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This collection departs from the observation that online forms of communication—the email, blog, text message, tweet—are actually haunted by old epistolary forms: the letter and the diary. By examining the omnipresence of writing across a variety of media, the collection adds the category of Epistolary Screens to genres of self-expression, both literary (letters, diaries, auto-biographies) and screenic (romance dramas, intercultural cinema, essay films, artists’ videos and online media). The category Epistolary encapsulates an increasingly paradoxical relation between writing and the self: first, it describes selves that are written in graphic detail via letters, diaries, blogs, texts, emails and tweets; second, it acknowledges that absence complicates communication, bringing people together in an entangled rather than ordered way. The collection concerns itself with the changing visual/textual texture of screen media and examines what is at stake for our understanding of self-expression when it takes Epistolary forms.

This collection departs from the observation that online forms of communication - the email, blog, text message, tweet - are actually haunted by old epistolary forms: the letter and the diary. By examining the omnipresence of writing across a variety of media, the collection adds the category of Epistolary Screens to genres of self-expression, both literary (letters, diaries, auto-biographies) and screenic (romance dramas, intercultural cinema, essay films, artists' videos and online media). The category Epistolary encapsulates an increasingly paradoxical relation between writing and the self: first, it describes selves that are written in graphic detail via letters, diaries, blogs, texts, emails and tweets; second, it acknowledges that absence complicates communication, bringing people together in an entangled rather than ordered way. The collection concerns itself with the changing visual/textual texture of screen media and examines what is at stake for our understanding of self-expression when it takes Epistolary forms.

AbstractThis chapter considers the melodramatic tradition as foundational for the resilience of epistolary discourse in popular cinema. Both prioritize the feminine detail, specifically the protagonist's ‘desire to express all’. Despite frequent relegation to the realm of the domestic (not unlike melodrama), letters have provided women in particular with a private, intimate space to express themselves. The examples explored here ask us to reconsider notions of courtship, with this epistolary ‘space’ creating an opportunity for connection, despite a lack of physical proximity. Building on Tania Modleski's statement that, in classical melodrama, ‘women carry the burden of feeling for everyone’, this chapter demonstrates how in many contemporary examples, the epistle carries the burden of feeling as the melodramatic heroine once did.Keywords: feminine detail; melodrama; mise-en-scène; romance films; Sex and the CityI Couldn't Help but WonderSex and the City: The Movie (2008) picks up four years after the final episode of Sex and the City's sixth televised season and focuses on the lead up to Carrie Bradshaw (Sarah Jessica Parker) and Mr Big's (Chris Noth) wedding and the events that follow. In an early and somewhat atypical scene, Carrie and Big are tightly framed in bed together, reading. Carrie reads a book entitled ‘Love Letters of Great Men’ which is a focal point of the scene. Mr Big (in what fans recognize as true Big fashion), questions Carrie's choice of reading material and dismisses the letter as an outdated way to express/confess love: ‘It's not my style. Besides, those guys had to write. They were separated from their loves by wars and hundreds and hundreds of miles. I’m right here’. Fast forward to the film's conclusion. Mr Big, having failed to show up to the pair's high-profile wedding, can only achieve forgiveness and resolution through this same book of famous love letters, which he borrows in an attempt to reconnect with Carrie. The letters ultimately become the catalyst for Carrie's forgiveness.Mr Big's narrative arc sets the scene for the two key ideas that will be explored in this chapter. The first idea concerns the epistolary subtext that attributes an emotional component to Mr Big that has been famously lacking throughout the franchise's six seasons. These borrowed love letters allow Big to tap into an intimate, more emotional side that is pivotal in Carrie's decision to forgive him.

AbstractIn this introduction we outline the notion of epistolary intent through which, we argue, the textual adds to and disrupts the audio-visual in particular ways. We also explain the use of the term ‘entanglements’ to encapsulate the disruptive nature of epistolary forms on screen. As a meshed shape for communication and intra-active exchange, entanglement describes complicated situations. We isolate three examples of epistolary disruption – with narratives, genres, and the audio-visual – in order to pin-point the intervention this book makes into existing scholarship. Finally, we outline the structure of the collection through summaries of the fourteen chapters.Keywords: epistolary intent; epistolary entanglement; intimacy; romance; testimonyA Great Epistolary AgeWe are living in a great epistolary age, even if no one acknowledges it. Our phones, by obviating phoning, have reestablished the omnipresence of text. Think of the sheer profusion of messages […] that we now send.As novelist Sally Rooney observes, sending a message to someone who is absent from us is a familiar part of our everyday lives in the twenty-first century, hence, we have all become writers in one form or another. Text has become intricately woven into our lives and plays an intimate part in the way we build relationships, therefore writing has inevitably found its way into screen narratives in the form of text messages and emails, sent and received. This collection is conceived as a response to the ‘omnipresence of text’ on screen and it explores how the visual/textual texture of screen media is changing. First, it argues that contemporary online forms of communication such as the email, blog, text message, tweet, are actually haunted by older epistolary forms such as the letter and the diary. Second, it examines what is at stake for our understanding of the self when it communicates through epistolary forms.By accounting for the ‘omnipresence of text’ across a variety of media, this collection intervenes in debates about how the textual adds to and/ or disrupts the audio-visual. On-screen epistolary forms adopt a number of different shapes. In mainstream cinema and television series epistolary forms have become narrational and plot devices. They operate as correspondence between characters who write messages, communicate, and form relationships. In less mainstream films and media epistolary forms often contend with an injunction.

SummaryBackgroundDetecting microsatellite instability (MSI) in colorectal cancer is crucial for clinical decision making, as it identifies patients with differential treatment response and prognosis. Universal MSI testing is recommended, but many patients remain untested. A critical need exists for broadly accessible, cost-efficient tools to aid patient selection for testing. Here, we investigate the potential of a deep learning-based system for automated MSI prediction directly from haematoxylin and eosin (H&E)-stained whole-slide images (WSIs). MethodsOur deep learning model (MSINet) was developed using 100 H&E-stained WSIs (50 with microsatellite stability [MSS] and 50 with MSI) scanned at 40× magnification, each from a patient randomly selected in a class-balanced manner from the pool of 343 patients who underwent primary colorectal cancer resection at Stanford University Medical Center (Stanford, CA, USA; internal dataset) between Jan 1, 2015, and Dec 31, 2017. We internally validated the model on a holdout test set (15 H&E-stained WSIs from 15 patients; seven cases with MSS and eight with MSI) and externally validated the model on 484 H&E-stained WSIs (402 cases with MSS and 77 with MSI; 479 patients) from The Cancer Genome Atlas, containing WSIs scanned at 40× and 20× magnification. Performance was primarily evaluated using the sensitivity, specificity, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUROC). We compared the model's performance with that of five gastrointestinal pathologists on a class-balanced, randomly selected subset of 40× magnification WSIs from the external dataset (20 with MSS and 20 with MSI). FindingsThe MSINet model achieved an AUROC of 0·931 (95% CI 0·771–1·000) on the holdout test set from the internal dataset and 0·779 (0·720–0·838) on the external dataset. On the external dataset, using a sensitivity-weighted operating point, the model achieved an NPV of 93·7% (95% CI 90·3–96·2), sensitivity of 76·0% (64·8–85·1), and specificity of 66·6% (61·8–71·2). On the reader experiment (40 cases), the model achieved an AUROC of 0·865 (95% CI 0·735–0·995). The mean AUROC performance of the five pathologists was 0·605 (95% CI 0·453–0·757). InterpretationOur deep learning model exceeded the performance of experienced gastrointestinal pathologists at predicting MSI on H&E-stained WSIs. Within the current universal MSI testing paradigm, such a model might contribute value as an automated screening tool to triage patients for confirmatory testing, potentially reducing the number of tested patients, thereby resulting in substantial test-related labour and cost savings. FundingStanford Cancer Institute and Stanford Departments of Pathology and Biomedical Data Science.

Clear cell carcinoma (CCC) is a histologically distinct carcinoma subtype that arises in several organ systems and is marked by cytoplasmic clearing, attributed to abundant intracellular glycogen. Previously, transcription factor hepatocyte nuclear factor 1-beta (HNF1B) was identified as a biomarker of ovarian CCC. Here, we set out to explore more broadly the relation between HNF1B and carcinomas with clear cell histology. HNF1B expression, evaluated by immunohistochemistry, was significantly associated with clear cell histology across diverse gynecologic and renal carcinomas (P<0.001), as was hypomethylation of the HNF1B promoter (P<0.001). From microarray analysis, an empirically-derived HNF1B signature was significantly enriched for computationally-predicted targets (with HNF1 binding sites) (P<0.03), as well as genes associated with glycogen metabolism, including glucose-6-phophatase, and strikingly the blood clotting cascade, including fibrinogen, prothrombin and factor XIII. Enrichment of the clotting cascade was also evident in microarray data from ovarian CCC versus other histotypes (P<0.01), and HNF1B-associated prothrombin expression was verified by immunohistochemistry (P = 0.015). Finally, among gynecologic carcinomas with cytoplasmic clearing, HNF1B immunostaining was linked to a 3.0-fold increased risk of clinically-significant venous thrombosis (P = 0.043), and with a 2.3-fold increased risk (P = 0.011) in a combined gynecologic and renal carcinoma cohort. Our results define HNF1B as a broad marker of clear cell phenotype, and support a mechanistic link to glycogen accumulation and thrombosis, possibly reflecting (for gynecologic CCC) derivation from secretory endometrium. Our findings also implicate a novel mechanism of tumor-associated thrombosis (a major cause of cancer mortality), based on the direct production of clotting factors by cancer cells.