Writing as Making: Positioning a WAC Initiative to Bridge Academic Discourse and Studio Learning

The shift from college to university curriculum at OCAD University in Toronto, an art and design school, has produced tensions between cultures of making and their perceived incompatibility with academic discourse. These tensions, however, afford opportunities to reflect upon the place of academic writing in relation to diverse forms of knowledge production within the university. Writing in the studio, which emphasizes creativity, process and peer critique, productively destabilizes conceptions of academic writing as a generalizable academic skill while fostering the codification of disciplinary knowledge in emergent academic discourses in art and design. These issues are discussed within the context of a university-wide Writing Across the Curriculum initiative

A Comprehensive Guide to Working with Higher Education Curriculum Development, Review & Renewal Projects

“A Comprehensive Guide to Working with Higher Education Curriculum Development, Review & Renewal Projects” is a collaborative effort drawing on the collective experience of the authors, who have worked in different institutional contexts across Canada and beyond. Our goal is to provide practical guidance by describing curriculum development, review, and renewal practices in plain language, using a scholarly, evidence-informed, critical, and self-reflective approach. In writing this guide, we drew variously from theories of learning, well-established scholarship in education and curriculum studies, models of change management as applied to education, and the practice of educational development as informed by our own experiences and shared knowledges, to identify what in our view are best or promising practices for curriculum development

Impact of Social Isolation during the COVID-19 Pandemic on Mental Health, Substance Use, and Homelessness: Qualitative Interviews with Behavioral Health Providers

The United States is experiencing a syndemic of homelessness, substance use disorder, and mental health conditions, which has been further exacerbated by the COVID-19 pandemic. Although it is expected that mitigation strategies will curb community transmission of COVID-19, the unintended consequences of social isolation on mental health and substance use are a growing public health concern. Awareness of changing mental health and substance use treatment needs due to the pandemic is critical to understanding what additional services and support are needed during and post-pandemic, particularly among people experiencing homelessness who have pre-existing serious mental illness or substance use disorder. To evaluate these effects and support our understanding of mental health and substance use outcomes of the COVID-19 pandemic, we conducted a qualitative study where behavioral health providers serving people experiencing homelessness described the impact of COVID-19 among their clients throughout the United States. Behavioral health providers shared that experiencing social isolation worsened mental health conditions and caused some people to return to substance use and fatally overdose. However, some changes initiated during the pandemic resulted in positive outcomes, such as increased client willingness to discuss mental health topics. Our findings provide additional evidence that the social isolation experienced during the pandemic has been detrimental to mental health and substance use outcomes, especially for people experiencing homelessness

Discovery and Clinical Proof-of-Concept of RLY-2608, a First-in-Class Mutant-Selective Allosteric PI3Kα Inhibitor That Decouples Antitumor Activity from Hyperinsulinemia.

UNLABELLED: PIK3CA (PI3Kα) is a lipid kinase commonly mutated in cancer, including ∼40% of hormone receptor-positive breast cancer. The most frequently observed mutants occur in the kinase and helical domains. Orthosteric PI3Kα inhibitors suffer from poor selectivity leading to undesirable side effects, most prominently hyperglycemia due to inhibition of wild-type (WT) PI3Kα. Here, we used molecular dynamics simulations and cryo-electron microscopy to identify an allosteric network that provides an explanation for how mutations favor PI3Kα activation. A DNA-encoded library screen leveraging electron microscopy-optimized constructs, differential enrichment, and an orthosteric-blocking compound led to the identification of RLY-2608, a first-in-class allosteric mutant-selective inhibitor of PI3Kα. RLY-2608 inhibited tumor growth in PIK3CA-mutant xenograft models with minimal impact on insulin, a marker of dysregulated glucose homeostasis. RLY-2608 elicited objective tumor responses in two patients diagnosed with advanced hormone receptor-positive breast cancer with kinase or helical domain PIK3CA mutations, with no observed WT PI3Kα-related toxicities. SIGNIFICANCE: Treatments for PIK3CA-mutant cancers are limited by toxicities associated with the inhibition of WT PI3Kα. Molecular dynamics, cryo-electron microscopy, and DNA-encoded libraries were used to develop RLY-2608, a first-in-class inhibitor that demonstrates mutant selectivity in patients. This marks the advance of clinical mutant-selective inhibition that overcomes limitations of orthosteric PI3Kα inhibitors. See related commentary by Gong and Vanhaesebroeck, p. 204 . See related article by Varkaris et al., p. 227 . This article is featured in Selected Articles from This Issue, p. 201