Intersections of new historicism and contemporary theory in renaissance literature

In this thesis, I use modern concepts of feminism, gender performativity, and psychoanalysis as a means to understand female characters and authors of Renaissance England in a new way. In my first article, I analyze various texts and performances of Queen Elizabeth I, as well as texts of Renaissance female authors who are now slowly entering our modern canon — notably, Aemilia Lanyer. The second article is a feminist investigation of Britomart from Spenser's The Faerie Queene. In both pieces, I argue that these women (historical and fictional) broaden the definition of queer, and ultimately of feminism, as a whole. The goal of this thesis is to utilize published and visual records of early modern women writers and fictional characters, and apply a theoretical lens to such texts, in order to analyze these texts in a multi-faceted, contemporary fashion and to establish new modes of thought within the discourse of gender performativity, feminisms and psychoanalytical theory

A Comparative Study of Foraging Behavior and Disturbance Regimes in Urban Versus Agricultural Habitats used by Cackling Geese Wintering in the Willamette Valley, Oregon

The Cackling goose (Branta hutchinsii minima) population has increased from a low of 20,000 in 1984 to the current population of 220,000-300,000 (Stehn 2012, Sanders 2013). As the Cackling goose population began to recover in the late 1990s, the majority of the population relocated from wintering in California to the Willamette Valley, Oregon (Pacific Flyway Council 1999, Mini 2012). Cackling geese in Oregon now commonly use exurban, suburban, and urban areas (Mini 2012). The reasons for Cackling goose use of urban areas are still unclear as they did not commonly use this habitat type on their traditional wintering areas in California or initially upon showing up in Oregon. Given what we know about habitat selection in geese and the Willamette Valley system, we tested three different hypotheses that seem to have the greatest utility for explaining the recent use of urban habitats in Oregon’s Willamette Valley: 1) Foraging opportunity in urban habitats is higher due to lower perceived, or actual, predation risks, 2) Foraging efficiency in urban habitats is higher in urban landscapes due to a difference in forage characteristics between landscape types, and 3) Quality of forage in urban habitats is higher due to a difference in nutritional content and regrowth rate. My field work centered on collecting data to test predictions deduced from my hypotheses. From November 2013-April 2014 and November 2014-April 2015, I conducted a total of 278 hour-long disturbance surveys and 238 behavioral time- activity budget scans in 109 different sites in the Willamette Valley, Oregon within urban areas in Portland, Eugene, and Salem and agricultural areas in the Willamette Valley National Wildlife Refuge Complex and nearby private fields. Consistent with the Safe Habitat Hypothesis, predator-related disturbances in urban landscapes were significantly lower than in agricultural landscapes: only one avian predator-related disturbance was observed in urban landscapes throughout the entire study. Geese spent more time feeding (69.0 ± 1.9% vs. 55.0 ± 2.1%), less time flying (3.0 ± 1.1% vs. 6.6 ± 1.3%) and less time vigilant (2.1 ± 0.2% vs. 5.6 ± 0.5%) in urban landscapes than in agricultural landscapes. The frequency of the eight disturbance types differed between landscape types (n = 988, χ² = 308, df = 8, P < 0.001). Vigilance (70% vs. 56%, χ² = 22.9, df = 1, P < 0.001) occurred more often in agricultural landscapes and walking away responses (19% vs. 3%, χ² = 64.49, df = 1, P < 0.001) occurred more often in urban landscapes. I measured forage biomass, daily regrowth rate, and nutritional content from 58 plots in December of 2014, and 60 plots in December of 2015 at a total of 6 fields in urban landscapes and 6 fields in agricultural landscapes. Mean grass biomass did not vary significantly between urban (32.0 ± 7.5 g m⁻²) and agricultural landscapes (22.0 ± 4.2 g m⁻², n = 12, P = 0.4), and average daily regrowth rate did not vary significantly between urban (0.08 ± 0.01 cm/d) and agricultural landscapes (0.12 ± 0.02 cm/d, n = 12, P = 0.09). Average grass height in agricultural landscapes was 7.1 ± 0.7 cm and average height in urban landscapes was 3.8 ± 0.3 cm. Percent crude protein did not vary significantly between urban (18.4 ± 0.97%) and agricultural landscapes (17.0 ± 1.3%, n = 12, P = 0.64). Percent ADF did not vary significantly between urban (35.3 ± 1.8%) and agricultural landscapes (36.7 ± 2.4%, n = 12, P = 0.84). My results are consistent with the Safe-habitat Hypothesis which states Cacklers may be now using urban landscapes partially in response to an increasing Bald Eagle population. Ultimately, if nutritional quality of forage is the same between landscapes types, but Cacklers are disturbed more often by predators in agricultural landscapes, Cacklers in urban landscapes may have a higher net energy gain than Cacklers foraging on refuges; therefore, use of urban areas by Cacklers might increase. Coordinated management plans with private landowners, public school districts, and Parks and Recreation departments in the Willamette Valley that maximize preferred foraging conditions on refuges and minimize preferred foraging conditions in urban areas may attract more geese to protected areas in agricultural landscapes

Training Graduate Students in Multiple Genres of Public and Academic Science Writing: An Assessment Using an Adaptable, Interdisciplinary Rubric

There is an urgent need for scientists to improve their communication skills with the public, especially for those involved in applying science to solve conservation or human health problems. However, little research has assessed the effectiveness of science communication training for applied scientists. We responded to this gap by developing a new, interdisciplinary training model, “SciWrite,” based on three central tenets from scholarship in writing and rhetoric: 1) habitual writing, 2) multiple genres for multiple audiences, and 3) frequent review and created an interdisciplinary rubric based on these tenets to evaluate a variety of writing products across genres. We used this rubric to assess three different genres written by 12 SciWrite-trained graduate science students and 74 non-SciWrite-trained graduate science students at the same institution. We found that written work from SciWrite students scored higher than those from non-SciWrite students in all three genres, and most notably thesis/dissertation proposals were higher quality. The rubric results also suggest that the variation in writing quality was best explained by the ability of graduate students to grasp higher-order writing skills (e.g., thinking about audience needs and expectations, clearly describing research goals, and making an argument for the significance of their research). Future programs would benefit from adopting similar training activities and goals as well as assessment tools that take a rhetorically informed approach

The Simons Observatory Large Aperture Telescope Receiver

The Simons Observatory (SO) Large Aperture Telescope Receiver (LATR) will be coupled to the Large Aperture Telescope located at an elevation of 5,200 m on Cerro Toco in Chile. The resulting instrument will produce arcminute-resolution millimeter-wave maps of half the sky with unprecedented precision. The LATR is the largest cryogenic millimeter-wave camera built to date with a diameter of 2.4 m and a length of 2.6 m. It cools 1200 kg of material to 4 K and 200 kg to 100 mk, the operating temperature of the bolometric detectors with bands centered around 27, 39, 93, 145, 225, and 280 GHz. Ultimately, the LATR will accommodate 13 40 cm diameter optics tubes, each with three detector wafers and a total of 62,000 detectors. The LATR design must simultaneously maintain the optical alignment of the system, control stray light, provide cryogenic isolation, limit thermal gradients, and minimize the time to cool the system from room temperature to 100 mK. The interplay between these competing factors poses unique challenges. We discuss the trade studies involved with the design, the final optimization, the construction, and ultimate performance of the system

Early Release Science of the Exoplanet WASP-39b with JWST NIRSpec G395H

Measuring the abundances of carbon and oxygen in exoplanet atmospheres is considered a crucial avenue for unlocking the formation and evolution of exoplanetary systems. Access to an exoplanet's chemical inventory requires high-precision observations, often inferred from individual molecular detections with low-resolution space-based and high-resolution ground-based facilities. Here we report the medium-resolution (R$\sim$600) transmission spectrum of an exoplanet atmosphere between 3-5 $\mu$m covering multiple absorption features for the Saturn-mass exoplanet WASP-39b, obtained with JWST NIRSpec G395H. Our observations achieve 1.46x photon precision, providing an average transit depth uncertainty of 221 ppm per spectroscopic bin, and present minimal impacts from systematic effects. We detect significant absorption from CO$_2$ (28.5$\sigma$) and H$_2$O (21.5$\sigma$), and identify SO$_2$ as the source of absorption at 4.1 $\mu$m (4.8$\sigma$). Best-fit atmospheric models range between 3 and 10x solar metallicity, with sub-solar to solar C/O ratios. These results, including the detection of SO$_2$, underscore the importance of characterising the chemistry in exoplanet atmospheres, and showcase NIRSpec G395H as an excellent mode for time series observations over this critical wavelength range.Comment: 44 pages, 11 figures, 3 tables. Resubmitted after revision to Natur

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570