thesis examines the influence of the magazine marketplace on the short fiction that Cheever produced between 1930 and 1964. It challenges the critical consensus by arguing that Cheever did not dissociate his authorship from commerciality at any point during his career, and consistently exploited the magazine marketplace to his financial and creative advantage, whether this meant temporarily producing stories for little magazines in the early 1930s and romance stories for mainstream titles in the 1940s, or selling his New Yorker rejections to its rivals, which he did throughout his career. Cheever also developed strong working relationships with his editors at The New Yorker during the 1940s and 1950s. This thesis re-evaluates these relationships by analysing comparatively the drafts, archival materials that have hitherto been neglected by critics, and published versions of some of Cheever’s best known New Yorker stories. In so doing, this thesis demonstrates the crucial role that editorial collaboration played in Cheever’s writing process

'Reading landscape' : interdisciplinary approaches to understanding place

<p>This paper outlines a collaborative project between a group of Fine Art and Geography students who helped develop and contribute to a conversation about recording ‘place’. Introducing methodologies from both disciplines, the project started from the premise of all environmental ‘recordings’ being ‘inputs’ and so questioned what could be defined as ‘data’ when encountering a location. Brunel’s Grand Entrance to the Thames Tunnel (London) provided the motivation for 10 objective and subjective ‘recordings’ which were subsequently distilled into a smaller subset and then used to produce a short film that was presented at an international conference. Important to the collaborative nature of the project were ongoing opportunities to share equipment, techniques, material and references across disciplines. It was an experiment to measure the potential for ‘mapping’ to capture physical and historical information, as well as embodied experience.</p

Compartmentalized spatial profiling of the tumor microenvironment in head and neck squamous cell carcinoma identifies immune checkpoint molecules and tumor necrosis factor receptor superfamily members as biomarkers of response to immunotherapy

Mucosal head and neck squamous cell carcinoma (HNSCC) are the seventh most common cancer, with approximately 50% of patients living beyond 5 years. Immune checkpoint inhibitors (ICIs) have shown promising results in patients with recurrent or metastatic (R/M) disease, however, only a subset of patients benefit from immunotherapy. Studies have implicated the tumor microenvironment (TME) of HNSCC as a major factor in therapy response, highlighting the need to better understand the TME, particularly by spatially resolved means to determine cellular and molecular components. Here, we employed targeted spatial profiling of proteins on a cohort of pre-treatment tissues from patients with R/M disease to identify novel biomarkers of response within the tumor and stromal margins. By grouping patient outcome categories into response or non-response, we show that immune checkpoint molecules, including PD-L1, B7-H3, and VISTA, were differentially expressed. Patient responders possessed significantly higher tumor expression of PD-L1 and B7-H3, but lower expression of VISTA. Analysis of response subgroups by Response Evaluation Criteria in Solid Tumors (RECIST) criteria indicated that tumor necrosis factor receptor (TNFR) superfamily members including OX40L, CD27, 4-1BB, CD40, and CD95/Fas, were associated with immunotherapy outcome. OX40L expression in tumor regions was higher in patient-responders than those with progressive disease (PD), while other TNFR members, CD27 and CD95/Fas were lower expressed in patients with a partial response (PR) compared to those with PD. Furthermore, we found that high 4-1BB expression in the tumor compartment, but not in the stroma, was associated with better overall survival (OS) (HR= 0.28, p-adjusted= 0.040). Moreover, high CD40 expression in tumor regions (HR= 0.27, p-adjusted= 0.035), and high CD27 expression in the stroma (HR= 0.2, p-adjusted=0.032) were associated with better survival outcomes. Taken together, this study supports the role of immune checkpoint molecules and implicates the TNFR superfamily as key players in immunotherapy response in our cohort of HNSCC. Validation of these findings in a prospective study is required to determine the robustness of these tissue signatures

Do Women With High eHealth Literacy Profit More From a Decision Aid on Mammography Screening? Testing the Moderation Effect of the eHEALS in a Randomized Controlled Trial

Background: Our decision aid on mammography screening developed according to the criteria of the International Patient Decision Aids Standards Collaboration increases knowledge compared to usual care. However, it remains unclear whether this decision aid is more effective in women with higher eHealth literacy. Our objective was to test whether the positive effect of the decision aid on knowledge is moderated by eHealth literacy.Methods: A total of 1,206 women aged 50 from Westphalia-Lippe, Germany, participated (response rate of 16.3%) in our study and were randomized to usual care (i.e., the standard information brochure sent with the programme's invitation letter) or the decision aid. eHealth literacy was assessed at baseline with the Electronic Health Literacy Scale (eHEALS); knowledge was assessed at baseline and post-intervention. First, we compared the 2-factor model of the German eHEALS (information-seeking and information-appraisal) found in previous research and the 3-factor model we hypothesized for decision aid use to the originally proposed 1-factor model. Second, we modeled the measurement model according to the superior factor model found in step one and tested whether the eHEALS moderated the effect of the decision aid on knowledge.Results: The 3-factor model of the eHEALS had a better model fit than the 1-factor or 2-factor model. Both information-seeking, information-appraisal, and information-use had no effect on knowledge post-intervention. All three interactions of the decision aid with information-seeking, information-appraisal, and information-use were not significant. Equally, neither education nor its interaction with the decision aid had an effect on knowledge post-intervention.Conclusion: The decision aid developed in this project increases knowledge irrespective of level of eHealth literacy. This means that not only women with high eHealth literacy profit from the decision aid but that the decision aid has been successfully conceptualized as a comprehensible information tool that can be used by women of varying eHealth literacy levels.Trial registration: German Clinical Trials Register DRKS00005176 (https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&amp;TRIAL_ID=DRKS00005176)

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study

PurposeRobust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness.MethodsWe conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients.ResultsWe show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients.ConclusionThese data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus

Identification and functional characterisation of TGFB-regulated and cell surface candidates in pancreatic cancer

This thesis is an investigation into the role of novel proteins that may influence pancreatic cancer cell migration and thereby tumour progression. Multiple approaches were used to select 41 candidate proteins for in-vitro loss-of-function experiments and several lead candidates were generated including GPRC5A and CRLF1. Further investigation is warranted to better define their cellular roles in pancreatic cancer

Targeting epithelial mesenchymal plasticity in pancreatic cancer: A compendium of preclinical discovery in a heterogeneous disease

Pancreatic Ductal Adenocarcinoma (PDAC) is a particularly insidious and aggressive disease that causes significant mortality worldwide. The direct correlation between PDAC incidence, disease progression, and mortality highlights the critical need to understand the mechanisms by which PDAC cells rapidly progress to drive metastatic disease in order to identify actionable vulnerabilities. One such proposed vulnerability is epithelial mesenchymal plasticity (EMP), a process whereby neoplastic epithelial cells delaminate from their neighbours, either collectively or individually, allowing for their subsequent invasion into host tissue. This disruption of tissue homeostasis, particularly in PDAC, further promotes cellular transformation by inducing inflammatory interactions with the stromal compartment, which in turn contributes to intratumoural heterogeneity. This review describes the role of EMP in PDAC, and the preclinical target discovery that has been conducted to identify the molecular regulators and effectors of this EMP program. While inhibition of individual targets may provide therapeutic insights, a single ‘master-key’ remains elusive, making their collective interactions of greater importance in controlling the behaviours’ of heterogeneous tumour cell populations. Much work has been undertaken to understand key transcriptional programs that drive EMP in certain contexts, however, a collaborative appreciation for the subtle, context-dependent programs governing EMP regulation is needed in order to design therapeutic strategies to curb PDAC mortality