The Montreal model: an integrative biomedical-psychedelic approach to ketamine for severe treatment-resistant depression

BackgroundSubanesthetic ketamine has accumulated meta-analytic evidence for rapid antidepressant effects in treatment-resistant depression (TRD), resulting in both excitement and debate. Many unanswered questions surround ketamine’s mechanisms of action and its integration into real-world psychiatric care, resulting in diverse utilizations that variously resemble electroconvulsive therapy, conventional antidepressants, or serotonergic psychedelics. There is thus an unmet need for clinical approaches to ketamine that are tailored to its unique therapeutic properties.MethodsThis article presents the Montreal model, a comprehensive biopsychosocial approach to ketamine for severe TRD refined over 6 years in public healthcare settings. To contextualize its development, we review the evidence for ketamine as a biomedical and as a psychedelic treatment of depression, emphasizing each perspectives’ strengths, weaknesses, and distinct methods of utilization. We then describe the key clinical experiences and research findings that shaped the model’s various components, which are presented in detail.ResultsThe Montreal model, as implemented in a recent randomized clinical trial, aims to synergistically pair ketamine infusions with conventional and psychedelic biopsychosocial care. Ketamine is broadly conceptualized as a brief intervention that can produce windows of opportunity for enhanced psychiatric care, as well as powerful occasions for psychological growth. The model combines structured psychiatric care and concomitant psychotherapy with six ketamine infusions, administered with psychedelic-inspired nonpharmacological adjuncts including rolling preparative and integrative psychological support.DiscussionOur integrative model aims to bridge the biomedical-psychedelic divide to offer a feasible, flexible, and standardized approach to ketamine for TRD. Our learnings from developing and implementing this psychedelic-inspired model for severe, real-world patients in two academic hospitals may offer valuable insights for the ongoing roll-out of a range of psychedelic therapies. Further research is needed to assess the Montreal model’s effectiveness and hypothesized psychological mechanisms

History Is a Verb: We Learn It Best When We Are Doing It: French and English Canadian Prospective Teachers and History

This article presents the results of a Canadian study of prospective history teachers conducted in 2012-2013. Using an online questionnaire to assess a broad range of questions pertaining to their knowledge of history, their trust in historical sources, their experiences in high school and university classes, and their views about school history, it offers new empirical evidence on how the growing generation of Canadian teachers are prepared for the teaching profession. Implications of this study for teacher education and practice teaching are also presented.Este artigo apresenta os resultados de um estudo canadense sobre futuros professores de história, realizado entre 2012 e 2013. O estudo oferece novas evidências empíricas sobre a maneira em que a nova geração de professores canadenses está sendo preparada profissionalmente, utilizando um questionário on-line para avaliar uma série de perguntas relacionadas com seus conhecimentos de história, sua confiança nas fontes históricas, suas experiências em sala de aula do ensino médio e universitário, e suas opiniões sobre a história que se ensina nos colégios. O artigo também apresenta as implicações desse estudo para a formação dos professores e sua prática docente.Este artículo presenta los resultados de un estudio canadiense sobre futuros profesores de historia realizado entre 2012 y 2013. El estudio ofrece nuevas evidencias empíricas sobre la manera en que la nueva generación de profesores canadienses se está preparando profesionalmente, utilizando un cuestionario en línea para evaluar una amplia gama de preguntas relacionadas con sus conocimientos de historia, su confianza en las fuentes históricas, sus experiencias en clases a nivel secundario y universitario, y sus opiniones sobre la historia que se enseña en los colegios. El artículo también presenta las implicaciones de este estudio para la formación de los profesores y su práctica docente

A surfaceome-based CRISPR-Cas9 screening reveals unexpected potent vulnerabilities for KRAS-addicted colorectal cancers

Introduction: Despite significant progresses in cytotoxic chemo- and targeted therapies, metastatic colorectal cancer (CRC) remains incurable in most cases. The most promising therapeutic strategy for advanced CRC is the use of monoclonal antibodies that block activation of the epidermal growth factor receptor (EGFR). However, activating mutations in KRAS were shown to be common drivers of acquired resistance, and recent retrospective studies have shown that they negatively predict responsiveness to anti-EGFR therapy. Despite continuous efforts, oncogenic KRAS is still considered the “Higgs boson” of anticancer drugs targets, warranting the need for alternative therapeutic approaches. While the role of oncogenic KRAS on regulating intracellular signaling events is well described, much less is known about its potential impact on the cell surface proteome (surfaceome), which yet constitutes the predominant source of therapeutic targets for FDA-approved drugs. Methodology & Results: Herein, we have developed an unbiased target-discovery approach that relies on proteomic quantification of KRAS-dependent surfaceome changes and subsequent assessment of their functional relevance through both in vitro and in vivo CRISPR-Cas9 screenings. Interestingly, our proteomic data allowed the identification of over 350 cell surface proteins from which 35% and regulated in a KRAS-dependent manner, which partly rely on transcription. Further functional investigations of these candidates revealed new insights in the understanding of KRAS addiction towards nutrients macropinocytosis and collectively suggest alternative vulnerabilities for KRAS-mutated CRC cells. Conclusion: Thus, our study allows identification of new druggable targets in KRAS-addicted CRC and validates the surfaceome-based CRISPR-Cas9 approach as a potent strategy to determine oncogene-specific vulnerabilities

Moving ideas: an exploration of students’ use of dialogue for writing in history

In this study, we explored how students make use of whole-class interaction in individual writing. Although various studies show the importance of classroom interaction for writing, little is known about how this works, particularly in history. Starting point is the idea that learning can move from the interpersonal level in classroom discourse to the intrapersonal level in subsequent individual writing. We analyzed nine student texts in history (Grade 11) and traced back the origins of the ideas used (documents or discussion). We found that students not only referenced both documents and classroom discussion in their texts but also that they developed additional ideas. We identified two ways in which students used classroom interaction in their texts: reproducing existing ideas or transforming existing ideas into new ones. Examples of both are discussed. Furthermore, we found differences in students’ use of the language of history in the discussion and in writing. When writing, students seemed to use more nominalizations and the language of time was more complex. We conclude that individual writing can benefit from whole-class discussion because students reproduced and transformed ideas in their writing, resulting in knowledge development, and because students’ use of the language of history became more proficient

Global fading of the temperature–growth coupling at alpine and polar treelines

Climate warming is expected to positively alter upward and poleward treelines which are controlled by low temperature and a short growing season. Despite the importance of treelines as a bioassay of climate change, a global field assessment and posterior forecasting of tree growth at annual scales is lacking. Using annually resolved tree-ring data located across Eurasia and the Americas, we quantified and modeled the relationship between temperature and radial growth at treeline during the 20th century. We then tested whether this temperature–growth association will remain stable during the 21st century using a forward model under two climate scenarios (RCP 4.5 and 8.5). During the 20th century, growth enhancements were common in most sites, and temperature and growth showed positive trends. Interestingly, the relationship between temperature and growth trends was contingent on tree age suggesting biogeographic patterns in treeline growth are contingent on local factors besides climate warming. Simulations forecast temperature–growth decoupling during the 21st century. The growing season at treeline is projected to lengthen and growth rates would increase and become less dependent on temperature rise. These forecasts illustrate how growth may decouple from climate warming in cold regions and near the margins of tree existence. Such projected temperature–growth decoupling could impact ecosystem processes in mountain and polar biomes, with feedbacks on climate warming. climate warming, forest limit, growth model, mountain ecosystems, tree ring

Global fading of the temperature–growth coupling at alpine and polar treelines

Climate warming is expected to positively alter upward and poleward treelines which are controlled by low temperature and a short growing season. Despite the importance of treelines as a bioassay of climate change, a global field assessment and posterior forecasting of tree growth at annual scales is lacking. Using annually resolved tree-ring data located across Eurasia and the Americas, we quantified and modeled the relationship between temperature and radial growth at treeline during the 20th century. We then tested whether this temperature–growth association will remain stable during the 21st century using a forward model under two climate scenarios (RCP 4.5 and 8.5). During the 20th century, growth enhancements were common in most sites, and temperature and growth showed positive trends. Interestingly, the relationship between temperature and growth trends was contingent on tree age suggesting biogeographic patterns in treeline growth are contingent on local factors besides climate warming. Simulations forecast temperature–growth decoupling during the 21st century. The growing season at treeline is projected to lengthen and growth rates would increase and become less dependent on temperature rise. These forecasts illustrate how growth may decouple from climate warming in cold regions and near the margins of tree existence. Such projected temperature–growth decoupling could impact ecosystem processes in mountain and polar biomes, with feedbacks on climate warming. climate warming, forest limit, growth model, mountain ecosystems, tree ring