Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07

BACKGROUND We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.

Ice-Bed Coupling Beneath and Beyond Ice Streams: Byrd Glacier, Antarctica

Ice sheet thickness is determined mainly by the strength of ice-bed coupling that controls holistic transitions from slow sheet flow to fast streamflow to buttressing shelf flow. Byrd Glacier has the largest ice drainage system in Antarctica and is the fastest ice stream entering Ross Ice Shelf. In 2004 two large subglacial lakes at the head of Byrd Glacier suddenly drained and increased the terminal ice velocity of Byrd Glacier from 820 m yr(-1) to 900 m yr(-1). This resulted in partial ice-bed recoupling above the lakes and partial decoupling along Byrd Glacier. An attempt to quantify this behavior is made using flowband and flowline models in which the controlling variable for ice height above the bed is the floating fraction phi of ice along the flowband and flowline. Changes in phi before and after drainage are obtained from available data, but more reliable data in the map plane are required before Byrd Glacier can be modeled adequately. A holistic sliding velocity is derived that depends on phi, with contributions from ice shearing over coupled beds and ice stretching over uncoupled beds, as is done in state-of-the-art sliding theories.

Literature after Postmodernism: Reconstructive Fantasies

Postmodernism, deconstruction and subversion have been the buzzwords of the last few decades. But not any longer. Ever since the end of the millennium an increasingly perceptible desire to turn towards other concerns can be noted. Only, what comes after postmodernism? Where are we going now? Irmtraud Huber suggests some answers to these questions, focusing on novels by Michael Chabon, Mark Z. Danielewski, Jonathan Safran Foer and David Mitchell and highlighting the ways in which they go beyond postmodernism and turn from deconstruction to reconstruction. Approaching the question from an unusual direction by exploring the novelists' particular use of the fantastic mode, this book offers both further insights into the present aesthetic shift and a new perspective on the literary fantastic.

Timely Tenses: Considering Present Tense Narration

When the jury of the Man Booker Prize 2010 chose three novels for their short-list that were written in present tense they earned some harsh criticism. To some, like Philipp Pullman, present tense narration seemed to be no more than an annoying fad, “a silly affectation,” which he criticises as a limitation to narrative possibility.1 Nevertheless, present tense narration is spreading fast, not only among Booker Prize nominees and winners. Indeed, it has become so common that it hardly seems to draw much attention anymore. But what is the appeal of present tense narration to contemporary authors? What effect does the choice of present tense narration have on the ways stories are told and read? This paper will address and compare the use of present tense narration in recent British novels by authors such as Hilary Mantel (Wolf Hall, Bring up the Bodies), Ali Smith (Hotel World, The Accidental ), Tom McCarthy (C) and others, looking for similarities and differences in their respective narrative rationale. In view of the heterogeneous and complex use of present tense in contemporary fiction, I would like to suggest, merely pointing to the pace of contemporary life and the simultaneity of new communication media does not suffice to adequately address a phenomenon that has become a characteristic feature of 21st century narration. 1 Laura Roberts. “Philip Pullman and Philip Hensher criticise Booker Prize for including present tense novels.” The Telegraph. 11. Sept. 2010.

Melodrama and Narrative Fiction: Towards a Typology

Recent research on melodrama has stressed its versatility and ubiquity by approaching it as a mode of expression rather than a theatrical genre. A variety of contexts in which melodrama is at work have been explored, but only little scholarly attention has been paid to the relationship between melodrama and novels, short stories and novellas. This article proposes a typology of melodrama in narrative prose fiction, examining four different categories: Melodrama and Sentimentalism, Depiction of Melodramatic Performances in Narrative Prose Fiction, Theatrical Antics and Aesthetics in Narrative Prose Fiction and Meta-Melodrama. Its aim is to clarify the ways in which melodrama, ever since its early days on the stages of late eighteenth-century Europe, has interacted with fictional prose narratives, thereby shaping the literary imagination in the Anglophone world.