Using ePortfolios to Support Student Writers

This session explores how the use of eportfolios can support students’ writing development. An eportfolio initiative director, writing center director, composition professor, and literature professor discuss the use of eportfolios in various contexts

Addressing overtreatment of screen detected DCIS; the LORIS trial

Abstract Overdiagnosis, and thus overtreatment, are inevitable consequences of most screening programmes; identification of ways of minimising the impact of overdiagnosis demands new prospective research, in particular the need to separate clinically relevant lesions that require active treatment from those that can be safely left alone or monitored and only need treated if they change characteristics. Breast cancer screening has led to a large increase in ductal carcinoma in situ (DCIS) diagnoses. This is a widely heterogeneous disease and most DCIS detected through screening is of high cytonuclear grade and therefore likely to be important clinically. However, the historic practice of surgical treatment for all DCIS is unlikely to be optimal for lower risk patients. A clearer understanding of how to manage DCIS is required. This article describes the background and development of ‘The low risk’ DCIS trial (LORIS), a phase III trial of surgery versus active monitoring. LORIS will determine if it is appropriate to manage women with screen detected or asymptomatic, low grade and intermediate grade DCIS with low grade features, by active monitoring rather than by surgical treatment

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

A population-based investigation into inequalities amongst Indigenous mothers and newborns by place of residence in the Northern Territory, Australia

BACKGROUND: Comparisons of birth outcomes between Australian Indigenous and non-Indigenous populations show marked inequalities. These comparisons obscure Indigenous disparities. There is much variation in terms of culture, language, residence, and access to services amongst Australian Indigenous peoples. We examined outcomes by region and remoteness for Indigenous subgroups and explored data for communities to inform health service delivery and interventions. METHODS: Our population-based study examined maternal and neonatal outcomes for 7,560 mothers with singleton pregnancies from Australia’s Northern Territory Midwives’ Data Collection (2003–2005) using uni- and multivariate analyses. Groupings were by Indigenous status; region (Top End (TE)/Central Australia (CA)); Remote/ Urban residence; and across two large TE communities. RESULTS: Of the sample, 34.1% were Indigenous women, of whom 65.6% were remote-dwelling versus 6.7% of non- Indigenous women. In comparison to CA Urban mothers: TE Remote (adjusted odds ratio [aOR] 1.47, 95%CI: 1.13, 1.90) and TE Urban mothers (aOR 1.36 (95% CI: 1.02, 1.80) were more likely, but CA Remote mothers (aOR 0.43; 95% CI: 0.31, 0.58) less likely to smoke during pregnancy; CA Remote mothers giving birth at >32 weeks gestation were less likely to have attended ≥ five antenatal visits (aOR 0.55; 95%CI: 0.36, 0.86); TE Remote (aOR 0.71; 95%CI: 0.53, 0.95) and CA Remote women (aOR 0.68; 95%CI: 0.49, 0.95) who experienced labour had lower odds of epidural/ spinal/narcotic pain relief; and TE Remote (aOR 0.47; 95%CI: 0.34, 0.66), TE Urban (aOR 0.67; 95%CI: 0.46, 0.96) and CA Remote mothers (aOR 0.52; 95%CI: 0.35, 0.76) all had lower odds of having a ‘normal’ birth. The aOR for preterm birth for TE Remote newborns was 2.09 (95%CI: 1.20, 3.64) and they weighed 137 g (95%CI: -216 g, -59 g) less than CA Urban babies. There were few significant differences for communities, except for smoking prevalence. CONCLUSIONS: This paper is one of few quantifying inequalities between groups of Australian Indigenous women and newborns at a regional level. Indigenous mothers and newborns do worse on some outcomes if they live remotely, especially if they live in the TE. Smoking prevention and high-quality antenatal care is fundamental to addressing many of the adverse outcomes identified in this paper.Malinda Steenkamp, Alice Rumbold, Lesley Barclay and Sue Kilde

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

Pedagogy in Action: Teaching and Writing as Rhetorical Performance

Drawing from work in composition studies, rhetorical theory, and feminist theory, this project builds on questions of identity, embodiment, and privilege to enrich conversations about writing pedagogy and teacher development in Composition and Rhetoric. I begin with the assumption that all acts of writing and teaching are performances, whether they are marked as such or not. I engage rhetorical and feminist theories to critically read classroom moments, student writing, and composition scholarship as I urge writing teachers to reflect on the extent to which their embodied pedagogical performances align with their theoretical commitments regarding student learning and teacher development. My work features two key rhetorical concepts, to prepon and to dynaton (the appropriate and the possible), to argue that careful attention to pedagogical performance reveals the constraints in rhetorical situations, which allows for more attention what is possible in teaching and writing. By bringing together pedagogical and rhetorical theories, my dissertation extends the work of the “performance turn” in Composition and Rhetoric and emphasizes how teachers and students negotiate the “appropriate” and the possible in both teaching and writing. Advisor: Shari Stenber

The Unique 16S rRNA Genes of Piezophiles Reflect both Phylogeny and Adaptation

In the ocean's most extreme depths, pressures of 70 to 110 megapascals prevent the growth of all but the most hyperpiezophilic (pressure-loving) organisms. The physiological adaptations required for growth under these conditions are considered to be substantial. Efforts to determine specific adaptations permitting growth at extreme pressures have thus far focused on relatively few γ-proteobacteria, in part due to the technical difficulties of obtaining piezophilic bacteria in pure culture. Here, we present the molecular phylogenies of several new piezophiles of widely differing geographic origins. Included are results from an analysis of the first deep-trench bacterial isolates recovered from the southern hemisphere (9.9-km depth) and of the first gram-positive piezophilic strains. These new data allowed both phylogenetic and structural 16S rRNA comparisons among deep-ocean trench piezophiles and closely related strains not adapted to high pressure. Our results suggest that (i) the Circumpolar Deep Water acts as repository for hyperpiezophiles and drives their dissemination to deep trenches in the Pacific Ocean and (ii) the occurrence of elongated helices in the 16S rRNA genes increases with the extent of adaptation to growth at elevated pressure. These helix changes are believed to improve ribosome function under deep-sea conditions