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    Study protocol for a multi-session randomized sham-controlled trial of PCC- and amygdala-targeted neurofeedback for the treatment of PTSD

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    Abstract Background Post-traumatic stress disorder (PTSD) is marked by distressing and often chronic symptoms, including the reliving and re-experiencing of trauma memories, avoidance, negative alterations in cognition and mood, heightened arousal and reactivity, and dissociation. Current psychotherapies and pharmacotherapies may yield suboptimal results for many individuals with PTSD, underscoring the need for new approaches. Recent neuroimaging research highlights functional disruptions in brainstem, cerebellar, limbic, and cortical networks underlying PTSD. Real-time functional magnetic resonance imaging neurofeedback (rt-fMRI-NFB) is an emerging intervention that has directly targeted limbic (i.e., the amygdala) and cortical (i.e., the posterior cingulate [PCC]) regions and has shown promising initial findings in PTSD. However, key research gaps remain, such as the need for rigorous randomized controlled trials (RCTs) to establish clinical efficacy and neurophysiological specificity, determine optimal brain targets, and evaluate dose-response relationships. Methods This double-blind, multi-session RCT investigates whether targeting distinct brain regions via rt-fMRI-NFB yields differential therapeutic effects in individuals with PTSD (n = 72). Participants will be randomly assigned to PCC-targeted rt-fMRI-NFB, amygdala-targeted rt-fMRI-NFB, or a sham-control group. Each participant will complete three rt-fMRI-NFB sessions over three weeks, with clinical assessments at baseline, after each session, and at a one-month follow-up. The sham group will receive a ‘yoked’ feedback signal from a random participant in one of the experimental groups. The primary outcome is PTSD symptom severity, measured using the PTSD Checklist for DSM-5 (PCL-5). Secondary outcomes include depressive symptoms, emotion regulation difficulties, dissociation, anxiety, interoceptive awareness, sleep quality, and state PTSD symptoms during trauma provocation. Neural outcomes will also be examined, focusing on brain activation and connectivity patterns. Additionally, qualitative interviews and actigraphy will assess participants’ subjective experiences and track sleep and physical activity patterns. Discussion This trial aims to address critical research gaps by evaluating the therapeutic potential of rt-fMRI-NFB targeting the PCC and amygdala in PTSD. By employing a wide range of data collection methods, this study will provide valuable insights into the clinical and neural effects of rt-fMRI-NFB. This study will be the first to investigate the phenomenological dimension and physiological impacts of rt-fMRI-NFB in this population. Taken together, these findings are expected to contribute to the development of targeted neurofeedback interventions and clarify the therapeutic mechanisms underlying rt-fMRI-NFB for PTSD. Trial registration This study has been registered with ClinicalTrials.gov under the trial registration number NCT05456958. It was initially registered on July 13th, 2022, and most recently updated on October 9th, 2024

    Improving Fetal Health Outcomes: Investigating the Impact of Gestational Obesity and NAD⁺ Supplementation on Cardiometabolic Health of Offspring

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    Introduction: Gestational obesity is an increasing concern in North America, associated with adverse pregnancy outcomes and long-term health risks in offspring. Chronic low grade inflammation and placental dysfunction are thought to mediate these effects, partly through depletion of nicotinamide adenine dinucleotide (NAD⁺), a vital coenzyme in cellular metabolism and mitochondrial function. Objective: This study aimed to investigate how maternal obesity affects offspring cardiometabolic health and to assess whether supplementation with the NAD⁺ precursor nicotinamide riboside (NR) during pregnancy and lactation can mitigate these effects. Methods: Female C57BL/6N mice were fed either a control (CNTRL) or high-fat high-sugar diet for 15 weeks prior to and during pregnancy and lactation. During gestation, mice were either treated with water (CNTRL H₂O = 20, HFHS H₂O = 7) or NR (400 mg/kg/day: CNTRL NR = 16, HFHS NR = 7). Offspring were weaned onto a standard chow diet and assessed for cardiometabolic outcomes between 12 and 47 weeks of age, including glucose tolerance, fat distribution, organ histology, and lipolysis response. Results: Offspring from HFHS-exposed dams showed early-onset weight gain, elevated fasted blood glucose (specifically in females), and impaired lipolysis in adipose tissues. No changes were observed in blood pressure through to adulthood. NR supplementation mitigated early weight gain and improved glucose handling in a sex-specific manner but did not rescue lipolytic defects or prevent long-term fat accumulation. Conclusion: Gestational obesity leads to sex-specific, long-term metabolic impairments in offspring, potentially mediated by NAD⁺ depletion. While NR supplementation during pregnancy provided early metabolic protection, it did not fully prevent the long-term consequences. These findings support the potential of NAD⁺ modulation as a therapeutic strategy but highlight the need for further investigation into timing, dosage, and sex-specific responses

    Origin and Age of Tabular Massive Ice and Ice Wedges in the Smoking Hills, Northwest Territories, Canada

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    The Smoking Hills area is located in the Northwest Territories, Canada. It contains many retrogressive thaw slumps that expose different permafrost units, including tabular massive ice and ice wedges. This study investigates the origin and age of these ice bodies to refine the glacial and permafrost history of the Smoking Hills region. Using cryostratigraphic observations, stable water isotope analysis, major ion geochemistry, and radiocarbon dating, samples from four retrogressive thaw slumps headwalls were analyzed. The results suggest that three of the sites contained buried glacial ice deposited during the Late Wisconsinan glaciation. Deformed and truncated ice wedges at one of the sites also show evidence of a glacial retreat during the Bølling–Allerød interstadial followed by a short glacial re-advance before of during the Younger Dryas. Holocene-aged ice wedges from a second retrogressive thaw slumps reflect the re-establishment of permafrost after the Wisconsin glaciation. Chemical anomalies in some ice units indicate a possible influence from the Smoking Hills Formation on Holocene-aged ground ice. These results highlight a dynamic glacial and permafrost history in the region

    Assessing the damage: analyzing the impact of the COVID-19 pandemic on accelerometer-assessed 24-hour movement behaviours in Brazilian adolescents

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    Abstract Background Although there is consistent evidence of unhealthy changes in the 24-h movement behaviours when comparing pre-COVID-19 periods to the early stages of the pandemic, there is limited research on long-term changes among adolescents. This study aimed to analyze both between- and within-participant differences in accelerometer-assessed 24-h movement behaviours by comparing cross-sectional and prospective data from the pre-COVID-19 period (August to December 2019) to the period following the reopening of schools for in-person classes in southern Brazil (August to December 2022). Methods This is a repeated cross-sectional design with a nested cohort. The 24-h movement behaviours (i.e., light physical activity [LIPA] and moderate-to-vigorous physical activity [MVPA], sedentary behaviour [SB], and sleep time [SPT]) were assessed by processing raw accelerometer data derived from a 24-h/7-day wrist-worn protocol. Compositional multilevel models were applied to compare the 24-h movement behaviour composition between time points for both cross-sectional and prospective data. Self-reported sociodemographic characteristics were examined as potential moderators. Results The cross-sectional and prospective samples comprised, respectively, 1276 (53% female, average age of 16.4 ± 1.1) and 249 (53% female, average age of 15.6 ± 0.8) participants. The 24-h movement behaviour composition differed between time-points in the cross-sectional (p < 0.001) and prospective samples (p < 0.001). Differences from 2019 to 2022 were explained by lower MVPA (-3.3 and -5.4 min/day in cross-sectional and prospective analysis, respectively) and a higher SB (4.7 and 34 min/day in cross-sectional and prospective analysis, respectively). No significant differences were observed for LIPA and SPT. Conclusions Differences in the 24-h movement behaviour composition comparing the cross-sectional samples, although statistically significant, were considered trivial and unlikely to have a substantial practical impact. However, considerable differences were observed in the prospective analysis. The results suggest that most of the observed changes over time were expected as a natural consequence of aging during high school, with only a small portion attributable to the residual impact of the pandemic

    L'expérience du parcours scolaire en contexte montréalais : une étude qualitative conduite auprès d'étudiant.e.s de deuxième génération d'origine maghrébine

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    Cette recherche vise à mieux comprendre l'expérience du parcours scolaire chez les étudiants de deuxième génération d'origine maghrébine. L'analyse qualitative des données met en évidence trois thèmes principaux : le parcours scolaire comme lieu de découverte de l'identité culturelle et vocationnelle, le caractère ambigu de l'expérience scolaire ainsi que le parcours scolaire comme un lieu d'affirmation par rapport à l'héritage familial. Les résultats démontrent que, malgré la pression de conformité et les obstacles rencontrés, les participant.e.s développent des stratégies de résilience et transforment leur parcours en un espace d'émancipation. Cette étude met en lumière l'importance d'un accompagnement scolaire adapté et d'un environnement éducatif favorisant l'inclusion et la valorisation des identités plurielles

    Protective Role of Foxo3a in the Regulatory T Cells and Dendritic Cells of IL-10-Deficient Mice

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    À la demande de l'auteur, le résumé a été retiré en raison de la nature confidentielle de la thèse. Il sera ajouté une fois la période d'embargo terminée. At the author’s request, the abstract has been removed due to the confidential nature of the thesis. It will be added once the embargo period has passed

    La révolution causale à l'ère de l'IA : Vers une approche hybride entre théorie scientifique et découverte automatisée

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    La “révolution causale” en sciences des données promet de transformer notre capacité à comprendre les relations causales complexes dans divers domaines. Cette présentation examine les rôles complémentaires des humains et des machines dans la modélisation causale, en prenant pour exemple la recherche sur le trouble de la personnalité limite. Nous analysons d’abord les limites des approches purement automatisées de découverte causale, particulièrement en présence de données manquantes ou partielles. Nous montrons ensuite comment les modèles théoriques issus des sciences sociales et de la santé peuvent servir de “priors” informatifs pour guider la construction de modèles causaux. En particulier, nous explorons l’utilisation du modèle écosocial de Krieger comme cadre théorique initial. Nous proposons une approche hybride qui combine systématiquement trois éléments : les modèles théoriques existants, l’expertise clinique, et les méthodes de découverte automatisée. Cette approche permet d’exploiter les forces complémentaires des humains (connaissance du contexte, jugement clinique) et des machines (traitement de grandes quantités de données, identification de motifs). Cette réflexion s’inscrit dans une perspective plus large sur l’automatisation en santé mentale, où la complémentarité homme-machine apparaît comme une piste à approfondir

    Women, Peace and Security in the Post-Soviet Space

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    As a global normative framework, the Women, Peace and Security (WPS) agenda is a direct outcome of both transnational feminism and the post-Cold War era. In this global dialogue predominantly between women from the Global North and the Global South, the voices of women located outside this dichotomy have often been marginalized. A look at the WPS agenda literature reveals a reflection of this marginalization and indicates a significant epistemic gap in the post-Soviet space. Missing are the voices of women from the former Soviet Union as experts, along with their unique lived experiences in a region heavily affected by Russian imperialism. Even the most comprehensive and radical critiques of the WPS agenda overlook perspectives from this region and fail to build feminist solidarities beyond a strictly Global North/South analytical focus. This thesis is an empirical exploration of uncharted territory in the WPS agenda as an academic field and a vibrant community for feminist dialogue between research, practice, and advocacy. As such, it is also about discerning the analytical lessons that can be drawn from this empirical investigation and how the distinct experiences of this region can enrich our understanding of certain concepts and theoretical debates in the WPS agenda literature. By analyzing the emergence, adoption, and implementation of WPS National Action Plans (NAPs) in Ukraine, Moldova, Georgia, and Armenia, this thesis seeks to: 1) raise awareness of the unique dynamics of the post-Soviet space and its implications for the WPS agenda, 2) make visible and center the voices, agency and advocacy of women working on the WPS agenda in this region, and 3) challenge some of the fundamental concepts and debates at the heart of the WPS agenda. Using a mixed methodology, including fieldwork interviews with 82 key informants, observations, and documentary analysis, this thesis proposes four main findings. First, the emergence and adoption of NAPs are heavily dependent on strategic feminist networks combining femocrats within the Government, UN Women, feminist civil society, and gender experts. Second, the nature of nearby conflict(s), as well as regional geopolitical insecurities, strongly influence the adoption and implementation of NAPs and how actors understand and use the WPS agenda. Third, the entire NAP process(es) is inseparable from broader processes of democratization, autocratization, nation-building, and Euro-Atlantic integration. Fourth, the post-Soviet space shows both region-specific dynamics and global trends in the implementation of the WPS agenda. This thesis's contribution is to show the confrontation between the theoretical ideals of feminist International Relations theories and the empirical realities of an unexplored and often ignored terrain: the post-Soviet space. Through the complexity of the lived, situated experiences and processes behind NAPs in Ukraine, Moldova, Georgia, and Armenia, the thesis exposes the limits and shortcomings of some of the current theorization of the WPS agenda by revealing important blind spots in the WPS literature and challenging some of its core debates and concepts

    Ancestral Sequence Reconstruction Approach to Acetylcholine Receptor Structure and Function

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    Ligand gated ion channels (LGICs) convert the binding of small molecules into opening of an intrinsic transmembrane pore. Acetylcholine receptors (AChRs), a prototypical LGIC, is present throughout the central nervous system and at neuromuscular junctions. The muscle-type AChR is the most genetically complex, composed of two α, and one each of the β, δ, and γ (fetal) / ε (adult) - subunits, arranged in a counterclockwise α-γ/ε-α-δ-β configuration around the central ion-conducting pore. Despite being studied for decades, a complete understanding of AChRs structure - function relationships, remains elusive. Using an ancestral sequence reconstruction approach, along with single-molecule patch-clamp electrophysiology, we have uncovered mechanistic insights into AChR function, with an ancestral β-subunit. Using the βAnc subunit, we demonstrate its ability to form spontaneously opening homopentamers despite lacking an evolutionarily tailored agonist binding site. βAnc was also able to form binary mixtures with human α-subunits, consequently installing agonist regulation of channel openings. Lastly, we demonstrate that βAnc is able to participate in agonist binding with the introduction of δ-residues to restore receptor priming. Additional studies combine single-molecule patch-clamping with single-particle cryo-electron microscopy, advancing our current understanding of AChR activation, through an intermediate ‘primed’ state, supporting a sequential activation model. Together, this work provides insight into the structure and function of AChRs

    Evaluating the Interfacial Mechanics of Distributed Strain Sensors Mounted to GFRP Reinforcing Bars

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    In-service reinforced concrete (RC) structures in harsh environments face significant challenges such as corrosion and cracking, which undermine their durability and resilience. To address these issues and reduce maintenance costs, a novel solution is proposed that integrates glass fibre reinforced polymer (GFRP) reinforcing bars with distributed fibre optic sensors (DFOS). This multifunctional system incorporates continuous structural health monitoring (SHM) capabilities into the electromagnetically neutral, high-strength, and lightweight properties of GFRP bars, while protecting sensors from cracking and fracture within the concrete matrix. Emerging sensing systems, such as optical frequency domain reflectometry (OFDR), offer sub-millimetre resolution in distributed strain measurements over long distances. This enables precise detection of strain peaks associated with concrete cracks at various locations along the RC structure throughout its service life. Despite considerable prior research and development, the strain transfer efficiency and monitoring stability of OFDR-based DFOS bonded to GFRP bars under various stress conditions had not been thoroughly investigated. To fill this gap, this study examined the performance of DFOS in capturing tensile strain in GFRP bars under cyclic and sustained loading. Experimental testing and numerical analysis were conducted to identify key influencing factors and define limits for efficient and stable monitoring. Strain profiles from multiple test specimens were then analyzed using a developed closed-form model that accounts for elasto-plastic strain transfer from the host material to the sensor through the adhesive interface. The experimental results demonstrated that OFDR-based DFOS reliably captured strain profiles along GFRP bars under varying loading conditions, including within the GFRP bar's serviceability limits and up to strain levels approaching 1.3%. Beyond this threshold, sustained high-stress exposure triggered plastic response in the adhesive interface, leading to gradual bondline degradation, permanent interfacial slip, and progressive strain reading anomalies (SRAs), observed by loss of accuracy in strain values measured along the DFOS-bonded length as it degraded over time. The numerical analysis closely aligned with experimental data, effectively capturing strain transfer behaviour during bond damage progression. This provides a practical framework for evaluating the quality of dynamic host–sensor interaction and potential monitoring efficiency loss under severe mechanical loading during service. Overall, the findings establish effective monitoring ranges and emphasize the importance of better understanding the strain transfer mechanisms of bonded DFOS systems, identified as a primary source of measurement error, for enabling reliable long-term strain monitoring in demanding environments

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