Taking the culturally resonant motif of the descent to the underworld as his guiding thread, David L. Pike traces the interplay between myth and history in medieval and modernist literature. Passage ...through Hell suggests new approaches to the practice of comparative literature, and a possible escape from the current morass of competing critical schools and ideologies. Pike's readings of Louis Ferdinand Céline and Walter Benjamin reveal the tensions at work in the modern appropriation of structures derived from ancient and medieval descents. His book shows how these structures were redefined in modernism and persist in contemporary critical practice. In order to recover the historical corpus of modernism, he asserts, it is necessary to acknowledge the attraction that medieval forms and motifs held for modernist literature and theory. By pairing the writings of the postwar German dramatist and novelist Peter Weiss with Dante's Commedia , and Christine de Pizan with Virginia Woolf, Pike argues for a new level of complexity in the relation between medieval and modern poetics. Pike's supple and persuasive reading of the Commedia resituates that text within the contradictions of medieval tradition. He contends that the Dantean allegory of conversion, altered to suit the exigencies of modernism, maintains its hold over current literature and theory. The postwar writers Pike treats—Weiss, Seamus Heaney, and Derek Walcott—exemplify alternate strategies for negotiating the legacy of modernism. The passage through hell emerges as a way of disentangling images of the past from their interpretation in the present.
With few exceptions, China Miéville's oeuvre is built out of urban imaginaries. Miéville's cities are dynamic and dialectically conceived spaces; their key element, where most of the action takes ...place and most of the energy is invested, is the slum in all its variations, generating and providing the primary setting for the weird horror at the heart of Miéville's imagination, for the attenuated but omnipresent utopianism both obscured and enabled by that horror, and for the space for thinking them through together. Steampunk and the New Weird have incorporated the city into post-genre fantasy in new ways. In particular, they propose an alternate genealogy of the urban fantastic in late nineteenth- and early twentieth-century modernism that both repudiates the slum as a space of recidivism and resistance and locates alternate possibilities within its alien confines. What Miéville and other contemporary writers recognize as newly available to us from the nineteenth century is not only the slum's vast image-storehouse of suffering and horror, but also its radically new epistemology. Miéville's New Weird has found a way to locate and spatialize not only the uncanny, but also the repressed abcanny, the known and knowable truths of capitalism, now so familiar to us that they circulate everywhere in the culture industry as dystopia and postapocalypse. The abcanny is that which is not, and never was, and never can be part of our imaginary or imagined by us.
Research into factors affecting treatment response or survival in patients with cancer frequently involves cohorts that span the most common range of clinical outcomes, as such patients are most ...readily available for study. However, attention has turned to highly unusual patients who have exceptionally favourable or atypically poor responses to treatment and/or overall survival, with the expectation that patients at the extremes may provide insights that could ultimately improve the outcome of individuals with more typical disease trajectories. While clinicians can often recount surprising patients whose clinical journey was very unusual, given known clinical characteristics and prognostic indicators, there is a lack of consensus among researchers on how best to define exceptional patients, and little has been proposed for the optimal design of studies to identify factors that dictate unusual outcome. In this Opinion article, we review different approaches to identifying exceptional patients with cancer and possible study designs to investigate extraordinary clinical outcomes. We discuss pitfalls with finding these rare patients, including challenges associated with accrual of patients across different treatment centres and time periods. We describe recent molecular and immunological factors that have been identified as contributing to unusual patient outcome and make recommendations for future studies on these intriguing patients.
Fewer than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSCs) survive more than five years after diagnosis, but those who have an exceptionally long survival could ...provide insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-stage HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair and more frequent somatic variants resulting in an increased predicted neoantigen load. Patients clustered into survival groups based on genomic and immune cell signatures, including three subsets of patients with BRCA1 alterations with distinctly different outcomes. Specific combinations of germline and somatic gene alterations, tumor cell phenotypes and differential immune responses appear to contribute to long-term survival in HGSC.
With few exceptions, China Miéville's oeuvre is built out of urban imaginaries. Miéville's cities are dynamic and dialectically conceived spaces; their key element, where most of the action takes ...place and most of the energy is invested, is the slum in all its variations, generating and providing the primary setting for the weird horror at the heart of Miéville's imagination, for the attenuated but omnipresent utopianism both obscured and enabled by that horror, and for the space for thinking them through together. Steampunk and the New Weird have incorporated the city into post-genre fantasy in new ways. In particular, they propose an alternate genealogy of the urban fantastic in late nineteenth- and early twentieth-century modernism that both repudiates the slum as a space of recidivism and resistance and locates alternate possibilities within its alien confines. What Miéville and other contemporary writers recognize as newly available to us from the nineteenth century is not only the slum's vast image-storehouse of suffering and horror, but also its radically new epistemology. Miéville's New Weird has found a way to locate and spatialize not only the uncanny, but also the repressed abcanny, the known and knowable truths of capitalism, now so familiar to us that they circulate everywhere in the culture industry as dystopia and postapocalypse. The abcanny is that which is not, and never was, and never can be part of our imaginary or imagined by us.
Researchers have identified important gender differences in the experience of caring for a family member or friend living with advanced disease; however, trends suggest that these differences may be ...diminishing over time in response to changing gender roles. In addition, while many studies have found caregiving experiences and outcomes to be poorer among female caregivers, noteworthy exceptions exist.
The primary aim of this exploratory study was to determine how, if at all, current day caregiving at end of life varies by gender.
We conducted a secondary analysis of data from a multisite randomized controlled trial of a family caregiving intervention performed between 2010 and 2014. We compared female and male hospice family caregivers on baseline variables using χ(2) tests for association of categorical variables and t-tests for continuous variables. Our sample included 289 family caregivers of individuals receiving services from one of two hospice agencies located in the northwestern United States. Demographic data and other categorical variables of interest were provided via caregiver self-report using an instrument created specifically for this study. Reaction to caregiving and caregiving burden were measured using the Caregiver Reaction Assessment (CRA).
As it related to caregiving, females had significantly lower self-esteem and more negative impact on their schedule, health, and family support than males. No gender differences were detected with regard to the impact of caregiving on individuals' finances.
Despite changing social expectations, pronounced gender differences persist in caregiving at the end of life.
MicroRNAs (miRNAs) are small non-coding RNAs that can exert multilevel inhibition/repression at a post-transcriptional or protein synthesis level during disease or development. Characterisation of ...miRNAs in adult mammalian brains by deep sequencing has been reported previously. However, to date, no small RNA profiling of the developing brain has been undertaken using this method. We have performed deep sequencing and small RNA analysis of a developing (E15.5) mouse brain.
We identified the expression of 294 known miRNAs in the E15.5 developing mouse brain, which were mostly represented by let-7 family and other brain-specific miRNAs such as miR-9 and miR-124. We also discovered 4 putative 22-23 nt miRNAs: mm_br_e15_1181, mm_br_e15_279920, mm_br_e15_96719 and mm_br_e15_294354 each with a 70-76 nt predicted pre-miRNA. We validated the 4 putative miRNAs and further characterised one of them, mm_br_e15_1181, throughout embryogenesis. Mm_br_e15_1181 biogenesis was Dicer1-dependent and was expressed in E3.5 blastocysts and E7 whole embryos. Embryo-wide expression patterns were observed at E9.5 and E11.5 followed by a near complete loss of expression by E13.5, with expression restricted to a specialised layer of cells within the developing and early postnatal brain. Mm_br_e15_1181 was upregulated during neurodifferentiation of P19 teratocarcinoma cells. This novel miRNA has been identified as miR-3099.
We have generated and analysed the first deep sequencing dataset of small RNA sequences of the developing mouse brain. The analysis revealed a novel miRNA, miR-3099, with potential regulatory effects on early embryogenesis, and involvement in neuronal cell differentiation/function in the brain during late embryonic and early neonatal development.
Natural antisense transcripts (NATs) are involved in cellular development and regulatory processes. Multiple NATs at the Sox4 gene locus are spatiotemporally regulated throughout murine cerebral ...corticogenesis. In the study, we evaluated the potential functional role of Sox4 NATs at Sox4 gene locus. We demonstrated Sox4 sense and NATs formed dsRNA aggregates in the cytoplasm of brain cells. Over expression of Sox4 NATs in NIH/3T3 cells generally did not alter the level of Sox4 mRNA expression or protein translation. Upregulation of a Sox4 NAT known as Sox4ot1 led to the production of a novel small RNA, Sox4_sir3. Its biogenesis is Dicer1-dependent and has characteristics resemble piRNA. Expression of Sox4_sir3 was observed in the marginal and germinative zones of the developing and postnatal brains suggesting a potential role in regulating neurogenesis. We proposed that Sox4 sense-NATs serve as Dicer1-dependent templates to produce a novel endo-siRNA- or piRNA-like Sox4_sir3.
•Sox4 gene locus encodes for multiple overlapping sense and NATs.•Sox4 sense and NATs form dsRNA aggregates in the brain cells.•Sox4 sense and NATs serve as a dsRNA template for Sox4_sir3 biogenesis.•Sox4ot1 is required to induce Sox4_sir3 production in vitro.•Sox4_sir3 resembles a siRNA or piRNA small RNAs.
The presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More ...research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery.
This analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression models were fit to assess the association between these exposures and having residual disease following PCS.
Menopausal estrogen-only therapy (ET) use was associated with 33% lower odds of having macroscopic residual disease compared to never use (OR = 0.67, 95%CI 0.46–0.97, p = 0.033). Compared to nulliparous women, parous women who did not breastfeed had 36% lower odds of having residual disease (OR = 0.64, 95%CI 0.43–0.94, p = 0.022), while there was no association among parous women who breastfed (OR = 0.90, 95%CI 0.65–1.25, p = 0.53).
The association between ET and having no macroscopic residual disease is plausible given a strong underlying biologic hypothesis between this exposure and diagnosis with HGSC. If this or the parity finding is replicated, these factors could be included in risk stratification models to determine whether HGSC patients should receive PCS or neoadjuvant chemotherapy.
•Menopausal estrogen-only therapy use was associated with 33% lower odds of having macroscopic residual disease following PCS.•Being a current smoker may be associated with higher odds of having macroscopic residual disease following PCS.•These factors could be included in models to determine if patients should receive PCS or neoadjuvant chemotherapy.
This paper argues that the symbolic meaning of the London Underground, more than those of other metropolitan subway systems, perfectly matches the primary meaning that subways possess as a cultural, ...and, especially, a cinematic space. In general, different subterranean spaces carry associations with different aspects of the complex attributes of the underground. The subway embodies its quotidian qualities; it is associated with work, daily routine, and the average citizen. This paper studies ways in which the Underground as cinematic setting negotiates the material and cultural attributes of the space, beginning with the intersection of modernity, technology and everyday life in films of the 1920s and 1930s. It then addresses conflicts within this model that emerge in science fiction, horror and fantasy of the 1960s and 1970s. The paper concludes by considering the relationship of the underground railway with the other urban subterranean space primarily featured in film, the sewer, and hypothesizes that the recent appearance, basically for the first time, of the London sewers on screen marks a shift in the cultural identity of underground space within the city.
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