University Of Montreal Research Articles

Mindful medical practice: An innovative core course to prepare medical students for clerkship.

BackgroundMedical students show a decline in empathy and ethical reasoning during medical school that is most marked during clerkship. We believe that part of the problem is that students do not have the skills and ways of being and relating necessary to deal effectively with the overwhelming clinical experience of clerkship.ApproachAt McGill University in Montreal, starting in January 2015, we have taught a course on mindful medical practice that combines a clinical focus on the combination of mindfulness and congruent relating that is aimed at giving students the skills and ways of being to function effectively in clerkship. The course is taught to all medical students in groups of 20, weekly for 7 weeks, in the 6 months immediately prior to clerkship, a time when students are very open to learning the skills they need to take effective care of patients.EvaluationThe course has been well accepted by students as evidenced by their engagement, their evaluations, and their comments in the essays that they write at the end of the course. In a follow-up session at the simulation centre one year later students remember clearly and enact what they were taught in the course.ReflectionThe next steps will be to conduct a formal evaluation of the effect of our teaching that will involve a combination of qualitative methods to clarify the nature of the impact on our students and a quantitative assessment of the difference the course makes to students’ experience and performance in clerkship.

FRI0417 IDENTIFICATION OF THE MOST IMPORTANT FEATURES OF KNEE OSTEOARTHRITIS PROGRESSORS USING MACHINE LEARNING METHODS

Background:Knee osteoarthritis (OA), a leading cause of disability worldwide, can be difficult to define as its development is often insidious and involves different subgroups. We still lack robust prediction models that are able to guide clinical decisions and stratify OA patients according to risk of disease progression.Objectives:This study aimed at identifying the most important features of knee OA progressors. To this end, we used machine learning (ML) algorithms on a large set of subjects and features to develop advanced prediction models that provide high classification and prediction performance.Methods:Participants, features and outcomes were from the Osteoarthritis Initiative. Features were from baseline (1107), including articular knee tissues (135) assessed by quantitative MRI. OA progressors were ascertained by four outcomes: cartilage volume loss in medial plateau at 48 and 96 months (Prop_CV_48M, 96M); Kellgren-Lawrence (KL) grade ≥2; and medial joint space narrowing (JSN) ≥1 at 48 months. Subjects’ numbers were as follows: 1598 for the outcome Prop_CV_96M, 1044 for the Prop_CV_48M, and 1468 for each KL grade ≥2 at 48 months and JSN ≥1 at 48 months. Six feature selection models were used to identify the common features in each outcome. Six classification methods were applied to measure the accuracy of the selected features in classifying the subjects into progressors and non-progressors. Classification of the best features was done using auto-ML interface and the area under the curve (AUC). To prioritize the top features, Sparse Partial Least Square (sPLS) method was used.Results:For the classification of the best common features in each outcome, Multi-Layer Perceptron (MLP) achieved the highest AUC in Prop_CV_96M, KL, and JSN (0.80, 0.88, 0.95), and Gradient Boosting Machine (GBM) for Prop_CV_48M (0.70). sPLS revealed that the baseline top five features to predict knee OA progressors are the joint space width (JSW), mean cartilage thickness of peripheral, medial, and central tibial plateau, and JSN.Conclusion:This is the first time that such a comprehensive study was performed for identifying the best features and classification methods for knee OA progressors. Data revealed that early prediction of knee OA progression can be done with high accuracy and based on only a few features. This study identifies the baseline X-ray and MRI-based features as the most important for predicting knee OA progressors. These results could be used for the development of a tool enabling prediction of knee OA progressors.Acknowledgments:This work was supported in part by the Osteoarthritis Research Unit of the University of Montreal Hospital Research Centre; the Chair in Osteoarthritis, University of Montreal, (both from Montreal, Quebec, Canada); and the Computational Biology Laboratory, Laval University Hospital Research Center, (Québec, Quebec, Canada). A Jamshidi received a bursary from the Canada First Research Excellence Fund through TransMedTech Institute, (Montreal, Quebec, Canada).Disclosure of Interests:Afshin Jamshidi: None declared, Mickaël Leclercq: None declared, Aurelie Labbe: None declared, Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, François Abram Employee of: ArthroLab Inc., Arnaud Droit: None declared, Johanne Martel-Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica

The deployment of the partnership with patients in the initial training of health professionals: Reflections and avenues of action based on the experience of the Faculty of Medicine of the University of Montreal

The deployment of the partnership with patients in the initial training of health professionals: Reflections and avenues of action based on the experience of the Faculty of Medicine of the University of Montreal

Toxicokinetics of bisphenol-S and its glucuronide in plasma and urine following oral and dermal exposure in volunteers for the interpretation of biomonitoring data

The measurement of bisphenol-S (BPS) and its glucurono-conjugate (BPSG) in urine may be used for the biomonitoring of exposure in populations. However, this requires a thorough knowledge of their toxicokinetics. The time courses of BPS and BPSG were assessed in accessible biological matrices of orally and dermally exposed volunteers. Under the approval of the Research Ethics Committee of the University of Montreal, six volunteers were orally exposed to a BPS-d8 deuterated dose of 0.1 mg/kg body weight (bw). One month later, 1 mg/kg bw of BPS-d8 were applied on 40 cm2 of the forearm and then washed 6 h after application. Blood samples were taken prior to dosing and at fixed time periods over 48 h after treatment; complete urine voids were collected pre-exposure and at pre-established intervals over 72 h postdosing. Following oral exposure, the plasma concentration–time courses of BPS-d8 and BPSG-d8 over 48 h evolved in parallel, and showed a rapid appearance and elimination. Average peak values (±SD) were reached at 0.7 ± 0.1 and 1.1 ± 0.4 h postdosing and mean (±SD) apparent elimination half-lives (t½) of 7.9 ± 1.1 and 9.3 ± 7.0 h were calculated from the terminal phase of BPS-d8 and BPSG-d8 in plasma, respectively. The fraction of BPS-d8 reaching the systemic circulation unchanged (i.e. bioavailability) was further estimated at 62 ± 5% on average (±SD) and the systemic plasma clearance at 0.57 ± 0.07 L/kg bw/h. Plasma concentration–time courses and urinary excretion rate profiles roughly evolved in parallel for both substances, as expected. The average percent (±SD) of the administered dose recovered in urine as BPS-d8 and BPSG-d8 over the 0–72 h period postdosing was 1.72 ± 1.3 and 54 ± 10%. Following dermal application, plasma levels were under the lower limit of quantification (LLOQ) at most time points. However, peak values were reached between 5 and 8 h depending on individuals, suggesting a slower absorption rate compared to oral exposure. Similarly, limited amounts of BPS-d8 and its conjugate were recovered in urine and peak excretion rates were reached between 5 and 11 h postdosing. The average percent (±SD) of the administered dose recovered in urine as BPS-d8 and BPSG-d8 was about 0.004 ± 0.003 and 0.09 ± 0.07%, respectively. This study provided greater precision on the kinetics of this contaminant in humans and, in particular, evidenced major differences between BPA and BPS kinetics with much higher systemic levels of active BPS than BPA, an observation explained by a higher oral bioavailability of BPS than BPA. These data should also be useful in developing a toxicokinetic model for a better interpretation of biomonitoring data.

Benedict Delisle Burns. 22 February 1915—6 September 2001

Ben Burns was a pioneer of operations research and of the statistical analysis of neuronal activity. During the war, Ben served in Solly Zuckermann's operations research unit, which included a period of active service in the Mediterranean. After the war he worked with G. L. Brown at the National Institute for Medical Research (NIMR), where he investigated the effects of agents that affected neuromuscular transmission. In 1950 he moved to the Physiology Department of McGill University in Montreal, where he explored the properties of neural networks in neurologically isolated slabs of cerebral cortex and established the mechanisms responsible for maintaining rhythmic periods of excitation in isolated nerve networks. He subsequently provided evidence that self-re-exciting neural networks were implicated in establishing the respiratory rhythm. While at McGill, Ben initiated a number of highly original cross-disciplinary studies concerning the physiological bases of learning, memory and attention. He returned to NIMR in 1966 to head the Division of Physiology and Pharmacology, where he continued his investigations of visual perception. Ben was an ingenious experimenter and devised a number of mechanical and electronic devices for the statistical analysis of nerve cell activity at a time when digital computers were largely unavailable for biological work. In his 1968 book, The uncertain nervous system , he expressed his view that the interdisciplinary nature of central neurophysiology required of those who studied it a knowledge of classical physiology, experimental psychology, applied mathematics and electronic engineering. His broad view of the subject inspired a generation of students.

Ophthalmology residency training program at the University of Montreal

Ophthalmology residency training program at the University of Montreal

The Odonata of Quebec: Specimen data from seven collections.

BackgroundThe Odonata, dragonflies and damselflies, constitute one of the more charismatic and better-studied orders of insects. The approximately 6,000 extant species on Earth can be variously found on all continents, except Antarctica. A relatively stable taxonomy, a relative ease of species identification and an aquatic immature stage has made the Odonata a taxon of interest in documenting the symptoms of global environmental change, especially at higher latitudes. The Odonata fauna of the north-temperate Canadian province of Quebec includes 150 species, many of which are at the northern limits of their geographic distribution.New informationQuebec hosts multiple entomological specimen depositories, including seven publicly-accessible research collections. One of these, the University of Montreal's Ouellet-Robert Entomological Collection, houses an exceptionally large collection of Odonata. An initial specimen data capture project for this collection gathered 31,595 Quebec Odonata occurrence records, but several Quebec species were missing and geographic coverage was biased towards the Montreal region. To complement this dataset, we undertook to digitise the Odonata records of six other public research collections. They are, in order of Quebec Odonata collection size, the Laval University Entomological Collection, McGill University's Lyman Entomological Museum, the Insectarium of Montreal Research Collection, the Quebec Government's Insect Collection, Bishop's University's Insect Collection and the Laurentian Forestry Centre's René-Martineau Insectarium. Of the 40,447 total specimen occurrence records, 36,951 are identified to the species level, including 137 of the 150 species officially-recorded in Quebec and 2 non-nominotypical subspecies. We here summarise the data and highlight the strengths and weaknesses of the datasets. The complete dataset is available with this publication (Suppl. material 1), whereas the specimen data associated with each collection are available as Darwin Core archives at Canadensys.net and will be updated as appropriate.

Enzyme smooths path to planar chiral macrocycles

Planar chiral molecules are relatively common in natural products, kind of funny looking, and largely ignored. Though they can be useful as pharmaceuticals or agrochemicals, they are difficult to make. Now, Shawn Collins and coworkers at the University of Montreal have developed an enzyme-catalyzed synthesis to form planar chiral molecules with high enantioselectivity (example shown) from readily available starting materials, which can be easily functionalized (Science 2020, DOI: 10.1126/science.aaz7381). The team made target compounds with up to 99% yield and 66–99% enantioselectivity. Instead of a more traditional metal catalyst, which can create toxic waste, Collins decided to look for one with a biological origin. The serine hydrolase Candida antarctica lipase B “is the organic chemist’s dream because it’s an enzyme that is superstable to high temperatures and actually more active in organic solvents than in water,” he says. The natural enzymatic pocket evolved to accommodate a secondary alcohol, so Collins

Wladimir Krysinski: International Comparatist

Wladimir Krysinski: International Comparatist Gerald Gillespie A citizen successively of Poland, France, and Canada, who eventually came to speak or read a dozen languages, Wladimir Krysinski exemplifies the invaluable cohort of international comparatists who tirelessly circulate throughout the world and help knit us together. He earned his master’s degree at Lodz in his native Poland in 1957 with a thesis on a major Polish modernist, and his doctorate in Strasbourg in his adopted second homeland of France in 1966 with a dissertation on Pirandello and a range of French modernists to existentialists. At that point Krysinski accepted an appointment at Carleton University in Ottawa, where he rose in the ranks to full professor of French and Comparative Literature by 1975. Accepting a full professorship in Slavic Studies and Comparative Literature at the University of Montreal in 1976, he continued exclusively as a comparatist from 1989 at this home base. He was also a member of the Editorial Board of the Canadian Review of Comparative Literature/Revue Canadienne de Littérature Comparée. In an astonishing display of scholarly energies, Krysinski also served as a guest professor on a score of occasions from 1963 onward in France, Canada, Italy, Brazil, Israel, Argentina, Germany, and Japan. His emphasis was on topics concerning modernist literature and theatre, and modernist to postmodernist theory, often reaching out to Latin American literature as a major love of his mature years in Canada. All the while, he remained an indefatigable participant at conferences at home in Canada and abroad, including such nations as Austria, (former) Yugoslavia, Spain, Ireland, Mexico, South Africa, Poland, the Netherlands, and China. Notably, several of Krysinski’s critical works in French have enjoyed even wider diffusion in translation. A glance at the WorldCat will quickly remind his fellow comparatists, above all those who are broader-gauged modernists, that his often [End Page 575] essayistic style has left a deep mark. Probably his most influential work worldwide, Carrefour des signes: Essais sur le roman moderne (1981), appeared somewhat later in Spanish as Encrucijada de signos (1997). The French version, Le paradigme inquiet: Pirandello et le champ comparatif de la modernité (1989), actually followed its Italian version, Il paradigma inquieto: Pirandello e lo spazio comparativo della modernità (1988), but waited a good while for the Spanish companion version, El paradigmo inquieto: Pirandello y el campo de la modernidad (1995). Krysinski became a strong critical presence in Latin America through such Italian, Spanish, and Portuguese-language works as La novela en sus modernidades: A favor y contra de Bajtin (1997), Il romanzo e la modernità (1998), Comparación y sentido: Varias focalizaciones y convergencias literarias (2006), and Dialéticas da transgressão: O novo e o moderno na literatura do secolo XX (2007). Gerald Gillespie Stanford University Works Cited Krysinski, Wladimir. Carrefour des signes: Essais sur le roman moderne. Mouton, 1981. Google Scholar ———. Comparación y sentido: Varias focalizaciones y convergencias literarias. Fondo Editorial de la U Católica Sedes Sapiente, 2006. Google Scholar ———. Dialéticas da transgressão: O novo e o moderno na literatura do secolo XX. Translated by Ignacio Antônio Neis, Michel Peterson, and Ricardo Iuri Canko, Perspectiva, 2007. Google Scholar ———. Encrucijada de signos: ensayos sobre la novela moderna. Translated by María del Carmen Bobes Naves and Jesús G. Maestro, Arco Libros, 1997. Google Scholar ———. La novela en sus modernidades: A favor y contra de Bajtin. Iberoamericana Vervuert, 1997. Google Scholar ———. Il paradigma inquieto: Pirandello e lo spazio comparativo della modernità. Translated and edited by Corrado Donati, EST, 1988. Google Scholar ———. Le paradigme inquiet: Pirandello et le champ comparatif de la modernité. Le Préambule, 1989. Google Scholar ———. El paradigmo inquieto: Pirandello y el campo de la modernidad. Translated by Alfonso de Toro and Milena Grass, Vervuert, 1995. Google Scholar ———. Il romanzo e la modernità. Translated by Massimiliano Manganelli, Armando Editore, 1998. Google Scholar Copyright © 2020 Canadian Comparative Literature Association

Mechanical properties of an experimental resin based composite containing silver nanoparticles and bioactive glass.

Objective:To compare the elastic modulus, flexural strength, and hardness of an experimental resin based composite (RBC) with and without containing silver nanoparticles (AgNPs) and bioactive glass (BAG) with a commercially available RBC.Methods:This study was conducted, during the period August 2016-May 2018, at the Department of Dental Materials, Peshawar Dental College, Peshawar (Pakistan) and Department of Chemistry, University of Montreal, Canada. Test specimens made in the commercial RBC acted as Group-1 (G1). An experimental RBC containing 70 wt % filler content was synthesized. It was first used as such to prepare test specimens to act as the experimental control group (G2). This RBC was then modified by adding various amounts of BAG (5%, 10% and 15%) and a fixed amount of 0.009% AgNPs to use the so modified RBCs for preparing the test specimens to belong to three groups (G3, G4 & G5). The AgNPs had been synthesized in situ by reduction of salt during photo-polymerization. Flexural strength (FS), elastic modulus (EM) and Vickers hardness were determined using universal testing machine and hardness tester respectively. Data were analyzed using one-way ANOVA and Tukey post-hoc test.Results:Except for G3 restorations showing significantly lower mean FS value, the FS for those in the other groups were not significantly different (p>0.05). Elastic modulus of the experimental RBC restorations was though higher than those of the others but the difference was statistically insignificant (p>0.05). Reduced Vickers hardness values were documented for the restorations in the G4 and G5 compared to those in the G3 but again the difference was insignificant (p>0.05). Flexural strength and hardness values of the test specimens in the experimental RBCs were significantly lower than those made in the commercial hybrid RBC (p<0.05).Conclusion:BAG and AgNPs addition to the experimental RBC in the mentioned concentration adversely affected the tested mechanical properties.

Liking, Likeness, Alikeness

Research Article| January 01 2020 Liking, Likeness, Alikeness Marcie Frank Marcie Frank Marcie Frank is professor of English at Concordia University in Montreal. Search for other works by this author on: This Site Google GLQ (2020) 26 (1): 203–205. https://doi.org/10.1215/10642684-7929272 Cite Icon Cite Share Icon Share Facebook Twitter LinkedIn MailTo Permissions Search Site Citation Marcie Frank; Liking, Likeness, Alikeness. GLQ 1 January 2020; 26 (1): 203–205. doi: https://doi.org/10.1215/10642684-7929272 Download citation file: Zotero Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search Books & JournalsAll JournalsGLQ Search Advanced Search The text of this article is only available as a PDF. Copyright © 2020 Duke University Press2020 Article PDF first page preview Close Modal Issue Section: Books in Brief You do not currently have access to this content.

Amphibian Population Declines: 30 Years of Progress in Confronting a Complex Problem

In 1989, it dawned on participants at the First World Congress of Herpetology that observed declines in amphibian populations might actually be global in scope and unprecedented in severity. Three decades of research since then has produced an enormous increase in our knowledge of amphibian ecology and appreciation of the complexity of possible causes for amphibian population declines. In September 2019, 30 yr after the First World Congress ended, a day-long, international symposium on amphibian population declines was held at the Redpath Museum of McGill University in Montreal, Canada. Symposium participants drew upon the knowledge gained over three decades of study to look ahead with fresh ideas to address this vital aspect of the global decline of biodiversity. Despite tremendous progress over the past three decades there is still much about amphibian ecology, population biology, and pathology that remains unknown. Amphibian declines have turned out to be more complex than originally expected and the result of multiple possible causes acting across landscapes, among taxa, or between populations in ways that are not at all uniform. The papers in this special issue of Herpetologica, which stem from the symposium, explore much of our current understanding of amphibian declines and their causes.

L’École des soignantes : compte-rendu participant d’une prophétie auto-réalisatrice

Plus qu’un divertissement et au-delà de la lecture salutaire pour prendre du recul sur la crise COVID-19, ce roman de Martin Winckler se veut une source d’inspiration et même une prophétie autoréalisatrice dont il ne tient qu’à nous de devenir partie prenante.

3. The North American Low-Back-Merger Shift: A Continental Sound Change

Research Article| December 01 2019 3. The North American Low-Back-Merger Shift: A Continental Sound Change Charles Boberg Charles Boberg CHARLES BOBERG is associate professor of linguistics at McGill University in Montreal, Canada. He is a coauthor, with William Labov and Sharon Ash, of The Atlas of North American English: Phonetics, Phonology, and Sound Change (Mouton de Gruyter, 2006) and the author of The English Language in Canada: Status, History and Comparative Analysis (Cambridge, 2010). Most recently he coedited, with John Nerbonne and Dominic Watt, The Handbook of Dialectology (Wiley Blackwell, 2018). His current research focuses on variation and change in the vocabulary and phonetics of Canadian English as well as on accent variation in North American film and television. Email: charles.boberg@mcgill.ca. Search for other works by this author on: This Site Google Publication of the American Dialect Society (2019) 104 (1): 56–73. https://doi.org/10.1215/00031283-8032935 Cite Icon Cite Share Icon Share Facebook Twitter LinkedIn MailTo Permissions Search Site Citation Charles Boberg; 3. The North American Low-Back-Merger Shift: A Continental Sound Change. Publication of the American Dialect Society 1 December 2019; 104 (1): 56–73. doi: https://doi.org/10.1215/00031283-8032935 Download citation file: Zotero Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search Books & JournalsAll JournalsAmerican Dialect SocietyThe Publication of the American Dialect Society Search Advanced Search The text of this article is only available as a PDF. Copyright © 2019 American Dialect Society2019 Article PDF first page preview Close Modal Issue Section: ARTICLE You do not currently have access to this content.

Addition of ATIR101, an Adjunctive Treatment Following T-Cell-Depleted Haploidentical HSCT, May Decrease Non-Relapse Mortality and May Improve Survival of Patients with Hematologic Malignancies, Irrespective of Prognostic Risk Factors

Introduction ATIR101 is a donor-derived, T-cell-enriched leukocyte preparation depleted ex vivo of host-alloreactive T cells. When administered as a single, adjunctive infusion after T-cell-depleted haploidentical hematopoietic stem cell transplantation (haplo HSCT), ATIR101 may reduce serious complications resulting from delayed immune reconstitution such as infections and relapse. In a Phase II study, patients with hematologic malignancies who received ATIR101 had an overall survival (OS) of 61% and no Grade III/IV acute graft-versus-host disease (GVHD) at 1 year post HSCT (Roy DC et al. ASH 2016). Similarly, an OS rate of 55% was reported in a second Phase II study (Olavarria E et al. EHA 2018). We report multivariable and subgroup analyses of a pooled dataset from these two Phase II studies of ATIR101, compared with a dataset of control patients meeting similar inclusion/exclusion criteria who underwent T-cell-depleted haplo HSCT without ATIR101, to assess the impact of potential prognostic factors on survival outcomes. Methods After showing comparability allowing the pooling of data, 1-year outcomes from two Phase II studies (CR-AIR-007, NCT01794299; CR-AIR-008, NCT02500550; data cut-off June 1, 2018) including 32 adult patients who received ATIR101 (2.0 × 106 cells/kg) were compared with a historic control of 35 patients treated with a T-cell-depleted haplo HSCT without ATIR101 in centers participating in ATIR101 trials (CR-AIR-006, NCT02188290). Patients with a hematologic malignancy (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], or myelodysplastic syndromes [MDS]) underwent myeloablative or reduced-intensity conditioning with or without total body irradiation (TBI) followed by a CD34+-selected stem cell graft from a haploidentical family donor. ATIR101, prepared from the same donor, was given approximately 28 days post HSCT to patients in the ATIR101 group without prophylactic immunosuppression post HSCT. Post hoc multivariable Cox regressions for non-relapse mortality (NRM) and OS were performed on the pooled ATIR101 and control datasets adjusting for treatment, diagnosis, conditioning regimen, remission status, European Society for Blood and Marrow Transplantation risk score, and total number of viable CD34+ (× 106 cells/kg) given to patients. Variables recognized as clinically important were forced into the model regardless of whether they were statistically significant. Results Overall, patient characteristics at baseline were balanced across groups (ATIR101 vs historic control): median age at HSCT (range) was 43 years (31-51) vs 43 years (28-54); patients had AML (66% vs 71%), ALL (28% vs 11%), or MDS (6% vs 17%); patients underwent myeloablative conditioning (100% vs 94%) with TBI (47% vs 66%) and were in complete remission (100% vs 83%) prior to transplantation. The incidence of Grade III/IV acute GVHD was similar in the ATIR101 and control groups (6%); however, only patients in the control group experienced severe chronic GVHD (2/35). Compared with the control group, the ATIR101 group showed a lower cumulative incidence of NRM (28% vs 66%; hazard ratio [HR]: 0.31; 95% confidence interval [95% CI]: 0.15-0.67; p=0.002) and a higher OS rate (63% vs 20%; HR: 0.34; 95% CI: 0.17-0.69; p=0.002). Adjusting for potential prognostic factors, the benefit of ATIR101 was confirmed in a multivariable analysis for both NRM (HR: 0.27; 95% CI: 0.09-0.78; p=0.016) and OS (HR: 0.28; 95% CI: 0.11-0.70; p=0.006; Table). The addition of ATIR101 treatment following T-cell-depleted haplo HSCT improved survival outcomes compared with T-cell-depleted haplo HSCT alone, irrespective of patient baseline characteristics, as shown in the subgroup analyses (Figure). Conclusions A single infusion of ATIR101 after a T-cell-depleted haplo HSCT in patients with hematologic malignancies appears to improve survival outcomes compared with a T-cell-depleted haplo HSCT alone. After adjusting for potential prognostic risk factors, the multivariable analysis appears to support the clinical benefit of ATIR101 on NRM and OS at 1 year post HSCT. A large, global, randomized Phase 3 study is currently enrolling to further examine the efficacy and safety of T-cell-depleted haplo HSCT + ATIR101 compared with T-cell-replete haplo HSCT with post-transplant cyclophosphamide (HATCY; NCT02999854). Disclosures Roy: Hopital Maisonneuve-Rosemont: Patents &amp; Royalties: Author on patent; University of Montreal: Patents &amp; Royalties: Author on patent; Kiadis Pharma: Other: Travel support. Walker:Kiadis Pharma: Other: Grant funding via institution (as a principal investigator). Maertens:Astellas Pharma: Other: Personal fees and non-financial support; Cidara: Other: Personal fees and non-financial support; F2G: Other: Personal fees and non-financial support; Gilead Sciences: Other: Grants, personal fees and non-financial support; Merck: Other: Personal fees and non-financial support; Pfizer: Other: Grant and personal fees; Amplyx: Other: Personal fees and non-financial support. Olavarria:Kiadis Pharma: Consultancy, Honoraria. Selleslag:Novartis: Consultancy, Honoraria, Speakers Bureau; Celyad: Other: Clinical trial research (no honoraria recieved). Wagner:Pfizer: Other: Advisory board; Novartis: Other: Advisory board; MEDAC: Other: Travel support; MSD: Other: Advisory board. Bönig:Kiadis Pharma: Other: Contract manufacturing of ATIR101; Celgene, Novartis, Sandoz Hexal: Consultancy; Sandoz Hexal, Uniqure: Research Funding; Miletenyi: Speakers Bureau. Bos:Celgene: Research Funding; Kiadis Pharma: Other: Shareholder (of Cytosen, acquired by Kiadis). Mielke:ISCT: Other: Travel support; Jazz Pharma: Honoraria, Other: Travel support, Speakers Bureau; DGHO: Other: Travel support.

Head-to-Head Comparison of Haploidentical HSCT Strategies for Hematologic Malignancies: Phase III Hatcy Study of T-Cell-Depleted HSCT with Adjunctive ATIR101 Versus T-Cell-Replete HSCT with Post‐Transplant Cyclophosphamide

Rationale: Haploidentical allogeneic hematopoietic stem cell transplantation (haplo HSCT) is increasingly used for the treatment of high-risk hematologic malignancies and overcomes limitations of finding a human leukocyte antigen (HLA)-matched donor in a timely manner. Although the most frequently used approach is a T-cell-replete stem cell source followed by in vivo depletion of alloreacting T cells using post-transplant chemotherapy with cyclophosphamide (PTCy), several other approaches have emerged, providing selected or manipulated donor-derived T cells to a T-cell-depleted or alpha/beta T-cell-CD19-depleted stem cell backbone. Here, we present the approach involving T-cell-depleted haplo HSCT complemented by ATIR101, an adjunctive infusion consisting of ex vivo selectively allodepleted, donor-derived, T-cell-enriched leukocytes. ATIR101 can facilitate early immune protection and provide anti-infectious and anti-leukemic activity while minimizing the risk of acute and chronic graft-versus-host disease (GVHD) without the need for post-transplant immunosuppression. ATIR101 is manufactured through the ex vivo use of TH9402 (a rhodamine derivative) and photodynamic treatment, selectively depleting the donor T cells that were activated by the recipient cells. The safety and efficacy of ATIR101 treatment following T-cell-depleted haplo HSCT have been investigated in Phase I and II studies in patients with hematologic malignancies (Roy DC et al. Br J Haematol 2019; ASH 2016, 2018). This strategy is currently being explored in a large, global, randomized Phase III study against a strategy of T-cell-replete HSCT with PTCy as the most commonly applied approach in haplo HSCT. Trial Overview: A randomized, multicenter, open-label Phase III trial (HATCY; CR‐AIR‐009; NCT02999854) is currently enrolling 250 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS) to undergo either T-cell-depleted haplo HSCT with adjunctive ATIR101 treatment or T-cell-replete haplo HSCT with PTCy. Trial Design and Methods: Inclusion and exclusion criteria are listed in Table 1. All patients undergo total body irradiation (TBI) or non-TBI myeloablative conditioning. Patients in the ATIR101 arm receive anti-thymocyte globulin (Sanofi, 2.5 mg/kg once daily for 4 days) prior to HSCT and an ATIR101 infusion at a dose of 2 × 106 viable T cells/kg between 28 and 32 days post HSCT. In this group, no post-HSCT immune suppression is administered. Patients in the PTCy arm receive cyclophosphamide (50 mg/kg) on Day 3 and 4 (or 5) post HSCT, with subsequent use of immune suppression for GVHD prophylaxis based on institutional guidelines. The primary endpoint of the study is GVHD- and relapse-free survival (GRFS), a composite endpoint defined as time from randomization until Grade III/IV acute GVHD, chronic GVHD requiring systemic immunosuppressive treatment, disease relapse, or death, whichever occurs first. GRFS was selected because it encompasses overall post-transplant health status, thereby closely reflecting a successful transplant outcome (Holtan SG, Blood 2015). Key secondary endpoints are overall survival, progression‐free survival, relapse‐related mortality, and transplant‐related mortality. A further objective of the study is to compare the effects of the two treatment strategies on quality of life. Approximately 50 sites are planned globally. The analysis is event driven: an interim analysis is planned at 105 GRFS events and the final analysis at 156 GRFS events. All patients will be followed up for at least 24 months post HSCT. Conclusion: This study will determine whether a strategy with a T-cell-depleted HSCT with adjunctive ex vivo selectively allodepleted, donor-derived, T-cell-enriched leukocytes (ATIR101) results in improved outcomes over a strategy with T-cell-replete HSCT with PTCy in patients undergoing haploidentical transplantation. The use of GRFS as a composite endpoint involving freedom of relapse and severe GVHD will allow a unique health-economic assessment and definition of value-based healthcare. Disclosures Roy: Kiadis Pharma: Other: Travel support; University of Montreal: Patents &amp; Royalties: Author on patent; Hopital Maisonneuve-Rosemont: Patents &amp; Royalties: Author on patent. Sanson:Kiadis Pharma: Employment. Hylton:Kiadis Pharma: Employment. Sandler:Kiadis Pharma: Employment. Mielke:Miltenyi: Consultancy, Honoraria, Other: Travel and speakers fee (via institution), Speakers Bureau; IACH: Other: Travel support; DGHO: Other: Travel support; Kiadis Pharma: Consultancy, Honoraria, Other: Travel support (via institution), Speakers Bureau; EBMT/EHA: Other: Travel support; Bellicum: Consultancy, Honoraria, Other: Travel (via institution); Celgene: Honoraria, Other: Travel support (via institution), Speakers Bureau; GILEAD: Consultancy, Honoraria, Other: travel (via institution), Speakers Bureau; ISCT: Other: Travel support; Jazz Pharma: Honoraria, Other: Travel support, Speakers Bureau.

UM171 Modified Cord Blood Achieves Excellent Survival and Disease Control after 2 Years of Follow-up in High and Very High Risk Malignancies

UM171 Modified Cord Blood Achieves Excellent Survival and Disease Control after 2 Years of Follow-up in High and Very High Risk Malignancies

Study of Attention Deficit and Hyperactivity Disorder Using the Method of Functional Tomography Based On Magnetic Encephalography Data

New method for the magnetic encephalography data analysis was proposed, making it possible to transform multichannel time series into the spatial structure of the human brain activity. In this paper we applied this method to the analysis of magnetic encephalograms, obtained from subjects with attention deficit and hyperactivity disorder. We have considered the experimental data, obtained with 275-channel magnetic encephalographs in McGill University and Montreal University. Magnetic encephalograms of the brain spontaneous activity were registered for 5 minutes in magnetically shielded room. Detailed multichannel spectra were obtained by the Fourier transform of the whole time series. For all spectral components, the inverse problem was solved in elementary current dipole model and the functional structure of the brain activity was calculated in the broad frequency band 0.3-50 Hz. It was found that frequency band relations are different in different experiments. We proposed to use these relations by the summary electric power produced by the sources in selected frequency band. The delta rhythm in frequency band 0.3 to 4 Hz was studied in detail. It was found, that many delta rhythm dipoles were localized outside the brain, and their spectrum consists of the heartbeat harmonics. It was concluded that in experiments considered, the delta rhythm represents the vascular activity of the head. To study the spatial distribution of all rhythms from theta to gamma the partial spectra of the brain divisions were calculated. The partial spectrum includes all frequencies produced by the dipole sources located in the region of brain selected at the magnetic resonance image. The method can be further applied to study encephalograms in various psychic disorders.

Partnering with patients in quality improvement: towards renewed practices for healthcare organization managers?

BackgroundAround the world, many healthcare organizations engage patients as a quality improvement strategy. In Canada, the University of Montreal has developed a model which consists in partnering with patient advisors, providers, and managers in quality improvement. This model was introduced through its Partners in Care Programs tested with several quality improvement teams in Quebec, Canada. Partnering with patients in quality improvement brings about new challenges for healthcare managers. This model is recent, and little is known about how managers contribute to implementing and sustaining it using key practices.MethodsIn-depth multi-level case studies were conducted within two healthcare organizations which have implemented a Partners in Care Program in quality improvement. The longitudinal design of this research enabled us to monitor the implementation of patient partnership initiatives from 2015 to 2017. In total, 38 interviews were carried out with managers at different levels (top-level, mid-level, and front-line) involved in the implementation of Partners in Care Programs. Additionally, seven focus groups were conducted with patients and providers.ResultsOur findings show that managers are engaged in four main types of practices: 1-designing the patient partnership approach so that it makes sense to the entire organization; 2-structuring patient partnership to support its deployment and sustainability; 3-managing patient advisor integration in quality improvement to avoid tokenistic involvement; 4-evaluating patient advisor integration to support continuous improvement. Designing and structuring patient partnership are based on typical management practices used to implement change initiatives in healthcare organizations, whereas managing and evaluating patient advisor integration require new daily practices from managers. Our results reveal that managers at all levels, from top to front-line, are concerned with the implementation of patient partnership in quality improvement.ConclusionThis research adds empirical support to the evidence regarding daily managerial practices used for implementing patient partnership initiatives in quality improvement and contributes to guiding healthcare organizations and managers when integrating such approaches.

Partnered Educational Governance: Rethinking Student Agency in Undergraduate Medical Education.

Historically, students have been "consumers" of undergraduate medical education (UME) rather than stakeholders in its design and implementation. Student input has been retrospective, and although UME leaders have been open to feedback, matters most important to students have often been overlooked, leaving students feeling largely unheard. Student representation has also lacked structure and unity of feedback.A vision for effective student representation drove the creation of a partnered educational governance (PEG) model at McGill University in Montreal, Quebec, Canada, where sharing of expertise between student representatives and UME leadership has improved the UME program and the educational experience of students.The PEG model is grounded in the literature on student government, the student-as-partner framework, and theories of accountability. As part of the model, the student Medical Education Committee, an organized structure for discussion and reporting to student constituents, was established. This structure allows student representatives, entrusted by their peers and faculty, to proactively provide input to UME committees in the development of policies and curricula. The partnership between students and faculty facilitates a shared understanding of educational challenges and potential solutions.Within the first year, meaningful changes associated with the PEG model included increased student engagement in key program decisions, such as the redesign of a research course and an update to the absences and leaves policy. The PEG model enables unified student representation that is accountable and representative-and has a significant impact on outcomes-while maintaining the UME program's ownership of and responsibility for the curriculum and policies.