Publications

User Experience of a Computer-Based Decision Aid for Prenatal Trisomy Screening: Mixed Methods Explanatory Study
Titilayo Tatiana Agbadje
Chantale Pilon
Pierre Bérubé
Jean-Claude Forest
François Rousseau
S. A. Rahimi
Yves Giguère
France Légaré
Re-expression of CA1 and entorhinal activity patterns preserves temporal context memory at long timescales
Futing Zou
Wanjia Guo
Emily J. Allen
Yihan Wu
Thomas Naselaris
Kendrick Kay
Brice A. Kuhl
J. Benjamin Hutchinson
Sarah DuBrow
Converging, cross-species evidence indicates that memory for time is supported by hippocampal area CA1 and entorhinal cortex. However, limit… (voir plus)ed evidence characterizes how these regions preserve temporal memories over long timescales (e.g., months). At long timescales, memoranda may be encountered in multiple temporal contexts, potentially creating interference. Here, using 7T fMRI, we measured CA1 and entorhinal activity patterns as human participants viewed thousands of natural scene images distributed, and repeated, across many months. We show that memory for an image’s original temporal context was predicted by the degree to which CA1/entorhinal activity patterns from the first encounter with an image were re-expressed during re-encounters occurring minutes to months later. Critically, temporal memory signals were dissociable from predictors of recognition confidence, which were carried by distinct medial temporal lobe expressions. These findings suggest that CA1 and entorhinal cortex preserve temporal memories across long timescales by coding for and reinstating temporal context information.
Digitalization and the Anthropocene
Felix Creutzig
Daron Acemoglu
Xuemei Bai
Paul N. Edwards
Marie Josefine Hintz
Lynn H. Kaack
Siir Kilkis
Stefanie Kunkel
Amy Luers
Nikola Milojevic-Dupont
Dave Rejeski
Jürgen Renn
Christoph Rosol
Daniela Russ
Thomas Turnbull
Elena Verdolini
Felix Wagner
Charlie Wilson
Aicha Zekar … (voir 1 de plus)
Marius Zumwald
Great claims have been made about the benefits of dematerialization in a digital service economy. However, digitalization has historically i… (voir plus)ncreased environmental impacts at local and planetary scales, affecting labor markets, resource use, governance, and power relationships. Here we study the past, present, and future of digitalization through the lens of three interdependent elements of the Anthropocene: ( a) planetary boundaries and stability, ( b) equity within and between countries, and ( c) human agency and governance, mediated via ( i) increasing resource efficiency, ( ii) accelerating consumption and scale effects, ( iii) expanding political and economic control, and ( iv) deteriorating social cohesion. While direct environmental impacts matter, the indirect and systemic effects of digitalization are more profoundly reshaping the relationship between humans, technosphere and planet. We develop three scenarios: planetary instability, green but inhumane, and deliberate for the good. We conclude with identifying leverage points that shift human–digital–Earth interactions toward sustainability.
Researcher perspectives on ethics considerations in epigenetics: an international survey
Charles Dupras
Terese Knoppers
Nicole Palmour
Elisabeth Beauchamp
Stamatina Liosi
Reiner Siebert
Alison May Berner
Stephan Beck
Yann Joly
Over the past decade, bioethicists, legal scholars and social scientists have started to investigate the potential implications of epigeneti… (voir plus)c research and technologies on medicine and society. There is growing literature discussing the most promising opportunities, as well as arising ethical, legal and social issues (ELSI). This paper explores the views of epigenetic researchers about some of these discussions. From January to March 2020, we conducted an online survey of 189 epigenetic researchers working in 31 countries. We questioned them about the scope of their field, opportunities in different areas of specialization, and ELSI in the conduct of research and knowledge translation. We also assessed their level of concern regarding four emerging non-medical applications of epigenetic testing—i.e., in life insurance, forensics, immigration and direct-to-consumer testing. Although there was strong agreement on DNA methylation, histone modifications, 3D structure of chromatin and nucleosomes being integral elements of the field, there was considerable disagreement on transcription factors, RNA interference, RNA splicing and prions. The most prevalent ELSI experienced or witnessed by respondents were in obtaining timely access to epigenetic data in existing databases, and in the communication of epigenetic findings by the media. They expressed high levels of concern regarding non-medical applications of epigenetics, echoing cautionary appraisals in the social sciences and humanities literature.
Small, correlated changes in synaptic connectivity may facilitate rapid motor learning
Barbara Feulner
Matthew G Perich
Raeed H. Chowdhury
Lee Miller
Juan A. Gallego
Abstract 25 ECTmatch: Optimizing Small-Scale Cord Blood Banking Through HLA Analysis
Maude Dumont-Lagacé
Albert Feghaly
Gabrielle Thauvette
Marie-Christine Meunier
William Lemieux
Diane Fournier
Lucie Richard
Guy Sauvageau
Sandra Cohen
Abstract Introduction Cord blood (CB) banks have had to rely on large inventories of CB units to try to serve the largest possible proportio… (voir plus)n of the population, all the while prioritizing collection of non-Caucasian ethnic groups. However, due to the high linkage disequilibrium of HLA genes and the high frequency of several HLA alleles in the population, CB banks contain hundreds of CB units that could be matched to the same patients, making the inventory somewhat redundant from a clinical standpoint. Objective ExCellThera developed ECTmatch, an algorithm dedicated to optimizing the selection of CB units based on in-depth HLA analysis in order to maximize the efficiency of the bank to suitably match the largest proportion of subjects within a small pool of donors. Methods The performance of ECTmatch was evaluated in a simulation aiming to select 100 CB units from the Héma-Québec CB bank that satisfied an arbitrary minimal cell content criteria of 120 × 107 TNC and 6 × 106 CD34+ cells (n = 2,987). Selection was performed to optimize matching for the Quebec population, with a minimal HLA-match of 5/8 for HLA-A, -B, -C, and -DRB1. Results ECTmatch provides a suitably matched donor for 71.5% of the Quebec population, compared with only 45.0% (±2.4%) with random selection. Because patients who require a CB transplant tend to have rarer HLAs, the performance of ECTmatch was evaluated for this specific subset of patients (n = 62). Again, ECTmatch outperformed random selection, by providing a donor for 54.8% of patients, compared with only 29.9% with random selection. Finally, while ECTmatch was developed to optimize CB selection specifically for the Quebec population, it still outperformed random selection for subjects from the other Canadian provinces or the USA. Discussion By selecting CB units based on HLA profiles, ECTmatch allows the creation of a highly useful inventory with a very low number of CB units. This approach to small-scale CB banking can be adapted to different population subsets and could be used to select a subset of CB units for pre-release for immediate clinical availability or for the creation of a pre-expanded CB inventory with maximal population coverage.
Interpretable domain adaptation using unsupervised feature selection on pre-trained source models
Luxin Zhang
Pascal Germain
Yacine Kessaci
C. Biernacki
A novel domain adaptation theory with Jensen-Shannon divergence
Qi CHEN
Jun Wen
Fan Zhou
Boyu Wang
The load planning and sequencing problem for double-stack trains
Moritz Ruf
Jean-François Cordeau
Two types of human TCR differentially regulate reactivity to self and non-self antigens
Jean-David Larouche
Jonathan Séguin
Jean-Philippe Laverdure
Ann Brasey
Gregory Ehx
Denis-Claude Roy
Lambert Busque
Silvy Lachance
Claude Perreault
Based on analyses of TCR sequences from over 1,000 individuals, we report that the TCR repertoire is composed of two ontogenically and funct… (voir plus)ionally distinct types of TCRs. Their production is regulated by variations in thymic output and terminal deoxynucleotidyl transferase (TDT) activity. Neonatal TCRs derived from TDT-negative progenitors persist throughout life, are highly shared among subjects, and are reported as disease-associated. Thus, 10%–30% of most frequent cord blood TCRs are associated with common pathogens and autoantigens. TDT-dependent TCRs present distinct structural features and are less shared among subjects. TDT-dependent TCRs are produced in maximal numbers during infancy when thymic output and TDT activity reach a summit, are more abundant in subjects with AIRE mutations, and seem to play a dominant role in graft-versus-host disease. Factors decreasing thymic output (age, male sex) negatively impact TCR diversity. Males compensate for their lower repertoire diversity via hyperexpansion of selected TCR clonotypes.
Association between Anxiety and Disease Pathophysiology in Participants of Longitudinal Observational Studies in Aging during the COVID-19 Lockdown
Stijn Servaes
Firoza Lussier
Cécile Tissot
Joseph Therriault
Gleb Bezgin
Yi-Ting Wang
Jenna Stevenson
Nesrine Rahmouni
Vanessa Pallen
Guillaume Elgbeili
Jaime Fernandez Arias
Min Su Kang
Andrea Benedet
Mira Chamoun
Tharick Pascoal
Kok Pin Ng
Suzanne King
Serge Gauthier
Pedro Rosa-Neto
Abstract

The burden imposed by the COVID-19 pandemic deferentially interferes with the outcomes of clinical trials of aging… (voir plus) and dementia. We examined the impact of the lockdown on cognitive impairment due to Alzheimer’s Disease (AD), anxiety, and COVID-19-related stress in participants from the Translational Biomarkers In Aging and Dementia (TRIAD) cohort using neuropsychiatric assessments, tau and amyloid PET. We found that, before the lockdown, anxiety was higher in cognitively impaired individuals (CI) and positively associated with brain tau load. However, during the lockdown, anxiety increased only in the cognitively unimpaired (CU) and was positively associated with COVID-19 related stress. Interestingly, we found that in patients, tau load was anti-correlated with higher anxiety during lockdown. Our findings contribute to a framework for interpreting the effects of the pandemic on neuropsychiatric symptoms among clinical trial participants. Collectively, our results suggest that caregivers are more vulnerable to external stressors than patients.

Synthesizing theories of human language with Bayesian program induction
Kevin Ellis
Adam Albright
Armando Solar-Lezama
Joshua B. Tenenbaum
Timothy J. O'Donnell
Automated, data-driven construction and evaluation of scientific models and theories is a long-standing challenge in artificial intelligence… (voir plus). We present a framework for algorithmically synthesizing models of a basic part of human language: morpho-phonology, the system that builds word forms from sounds. We integrate Bayesian inference with program synthesis and representations inspired by linguistic theory and cognitive models of learning and discovery. Across 70 datasets from 58 diverse languages, our system synthesizes human-interpretable models for core aspects of each language’s morpho-phonology, sometimes approaching models posited by human linguists. Joint inference across all 70 data sets automatically synthesizes a meta-model encoding interpretable cross-language typological tendencies. Finally, the same algorithm captures few-shot learning dynamics, acquiring new morphophonological rules from just one or a few examples. These results suggest routes to more powerful machine-enabled discovery of interpretable models in linguistics and other scientific domains.