Material Memory: Willa Cather, “My First Novels [There Were Two]”, and The Colophon: A Book Collector’s Quarterly

Willa Cather\u27s 1931 essay My First Novels [There Were Two] is an often-cited statement on place in the author\u27s literary oeuvre. In the essay, Cather distances herself from her first novel \u27Alexander\u27s Bridge\u27 (1912) and its imitative, Jamesian motifs and setting. Her second novel \u27O Pioneers!\u27, she writes, was a kind of second first novel, one written entirely for myself and preoccupied with the story of Scandinavians and Bohemians who had been neighbors of ours when I lived on a ranch in Nebraska. As Merrill Maguire Skaggs, Robert Thacker and Emmy Stark Zitter have argued, My First Novels [There Were Two] is also an important document in the author\u27s retrospective construction of authorial identity.* Yet scholars have not, to date, fully explored the occasion for this essay\u27s publication nor the periodical in which it was published. Material Memory: Willa Cather, \u27My First Novels [There Were Two]\u27, and The Colophon: A Book Collector’s Quarterly shows how Cather came to publish her essay of literary debut in The Colophon: A Book Collector\u27s Quarterly. The paper follows George\u27s Bornstein\u27s approach in Material Modernism, which connects literary modernism to a distinct set of material concerns and manifestations. The presentation documents Cather\u27s participation in an intermittent series for the periodical in which various writers of national renown told stories of their first novels and traces connections between Cather and Colophon founder Elmer Adler. *See the following sources: Skaggs, Merrill Maguire. Cather\u27s Violent Assimilation of Henry James\u27s Art. In \u27Violence, the Arts and Willa Cather\u27. Fairleigh Dickinson University Press, 2007; Thacker, Robert. She\u27s Not a Puzzle So Arbitrarily Solved: Willa Cather\u27s Violent Self-Construction In \u27Violence, the Arts and Willa Cather\u27, Fairleigh Dickinson University Press, 2007; Zitter, Emmy Stark. Making Herself Born: Ghost Writing and Willa Cather\u27s Developing Autobiography Biography 19.3 (1996): 283-301

Digits: Two Reports on New Units of Scholarly Publication

The Digits team (Matt Burton, Matthew J. Lavin, Jessica Otis, and Scott B. Weingart) convened around the question of how we might share, preserve, and legitimize scholarship freed from the affordances of print. For the A.W. Mellon-funded Digits Planning Grant (2016-2018), the PIs had three goals: - Investigate the use of software containers for research in the sciences, social sciences, and humanities. - Assess the infrastructural needs of digital humanists around publishing and preserving web-centric scholarship. - Gather a team of experts to guide the above activities and plan how they might inform a beneficial intervention into the scholarly ecosystem. Through our investigation into the scholarly uses of containers, we discovered that the technical infrastructure needed to connect containers with digital publications is underdeveloped. We see potential for container technologies to facilitate existing digital scholarly publications and afford new forms of computational scholarship, but this process would first require a series of infrastructural bridges. The digital scholarship needs assessment we conducted, as well as our advisory board meetings, made it clear that a targeted technological intervention alone would not be enough to welcome web-first publications into the scholarly ecosystem; in-tandem cultural and institutional changes are also necessary

Seminal plasma enables selection and monitoring of active surveillance candidates using nuclear magnetic resonance-based metabolomics: A preliminary investigation

Background: Diagnosis and monitoring of localized prostate cancer requires discovery and validation of noninvasive biomarkers. Nuclear magnetic resonance (NMR)-based metabolomics of seminal plasma reportedly improves diagnostic accuracy, but requires validation in a high-risk clinical cohort. Materials and methods: Seminal plasma samples of 151 men being investigated for prostate cancer were analyzed with 1H-NMR spectroscopy. After adjustment for buffer (add-to-subtract) and endogenous enzyme influence on metabolites, metabolite profiling was performed with multivariate statistical analysis (principal components analysis, partial least squares) and targeted quantitation. Results: Seminal plasma metabolites best predicted low- and intermediate-risk prostate cancer with differences observed between these groups and benign samples. Lipids/lipoproteins dominated spectra of high grade samples with less metabolite contributions. Overall prostate cancer prediction using previously described metabolites was not validated. Conclusion: Metabolomics of seminal plasma in vitro may assist urologists with diagnosis and monitoring of either low or intermediate grade prostate cancer. Less clinical benefit may be observed for high-risk patients. Further investigation in active surveillance cohorts, and/or in combination with in vivo magnetic resonance spectroscopic imaging may further optimize localized prostate cancer outcomes

Prostate-based biofluids for the detection of prostate cancer: A comparative study of the diagnostic performance of cell-sourced RNA biomarkers

Background Prostate cancer (PCa) diagnosis requires improvement with the aid of more accurate biomarkers. Postejaculate urethral washings (PEUW) could be a physiological equivalent to urine obtained following rectal prostatic massage, the current basis for the prostate cancer antigen 3 (PCA3) test. The aim of this study was to investigate if PEUW contained prostate-based material, evidenced by the presence of prostate specific antigen (PSA), and to evaluate the diagnostic performance of PEUW-based biomarkers. Methods Male patients referred for elevated serum PSA or abnormal digital rectal examination provided ejaculate and PEUW samples. PSA, PCA3, and β2-microglobulin (β2M) were quantified in ejaculate and PEUW and compared with absolute and clinically significant (according to D\u27Amico criteria) PCa presence, as determined by biopsies. Diagnostic performance was determined and compared with serum PSA using receiver operating characteristic analysis. Results From 83 patients who provided PEUW samples, paired analysis with ejaculate samples was possible for 38 patients, while analysis in an unpaired, extended cohort was possible for 62 patients. PSA and PCA3 were detected in PEUW, normalized to β2M, and PCA3:PSA was calculated. In predicting absolute PCa status, PCA3:β2M in ejaculate [area under the curve (AUC) 0.717] and PEUW (AUC 0.569) were insignificantly better than PCA3:PSA (AUC 0.668 and 0.431, respectively) and comparable with serum PSA (AUC 0.617) with similar trends observed for the extended cohort. When considering clinically significant PCa presence, serum PSA in the comparison (AUC 0.640) and extended cohorts (AUC 0.665) was comparable with PCA3: β2M (AUC 0.667) and PCA3:PSA (AUC 0.605) in ejaculate, with lower estimates for PEUW in the comparison (PCA3: β2M AUC 0.496; PCA3:PSA AUC 0.342) and extended (PCA3: β2M AUC 0.497; PCA3:PSA AUC 0.469) cohorts. The statistical analysis was limited by sample size. Conclusion PEUW contains prostatic material, but has limited diagnostic accuracy when considering cell-derived DNA analysis. PCA3-based markers in ejaculate are comparable to serum PSA and digital rectal examination–urine markers

Predicting In-Hospital Mortality in Patients Undergoing Percutaneous Coronary Intervention

Background Standardization of risk is critical in benchmarking and quality improvement efforts for percutaneous coronary interventions (PCI). In 2018, the CathPCI Registry was updated to include additional variables to better classify higher-risk patients. Objectives We sought to develop a model for predicting in-hospital mortality risk following PCI incorporating these additional variables. Methods Data from 706,263 PCIs performed between 7/2018-6/2019 at 1,608 sites were used to develop and validate a new full and pre-catheterization model to predict in-hospital mortality, and a simplified bedside risk score. The sample was randomly split into a development (70%, n=495,005) and validation cohort (30%, n=211,258). We created 1,000 bootstrapped samples of the development cohort and used stepwise selection logistic regression on each sample. The final model included variables that were selected in at least 70% of the bootstrapped samples and those identified a priori due to clinical relevance. Results In-hospital mortality following PCI varied based on clinical presentation. Procedural urgency, cardiovascular instability, and level of consciousness after cardiac arrest were most predictive of in-hospital mortality. The full model performed well, with excellent discrimination (c-index: 0.943) in the validation cohort and good calibration across different clinical and procedural risk cohorts. The median hospital risk-standardized mortality rate was 1.9% and ranged from 1.1% to 3.3% (interquartile range: 1.7%-2.1%). Conclusions The risk of mortality following PCI can be predicted in contemporary practice by incorporating variables that reflect clinical acuity. This model, which includes data previously not captured, is a valid instrument for risk stratification and for quality improvement efforts

Rad21-Cohesin Haploinsufficiency Impedes DNA Repair and Enhances Gastrointestinal Radiosensitivity in Mice

Approximately half of cancer-affected patients receive radiotherapy (RT). The doses delivered have been determined upon empirical experience based upon average radiation responses. Ideally higher curative radiation doses might be employed in patients with genuinely normal radiation responses and importantly radiation hypersensitive patients would be spared the consequences of excessive tissue damage if they were indentified before treatment. Rad21 is an integral subunit of the cohesin complex, which regulates chromosome segregation and DNA damage responses in eukaryotes. We show here, by targeted inactivation of this key cohesin component in mice, that Rad21 is a DNA-damage response gene that markedly affects animal and cell survival. Biallelic deletion of Rad21 results in early embryonic death. Rad21 heterozygous mutant cells are defective in homologous recombination (HR)-mediated gene targeting and sister chromatid exchanges. Rad21+/− animals exhibited sensitivity considerably greater than control littermates when challenged with whole body irradiation (WBI). Importantly, Rad21+/− animals are significantly more sensitive to WBI than Atm heterozygous mutant mice. Since supralethal WBI of mammals most typically leads to death via damage to the gastrointestinal tract (GIT) or the haematopoietic system, we determined the functional status of these organs in the irradiated animals. We found evidence for GIT hypersensitivity of the Rad21 mutants and impaired bone marrow stem cell clonogenic regeneration. These data indicate that Rad21 gene dosage is critical for the ionising radiation (IR) response. Rad21 mutant mice thus represent a new mammalian model for understanding the molecular basis of irradiation effects on normal tissues and have important implications in the understanding of acute radiation toxicity in normal tissues

Metabolomics: A Novel Approach to Early and Noninvasive Prostate Cancer Detection

Prostate cancer (PCa) is the most commonly diagnosed visceral cancer in men and is responsible for the second highest cancer-related male mortality rate in Western countries, with increasing rates being reported in Korea, Japan, and China. Considering the low sensitivity of prostate-specific antigen (PSA) testing, it is widely agreed that reliable, age-independent markers of the presence, nature, and progression of PCa are required to facilitate diagnosis and timely treatment. Metabolomics or metabonomics has recently emerged as a novel method of PCa detection owing to its ability to monitor changes in the metabolic signature, within biofluids or tissue, that reflect changes in phenotype and function. This review outlines the physiology of prostate tissue and prostatic fluid in health and in malignancy in relation to metabolomics as well as the principles underlying the methods of metabolomic quantification. Promising metabolites, metabolic profiles, and their correlation with the presence and stage of PCa are summarized. Application of metabolomics to biofluids and in vivo quantification as well as the direction of current research in supplementing and improving current methods of detection are discussed. The current debate in the urology literature on sarcosine as a potential biomarker for PCa is reviewed and discussed. Metabolomics promises to be a valuable tool in the early detection of PCa that may enable earlier treatment and improved clinical outcomes

Parvovirus Minute Virus of Mice Induces a DNA Damage Response That Facilitates Viral Replication

Infection by DNA viruses can elicit DNA damage responses (DDRs) in host cells. In some cases the DDR presents a block to viral replication that must be overcome, and in other cases the infecting agent exploits the DDR to facilitate replication. We find that low multiplicity infection with the autonomous parvovirus minute virus of mice (MVM) results in the activation of a DDR, characterized by the phosphorylation of H2AX, Nbs1, RPA32, Chk2 and p53. These proteins are recruited to MVM replication centers, where they co-localize with the main viral replication protein, NS1. The response is seen in both human and murine cell lines following infection with either the MVMp or MVMi strains. Replication of the virus is required for DNA damage signaling. Damage response proteins, including the ATM kinase, accumulate in viral-induced replication centers. Using mutant cell lines and specific kinase inhibitors, we show that ATM is the main transducer of the signaling events in the normal murine host. ATM inhibitors restrict MVM replication and ameliorate virus-induced cell cycle arrest, suggesting that DNA damage signaling facilitates virus replication, perhaps in part by promoting cell cycle arrest. Thus it appears that MVM exploits the cellular DNA damage response machinery early in infection to enhance its replication in host cells

Neutrophil Responses to Sterile Implant Materials

In vivo implantation of sterile materials and devices results in a foreign body immune response leading to fibrosis of implanted material. Neutrophils, one of the first immune cells to be recruited to implantation sites, have been suggested to contribute to the establishment of the inflammatory microenvironment that initiates the fibrotic response. However, the precise numbers and roles of neutrophils in response to implanted devices remains unclear. Using a mouse model of peritoneal microcapsule implantation, we show 30–500 fold increased neutrophil presence in the peritoneal exudates in response to implants. We demonstrate that these neutrophils secrete increased amounts of a variety of inflammatory cytokines and chemokines. Further, we observe that they participate in the foreign body response through the formation of neutrophil extracellular traps (NETs) on implant surfaces. Our results provide new insight into neutrophil function during a foreign body response to peritoneal implants which has implications for the development of biologically compatible medical devices