1,760 results on '"Rochon P"'
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2. Resting eggs bank and their hatching pattern in two co-occuring anostracans Phallocryptus spinosus and Branchinectella media (Crustacea) from saline lakes of the Aurès region (Northeastern Algeria)
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Rais, Lynda, Amarouayache, Mounia, and Rochon, André
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- 2024
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3. L2-Cohomology of quasi-fibered boundary metrics
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Kottke, Chris and Rochon, Frédéric
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- 2024
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4. Warped quasi-asymptotically conical Calabi-Yau metrics
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Conlon, Ronan J. and Rochon, Frédéric
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Mathematics - Differential Geometry ,Mathematics - Algebraic Geometry ,Mathematics - Analysis of PDEs ,53C55, 58J05 - Abstract
We construct many new examples of complete Calabi-Yau metrics of maximal volume growth on certain smoothings of Cartesian products of Calabi-Yau cones with smooth cross-sections. A detailed description of the geometry at infinity of these metrics is given in terms of a compactification by a manifold with corners obtained through the notion of weighted blow-up for manifolds with corners. A key analytical step in the construction of these Calabi-Yau metrics is to derive good mapping properties of the Laplacian on some suitable weighted H\"older spaces. Our methods also produce singular Calabi-Yau metrics with an isolated conical singularity modelled on a Calabi-Yau cone distinct from the tangent cone at infinity, in particular yielding a transition behavior between different Calabi-Yau cones as conjectured by Yang Li. This is used to exhibit many examples where the tangent cone at infinity does not uniquely specify a complete Calabi-Yau metric with exact K\"ahler form., Comment: 64 pages, added the construction of singular Calabi-Yau metrics with an isolated conical singularity modelled on a Calabi-Yau cone distinct from the tangent cone at infinity, thus interpolating between two different Calabi-Yau cones
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- 2023
5. Characterizing mortality in patients with AQP4‐Ab+ neuromyelitis optica spectrum disorder
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Anna Francis, Emily Gibbons, Jeffrey Yu, Karissa Johnston, Hannah Rochon, Lauren Powell, Maria Isabel Leite, Saif Huda, Adrian Kielhorn, and Jacqueline Palace
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Neuromyelitis optica spectrum disorder is an autoimmune disease, causing severe disability due to relapses, but recent mortality data are limited. Among 396 patients seropositive for anti‐aquaporin‐4 antibody from 2014 to 2020 in the United Kingdom, 39 deaths occurred: 19 (48.7%) were unrelated to disease; 14 (35.9%) were severe disability‐ or relapse‐related; and 4 (10.3%) were attributed to malignancy/infection. Mean annual mortality was 1.92% versus 0.63% in the matched population. The standardized mortality ratio was 3.04 (95% confidence interval 1.67–5.30) with 1.29% excess mortality per year in patients. Median Expanded Disability Status Scale before death was 7.0. Results highlight the importance of preventing relapses that drive disability.
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- 2024
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6. Data science in pharmaceutical R&D: the DISRUPT-DS industry roundtable
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Khan, Najat S., Senderovitz, Thomas, Weatherall, James, Branson, Janice, Egersdoerfer, Benedikt, Genevois-Marlin, Eric, Jasti, Sai, Kazi, Mustaqhusain, Kumble, Ranjit, Loerch, Patrick, Rochon, Justine, Sethuraman, Venkat, Studney, Matt, Wu, Xiaoying, Copping, Ryan, Chandran, Priya, Jayatunga, Madura, Jayanth, Dhruv, and Meier, Christoph
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- 2024
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7. Author Correction: Characterizing the profiles of patients with acute concussion versus prolonged post-concussion symptoms in Ontario
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Scott, Olivia F. T., Bubna, Mikaela, Boyko, Emily, Hunt, Cindy, Kristman, Vicki L., Gargaro, Judith, Khodadadi, Mozhgan, Chandra, Tharshini, Kabir, Umme Saika, Kenrick-Rochon, Shannon, Cowle, Stephanie, Burke, Matthew J., Zabjek, Karl F., Dosaj, Anil, Mushtaque, Asma, Baker, Andrew J., Bayley, Mark T., and Tartaglia, Maria Carmela
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- 2024
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8. Structural basis for regulated assembly of the mitochondrial fission GTPase Drp1
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Rochon, Kristy, Bauer, Brianna L., Roethler, Nathaniel A., Buckley, Yuli, Su, Chih-Chia, Huang, Wei, Ramachandran, Rajesh, Stoll, Maria S. K., Yu, Edward W., Taylor, Derek J., and Mears, Jason A.
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- 2024
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9. Allosteric control of dynamin-related protein 1 through a disordered C-terminal Short Linear Motif
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Pérez-Jover, Isabel, Rochon, Kristy, Hu, Di, Mahajan, Mukesh, Madan Mohan, Pooja, Santos-Pérez, Isaac, Ormaetxea Gisasola, Julene, Martinez Galvez, Juan Manuel, Agirre, Jon, Qi, Xin, Mears, Jason A., Shnyrova, Anna V., and Ramachandran, Rajesh
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- 2024
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10. Regulating Gatekeeper AI and Data: Transparency, Access, and Fairness under the DMA, the GDPR, and beyond
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Hacker, Philipp, Cordes, Johann, and Rochon, Janina
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Computer Science - Computers and Society ,Computer Science - Artificial Intelligence ,I.2 - Abstract
Artificial intelligence is not only increasingly used in business and administration contexts, but a race for its regulation is also underway, with the EU spearheading the efforts. Contrary to existing literature, this article suggests, however, that the most far-reaching and effective EU rules for AI applications in the digital economy will not be contained in the proposed AI Act - but have just been enacted in the Digital Markets Act. We analyze the impact of the DMA and related EU acts on AI models and their underlying data across four key areas: disclosure requirements; the regulation of AI training data; access rules; and the regime for fair rankings. The paper demonstrates that fairness, in the sense of the DMA, goes beyond traditionally protected categories of non-discrimination law on which scholarship at the intersection of AI and law has so far largely focused on. Rather, we draw on competition law and the FRAND criteria known from intellectual property law to interpret and refine the DMA provisions on fair rankings. Moreover, we show how, based on CJEU jurisprudence, a coherent interpretation of the concept of non-discrimination in both traditional non-discrimination and competition law may be found. The final part sketches specific proposals for a comprehensive framework of transparency, access, and fairness under the DMA and beyond., Comment: under peer-review
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- 2022
11. Protocol for a phase 3, randomised, active-control study of four-factor prothrombin complex concentrate versus frozen plasma in bleeding adult cardiac surgery patients requiring coagulation factor replacement: the LEX-211 (FARES-II) trial
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Éric Dumont, Lusine Abrahamyan, Stuart Mccluskey, Angela Jerath, Humara Poonawala, Andrew Stevens, Jeannie Callum, Alan Tinmouth, Daniel Wong, Gianluigi Bisleri, Tarit Saha, David Mazer, Hilary Grocott, Jane Yang, Jeff Kinney, Yoan Lamarche, Damon Scales, George Tomlinson, Fuad Moussa, Andrew Shih, Michelle Zeller, Melanie Tokessy, Keyvan Karkouti, Vivek Rao, Summer Syed, Lilia Kaustov, Sophia Wong, Lani Lieberman, Kamrouz Ghadimi, Philippe Demers, Penny Johnson, Jerrold H Levy, Justyna Bartoszko, Miki Peer, Michael Law, Michelle Wong, Mackenzie Quantz, Antoine Rochon, Fraser Rubens, Shagun Jain, Yulia Lin, Katerina Pavenski, Deep Grewal, Deborah DuMerton, Darrin Payne, Saba Ansari, Robert Mayer, Rebecca Randall, Aftab Malik, Bethany Smethurst, Laura Molnar, Angela Sirosky-Yanyk, Mark Peterson, Christopher Harle, Etienne Couture, Diem Tran, Cristina Solomon, Sigurd Knaub, Kenichi A Tanaka, Blaine Achen, Sukhpal Brar, Matthew Coley, Dana Devine, Alana Flexman, Camila Machado de Souza, Maria Rosal Martins, Terri Sun, Rob Tanzola, Mathew Yan, Raffael Zamper, Jo Carrol, Nishanthi Liyanage, Simryn Selby, Reezanoor Kabir, Shelley Oliver, Alioska Escorcia, Susana Medic, Michelle Mozel, Ramanjot Kaur, Kelly Bizovie, Sarah Buchko, Raven Arly Gonzales, Korey Sutherland, Jenna Van Roekel, Alveena Babul, Ken Tanaka, Kofi Vandyck, Amir Butt, Hisako Okada, Robert Tanzola, Reegan Tod, Aiden Scholey, Wafaa Haider, Ester Cisneros-Aguilera, Alexandre Bergeron, Genevieve Belanger, Darren Mullane, Bevan Hughes, Sakara Hutspardol, Shirley Lim, Jian Mi, Debbie Kalar, Matthew Eang, Erick Lorenzana-Saldivar, Edward P Chen, Akash Gupta, Philip Lau, Pablo Perez D’Empaire, Chantal Armali, Amie Malkin, Connie Colavecchia, Harley Meirovich, Annie Bergeron, Francois Laforge, Kim Paradis, Nathalie Gagne, Marie Soleil Saillant, Marie-Claude Vézina, Olivier Royer, Marie-Ève Charest, Lee-Anne Fochesato, Yuxin Bai, Iqbal Jaffar, Nour Alhomsi, Janine Guevarra, Erin Jamula, Wan Chien (Betty) Hsu, Abbey Drew, Hakan Buyukdere, Drashtee Patel, Elizabeth Watt, Hadia Arabi Katbi, Kim Luciano, Amy Moorehead, Kamola Kasimova, Farzana Tasmin, Cielo Bingley, Victoria Barkley, Tob Reegan, Marianna Qu, Jessica Xiong, Sophie Robichaud, Christy Peterson, Manu Jairath, Mathew Tang, Jennita Aariaratnam, Leron DuMerton, Lucas Drew, Sahrish Masood, Toni Tidy, and Elizabeth Krok
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Medicine - Abstract
Introduction Reduced thrombin generation is an important component of post cardiopulmonary bypass (CPB) coagulopathy. To replenish coagulation factors and enhance thrombin generation in bleeding surgical patients, frozen plasma (FP) and four-factor prothrombin complex concentrate (4F-PCC) are used. However, the efficacy–safety balance of 4F-PCC relative to FP in cardiac surgery is unconfirmed.Methods and analysis LEX-211 (FARES-II) is an active-control, randomised, phase 3 study comparing two coagulation factor replacement therapies in bleeding adult cardiac surgical patients at 12 hospitals in Canada and the USA. The primary objective is to determine whether 4F-PCC (Octaplex/Balfaxar, Octapharma) is clinically non-inferior to FP for haemostatic effectiveness. Inclusion criteria are any index (elective or non-elective) cardiac surgery employing CPB and coagulation factor replacement with 4F-PCC or FP ordered in the operating room for bleeding management. Patients will be randomised to receive 1500 or 2000 international units of 4F-PCC or 3 or 4 units of FP, depending on body weight. The primary endpoint of haemostatic treatment response is ‘effective’ if no additional haemostatic intervention is required from 60 min to 24 hours after the first initiation of 4F-PCC or FP; or ‘ineffective’ if any other haemostatic intervention (including a second dose of study drug) is required. An estimated 410 evaluable patients will be required to demonstrate non-inferiority (one-sided α of 0.025, power ≥90%, non-inferiority margin 0.10). Secondary outcomes include transfusions, bleeding-related clinical endpoints, coagulation parameters and safety.Ethics and dissemination The trial has been approved by the institutional review boards of all participating centres. Trial completion is anticipated at the end of 2024, and results will be disseminated via publications in peer-reviewed journals and conference presentations in 2025. The results will advance our understanding of coagulation management in bleeding surgical patients, potentially reducing the need for allogeneic blood products and improving outcomes in surgical patients.Trial registration number NCT05523297.
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- 2024
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12. Integrating gender analysis into research: reflections from the Gender-Net Plus workshop
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Christopher R. Cederroth, Brian D. Earp, Hernando C. Gómez Prada, Carlotta M. Jarach, Shlomit A. Lir, Colleen M. Norris, Louise Pilote, Valeria Raparelli, Paula Rochon, Nina Sahraoui, Cassandra Simmon, Bilkis Vissandjee, Chloé Mour, Mathieu Arbogast, José María Armengol, and Robin Mason
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Gender ,Sex ,Intersectional ,Health research ,Social sciences ,Humanities ,Medicine (General) ,R5-920 - Abstract
Summary: Gender equality has been a crosscutting issue in Horizon 2020 with three objectives: gender balance in decision-making, gender balance and equal opportunities in project teams at all levels, and inclusion of the gender dimension in research and innovation content. Between 2017 and 2022, the EU funded, in collaboration with national agencies, 13 transnational projects under “GENDER-NET Plus” that explored how to best integrate both sex and gender into studies ranging from social sciences, humanities, and health research. As the projects neared completion, forty researchers from these interdisciplinary teams met in November 2022 to share experiences, discuss challenges, and consider the best ways forward to incorporate sex and gender in research. Here, we summarize the reflections from this workshop and provide some recommendations for i) how to plan the studies (e.g., how to define sex and/or gender and their dimensions, rationale for the hypotheses, identification of data that can best answer the research question), ii) how to conduct them (e.g., adjust definitions and dimensions, perform pilot studies to ensure proper use of terminology and revise until consensus is achieved), and iii) how to analyze and report the findings being mindful of any real-world impact.
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- 2024
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13. The use of external controls: To what extent can it currently be recommended?
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Burger, Hans Ulrich, Gerlinger, Christoph, Harbron, Chris, Koch, Armin, Posch, Martin, Rochon, Justine, and Schiel, Anja
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Statistics - Applications ,62P10 - Abstract
With more and better clinical data being captured outside of clinical studies and greater data sharing of clinical studies, external controls may become a more attractive alternative to randomized clinical trials. Both industry and regulators recognize that in situations where a randomized study cannot be performed, external controls can provide the needed contextualization to allow a better interpretation of studies without a randomized control. It is also agreed that external controls will not fully replace randomized clinical trials as the gold standard for formal proof of efficacy in drug development and the yardstick of clinical research. However, it remains unclear in which situations conclusions about efficacy and a positive benefit/risk can reliably be based on the use of an external control. This paper will provide an overview on types of external control, their applications and the different sources of bias their use may incur, and discuss potential mitigation steps. It will also give recommendations on how the use of external controls can be justified.
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- 2022
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14. Structural basis for regulated assembly of the mitochondrial fission GTPase Drp1
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Kristy Rochon, Brianna L. Bauer, Nathaniel A. Roethler, Yuli Buckley, Chih-Chia Su, Wei Huang, Rajesh Ramachandran, Maria S. K. Stoll, Edward W. Yu, Derek J. Taylor, and Jason A. Mears
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Science - Abstract
Abstract Mitochondrial fission is a critical cellular event to maintain organelle function. This multistep process is initiated by the enhanced recruitment and oligomerization of dynamin-related protein 1 (Drp1) at the surface of mitochondria. As such, Drp1 is essential for inducing mitochondrial division in mammalian cells, and homologous proteins are found in all eukaryotes. As a member of the dynamin superfamily of proteins (DSPs), controlled Drp1 self-assembly into large helical polymers stimulates its GTPase activity to promote membrane constriction. Still, little is known about the mechanisms that regulate correct spatial and temporal assembly of the fission machinery. Here we present a cryo-EM structure of a full-length Drp1 dimer in an auto-inhibited state. This dimer reveals two key conformational rearrangements that must be unlocked through intramolecular rearrangements to achieve the assembly-competent state observed in previous structures. This structural insight provides understanding into the mechanism for regulated self-assembly of the mitochondrial fission machinery.
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- 2024
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15. Allosteric control of dynamin-related protein 1 through a disordered C-terminal Short Linear Motif
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Isabel Pérez-Jover, Kristy Rochon, Di Hu, Mukesh Mahajan, Pooja Madan Mohan, Isaac Santos-Pérez, Julene Ormaetxea Gisasola, Juan Manuel Martinez Galvez, Jon Agirre, Xin Qi, Jason A. Mears, Anna V. Shnyrova, and Rajesh Ramachandran
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Science - Abstract
Abstract The mechanochemical GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial and peroxisomal fission, but the regulatory mechanisms remain ambiguous. Here we find that a conserved, intrinsically disordered, six-residue Short Linear Motif at the extreme Drp1 C-terminus, named CT-SLiM, constitutes a critical allosteric site that controls Drp1 structure and function in vitro and in vivo. Extension of the CT-SLiM by non-native residues, or its interaction with the protein partner GIPC-1, constrains Drp1 subunit conformational dynamics, alters self-assembly properties, and limits cooperative GTP hydrolysis, surprisingly leading to the fission of model membranes in vitro. In vivo, the involvement of the native CT-SLiM is critical for productive mitochondrial and peroxisomal fission, as both deletion and non-native extension of the CT-SLiM severely impair their progression. Thus, contrary to prevailing models, Drp1-catalyzed membrane fission relies on allosteric communication mediated by the CT-SLiM, deceleration of GTPase activity, and coupled changes in subunit architecture and assembly-disassembly dynamics.
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- 2024
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16. Products of manifolds with fibered corners
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Kottke, Chris and Rochon, Frédéric
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Mathematics - Differential Geometry - Abstract
Manifolds with fibered corners arise as resolutions of stratified spaces, in many body compactifications of vector spaces, moduli spaces, and other settings. We define a category of fibered corners manifolds which has products and transverse fiber products, generalizing both the resolutions of products of stratified spaces and many body products, which are special cases. The product in the fibered corners category is a resolution of the cartesian product by blow-up which we call the 'ordered product'. This ordered product is a natural product for wedge (aka incomplete edge) metrics and quasi-fibered boundary metrics, a class which includes QAC and QALE metrics., Comment: 55 pages. v3 includes minor corrections and clarifications suggested by the reviewers
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- 2022
17. On the Algebraic Foundation of the Mandelbulb
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Boily, Vanessa and Rochon, Dominic
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Mathematics - Dynamical Systems ,32A30, 30G35, 00A69 - Abstract
In this paper, we generalize the Mandelbrot set using quaternions and spherical coordinates. In particular, we use pure quaternions to define a spherical product. This product, which is inspired by the product of complex numbers, add the angles and multiply the radii of the spherical coordinates. We show that the algebraic structure of pure quaternions with the spherical product is a commutative unital magma. Then, we present several generalizations of the Mandelbrot set. Among them, we present a set that is visually identical to the so-called Mandelbulb. We show that this set is bounded and that it can be generated by an escape time algorithm. We also define another generalization, the bulbic Mandelbrot set. We show that one of its 2D cuts has the same dynamics as the Mandelbrot set and that we can generate this set only with a quaternionic product, without using the spherical product., Comment: 24 pages, 27 images
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- 2022
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18. Measuring Communication as a Core Outcome in Aphasia Trials: Results of the ROMA-2 International Core Outcome Set Development Meeting
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Wallace, Sarah J., Worrall, Linda, Rose, Tanya A., Alyahya, Reem S. W., Babbitt, Edna, Beeke, Suzanne, de Beer, Carola, Bose, Arpita, Bowen, Audrey, Brady, Marian C., Breitenstein, Caterina, Bruehl, Stefanie, Bryant, Lucy, Cheng, Bonnie B. Y., Cherney, Leora R., Conroy, Paul, Copland, David A., Croteau, Claire, Cruice, Madeline, Dipper, Lucy, Hilari, Katerina, Howe, Tami, Kelly, Helen, Kiran, Swathi, Laska, Ann-Charlotte, Marshall, Jane, Murray, Laura L., Patterson, Janet, Pearl, Gill, Quinting, Jana, Rochon, Elizabeth, Rose, Miranda L., Rubi-Fessen, Ilona, Sage, Karen, Simmons-Mackie, Nina, Visch-Brink, Evy, Volkmer, Anna, Webster, Janet, Whitworth, Anne, and Le Dorze, Guylaine
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Background: Evidence-based recommendations for a core outcome set (COS; minimum set of outcomes) for aphasia treatment research have been developed (the Research Outcome Measurement in Aphasia--ROMA, COS). Five recommended core outcome constructs: communication, language, quality of life, emotional well-being and patient-reported satisfaction/impact of treatment, were identified through three international consensus studies. Constructs were paired with outcome measurement instruments (OMIs) during an international consensus meeting (ROMA-1). Before the current study (ROMA-2), agreement had not been reached on OMIs for the constructs of communication or patient-reported satisfaction/impact of treatment. Aim: To establish consensus on a communication OMI for inclusion in the ROMA COS. Methods & Procedures: Research methods were based on recommendations from the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Participants with expertise in design and conduct of aphasia trials, measurement instrument development/testing and/or communication outcome measurement were recruited through an open call. Before the consensus meeting, participants agreed on a definition of communication, identified appropriate OMIs, extracted their measurement properties and established criteria for their quality assessment. During the consensus meeting they short-listed OMIs and participants without conflicts of interest voted on the two most highly ranked instruments. Consensus was defined a priori as agreement by [greater than or equal to] 70% of participants. Outcomes & Results: In total, 40 researchers from nine countries participated in ROMA-2 (including four facilitators and three-panel members who participated in pre-meeting activities only). A total of 20 OMIs were identified and evaluated. Eight short-listed communication measures were further evaluated for their measurement properties and ranked. Participants in the consensus meeting (n = 33) who did not have conflicts of interest (n = 29) voted on the top two ranked OMIs: The Scenario Test (TST) and the Communication Activities of Daily Living--3 (CADL-3). TST received 72% (n = 21) of 'yes' votes and the CADL-3 received 28% (n = 8) of 'yes' votes. Conclusions & Implications: Consensus was achieved that TST was the preferred communication OMI for inclusion in the ROMA COS. It is currently available in the original Dutch version and has been adapted into English, German and Greek. Further consideration must be given to the best way to measure communication in people with mild aphasia. Development of a patient-reported measure for satisfaction with/impact of treatment and multilingual versions of all OMIs of the COS is still required. Implementation of the ROMA COS would improve research outcome measurement and the quality, relevance, transparency, replicability and efficiency of aphasia treatment research.
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- 2023
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19. The Longitudinal Trajectory of Discourse from the Hyperacute to the Chronic Phase in Mild to Moderate Poststroke Aphasia Recovery: A Case Series Study
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Brisebois, Amélie, Brambati, Simona Maria, Rochon, Elizabeth, Leonard, Carol, and Marcotte, Karine
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Background: Discourse analysis has recently received much attention in the aphasia literature. Even if post-stroke language recovery occurs throughout the longitudinal continuum of recovery, very few studies have documented discourse changes from the hyperacute to the chronic phases of recovery. Aims: To document a multilevel analysis of discourse changes from the hyperacute phase to the chronic phase of post-stroke recovery using a series of single cases study designs. Methods & Procedures: Four people with mild to moderate post-stroke aphasia underwent four assessments (hyperacute: 0-24 h; acute: 24-72 h; subacute: 7-14 days; and chronic: 6-12 months post-onset). Three discourse tasks were performed at each time point: a picture description, a personal narrative and a story retelling. Multilevel changes in terms of macro- and microstructural aspects were analysed. The results of each discourse task were combined for each time point. Individual effect sizes were computed to evaluate the relative strength of changes in an early and a late recovery time frame. Outcomes & Results: Macrostructural results revealed improvements throughout the recovery continuum in terms of coherence and thematic efficiency. Also, the microstructural results demonstrated linguistic output improvement for three out of four participants. Namely, lexical diversity and the number of correct information units/min showed a greater gain in the early compared with the late recovery phase. Conclusions & Implications: This study highlights the importance of investigating all discourse processing levels as the longitudinal changes in discourse operate differently at each phase of recovery. Overall results support future longitudinal discourse investigation in people with post-stroke aphasia.
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- 2023
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20. Cytoglobin regulates NO-dependent cilia motility and organ laterality during development
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Elizabeth R. Rochon, Jianmin Xue, Manush Sayd Mohammed, Caroline Smith, Anders Hay-Schmidt, Anthony W. DeMartino, Adam Clark, Qinzi Xu, Cecilia W. Lo, Michael Tsang, Jesus Tejero, Mark T. Gladwin, and Paola Corti
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Science - Abstract
Abstract Cytoglobin is a heme protein with unresolved physiological function. Genetic deletion of zebrafish cytoglobin (cygb2) causes developmental defects in left-right cardiac determination, which in humans is associated with defects in ciliary function and low airway epithelial nitric oxide production. Here we show that Cygb2 co-localizes with cilia and with the nitric oxide synthase Nos2b in the zebrafish Kupffer’s vesicle, and that cilia structure and function are disrupted in cygb2 mutants. Abnormal ciliary function and organ laterality defects are phenocopied by depletion of nos2b and of gucy1a, the soluble guanylate cyclase homolog in fish. The defects are rescued by exposing cygb2 mutant embryos to a nitric oxide donor or a soluble guanylate cyclase stimulator, or with over-expression of nos2b. Cytoglobin knockout mice also show impaired airway epithelial cilia structure and reduced nitric oxide levels. Altogether, our data suggest that cytoglobin is a positive regulator of a signaling axis composed of nitric oxide synthase–soluble guanylate cyclase–cyclic GMP that is necessary for normal cilia motility and left-right patterning.
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- 2023
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21. Characterizing the profiles of patients with acute concussion versus prolonged post-concussion symptoms in Ontario
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Olivia F. T. Scott, Mikaela Bubna, Emily Boyko, Cindy Hunt, Vicki L. Kristman, Judith Gargaro, Mozhgan Khodadadi, Tharshini Chandra, Umme Saika Kabir, Shannon Kenrick-Rochon, Stephanie Cowle, Matthew J. Burke, Karl F. Zabjek, Anil Dosaj, Asma Mushtaque, Andrew J. Baker, Mark T. Bayley, CONNECT, and Maria Carmela Tartaglia
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Medicine ,Science - Abstract
Abstract Identifying vulnerability factors for developing persisting concussion symptoms is imperative for determining which patients may require specialized treatment. Using cross-sectional questionnaire data from an Ontario-wide observational concussion study, we compared patients with acute concussion (≤ 14 days) and prolonged post-concussion symptoms (PPCS) (≥ 90 days) on four factors of interest: sex, history of mental health disorders, history of headaches/migraines, and past concussions. Differences in profile between the two groups were also explored. 110 patients with acute concussion and 96 patients with PPCS were included in our study. The groups did not differ on the four factors of interest. Interestingly, both groups had greater proportions of females (acute concussion: 61.1% F; PPCS: 66.3% F). Patient profiles, however, differed wherein patients with PPCS were significantly older, more symptomatic, more likely to have been injured in a transportation-related incident, and more likely to live outside a Metropolitan city. These novel risk factors for persisting concussion symptoms require replication and highlight the need to re-evaluate previously identified risk factors as more and more concussions occur in non-athletes and different risk factors may be at play.
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- 2023
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22. Study of 72 pulsars discovered in the PALFA survey: Timing analysis, glitch activity, emission variability, and a pulsar in an eccentric binary
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Parent, E., Sewalls, H., Freire, P. C. C., Matheny, T., Lyne, A. G., Perera, B. B. P., Cardoso, F., McLaughlin, M. A., Allen, B., Brazier, A., Camilo, F., Chatterjee, S., Cordes, J. M., Crawford, F., Deneva, J. S., Dong, F. A., Ferdman, R. D., Fonseca, E., Hessels, J. W. T., Kaspi, V. M., Knispel, B., van Leeuwen, J., Lynch, R. S., Meyers, B. M., McKee, J. W., Mickaliger, M. B., Patel, C., Ransom, S. M., Rochon, A., Scholz, P., Stairs, I. H., Stappers, B. W., Tan, C. M., and Zhu, W. W.
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Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
We present new discoveries and results from long-term timing of 72 pulsars discovered in the Arecibo PALFA survey, including precise determination of astrometric and spin parameters, and flux density and scatter broadening measurements at 1.4 GHz. Notable discoveries include two young pulsars (characteristic ages $\sim$30 kyr) with no apparent supernova remnant associations, three mode changing, 12 nulling and two intermittent pulsars. We detected eight glitches in five pulsars. Among them is PSR J1939+2609, an apparently old pulsar (characteristic age $\sim$1 Gy), and PSR J1954+2529, which likely belongs to a newly-emerging class of binary pulsars. The latter is the only pulsar among the 72 that is clearly not isolated: a non-recycled neutron star with a 931-ms spin period in an eccentric ($e\,=\,0.114$) wide ($P_b\,=\,82.7\,$d) orbit with a companion of undetermined nature having a minimum mass of $\sim0.6\,M_{\odot}$. Since operations at Arecibo ceased in 2020 August, we give a final tally of PALFA sky coverage, and compare its 207 pulsar discoveries to the known population. On average, they are 50% more distant than other Galactic plane radio pulsars; PALFA millisecond pulsars (MSP) have twice the dispersion measure per unit spin period than the known population of MSP in the Plane. The four intermittent pulsars discovered by PALFA more than double the population of such objects, which should help to improve our understanding of pulsar magnetosphere physics. The statistics for these, RRATS, and nulling pulsars suggest that there are many more of these objects in the Galaxy than was previously thought., Comment: 39 pages, 18 figures, 9 tables. Accepted for publication in ApJ
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- 2021
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23. Relationship between the Mandelbrot Algorithm and the Platonic Solids
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Vallières, André and Rochon, Dominic
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Mathematics - Dynamical Systems ,32A30, 30G35, 00A69, 51M20 - Abstract
This paper focuses on the dynamics of the eight tridimensional principal slices of the tricomplex Mandelbrot set: the Tetrabrot, the Arrowheadbrot, the Mousebrot, the Turtlebrot, the Hourglassbrot, the Metabrot, the Airbrot (octahedron) and the Firebrot (tetrahedron). In particular, we establish a geometrical classification of these 3D slices using the properties of some specific sets that correspond to projections of the bicomplex Mandelbrot set on various two-dimensional vector subspaces, and we prove that the Firebrot is a regular tetrahedron. Finally, we construct the so-called "Stella octangula" as a tricomplex dynamical system composed of the union of the Firebrot and its dual, and after defining the idempotent 3D slices of $\mathcal{M}_{3}$, we show that one of them corresponds to a third Platonic solid: the cube.
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- 2021
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24. Cytoglobin regulates NO-dependent cilia motility and organ laterality during development
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Rochon, Elizabeth R., Xue, Jianmin, Mohammed, Manush Sayd, Smith, Caroline, Hay-Schmidt, Anders, DeMartino, Anthony W., Clark, Adam, Xu, Qinzi, Lo, Cecilia W., Tsang, Michael, Tejero, Jesus, Gladwin, Mark T., and Corti, Paola
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- 2023
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25. Characterizing the profiles of patients with acute concussion versus prolonged post-concussion symptoms in Ontario
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Scott, Olivia F. T., Bubna, Mikaela, Boyko, Emily, Hunt, Cindy, Kristman, Vicki L., Gargaro, Judith, Khodadadi, Mozhgan, Chandra, Tharshini, Kabir, Umme Saika, Kenrick-Rochon, Shannon, Cowle, Stephanie, Burke, Matthew J., Zabjek, Karl F., Dosaj, Anil, Mushtaque, Asma, Baker, Andrew J., Bayley, Mark T., and Tartaglia, Maria Carmela
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- 2023
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26. Factors associated with loneliness in immigrant and Canadian-born older adults in Ontario, Canada: a population-based study
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Lu, Mindy, Bronskill, Susan E., Strauss, Rachel, Boblitz, Alexa, Guan, Jun, Im, James H.B., Rochon, Paula A., Gruneir, Andrea, and Savage, Rachel D.
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- 2023
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27. The changing epidemiology of preterm labour and delivery: A systematic literature review
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Tina Li, Hannah Rochon, Shelagh M. Szabo, Emilia Kourmaeva, Megan Manuel, and Vanessa Perez Patel
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epidemiology ,observational studies ,obstetrics ,preterm birth ,preterm labour ,Reproduction ,QH471-489 ,Women. Feminism ,HQ1101-2030.7 - Abstract
Abstract Objective To identify and synthesize epidemiologic data for preterm labour (PTL) and preterm birth (PTB). Methods A systematic search, with protocol registered in PROSPERO, was implemented in MEDLINE and EMBASE and supplemented by web‐based and grey literature searches. Observational, population‐based studies in the United States, Canada, United Kingdom, France, Germany, Spain, and Italy, published in English between 2012 and 2022 were considered for inclusion. Estimates by country were reported and stratified by gestational age, birth plurality, and race/ethnicity, data permitting. Results Ten publications and nine grey literature reports were included. Epidemiologic estimates of PTL were reported for the United Kingdom and France: PTL was diagnosed in 2.2% of pregnancies and preceded 50% of PTBs. PTB rates were reported for the United States, Canada, United Kingdom, France, and Spain. Among live births in these countries, annual PTB incidence ranged from 5.9% (Spain, 2020) to 10.2% (United States, 2019). Most countries reported the PTB incidence by gestational age; reports by birth plurality or race/ethnicity were scarce. PTB rates for Germany or Italy were not identified. Conclusions While PTBs were well‐reported overall and by gestational age, how rates varied by plurality, race/ethnicity and etiology is unclear. Epidemiologic estimates for PTL, a leading cause of PTB, were rarely reported in the literature. Population‐based research is needed to understand the burden of PTL and for decision making regarding the management of this condition.
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- 2024
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28. Resilience among organ donation coordinators: a Canadian mixed-methods study
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Amina R. Silva, Andrea Rochon, Laura Hornby, Ken Lotherington, Lee James, Richard Webster, Ewa Sucha, Aimee Sarti, Sonny Dhanani, and Vanessa Silva e Silva
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coping strategies ,organ donation ,organ donor coordinators ,protective factors ,resilience ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundOrgan and Tissue Donation Coordinators (OTDCs) are key to the success of deceased organ donation processes. However, reduced resilience can leave them susceptible to the incidence of work-related issues and decrease the quality of the care provided. Therefore, this study aimed to examine the extent of resilience and influencing aspects among OTDCs in Canada.MethodsMixed-method (QUAN-qual) explanatory sequential design. Quantitative data was collected using an online cross-sectional survey approach with demographic data and the validated scales and analyzed using descriptive and inferential statistics. Qualitative data was collected using a descriptive approach with a semi-structured interview guide and analyzed using content analysis.ResultsOne hundred twenty participants responded to the survey, and 39 participants were interviewed. Most participants from the survey were female (82%), registered nurses (97%) and on average 42 years old. The quantitative data revealed that OTDCs had a high level of perceived compassion satisfaction (ProQOL-CS = 36.3) but a resilience score (CD-RISC = 28.5) lower than other groups of healthcare professionals. OTDCs with over a year of experience in the role were more likely to have higher levels of resilience. The qualitative data identified that participants saw resilience as crucial for their work-related well-being. Although coping strategies were identified as a key factor that enhance resilience, many OTDCs reported difficulty in developing healthy coping strategies, and that the use of unhealthy mechanisms (e.g., alcohol and smoking) can result in negative physical consequences (e.g., weight gain) and reduced resilience levels.ConclusionParticipants reported using a series of coping and protective strategies to help build resilience, but also difficulty in developing healthy mechanisms. The lack of healthy coping strategies were seen as contributing to negative work-related issues (e.g., burnout). Our findings are being used to develop tailored interventions to improve resilience and healthy coping strategies among organ donor coordinators in Canada.
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- 2024
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29. Myoglobin modulates the Hippo pathway to promote cardiomyocyte differentiation
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Krithika Rao, Elizabeth Rochon, Anuradha Singh, Rajaganapathi Jagannathan, Zishan Peng, Haris Mansoor, Bing Wang, Mousumi Moulik, Manling Zhang, Anita Saraf, Paola Corti, and Sruti Shiva
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Natural sciences ,Biological sciences ,Biochemistry ,Cell biology ,Specialized functions of cells ,Science - Abstract
Summary: The endogenous mechanisms that propagate cardiomyocyte differentiation and prevent de-differentiation remain unclear. While the expression of the heme protein myoglobin increases by over 50% during cardiomyocyte differentiation, a role for myoglobin in regulating cardiomyocyte differentiation has not been tested. Here, we show that deletion of myoglobin in cardiomyocyte models decreases the gene expression of differentiation markers and stimulates cellular proliferation, consistent with cardiomyocyte de-differentiation. Mechanistically, the heme prosthetic group of myoglobin catalyzes the oxidation of the Hippo pathway kinase LATS1, resulting in phosphorylation and inactivation of yes-associated protein (YAP). In vivo, myoglobin-deficient zebrafish hearts show YAP dephosphorylation and accelerated cardiac regeneration after apical injury. Similarly, myoglobin knockdown in neonatal murine hearts shows increased YAP dephosphorylation and cardiomyocyte cycling. These data demonstrate a novel role for myoglobin as an endogenous driver of cardiomyocyte differentiation and highlight myoglobin as a potential target to enhance cardiac development and improve cardiac repair and regeneration.
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- 2024
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30. Trehalose promotes atherosclerosis regression in female mice
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Sabrina Robichaud, Valérie Rochon, Christina Emerton, Thomas Laval, and Mireille Ouimet
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atherosclerosis ,autophagy ,regression ,trehalose ,cholesterol ,inflammation ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
IntroductionAtherosclerosis is a chronic inflammatory disease caused by the deposition of lipids within the artery wall. During atherogenesis, efficient autophagy is needed to facilitate efferocytosis and cholesterol efflux, limit inflammation and lipid droplet buildup, and eliminate defective mitochondria and protein aggregates. Central to the regulation of autophagy is the transcription factor EB (TFEB), which coordinates the expression of lysosomal biogenesis and autophagy genes. In recent years, trehalose has been shown to promote TFEB activation and protect against atherogenesis. Here, we sought to investigate the role of autophagy activation during atherosclerosis regression.Methods and resultsAtherosclerosis was established in C57BL/6N mice by injecting AAV-PCSK9 and 16 weeks of Western diet feeding, followed by switching to a chow diet to induce atherosclerosis regression. During the regression period, mice were either injected with trehalose concomitant with trehalose supplementation in their drinking water or injected with saline for 6 weeks. Female mice receiving trehalose had reduced atherosclerosis burden, as evidenced by reduced plaque lipid content, macrophage numbers and IL-1β content in parallel with increased plaque collagen deposition, which was not observed in their male counterparts. In addition, trehalose-treated female mice had lower levels of circulating leukocytes, including inflammatory monocytes and CD4+ T cells. Lastly, we found that autophagy flux in male mice was basally higher than in female mice during atherosclerosis progression.ConclusionsOur data demonstrate a sex-specific effect of trehalose in atherosclerosis regression, whereby trehalose reduced lipid content, inflammation, and increased collagen content in female mice but not in male mice. Furthermore, we discovered inherent differences in the autophagy flux capacities between the sexes: female mice exhibited lower plaque autophagy than males, which rendered the female mice more responsive to atherosclerosis regression. Our work highlights the importance of understanding sex differences in atherosclerosis to personalize the development of future therapies to treat cardiovascular diseases.
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- 2024
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31. Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in the Elderly with Alzheimer's Disease (D-PRESCRIBE-AD): Trial protocol and rationale of an open-label pragmatic, prospective randomized controlled trial.
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Sonal Singh, Noelle M Cocoros, Xiaojuan Li, Kathleen M Mazor, Mary T Antonelli, Lauren Parlett, Mark Paullin, Thomas P Harkins, Yunping Zhou, Paula A Rochon, Richard Platt, Inna Dashevsky, Carly Massino, Cassandra Saphirak, Sybil L Crawford, and Jerry H Gurwitz
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Medicine ,Science - Abstract
ContextPotentially inappropriate prescribing of medications in older adults, particular those with dementia, can lead to adverse drug events including falls and fractures, worsening cognitive impairment, emergency department visits, and hospitalizations. Educational mailings from health plans to patients and their providers to encourage deprescribing conversations may represent an effective, low-cost, "light touch", approach to reducing the burden of potentially inappropriate prescription use in older adults with dementia.ObjectivesThe objective of the Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer's Disease (D-PRESCRIBE-AD) trial is to evaluate the effect of a health plan based multi-faceted educational outreach intervention to community dwelling patients with dementia who are currently prescribed sedative/hypnotics, antipsychotics, or strong anticholinergics.MethodsThe D-PRESCRIBE-AD is an open-label pragmatic, prospective randomized controlled trial (RCT) comparing three arms: 1) educational mailing to both the health plan patient and their prescribing physician (patient plus physician arm, n = 4814); 2) educational mailing to prescribing physician only (physician only arm, n = 4814); and 3) usual care (n = 4814) among patients with dementia enrolled in two large United States based health plans. The primary outcome is the absence of any dispensing of the targeted potentially inappropriate prescription during the 6-month study observation period after a 3-month black out period following the mailing. Secondary outcomes include dose-reduction, polypharmacy, healthcare utilization, mortality and therapeutic switching within targeted drug classes.ConclusionThis large pragmatic RCT will contribute to the evidence base on promoting deprescribing of potentially inappropriate medications among older adults with dementia. If successful, such light touch, inexpensive and highly scalable interventions have the potential to reduce the burden of potentially inappropriate prescribing for patients with dementia. ClinicalTrials.gov Identifier: NCT05147428.
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- 2024
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32. NOMAD version 4: Nonlinear optimization with the MADS algorithm
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Audet, Charles, Digabel, Sébastien Le, Montplaisir, Viviane Rochon, and Tribes, Christophe
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Mathematics - Optimization and Control ,Computer Science - Mathematical Software - Abstract
NOMAD is software for optimizing blackbox problems. In continuous development since 2001, it constantly evolved with the integration of new algorithmic features published in scientific publications. These features are motivated by real applications encountered by industrial partners. The latest major release of NOMAD, version 3, dates from 2008. Minor releases are produced as new features are incorporated. The present work describes NOMAD 4, a complete redesign of the previous version, with a new architecture providing more flexible code, added functionalities and reusable code. We introduce algorithmic components, which are building blocks for more complex algorithms, and can initiate other components, launch nested algorithms, or perform specialized tasks. They facilitate the implementation of new ideas, including the MegaSearchPoll component, warm and hot restarts, and a revised version of the PSD-MADS algorithm. Another main improvement of NOMAD 4 is the usage of parallelism, to simultaneously compute multiple blackbox evaluations, and to maximize usage of available cores. Running different algorithms, tuning their parameters, and comparing their performance for optimization is simpler than before, while overall optimization performance is maintained between versions 3 and 4. NOMAD is freely available at www.gerad.ca/nomad and the whole project is visible at github.com/bbopt/nomad.
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- 2021
33. STOPP/START version 3: even better with age
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Rochon, Paula A., Stall, Nathan M., Reppas-Rindlisbacher, Christina, and Gurwitz, Jerry H.
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- 2023
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34. Implementing uterine balloon tamponade (UBT) device for immediate postpartum hemorrhage management: Leveraging resource allocation and highlighting noteworthy experiences
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Mian Dehi Boston, Guie Privat, Apollinaire Horo, Aka Edele, Kouakou Konan Virginie, Aholoupke Bruno, Koné Seydou, Rochon Sarah, Boni Serge, and Burke Thomas F
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Implementation ,Uterine balloon tamponade ,Post-partum hemorrhage ,Health providers ,Health regions ,Gynecology and obstetrics ,RG1-991 - Abstract
Background: The use of uterine balloon tamponade (UBT) devices for intrauterine packing and management of vaginal bleeding by uterine atony has shown promising results in improving the quality of care and reducing maternal mortality. Objective: This report aims to provide an overview of progress made in implementing UBT devices in northern Cote d'Ivoire. Material and methods: A four-year retrospective study was conducted in the North-East (163,645), North-Center (351,909), and North-West (57,983). In 2017, UBT was adopted by members of the healthcare system. Subsequently, 5 national and 32 regional trainers have been trained. The training session was a theoretical and practical program with a low simulator. UBT is a male condom tied to a urinary catheter, filled with liquid. Positive outcomes included stopping bleeding, avoiding the need for surgery, and preventing maternal deaths (MD). In 2018, 3,515 UBT devices were distributed. In 2019, monitoring tools and transmission circuits of the data were validated. In 2020, the collection of data and local manufacturing was launched. Results: During the process, 978 health workers, mainly midwife (52.0%) and nurses (32.2%) out of the 1,295 assigned were trained. The number of trained individuals decreased from 209 in 2019 to 160 in 2020. A total of 1,715 UBT devices were locally manufactured, adding to the existing gift of 5,080 devices, with total availability of 6,795. The distribution of devices increased from 2017 to 2019 but decreased in 2020. Success rates increased from 87.3% in 2017 (365/418) to 95.0% in 2019 (556/585) and slightly decreased in 2020 to 98.0% (681/695). Adverse outcomes (144/2,193), included MD (35/2,193) and medical evacuation to the surgical center (109/2,193). Conclusion: The implementation of UBT in northern Cote d'Ivoire successfully reduced maternal death rates caused by immediate post-partum hemorrhage (IPPH). However, to ensure sustainability, further improvements are needed, including increased monitoring, ongoing training, and device availability.
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- 2023
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35. $L^2$-cohomology of quasi-fibered boundary metrics
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Kottke, Chris and Rochon, Frédéric
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Mathematics - Differential Geometry ,Mathematical Physics ,Mathematics - Geometric Topology ,58J10, 55N33 - Abstract
We develop new techniques to compute the weighted $L^2$-cohomology of quasi-fibered boundary metrics (QFB-metrics). Combined with the decay of $L^2$-harmonic forms obtained in a companion paper, this allows us to compute the reduced $L^2$-cohomology for various classes of QFB-metrics. Our results applies in particular to the Nakajima metric on the Hilbert scheme of $n$ points on $\mathbb{C}^2$, for which we can show that the Vafa-Witten conjecture holds. Using the compactification of the monopole moduli space announced by Fritzsch, the first author and Singer, we can also give a proof of the Sen conjecture for the monopole moduli space of magnetic charge 3., Comment: 32 pages, addressed comments of a referee
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- 2021
36. Quasi-fibered boundary pseudodifferential operators
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Kottke, Chris and Rochon, Frédéric
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Mathematics - Differential Geometry ,Mathematics - Analysis of PDEs ,58J40, 58J05 - Abstract
We develop a pseudodifferential calculus for differential operators associated to quasi-fibered boundary metrics (QFB metrics), a class of metrics including the quasi-asymptotically conical metrics (QAC metrics) of Degeratu-Mazzeo and the quasi-asymptotically locally Euclidean metrics (QALE metrics) of Joyce. Introducing various principal symbols, we introduce the notion of fully elliptic QFB operators and show that those are Fredholm when acting on QFB Sobolev spaces. For QAC metrics, we also develop a pseudodifferential calculus for the conformally related class of Qb metrics. We use these calculi to construct a parametrix for the Hodge-deRham operator of certain QFB metrics, allowing us to show that it is Fredholm on suitable Sobolev spaces and that the space of $L^2$ harmonic forms is finite dimensional. Our parametrix is obtained by inverting certain model operators at infinity, inversions that we achieve in part through a fine understanding of the low energy limit of the resolvent of the Hodge-deRham operator. Our parametrix also implies that $L^2$ harmonic forms decay faster at infinity than an arbitrary $L^2$ form, the extra decay being quantified in terms of a small negative power of the distance function. This decay of $L^2$ harmonic forms is used in a companion paper to study the $L^2$ cohomology of some $QFB$ metrics., Comment: 127 pages, 1 figure, improved the results from depth 2 to arbitrary depth through a fine understanding of the low energy limit of the resolvent of the Hodge-deRham operator
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- 2021
37. Metabolic Syndrome Mediates ROS-miR-193b-NFYA–Dependent Downregulation of Soluble Guanylate Cyclase and Contributes to Exercise-Induced Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction
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Satoh, Taijyu, Wang, Longfei, Espinosa-Diez, Cristina, Wang, Bing, Hahn, Scott A, Noda, Kentaro, Rochon, Elizabeth R, Dent, Matthew R, Levine, Andrea R, Baust, Jeffrey J, Wyman, Samuel, Wu, Yijen L, Triantafyllou, Georgios A, Tang, Ying, Reynolds, Mike, Shiva, Sruti, St. Hilaire, Cynthia, Gomez, Delphine, Goncharov, Dmitry A, Goncharova, Elena A, Chan, Stephen Y, Straub, Adam C, Lai, Yen-Chun, McTiernan, Charles F, and Gladwin, Mark T
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Nutrition ,Obesity ,Diabetes ,Cardiovascular ,Heart Disease ,Aetiology ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,2.1 Biological and endogenous factors ,Animals ,Animals ,Genetically Modified ,Biomarkers ,CCAAT-Binding Factor ,Disease Models ,Animal ,Disease Susceptibility ,Exercise ,Gene Expression Regulation ,Heart Failure ,Humans ,Hypertension ,Pulmonary ,Metabolic Syndrome ,MicroRNAs ,Mitochondria ,Heart ,Myocytes ,Smooth Muscle ,Phenotype ,Rats ,Reactive Oxygen Species ,Signal Transduction ,Soluble Guanylyl Cyclase ,Stress ,Physiological ,Stroke Volume ,Ventricular Dysfunction ,Right ,MIRN193 microRNA ,human ,nitric oxide ,nuclear factor Y ,pulmonary hypertension ,MIRN193 microRNA ,human ,Cardiorespiratory Medicine and Haematology ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences ,Sports science and exercise - Abstract
BackgroundMany patients with heart failure with preserved ejection fraction have metabolic syndrome and develop exercise-induced pulmonary hypertension (EIPH). Increases in pulmonary vascular resistance in patients with heart failure with preserved ejection fraction portend a poor prognosis; this phenotype is referred to as combined precapillary and postcapillary pulmonary hypertension (CpcPH). Therapeutic trials for EIPH and CpcPH have been disappointing, suggesting the need for strategies that target upstream mechanisms of disease. This work reports novel rat EIPH models and mechanisms of pulmonary vascular dysfunction centered around the transcriptional repression of the soluble guanylate cyclase (sGC) enzyme in pulmonary artery (PA) smooth muscle cells.MethodsWe used obese ZSF-1 leptin-receptor knockout rats (heart failure with preserved ejection fraction model), obese ZSF-1 rats treated with SU5416 to stimulate resting pulmonary hypertension (obese+sugen, CpcPH model), and lean ZSF-1 rats (controls). Right and left ventricular hemodynamics were evaluated using implanted catheters during treadmill exercise. PA function was evaluated with magnetic resonance imaging and myography. Overexpression of nuclear factor Y α subunit (NFYA), a transcriptional enhancer of sGC β1 subunit (sGCβ1), was performed by PA delivery of adeno-associated virus 6. Treatment groups received the SGLT2 inhibitor empagliflozin in drinking water. PA smooth muscle cells from rats and humans were cultured with palmitic acid, glucose, and insulin to induce metabolic stress.ResultsObese rats showed normal resting right ventricular systolic pressures, which significantly increased during exercise, modeling EIPH. Obese+sugen rats showed anatomic PA remodeling and developed elevated right ventricular systolic pressure at rest, which was exacerbated with exercise, modeling CpcPH. Myography and magnetic resonance imaging during dobutamine challenge revealed PA functional impairment of both obese groups. PAs of obese rats produced reactive oxygen species and decreased sGCβ1 expression. Mechanistically, cultured PA smooth muscle cells from obese rats and humans with diabetes or treated with palmitic acid, glucose, and insulin showed increased mitochondrial reactive oxygen species, which enhanced miR-193b-dependent RNA degradation of nuclear factor Y α subunit (NFYA), resulting in decreased sGCβ1-cGMP signaling. Forced NYFA expression by adeno-associated virus 6 delivery increased sGCβ1 levels and improved exercise pulmonary hypertension in obese+sugen rats. Treatment of obese+sugen rats with empagliflozin improved metabolic syndrome, reduced mitochondrial reactive oxygen species and miR-193b levels, restored NFYA/sGC activity, and prevented EIPH.ConclusionsIn heart failure with preserved ejection fraction and CpcPH models, metabolic syndrome contributes to pulmonary vascular dysfunction and EIPH through enhanced reactive oxygen species and miR-193b expression, which downregulates NFYA-dependent sGCβ1 expression. Adeno-associated virus-mediated NFYA overexpression and SGLT2 inhibition restore NFYA-sGCβ1-cGMP signaling and ameliorate EIPH.
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- 2021
38. Online Dating for People with Disabilities: A Scoping Review
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Miron, Mirabelle, Goulet, Katia, Auger, Louis-Pierre, Robillard, Chantal, Dumas, Catherine, Rochon, François, and Kairy, Dahlia
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- 2023
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39. Factors associated with loneliness in immigrant and Canadian-born older adults in Ontario, Canada: a population-based study
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Mindy Lu, Susan E. Bronskill, Rachel Strauss, Alexa Boblitz, Jun Guan, James H.B. Im, Paula A. Rochon, Andrea Gruneir, and Rachel D. Savage
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Loneliness ,Immigration ,Population health ,Canadian community health survey ,Geriatrics ,RC952-954.6 - Abstract
Abstract Background While loneliness is common in older adults, some immigrant groups are at higher risk. To inform tailored interventions, we identified factors associated with loneliness among immigrant and Canadian-born older adults living in Ontario, Canada. Methods We conducted a cross-sectional analysis of 2008/09 data from the Canadian Community Health Survey (Healthy Aging Cycle) and linked health administrative data for respondents 65 years and older residing in Ontario, Canada. Loneliness was measured using the Three-Item Loneliness Scale, with individuals categorized as ‘lonely’ if they had an overall score of 4 or greater. For immigrant and Canadian-born older adults, we developed separate multivariable logistic regression models to assess individual, relationship and community-level factors associated with loneliness. Results In a sample of 968 immigrant and 1703 Canadian-born older adults, we found a high prevalence of loneliness (30.8% and 34.0%, respectively). Shared correlates of loneliness included low positive social interaction and wanting to participate more in social, recreational or group activities. In older immigrants, unique correlates included: widowhood, poor health (i.e., physical, mental and social well-being), less time in Canada, and lower neighborhood-level ethnic diversity and income. Among Canadian-born older adults, unique correlates were: female sex, poor mental health, weak sense of community belonging and living alone. Older immigrant females, compared to older immigrant males, had greater prevalence (39.1% vs. 21.9%) of loneliness. Conclusions Although both groups had shared correlates of loneliness, community-level factors were more strongly associated with loneliness in immigrants. These findings enhance our understanding of loneliness and can inform policy and practice tailored to immigrants.
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- 2023
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40. Low energy limit for the resolvent of some fibered boundary operators
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Kottke, Chris and Rochon, Frédéric
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Mathematics - Differential Geometry ,Mathematics - Analysis of PDEs ,Mathematics - Spectral Theory ,58J05, 58J40 - Abstract
For certain Dirac operators $\eth_{\phi}$ associated to a fibered boundary metric $g_{\phi}$, we provide a pseudodifferential characterization of the limiting behavior of $(\eth_{\phi}+k\gamma)^{-1}$ as $k\searrow 0$, where $\gamma$ is a self-adjoint operator anti-commuting with $\eth_{\phi}$ and whose square is the identity. This yields in particular a pseudodifferential characterization of the low energy limit of the resolvent of $\eth_{\phi}^2$, generalizing a result of Guillarmou and Sher about the low energy limit of the resolvent of the Hodge Laplacian of an asymptotically conical metric. As an application, we use our result to give a pseudodifferential characterization of the inverse of some suspended version of the operator $\eth_{\phi}$. One important ingredient in the proof of our main theorem is that the Dirac operator $\eth_{\phi}$ is Fredholm when acting on suitable weighted Sobolev spaces. This result has been known to experts for some time and we take this as an occasion to provide a complete explicit proof., Comment: 51 pages, 7 figures, improved the presentation, corrected the statements and proofs of Theorem 2.9 and Lemma 7.6
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- 2020
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41. Products of manifolds with fibered corners
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Kottke, Chris and Rochon, Frédéric
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- 2023
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42. Bio-Experiential Technology to Support Persons With Dementia and Care Partners at Home (TEND): Protocol for an Intervention Development Study
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Elizabeth A Rochon, Maimouna Sy, Mirelle Phillips, Erik Anderson, Evan Plys, Christine Ritchie, and Ana-Maria Vranceanu
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Medicine ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
BackgroundAlzheimer disease and related dementias are debilitating and incurable diseases. Persons with dementia and their informal caregivers (ie, dyads) experience high rates of emotional distress and negative health outcomes. Several barriers prevent dyads from engaging in psychosocial care including cost, transportation, and a lack of treatments that target later stages of dementia and target the dyad together. Technologically informed treatment and serious gaming have been shown to be feasible and effective among persons living with dementia and their care partners. To increase access, there is a need for technologically informed psychosocial interventions which target the dyad, together in the home. ObjectiveThis study aims to develop the toolkit for experiential well-being in dementia, a dyadic, “bio-experiential” intervention for persons with dementia and their caregivers. Per our conceptual model, the toolkit for experiential well-being in dementia platform aims to target sustained attention, positive emotions, and active engagement among dyads. In this paper, we outline the protocol and conceptual model for intervention development and partnership with design and development experts. MethodsWe followed the National Institutes of Health (NIH) stage model (stage 1A) and supplemented the model with principles of user-centered design. The first step includes understanding user needs, goals, and strengths. We met this step by engaging in methodology and definition synthesis and conducting focus groups with dementia care providers (N=10) and persons with dementia and caregivers (N=11). Step 2 includes developing and refining the prototype. We will meet this step by engaging dyads in up to 20 iterations of platform β testing workshops. Step 3 includes observing user interactions with the prototype. We will meet this step by releasing the platform for feasibility testing. ResultsKey takeaways from the focus groups include balancing individualization and the dyadic relationship and avoiding confusing stimuli. As of September 2023, we have completed focus groups with providers, persons with dementia, and their caregivers. Additionally, we have conducted 4 iterations of β testing workshops with dyads. Feedback from focus groups informed the β testing workshops; data have not yet been formally analyzed and will be reported in future publications. ConclusionsTechnological interventions, particularly “bio-experiential” technology, can be used in dementia care to support emotional health among persons with a diagnosis and caregivers. Here, we outline a collaborative intervention development process of bio-experiential technology through a research, design, and development partnership. Next, we are planning to test the platform’s feasibility as well as its impact on clinical outcomes and mechanisms of action. International Registered Report Identifier (IRRID)DERR1-10.2196/52799
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- 2023
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43. A Mindfulness-Based Resiliency Program for Caregivers of Patients With Severe Acute Brain Injury Transitioning Out of Critical Care: Protocol for an Open Pilot Trial
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Alexander Mattia Presciutti, Emily Woodworth, Elizabeth Rochon, Molly Neale, Melissa Motta, Joseph Piazza, Ana-Maria Vranceanu, and David Yi-Gin Hwang
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Medicine ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
BackgroundCaregivers of patients with severe acute brain injuries (SABI) that lead to coma and require intensive care unit (ICU) treatment often experience chronic emotional distress. To address this need, we developed the Coma Family (COMA-F) program, a mindfulness-based resiliency intervention for these caregivers. ObjectiveWe will conduct an open pilot trial of COMA-F (National Institutes of Health Stage IA). Here we describe our study protocol and proposed intervention content. MethodsWe will enroll 15 caregivers of patients with SABIs during their loved one’s hospital course from 3 enrollment centers. A clinical psychologist will deliver the COMA-F intervention (6 sessions) over Zoom (Zoom Video Communications, Inc) or in person. We will iterate COMA-F after each caregiver completes the intervention and an exit interview. English-speaking adults who have emotional distress confirmed by the clinical team and are the primary caregivers of a patient with SABI are eligible. The adult patient must have been admitted to the neuro-ICU for SABI and (1) have had a Glasgow Coma Scale score below 9 while not intubated or an inability to follow meaningful commands while intubated at any point during their hospitalization for >24 hours due to SABI; (2) will be undergoing either tracheostomy or percutaneous endoscopic or surgical gastrostomy tube placement or have already received one or both; and (3) have a prognosis of survival >3 months. We will identify eligible caregivers through screening patients’ medical records and through direct referrals from clinicians in the neuro-ICU. During the intervention we will teach caregivers mind-body and resilience skills, including deep breathing, mindfulness, meditation, dialectical thinking, acceptance, cognitive restructuring, effective communication, behavioral activation, and meaning-making. Caregivers will complete self-report assessments (measures of emotional distress and resilience) before and after the intervention. Primary outcomes are feasibility (recruitment, quantitative measures, adherence, and therapist fidelity) and acceptability (treatment satisfaction, credibility, and expectancy). We will conduct brief qualitative exit interviews to gather feedback on refining the program and study procedures. We will examine frequencies and proportions to determine feasibility and acceptability and will analyze qualitative exit interview data using thematic analysis. We will also conduct 2-tailed t tests to explore signals of improvement in emotional distress and treatment targets. We will then conduct an explanatory-sequential mixed methods analysis to integrate quantitative and qualitative data to refine the COMA-F manual and study procedures. ResultsThis study has been approved by the institutional review board at 1 of the 3 enrollment centers (2023P000536), with approvals at the other 2 centers pending. We anticipate that the study will be completed by late 2024. ConclusionsWe will use our findings to refine the COMA-F intervention and prepare for a feasibility randomized controlled trial. Trial RegistrationClinicalTrials.gov NCT05761925; https://clinicaltrials.gov/study/NCT05761925 International Registered Report Identifier (IRRID)PRR1-10.2196/50860
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- 2023
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44. Investigator experiences with financial conflicts of interest in clinical trials
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Van Laethem Marleen, Kalkar Sunila R, Wu Wei, Moher David, Ferris Lorraine E, Lexchin Joel, Hoey John, Sekeres Melanie, Rochon Paula A, Gruneir Andrea, Gold Jennifer, Maskalyk James, Streiner David L, Taback Nathan, and Chan An-Wen
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Medicine (General) ,R5-920 - Abstract
Abstract Background Financial conflicts of interest (fCOI) can introduce actions that bias clinical trial results and reduce their objectivity. We obtained information from investigators about adherence to practices that minimize the introduction of such bias in their clinical trials experience. Methods Email survey of clinical trial investigators from Canadian sites to learn about adherence to practices that help maintain research independence across all stages of trial preparation, conduct, and dissemination. The main outcome was the proportion of investigators that reported full adherence to preferred trial practices for all of their trials conducted from 2001-2006, stratified by funding source. Results 844 investigators responded (76%) and 732 (66%) provided useful information. Full adherence to preferred clinical trial practices was highest for institutional review of signed contracts and budgets (82% and 75% of investigators respectively). Lower rates of full adherence were reported for the other two practices in the trial preparation stage (avoidance of confidentiality clauses, 12%; trial registration after 2005, 39%). Lower rates of full adherence were reported for 7 practices in the trial conduct (35% to 43%) and dissemination (53% to 64%) stages, particularly in industry funded trials. 269 investigators personally experienced (n = 85) or witnessed (n = 236) a fCOI; over 70% of these situations related to industry trials. Conclusion Full adherence to practices designed to promote the objectivity of research varied across trial stages and was low overall, particularly for industry funded trials.
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- 2011
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45. Genome-scale phylogenetic analyses confirm Olpidium as the closest living zoosporic fungus to the non-flagellated, terrestrial fungi.
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Chang, Ying, Rochon, D'Ann, Sekimoto, Satoshi, Wang, Yan, Chovatia, Mansi, Sandor, Laura, Salamov, Asaf, Grigoriev, Igor V, Stajich, Jason E, and Spatafora, Joseph W
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The zoosporic obligate endoparasites, Olpidium, hold a pivotal position to the reconstruction of the flagellum loss in fungi, one of the key morphological transitions associated with the colonization of land by the early fungi. We generated genome and transcriptome data from non-axenic zoospores of Olpidium bornovanus and used a metagenome approach to extract phylogenetically informative fungal markers. Our phylogenetic reconstruction strongly supported Olpidium as the closest zoosporic relative of the non-flagellated terrestrial fungi. Super-alignment analyses resolved Olpidium as sister to the non-flagellated terrestrial fungi, whereas a super-tree approach recovered different placements of Olpidium, but without strong support. Further investigations detected little conflicting signal among the sampled markers but revealed a potential polytomy in early fungal evolution associated with the branching order among Olpidium, Zoopagomycota and Mucoromycota. The branches defining the evolutionary relationships of these lineages were characterized by short branch lengths and low phylogenetic content and received equivocal support for alternative phylogenetic hypotheses from individual markers. These nodes were marked by important morphological innovations, including the transition to hyphal growth and the loss of flagellum, which enabled early fungi to explore new niches and resulted in rapid and temporally concurrent Precambrian diversifications of the ancestors of several phyla of fungi.
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- 2021
46. ThinkCascades: A Tool for Identifying Clinically Important Prescribing Cascades Affecting Older People
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McCarthy, Lisa M., Savage, Rachel, Dalton, Kieran, Mason, Robin, Li, Joyce, Lawson, Andrea, Wu, Wei, Sternberg, Shelley A., Byrne, Stephen, Petrovic, Mirko, Onder, Graziano, Cherubini, Antonio, O’Mahony, Denis, Gurwitz, Jerry H., Pegreffi, Francesco, and Rochon, Paula A.
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- 2022
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47. Author Correction: Characterizing the profiles of patients with acute concussion versus prolonged post-concussion symptoms in Ontario
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Olivia F. T. Scott, Mikaela Bubna, Emily Boyko, Cindy Hunt, Vicki L. Kristman, Judith Gargaro, Mozhgan Khodadadi, Tharshini Chandra, Umme Saika Kabir, Shannon Kenrick-Rochon, Stephanie Cowle, Matthew J. Burke, Karl F. Zabjek, Anil Dosaj, Asma Mushtaque, Andrew J. Baker, Mark T. Bayley, CONNECT, and Maria Carmela Tartaglia
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Medicine ,Science - Published
- 2024
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48. Addressing the Chronic Pain–Early Cognitive Decline Comorbidity Among Older Adults: Protocol for the Active Brains Remote Efficacy Trial
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Ana-Maria Vranceanu, Nathaniel R Choukas, Elizabeth A Rochon, Brooke Duarte, Malvina O Pietrzykowski, Katherine McDermott, Julia E Hooker, Ronald Kulich, Yakeel T Quiroz, Robert A Parker, Eric A Macklin, Christine Ritchie, and Ryan A Mace
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Medicine ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
BackgroundChronic pain and early cognitive decline, which are costly to treat and highly prevalent among older adults, commonly co-occur, exacerbate one another over time, and can accelerate the development and progression of Alzheimer disease and related dementias. We developed the first mind-body activity program (Active Brains [AB]) tailored to the needs of older adults with chronic pain and early cognitive decline. Results from our previous study strongly supported the feasibility of conducting AB remotely and provided evidence for improvements in outcomes. ObjectiveWe are conducting a single-blinded, National Institutes of Health stage-2, randomized clinical trial to establish the efficacy of AB versus a time-matched and dose-matched education control (Health Enhancement Program [HEP]) in improving self-reported and objective outcomes of physical, cognitive, and emotional functions in 260 participants. The methodology described in this paper was informed by the lessons learned from the first year of the trial. MethodsParticipants are identified and recruited through multidisciplinary clinician–referred individuals (eg, pain psychologists and geriatricians), the Rally Research platform, social media, and community partnerships. Interested participants complete eligibility screening and electronic informed consent. Baseline assessments include self-report, performance-based measures (eg, 6-min walk test) and objective measures (eg, Repeatable Battery for the Assessment of Neuropsychological Status). Participants are mailed a wrist-worn ActiGraph device (ActiGraph LLC) to passively monitor objective function (eg, steps) during the week between the baseline assessment and the beginning of the programs, which they continue to wear throughout the programs. After baseline assessments, participants are randomized to either AB or HEP and complete 8 weekly, remote, group sessions with a Massachusetts General Hospital psychologist. The AB group receives a Fitbit (Fitbit Inc) to help reinforce increased activity. Assessments are repeated after the intervention and at the 6-month follow-up. Coprimary outcomes include multimodal physical function (self-report, performance based, and objective). Secondary outcomes are cognitive function (self-report and objective), emotional function, and pain. ResultsWe began recruitment in July 2022 and recruited 37 participants across 4 cohorts. Of them, all (n=37, 100%) have completed the baseline assessment, 26 (70%) have completed the posttest assessment, and 9 (24%) are actively enrolled in the intervention (total dropout: n=2, 5%). In the three cohorts (26/37, 70%) that have completed the AB or HEP, 26 (100%) participants completed all 8 group sessions (including minimal makeups), and watch adherence (1937/2072, 93.48%, average across ActiGraph and Fitbit devices) has been excellent. The fourth cohort is ongoing (9/37, 24%), and we plan to complete enrollment by March 2026. ConclusionsWe aim to establish the efficacy of the AB program over a time-matched and dose-matched control in a live video-based trial and test the mechanisms through theoretically driven mediators and moderators. Findings will inform the development of a future multisite effectiveness-implementation trial. Trial RegistrationClinicalTrials.gov NCT05373745; https://classic.clinicaltrials.gov/ct2/show/NCT05373745 International Registered Report Identifier (IRRID)DERR1-10.2196/47319
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- 2023
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49. Methemoglobin as a marker of acute anemic stress in cardiac surgery
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Nikhil Mistry, Gregory M.T. Hare, Nadine Shehata, Robert S. Kramer, Hosam F. Fawzy, Robert A. Baker, Paula Carmona, Richard Saczkowski, Daniela Filipescu, Christella S. Alphonsus, Antoine Rochon, Alexander J. Gregory, Boris Khanykin, Jonathan D. Leff, Eva Mateo, Dimos Karangelis, Juan C. Tellez, Tarit Saha, Dennis T. Ko, Duminda N. Wijeysundera, Subodh Verma, and C. David Mazer
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Health sciences ,Surgery ,Cardiovascular medicine ,Public health ,Science - Abstract
Summary: Biological evidence supports plasma methemoglobin as a biomarker for anemia-induced tissue hypoxia. In this translational planned substudy of the multinational randomized controlled transfusion thresholds in cardiac surgery (TRICS-III) trial, which included adults undergoing cardiac surgery requiring cardiopulmonary bypass with a moderate-to-high risk of death, we investigated the relationship between perioperative hemoglobin concentration (Hb) and methemoglobin; and evaluated its association with postoperative outcomes. The primary endpoint was a composite of death, myocardial infarction, stroke, and severe acute kidney injury at 28 days. We observe weak non-linear associations between decreasing Hb and increasing methemoglobin, which were strongest in magnitude at the post-surgical time point. Increased levels of post-surgical methemoglobin were associated with a trend toward an elevated risk for stroke and exploratory neurological outcomes. Our generalizable study demonstrates post-surgical methemoglobin may be a marker of anemia-induced organ injury/dysfunction, and may have utility for guiding personalized approaches to anemia management. Clinicaltrials.gov registration NCT02042898.
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- 2023
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50. Enhanced recovery protocol after cesarean delivery: impact on opioid use and pain perceptionAJOG MFM at a Glance
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Ememobong O. Ubom, MD, Carrie Wang, BA, Farina Klocksieben, MPH, Amanda B. Flicker, MD, Liany Diven, MD, Meredith Rochon, MD, and Joanne N. Quiñones, MD, MSCE
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analgesics (opioid) ,cesarean delivery ,Enhanced Recovery After Surgery ,pain ,perioperative care ,Gynecology and obstetrics ,RG1-991 - Abstract
BACKGROUND: Opioids are routinely prescribed to patients postoperatively after cesarean delivery. With rates of cesarean deliveries increasing globally and the opioid epidemic continuing to have deleterious effects, finding methods to achieve effective pain control without opioids is of increasing importance. The ERAS (Enhanced Recovery After Surgery) protocol applied following cesarean delivery engages multimodal perioperative management techniques to encourage early recovery. In the obstetrical surgery setting, these interventions include increasing scheduled nonsteroidal anti-inflammatory drug administration and laxative use to improve postoperative gastrointestinal motility and pain scores. Postcesarean patients are also encouraged to use abdominal binders, incentive spirometry, and early movement as pain modulators. OBJECTIVE: This quality improvement study aimed to measure whether the introduction of an ERAS protocol following cesarean delivery at a United States–based health network would improve outcomes such as the use of opioid medications for pain and pain control. STUDY DESIGN: This single-center retrospective cohort study compared patients who gave birth via cesarean delivery before (n=1425) and after (n=3478) the implementation of the postsurgical recovery protocol. Outcomes of interest included total postoperative opioid medications used, discharge opioid prescription, average pain score, pain scores by postoperative day, and highest pain score. Patients with a history of opioid use disorder, those who underwent a cesarean hysterectomy, and those who experienced a major surgical complication at delivery were excluded. Data were collected from the electronic medical record. RESULTS: Patients in the postimplementation period used significantly fewer opioid medications than those who gave birth before the protocol was introduced at the institution. The total median opioid use before implementation was 75 morphine milligram equivalents (interquartile range, 45–112.5) vs 30 (interquartile range, 15–52.5) after implementation (P
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- 2023
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