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8. Transcriptomic and proteomic profiles of fetal versus adult mesenchymal stromal cells and mesenchymal stromal cell-derived extracellular vesicles

Author

Emine Begüm Gençer, Yuk Kit Lor, Fawaz Abomaray, Samir El Andaloussi, Maria Pernemalm, Nidhi Sharma, Daniel W Hagey, André Görgens, Manuela O Gustafsson, Katarina Le Blanc, Mawaddah Asad Toonsi, Lilian Walther-Jallow, and Cecilia Götherström

Subjects
Mesenchymal stromal cells, Fetal mesenchymal stem cells, Biosignature, Transcriptomic, Proteomic, Extracellular vesicles, Medicine (General), R5-920, Biochemistry, QD415-436
Abstract

Abstract Background Mesenchymal stem/stromal cells (MSCs) can regenerate tissues through engraftment and differentiation but also via paracrine signalling via extracellular vesicles (EVs). Fetal-derived MSCs (fMSCs) have been shown, both in vitro and in animal studies, to be more efficient than adult MSC (aMSCs) in generating bone and muscle but the underlying reason for this difference has not yet been clearly elucidated. In this study, we aimed to systematically investigate the differences between fetal and adult MSCs and MSC-derived EVs at the phenotypic, RNA, and protein levels. Methods We carried out a detailed and comparative characterization of culture-expanded fetal liver derived MSCs (fMSCs) and adult bone marrow derived MSCs (aMSCs) phenotypically, and the MSCs and MSC-derived EVs were analysed using transcriptomics and proteomics approaches with RNA Sequencing and Mass Spectrometry. Results Fetal MSCs were smaller, exhibited increased proliferation and colony-forming capacity, delayed onset of senescence, and demonstrated superior osteoblast differentiation capability compared to their adult counterparts. Gene Ontology analysis revealed that fMSCs displayed upregulated gene sets such as “Positive regulation of stem cell populations”, “Maintenance of stemness” and “Muscle cell development/contraction/Myogenesis” in comparison to aMSCs. Conversely, aMSCs displayed upregulated gene sets such as “Complement cascade”, “Adipogenesis”, “Extracellular matrix glycoproteins” and “Cellular metabolism”, and on the protein level, “Epithelial cell differentiation” pathways. Signalling entropy analysis suggested that fMSCs exhibit higher signalling promiscuity and hence, higher potency than aMSCs. Gene ontology comparisons revealed that fetal MSC-derived EVs (fEVs) were enriched for “Collagen fibril organization”, “Protein folding”, and “Response to transforming growth factor beta” compared to adult MSC-derived EVs (aEVs), whereas no significant difference in protein expression in aEVs compared to fEVs could be detected. Conclusions This study provides detailed and systematic insight into the differences between fMSCs and aMSCs, and MSC-derived EVs. The key finding across phenotypic, transcriptomic and proteomic levels is that fMSCs exhibit higher potency than aMSCs, meaning they are in a more undifferentiated state. Additionally, fMSCs and fMSC-derived EVs may possess greater bone forming capacity compared to aMSCs. Therefore, using fMSCs may lead to better treatment efficacy, especially in musculoskeletal diseases.

Published
2024
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12. Data-Driven Iterative Refinements to Educational Development Services: Directly Measuring the Impacts of Consultations on Course and Syllabus Design

Author

Hershock, Chad, Pottmeyer, Laura Ochs, Harrell, Jessica, le Blanc, Sophie, Rodriguez, Marisella, Stimson, Jacqueline, Walsh, Katharine Phelps, and Weiss, Emily Daniels

Abstract

Evidence-based practice in educational development includes leveraging data to iteratively refine center for teaching and learning (CTL) services. However, CTL data collection is often limited to counts and satisfaction surveys rather than direct measures of outcomes. To directly assess impacts of consultations on course and syllabus design, we analyzed 94 clients' syllabi (32 faculty, 62 graduate students and postdocs) before and after consultations. Faculty and non-faculty clients demonstrated significant change following consultations (6% and 10% gains in syllabus rubric scores, representing 50% and 31% of possible gains and effect sizes of 0.73 and 1.04 standard deviations, respectively). We compared faculty clients to quasi-experimental control groups that did not receive consultations. Syllabi from non-clients scored lower and did not demonstrate similar changes across semesters. Attendance at a CTL seminar on course and syllabus design did not explain variation in clients' syllabi. We discuss implications for assessment of CTL services and how we leveraged formative assessments to inform and iteratively refine our educational development practices.

Published
2022
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13. Elevated tryptase level in a child with idiopathic anaphylaxis: a case of hereditary alpha-tryptasemia

Author

Vicky Le Blanc and Wade T. A. Watson

Subjects
Hereditary alpha-tryptasemia, Idiopathic anaphylaxis, Elevated tryptase level, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Hereditary alpha-tryptasemia (HαT) is an autosomal dominant disorder estimated to affect 5% of the population. High baseline tryptase level is a consistent finding, but there is a great variability of clinic manifestations, including no symptoms at all. We describe a case of HαT in a 5 years 8 months old girl manifesting with idiopathic anaphylaxis and elevated baseline tryptase level. As more cases of HαT are described, a better understanding of the clinical phenotype will be acquired.

Published
2024
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14. Patient-specific modeling of stroma-mediated chemoresistance of pancreatic cancer using a three-dimensional organoid-fibroblast co-culture system

Author

Sebastian Schuth, Solange Le Blanc, Teresa G. Krieger, Julia Jabs, Miriam Schenk, Nathalia A. Giese, Markus W. Büchler, Roland Eils, Christian Conrad, and Oliver Strobel

Subjects
Pancreatic cancer, Patient-derived organoids, Cancer-associated fibroblasts, Drug screening, Personalized oncology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Cancer-associated fibroblasts (CAFs) are considered to play a fundamental role in pancreatic ductal adenocarcinoma (PDAC) progression and chemoresistance. Patient-derived organoids have demonstrated great potential as tumor avatars for drug response prediction in PDAC, yet they disregard the influence of stromal components on chemosensitivity. Methods We established direct three-dimensional (3D) co-cultures of primary PDAC organoids and patient-matched CAFs to investigate the effect of the fibroblastic compartment on sensitivity to gemcitabine, 5-fluorouracil and paclitaxel treatments using an image-based drug assay. Single-cell RNA sequencing was performed for three organoid/CAF pairs in mono- and co-culture to uncover transcriptional changes induced by tumor-stroma interaction. Results Upon co-culture with CAFs, we observed increased proliferation and reduced chemotherapy-induced cell death of PDAC organoids. Single-cell RNA sequencing data evidenced induction of a pro-inflammatory phenotype in CAFs in co-cultures. Organoids showed increased expression of genes associated with epithelial-to-mesenchymal transition (EMT) in co-cultures and several potential receptor-ligand interactions related to EMT were identified, supporting a key role of CAF-driven induction of EMT in PDAC chemoresistance. Conclusions Our results demonstrate the potential of personalized PDAC co-cultures models not only for drug response profiling but also for unraveling the molecular mechanisms involved in the chemoresistance-supporting role of the tumor stroma.

Published
2022
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15. The race that never slows: Otolaryngology - Head and Neck Surgery residency applicant parameters over time

Author

Kaylie Schachter, Ashley Tritt, Meredith Young, Jessica Hier, Emily Kay-Rivest, Gabriella Le Blanc, and Lily HP Nguyen

Subjects
Education (General), L7-991, Medicine (General), R5-920
Abstract

Background: There has been an increasing number of Canadian medical graduates who have gone unmatched in the residency selection process. Medical students have been engaging in extracurricular activities outside the formal curriculum which may help to distinguish themselves from their peers in the selection process. To understand how competitiveness in residency selection shapes applicant demographic characteristics and behaviours, this study set out to explore the demographic characteristics and prevalence of reported extra-curricular activities by applicants to Canadian Otolaryngology – Head & Neck Surgery (OTL-HNS) residency across time. Methods: A retrospective, descriptive study reviewed specific sections of the curriculum vitae (CV) of applicants to OTL-HNS programs in Canada. These sections were self-reported, and included research productivity, involvement in volunteer and leadership activities, membership in associations, and honours or awards granted. Data was quantified and analyzed descriptively. Results: Between 2013 to 2017, a total of 267 applicants reported a median of 12.6 research publications, 9.6 volunteer activities, six leadership activities, six association memberships and 9.8 honours/awards. Applicants were younger over time, with proportions of applicants over 30 years old decreasing from 56% in 2013 to 9% in 2017. Conclusion: Applicants to Canadian OTL-HNS residency programs are reporting consistently high numbers of extracurricular activities and were of increasingly younger ages. Medical students are investing significant time and energy to pursue these activities which are above and beyond the formal curriculum, possibly contributing to decreased diversity in applicants for competitive residencies, increasing the likelihood of misrepresentation in residency applications, and likely contributing to medical student burnout.

Published
2023
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16. Genetic ablation of ketohexokinase C isoform impairs pancreatic cancer development

Author

Ilaria Guccini, Guanghui Tang, Trang Thuy To, Laura Di Rito, Solange Le Blanc, Oliver Strobel, Mariantonietta D’Ambrosio, Emiliano Pasquini, Marco Bolis, Pamuditha Silva, Hasan Ali Kabakci, Svenja Godbersen, Andrea Alimonti, Gerald Schwank, and Markus Stoffel

Subjects
Natural sciences, Biological sciences, Biochemistry, Systems biology, Cancer systems biology, Science
Abstract

Summary: Although dietary fructose is associated with an elevated risk for pancreatic cancer, the underlying mechanisms remain elusive. Here, we report that ketohexokinase (KHK), the rate-limiting enzyme of fructose metabolism, is a driver of PDAC development. We demonstrate that fructose triggers KHK and induces fructolytic gene expression in mouse and human PDAC. Genetic inactivation of KhkC enhances the survival of KPC-driven PDAC even in the absence of high fructose diet. Furthermore, it decreases the viability, migratory capability, and growth of KPC cells in a cell autonomous manner. Mechanistically, we demonstrate that genetic ablation of KHKC strongly impairs the activation of KRAS-MAPK pathway and of rpS6, a downstream target of mTORC signaling. Moreover, overexpression of KHKC in KPC cells enhances the downstream KRAS pathway and cell viability. Our data provide new insights into the role of KHK in PDAC progression and imply that inhibiting KHK could have profound implications for pancreatic cancer therapy.

Published
2023
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17. Power scaling of LED-pumped alexandrite: The road to high gain multipass amplifiers

Author

Thellier Elio, Taleb Hussein, Le Blanc Catherine, Pichon Pierre, Druon Frédéric, Georges Patrick, and Balembois François

Subjects
Physics, QC1-999
Abstract

Our experiment demonstrates that LED-pumping through luminescent concentrator enables sufficient pump power for viable alexandrite amplifier gain. In 10 passes we obtain a gain of 19 with 10 W output power, for 50 µs pulses at 20 Hz and 760 nm.

Published
2024
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19. Grading of minor salivary gland immuno-histopathology post-allogenic hematopoietic cell transplantation

Author

V. Tollemar, H. Arvidsson, H. Häbel, N. Tudzarovski, K. Garming Legert, K. Le Blanc, G. Warfvinge, and R.V. Sugars

Subjects
Oral cGVHD, Histopathology, Grading, Large cohort, Hematopoietic cell transplantation, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Objectives: The oral cavity commonly displays mucosal lichenoid lesions and salivary gland dysfunction, which are considered different chronic Graft-versus-Host Disease (cGVHD) pathophysiology’s. However, diagnostics of salivary gland (sg-)cGVHD are limited. The objectives of the current study are to evaluate the minor salivary gland (MSG) histo-immunopathological profiles post allogenic hematopoietic cell transplantation based on sg-cGVHD criteria. Design: Histopathology was characterized according to two published grading strategies. Firstly, the National Institute of Health (NIH) assessed peri-ductal/acinar infiltration, exocytosis, damage, and fibrosis, and a points-based grading scheme was established (0–16 points, Grade (G) 0 to IV). Second, a modified Sjögren’s Syndrome focus-score with parenchymal damage was also adapted, (0–10 points, Score 0 to 2). 146 MSG biopsies from 79 patients were compared, using the histopathological specific criteria for sg-cGVHD pathology. Quantitative immunohistochemistry for T-cells (CD4, CD8), B-cells (CD19, CD20), monocytic cells (CD68) and dendritic cells (CD1a) were also assessed. Results: The large-scale cohort validated the use of both grading schemes. GIII-GIV and score 2 signified a histopathological diagnosis of “likely” sg-cGVHD. Immunopathological severity was associated with increased T-cells (CD4 and CD8) and monocytic (CD68) infiltrate, with minimal involvement of B-cells (CD19 and CD20), and Langerhans cells (CD1a). Conclusions: Both schemes were verified as being suitable for histological grading to improve assessment and diagnosis of sg-cGVHD. The NIH cGVHD grading appears to be more beneficial for research purposes, including final diagnostics of “no/inactive”, “possible” or “likely” cGVHD. The study highlights the intricacies of sg-cGVHD pathology; and the need for standardized assessment to improve patient management associated to sg-cGVHD.

Published
2023
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21. Prognostic Factors for Early Recurrence After Resection of Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Author

Leonhardt, Carl-Stephan, Gustorff, Charlotte, Klaiber, Ulla, Le Blanc, Solange, Stamm, Tanja A., Verbeke, Caroline S., Prager, Gerald W., and Strobel, Oliver

Abstract

More than half of pancreatic ductal adenocarcinomas (PDACs) recur within 12 months after curative-intent resection. This systematic review and meta-analysis was conducted to identify all reported prognostic factors for early recurrence in resected PDACs. After a systematic literature search, a meta-analysis was conducted using a random effects model. Separate analyses were performed for adjusted vs unadjusted effect estimates as well as reported odds ratios (ORs) and hazard ratios (HRs). Risk of bias was assessed using the Quality in Prognostic Studies tool, and evidence was rated according to Grading of Recommendations Assessment, Development and Evaluation recommendations. After 2903 abstracts were screened, 65 studies were included. Of these, 28 studies (43.1%) defined early recurrence as evidence of recurrence within 6 months, whereas 34 (52.3%) defined it as evidence of recurrence within 12 months after surgery. Other definitions were uncommon. Analysis of unadjusted ORs and HRs revealed 41 and 5 prognostic factors for early recurrence within 6 months, respectively. When exclusively considering adjusted data, we identified 25 and 10 prognostic factors based on OR and HR, respectively. Using a 12-month definition, we identified 38 (OR) and 15 (HR) prognostic factors from unadjusted data and 38 (OR) and 30 (HR) prognostic factors from adjusted data, respectively. On the basis of frequency counts of adjusted data, preoperative carbohydrate antigen 19-9, N status, nondelivery of adjuvant therapy, grading, and tumor size based on imaging were identified as key prognostic factors for early recurrence. Reported prognostic factors of early recurrence vary considerably. Identified key prognostic factors could aid in the development of a risk stratification framework for early recurrence. However, prospective validation is necessary. [Display omitted] Pancreatic cancer frequently recurs after surgery, this work identified all risk factors reported in the literature that lead to early recurrence and can thus help identify vulnerable patient groups. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Barriers and facilitators towards recovery and health service utilization among Haredi Jews with mental illness

Author

R. Whitley, E. Jarvis, M.-N. Le Blanc, and E. Rohr

Subjects
Psychiatry, RC435-571
Abstract

Introduction Evidence suggests that minorities tend to under-utilize mental health services, and may face specific barriers and facilitators towards recovery. One community which remains particularly under-researched in the Western World are Haredi Jews — a diverse group of individuals characterized by a shared devotion to traditional Talmudic and Halakhah teachings and observances. Objectives The overarching aim of this study is to document and analyze barriers and facilitators towards recovery and mental health service utilization among Haredi Jews with a history of mental distress. Specific objectives include: (i) eliciting and understanding participants’ mental health knowledge, beliefs, behaviours & attitudes; (ii) exploring their pathways and barriers to mental health care, especially examining the role of religiosity, religious community and rabbinical advice; and (iii) investigating their experience within the official mental health care system. Methods To gain an in-depth understanding, we conducted a qualitative study. This involved semi-structured interviews with 24 participants who (i) identified as Haredi Jews; (ii) had used mental health services; and (iii) were 18+ years of age. It also included interviews with several key stakeholders, for example local Rabbis and other community leaders. Data was analyzed using thematic analysis techniques. Results Participants typically had experienced mild to moderate mental distress, and tended to view mental health services in a positive light, mainly expressing satisfaction with services received. The analysis revealed three important facilitators and three important barriers to recovery. Facilitators comprised of (i) high levels of social support within the community, including specific well-being support groups; (ii) a positive relationship and connection with G-d, considered to provide guidance and support during troubled times; and (iii) the presence of many bridges and resources within the local Haredi community, including community-run health services, and Rabbis who encouraged mental health care utilization where appropriate. Barriers comprised of (i) stigma related to marriageability of self and offspring, inhibiting disclosure and mental health care use; (ii) acknowledged lack of awareness and knowledge about mental health, mental illness, treatments, and therapies; and (iii) generic health service issues, including long waitlists, limited availability and lack of appropriate therapists. Conclusions Study participants tended to have positive views of psychiatric services, and utilized different health care and community-based resources to help foster recovery. However, ongoing issues of stigma and low levels of mental health literacy may inhibit mental health care use and recovery. This implies a need for religiously-informed and community-grounded mental health literacy campaigns among Haredi Jewish communities. Disclosure of Interest None Declared

Published
2023
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26. Single-cell analysis of patient-derived PDAC organoids reveals cell state heterogeneity and a conserved developmental hierarchy

Author

Teresa G. Krieger, Solange Le Blanc, Julia Jabs, Foo Wei Ten, Naveed Ishaque, Katharina Jechow, Olivia Debnath, Carl-Stephan Leonhardt, Anamika Giri, Roland Eils, Oliver Strobel, and Christian Conrad

Subjects
Science
Abstract

Pancreatic tumors are frequently divided into basal and classical subtypes. Here, the authors use single cell sequencing to investigate organoids derived from pancreatic cancer tissue and find a hierarchy of distinct cell states, and classical and basal cells existing within the same tumor.

Published
2021
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28. Should We Reconsider PneumocystisPneumonia Presentation and Treatment According to Its Underlying Disease?

Author

Gaborit, Benjamin, Lécuyer, Romain, Issa, Nahéma, Camou, Fabrice, Lavergne, Rose-anne, Gabriel, Frederic, Morio, Florent, Canet, Emmanuel, Raffi, François, Boutoille, David, Cady, Anne, Gousseff, Marie, Crabol, Yoann, Néel, Antoine, Tessoulin, Benoît, Raffi, Francois, Boutoille, David, Biron, Charlotte, Lefebvre, Maeva, Gaborit, Benjamin Jean, Le Turnier, Paul, Deschanvres, Colin, Lecomte, Raphael, Chauveau, Marie, Lécuyer, Romain, Asquier-Khati, Antoine, Pineau, Valentin, Prime, Marie, Delaunay, Clarisse, Essid, Hakim, Le Pape, Patrice, Morio, Florent, Lavergne, Rose-Anne, Jeddi, Fakhri, Corvec, Stéphane, Bemer, Pascale, Caillon, Jocelyne, Guillouzouic, Aurélie, Leroy, Anne-Gaëlle, Lakhal, Karim, Cinotti, Raphaël, Roquilly, Antoine, Jean Reignier, Mickael Vourc’h;, Canet, Emmanuel, Blanc, François Xavier, Bretonniere, Cédric, Morin, Jean, Le Blanc, Camille, Alami, Hakim, Camou, Fabrice, Issa, Nahéma, Guisset, Olivier, Mourissoux, Gaelle, Accoceberry, Isabelle, Gabriel, Frederic, Coron, Noémie, Delhaes, Laurence, Imbert, Sébastien, Lefranc, Maxime, Lussac-Sorton, Florian, Rougeron, Amandine, Gousseff, Marie, Crabol, Yoann, Corvaisier, Grégory, Lautredoux, Florent, Anne Cady, Romain Lécuyerand, Auger, Myriam, and Pouedras, Pascal

Published
2024
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29. Sustainable employability, technology acceptance and task performance in workers collaborating with cobots: a pilot study

Author

Picco, E, Miglioretti, M, M Le Blanc, P, Eleonora Picco, Massimo Miglioretti, Pascale M Le Blanc, Picco, E, Miglioretti, M, M Le Blanc, P, Eleonora Picco, Massimo Miglioretti, and Pascale M Le Blanc

Abstract

Sustainable Employability (SE) and task performance of workers-collaborating-with-cobots is challenged. Whether SE policies can impact workers’ task performance in digitalized workplaces is still unknown. Drawing on two SE models, this study aims to ascertain whether the relationship between SE policies and task performance is mediated by health and productive capabilities, and whether this effect is moderated by the levels of User Acceptance and Use of Technology (UTAUT) predictors. 88 employees collaborating with cobots, or expected to do so in the near future, answered a cross-sectional survey. SE policies were positively related to task performance via health and productive capabilities. This indirect effect was moderated by the levels of UTAUT predictors, being significant only at low or medium levels of the moderators. SE policies contribute to employee capabilities, and in turn to workers’ task performance. Fostering health and productive capabilities is fundamental when employee levels of cobots’ acceptance are not high yet.

Published
2024

32. Leonhard Christoph Sturm, lecteur de Germain Brice

Author

Marianne Cojannot-Le Blanc

Subjects
Sturm (Leonhard Christoph), Brice (Germain), Parisian architecture, Perrault (Claude), Perrault (Charles), Mansart (François), Fine Arts, History of the arts, NX440-632, History of France, DC1-947
Abstract

City guides, accounts of voyages and journals are mainly used in art history as sources for the objects they refer to. A critique of their formulation can be undertaken, but it is rarer for their content to be examined from the perspective of a European-wide intertextuality. This essay is a comparative analysis of Leonhard Christoph Sturm’s Architecktonische Reise-Anmerckungen and the Description nouvelle de la ville de Paris by Germain Brice, examining the relevance of such a comparative reading.

Published
2022
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33. Serum 25-hydroxyvitamin D level and incident type 2 diabetes in older men, the Osteoporotic Fractures in Men (MrOS) study

Author

Napoli, Nicola, Schafer, Anne L, Lui, Li-Yung, Cauley, Jane A, Strotmeyer, Elsa S, Le Blanc, Erin S, Hoffman, Andrew R, Lee, Christine G, Black, Dennis M, and Schwartz, Ann V

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Clinical Sciences, Clinical Research, Nutrition, Diabetes, Prevention, Aging, Obesity, 2.1 Biological and endogenous factors, Metabolic and endocrine, Aged, Diabetes Mellitus, Type 2, Humans, Incidence, Male, Osteoporotic Fractures, Vitamin D, Type 2 diabetes, Older men, Biological Sciences, Engineering, Medical and Health Sciences, Endocrinology & Metabolism, Clinical sciences
Abstract

The association between vitamin D status and diabetes risk is inconsistent among observational studies, and most of the available studies have been with women. In the present study we investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and incident type 2 diabetes (T2D) in older men (≥65years old) who participated in the multisite Osteoporotic Fractures in Men (MrOS) study enrolled from March 2000 to April 2002. Baseline 25(OH)D levels were available in 1939 subjects without prevalent T2D. Clinical information, body mass index (BMI) and other factors related to T2D were assessed at the baseline visit. Incident diabetes, defined by self-report and medication use, was determined over an average follow-up of 6.4years. At baseline, participants were, on average, 73.3 (±5.7) years old, had a mean BMI in the overweight range (27.2kg/m(2)±3.6) and had total serum 25(OH)D of 26.1ng/ml (±8.3). Incident diabetes was diagnosed in 139 subjects. Cox regression analysis showed a trend toward a protective effect of higher 25(OH)D levels with a lower risk of T2D (HR 0.87, 95% CI: 0.73-1.04 per 1 SD increase of 25(OH)D). After adjusted for BMI and other potential confounders, the relationship between 25(OH)D levels and incident diabetes was further attenuated (HR 1.03, 95% CI 0.85-1.25). No significant difference in the incidence of diabetes emerged after analyzing study subjects according to baseline 25(OH)D quartiles. In conclusion, 25(OH)D levels were not associated with incident T2D in older men.

Published
2016

34. Treatment of chronic GvHD with mesenchymal stromal cells induces durable responses: A phase II study

Author

Erik Boberg, Lena vonBahr, Gabriel Afram, Carina Lindström, Per Ljungman, Nina Heldring, Peter Petzelbauer, Karin Garming Legert, Nadir Kadri, and Katarina Le Blanc

Subjects
cellular therapy, clinical trials, hematopoietic stem cell transplantation, mesenchymal stem cells, thymus, Medicine (General), R5-920, Cytology, QH573-671
Abstract

Abstract Steroid‐refractory chronic graft‐vs‐host disease (cGvHD) contributes to morbidity after allogeneic hematopoietic stem cell transplantation. Here, we report on 11 patients with severe, refractory cGvHD treated with repeated infusions of allogeneic bone marrow‐derived mesenchymal stromal cells (MSC) over a 6‐ to 12‐month period. Six patients responded to MSC treatment following National Institutes of Health response criteria, accompanied by improvement in GvHD‐related symptoms and quality of life. This response was durable, with systemic immunosuppressive therapy withdrawn from two responders, and a further two free from steroids and tapering calcineurin inhibitors. All responders displayed a distinct immune phenotype characterized by higher levels of naïve T cells and B cells before treatment compared with the nonresponders, and a significantly higher fraction of CD31+ naïve CD4+ T cells. MSC treatment was associated with significant increases in naïve T cells, B cells, and Tregs 7 days after each infusion. Skin biopsies showed resolution of epidermal pathology. CXCL9 and CXCL10 showed differential responses in responder and nonresponder patients. Our data support the use of MSC infusions as treatment for steroid‐refractory cGvHD with durable responses. We propose CXCL9 and CXCL10 as early biomarkers for responsiveness to MSC treatment. Our results highlight the importance of the MSC recipient immune phenotype in promoting treatment response. This trial was registered at www.ClinicalTrials.gov as #NCT01522716.

Published
2020
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35. Combination of the W boson polarization measurements in top quark decays using ATLAS and CMS data at s $$ \sqrt{s} $$ = 8 TeV

Author

The ATLAS collaboration, G. Aad, B. Abbott, D. C. Abbott, A. Abed Abud, K. Abeling, D. K. Abhayasinghe, S. H. Abidi, O. S. Abou Zeid, N. L. Abraham, H. Abramowicz, H. Abreu, Y. Abulaiti, B. S. Acharya, B. Achkar, L. Adam, C. Adam Bourdarios, L. Adamczyk, L. Adamek, J. Adelman, M. Adersberger, A. Adiguzel, S. Adorni, T. Adye, A. A. Affolder, Y. Afik, C. Agapopoulou, M. N. Agaras, A. Aggarwal, C. Agheorghiesei, J. A. Aguilar-Saavedra, A. Ahmad, F. Ahmadov, W. S. Ahmed, X. Ai, G. Aielli, S. Akatsuka, T. P. A. Åkesson, E. Akilli, A. V. Akimov, K. AlKhoury, G. L. Alberghi, J. Albert, M. J. Alconada Verzini, S. Alderweireldt, M. Aleksa, I. N. Aleksandrov, C. Alexa, T. Alexopoulos, A. Alfonsi, F. Alfonsi, M. Alhroob, B. Ali, S. Ali, M. Aliev, G. Alimonti, C. Allaire, B. M. M. Allbrooke, B. W. Allen, P.P. Allport, A. Aloisio, F. Alonso, C. Alpigiani, A. A. Alshehri, E. Alunno Camelia, M. Alvarez Estevez, M. G. Alviggi, Y. Amaral Coutinho, A. Ambler, L. Ambroz, C. Amelung, D. Amidei, S. P. Amor Dos Santos, S. Amoroso, C. S. Amrouche, F. An, C. Anastopoulos, N. Andari, T. Andeen, C. F. Anders, J. K. Anders, S. Y. Andrean, A. Andreazza, V. Andrei, C. R. Anelli, S. Angelidakis, A. Angerami, A. V. Anisenkov, A. Annovi, C. Antel, M. T. Anthony, E. Antipov, M. Antonelli, D. J. A. Antrim, F. Anulli, M. Aoki, J. A. Aparisi Pozo, M. A. Aparo, L. Aperio Bella, V. Araujo Ferraz, R. Araujo Pereira, C. Arcangeletti, A. T. H. Arce, F. A. Arduh, J-F. Arguin, S. Argyropoulos, J.-H. Arling, A. J. Armbruster, A. Armstrong, O. Arnaez, H. Arnold, Z. P. Arrubarrena Tame, G. Artoni, S. Artz, S. Asai, T. Asawatavonvanich, N. Asbah, E. M. Asimakopoulou, L. Asquith, J. Assahsah, K. Assamagan, R. Astalos, R. J. Atkin, M. Atkinson, N. B. Atlay, H. Atmani, K. Augsten, G. Avolio, M. K. Ayoub, G. Azuelos, H. Bachacou, K. Bachas, M. Backes, F. Backman, P. Bagnaia, M. Bahmani, H. Bahrasemani, A. J. Bailey, V. R. Bailey, J. T. Baines, C. Bakalis, O. K. Baker, P. J. Bakker, D. Bakshi Gupta, S. 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Vargas Hernandez, A. Buccilli, S. I. Cooper, S. V. Gleyzer, C. Henderson, P. Rumerio, C. West, A. Albert, D. Arcaro, Z. Demiragli, D. Gastler, C. Richardson, J. Rohlf, D. Sperka, D. Spitzbart, I. Suarez, L. Sulak, D. Zou, G. Benelli, B. Burkle, X. Coubez, D. Cutts, Y. t. Duh, M. Hadley, U. Heintz, J. M. Hogan, K. H. M. Kwok, E. Laird, G. Landsberg, K. T. Lau, M. Narain, S. Sagir, R. Syarif, E. Usai, W. Y. Wong, D. Yu, W. Zhang, R. Band, C. Brainerd, R. Breedon, M. Calderon De La Barca Sanchez, M. Chertok, J. Conway, R. Conway, P. T. Cox, R. Erbacher, C. Flores, G. Funk, F. Jensen, W. Ko, O. Kukral, R. Lander, M. Mulhearn, D. Pellett, J. Pilot, M. Shi, D. Taylor, K. Tos, M. Tripathi, F. Zhang, M. Bachtis, C. Bravo, R. Cousins, A. Dasgupta, A. Florent, J. Hauser, M. Ignatenko, N. Mccoll, W. A. Nash, S. Regnard, D. Saltzberg, C. Schnaible, B. Stone, V. Valuev, K. Burt, R. Clare, J. W. Gary, S. M. A. Ghiasi Shirazi, G. Hanson, G. Karapostoli, O. R. Long, N. Manganelli, M. Olmedo Negrete, M. I. Paneva, W. Si, S. Wimpenny, B. R. Yates, J. G. Branson, S. Cittolin, S. Cooperstein, N. Deelen, M. Derdzinski, J. Duarte, R. Gerosa, D. Gilbert, B. Hashemi, D. Klein, V. Krutelyov, J. Letts, M. Masciovecchio, S. May, S. Padhi, M. Pieri, V. Sharma, M. Tadel, F. Würthwein, A. Yagil, G. Zevi Della Porta, N. Amin, R. Bhandari, C. Campagnari, M. Citron, V. Dutta, J. Incandela, B. Marsh, H. Mei, A. Ovcharova, H. Qu, J. Richman, U. Sarica, D. Stuart, S. Wang, D. Anderson, A. Bornheim, O. Cerri, I. Dutta, J. M. Lawhorn, N. Lu, J. Mao, H. B. Newman, T. Q. Nguyen, J. Pata, M. Spiropulu, J. R. Vlimant, S. Xie, R. Y. Zhu, J. Alison, M. B. Andrews, T. Ferguson, T. Mudholkar, M. Paulini, M. Sun, I. Vorobiev, M. Weinberg, J. P. Cumalat, W. T. Ford, E. MacDonald, T. Mulholland, R. Patel, A. Perloff, K. Stenson, K. A. Ulmer, S. R. Wagner, J. Alexander, Y. Cheng, J. Chu, A. Datta, A. Frankenthal, K. Mcdermott, J. R. Patterson, D. Quach, A. Ryd, S. M. Tan, Z. Tao, J. Thom, P. Wittich, M. Zientek, S. Abdullin, M. Albrow, M. Alyari, G. Apollinari, A. Apresyan, A. Apyan, L. A. T. Bauerdick, A. Beretvas, D. Berry, J. Berryhill, P. C. Bhat, K. Burkett, J. N. Butler, A. Canepa, G. B. Cerati, H. W. K. Cheung, F. Chlebana, M. Cremonesi, V. D. Elvira, J. Freeman, Z. Gecse, E. Gottschalk, L. Gray, D. Green, S. Grünendahl, O. Gutsche, J. Hanlon, R. M. Harris, S. Hasegawa, R. Heller, J. Hirschauer, B. Jayatilaka, S. Jindariani, M. Johnson, U. Joshi, T. Klijnsma, B. Klima, M. J. Kortelainen, B. Kreis, S. Lammel, J. Lewis, D. Lincoln, R. Lipton, T. Liu, J. Lykken, K. Maeshima, J. M. Marraffino, D. Mason, P. McBride, P. Merkel, S. Mrenna, S. Nahn, V. O’Dell, V. Papadimitriou, K. Pedro, C. Pena, F. Ravera, A. Reinsvold Hall, L. Ristori, B. Schneider, E. Sexton-Kennedy, N. Smith, A. Soha, W. J. Spalding, L. Spiegel, S. Stoynev, J. Strait, L. Taylor, S. Tkaczyk, N. V. Tran, L. Uplegger, E. W. Vaandering, R. Vidal, M. Wang, H. A. Weber, A. Woodard, D. Acosta, P. Avery, D. Bourilkov, L. Cadamuro, V. Cherepanov, F. Errico, R. D. Field, D. Guerrero, B. M. Joshi, M. Kim, J. Konigsberg, A. Korytov, K. H. Lo, K. Matchev, N. Menendez, G. Mitselmakher, D. Rosenzweig, K. Shi, X. Zuo, Y. R. Joshi, T. Adams, A. Askew, S. Hagopian, V. Hagopian, K. F. Johnson, R. Khurana, T. Kolberg, G. Martinez, T. Perry, H. Prosper, C. Schiber, R. Yohay, M. M. Baarmand, M. Hohlmann, D. Noonan, M. Rahmani, M. Saunders, F. Yumiceva, M. R. Adams, L. Apanasevich, R. R. Betts, R. Cavanaugh, S. Dittmer, O. Evdokimov, C. E. Gerber, D. A. Hangal, D. J. Hofman, V. Kumar, C. Mills, G. Oh, T. Roy, M. B. Tonjes, N. Varelas, J. Viinikainen, X. Wang, Z. Wu, M. Alhusseini, B. Bilki, K. Dilsiz, S. Durgut, R. P. Gandrajula, M. Haytmyradov, V. Khristenko, O. K. Köseyan, J.-P. Merlo, A. Mestvirishvili, A. Moeller, J. Nachtman, H. Ogul, Y. Onel, F. Ozok, A. Penzo, C. Snyder, E. Tiras, J. Wetzel, K. Yi, B. Blumenfeld, A. Cocoros, N. Eminizer, A. V. Gritsan, W. T. Hung, S. Kyriacou, P. Maksimovic, C. Mantilla, J. Roskes, M. Swartz, T. Á. Vámi, C. Baldenegro Barrera, P. Baringer, A. Bean, S. Boren, A. Bylinkin, T. Isidori, S. Khalil, J. King, G. Krintiras, A. Kropivnitskaya, C. Lindsey, D. Majumder, W. Mcbrayer, N. Minafra, M. Murray, C. Rogan, C. Royon, S. Sanders, E. Schmitz, J. D. Tapia Takaki, J. Williams, G. Wilson, S. Duric, A. Ivanov, K. Kaadze, D. Kim, Y. Maravin, D. R. Mendis, T. Mitchell, A. Modak, A. Mohammadi, F. Rebassoo, D. Wright, A. Baden, O. Baron, A. Belloni, S. C. Eno, Y. Feng, N. J. Hadley, S. Jabeen, G. Y. Jeng, R. G. Kellogg, A. C. Mignerey, S. Nabili, M. Seidel, A. Skuja, S. C. Tonwar, L. Wang, K. Wong, D. Abercrombie, B. Allen, S. Brandt, W. Busza, I. A. Cali, M. D’Alfonso, G. Gomez Ceballos, M. Goncharov, P. Harris, D. Hsu, M. Hu, M. Klute, D. Kovalskyi, Y.-J. Lee, P. D. Luckey, B. Maier, A. C. Marini, C. Mcginn, C. Mironov, S. Narayanan, X. Niu, C. Paus, D. Rankin, C. Roland, G. Roland, Z. Shi, G. S. F. Stephans, K. Sumorok, K. Tatar, D. Velicanu, T. W. Wang, B. Wyslouch, R. M. Chatterjee, A. Evans, S. Guts, P. Hansen, J. Hiltbrand, Sh. Jain, Y. Kubota, Z. Lesko, J. Mans, M. Revering, R. Rusack, R. Saradhy, N. Schroeder, N. Strobbe, M. A. Wadud, J. G. Acosta, S. Oliveros, K. Bloom, D. R. Claes, C. Fangmeier, L. Finco, F. Golf, R. Kamalieddin, I. Kravchenko, J. E. Siado, G. R. Snow, B. Stieger, W. Tabb, G. Agarwal, C. Harrington, I. Iashvili, A. Kharchilava, C. McLean, D. Nguyen, A. Parker, J. Pekkanen, S. Rappoccio, B. Roozbahani, G. Alverson, E. Barberis, C. Freer, Y. Haddad, A. Hortiangtham, G. Madigan, B. Marzocchi, D. M. Morse, V. Nguyen, T. Orimoto, L. Skinnari, A. Tishelman-Charny, T. Wamorkar, B. Wang, A. Wisecarver, D. Wood, J. Bueghly, G. Fedi, A. Gilbert, T. Gunter, K. A. Hahn, N. Odell, M. H. Schmitt, K. Sung, M. Velasco, R. Bucci, N. Dev, R. Goldouzian, M. Hildreth, K. Hurtado Anampa, C. Jessop, D. J. Karmgard, K. Lannon, W. Li, N. Loukas, N. Marinelli, I. Mcalister, F. Meng, Y. Musienko, R. Ruchti, P. Siddireddy, G. Smith, S. Taroni, M. Wayne, A. Wightman, M. Wolf, J. Alimena, B. Bylsma, B. Cardwell, L. S. Durkin, B. Francis, C. Hill, W. Ji, A. Lefeld, T. Y. Ling, B. L. Winer, G. Dezoort, P. Elmer, J. Hardenbrook, N. Haubrich, S. Higginbotham, A. Kalogeropoulos, S. Kwan, D. Lange, M. T. Lucchini, J. Luo, D. Marlow, K. Mei, I. Ojalvo, J. Olsen, C. Palmer, P. Piroué, D. Stickland, C. Tully, S. Norberg, A. Barker, V. E. Barnes, R. Chawla, S. Das, L. Gutay, M. Jones, A. W. Jung, B. Mahakud, D. H. Miller, G. Negro, N. Neumeister, C. C. Peng, S. Piperov, H. Qiu, J. F. Schulte, N. Trevisani, R. Xiao, W. Xie, T. Cheng, J. Dolen, N. Parashar, A. Baty, U. Behrens, S. Dildick, K. M. Ecklund, S. Freed, F. J. M. Geurts, M. Kilpatrick, Arun Kumar, B. P. Padley, R. Redjimi, J. Roberts, J. Rorie, W. Shi, A. G. Stahl Leiton, Z. Tu, A. Zhang, A. Bodek, P. de Barbaro, R. Demina, J. L. Dulemba, C. Fallon, T. Ferbel, M. Galanti, A. Garcia-Bellido, O. Hindrichs, A. Khukhunaishvili, E. Ranken, R. Taus, B. Chiarito, J. P. Chou, A. Gandrakota, Y. Gershtein, E. Halkiadakis, A. Hart, M. Heindl, E. Hughes, S. Kaplan, I. Laflotte, A. Lath, R. Montalvo, K. Nash, M. Osherson, S. Salur, S. Schnetzer, S. Somalwar, R. Stone, S. Thomas, H. Acharya, A. G. Delannoy, S. Spanier, O. Bouhali, M. Dalchenko, M. De Mattia, A. Delgado, R. Eusebi, J. Gilmore, T. Huang, T. Kamon, S. Luo, S. Malhotra, D. Marley, R. Mueller, D. Overton, L. Perniè, D. Rathjens, A. Safonov, N. Akchurin, J. Damgov, F. De Guio, V. Hegde, S. Kunori, K. Lamichhane, T. Mengke, S. Muthumuni, T. Peltola, S. Undleeb, I. Volobouev, A. Whitbeck, S. Greene, A. Gurrola, R. Janjam, W. Johns, C. Maguire, A. Melo, H. Ni, K. Padeken, F. Romeo, P. Sheldon, S. Tuo, J. Velkovska, M. Verweij, M. W. Arenton, P. Barria, B. Cox, G. Cummings, J. Hakala, R. Hirosky, M. Joyce, A. Ledovskoy, C. Neu, B. Tannenwald, E. Wolfe, F. Xia, R. Harr, P. E. Karchin, N. Poudyal, J. Sturdy, P. Thapa, K. Black, T. Bose, J. Buchanan, C. Caillol, D. Carlsmith, S. Dasu, I. De Bruyn, L. Dodd, C. Galloni, H. He, M. Herndon, A. Hervé, U. Hussain, A. Lanaro, A. Loeliger, R. Loveless, J. Madhusudanan Sreekala, A. Mallampalli, D. Pinna, T. Ruggles, A. Savin, W. H. Smith, D. Teague, and S. Trembath-reichert

Subjects
Hadron-Hadron scattering (experiments), Top physics, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Abstract The combination of measurements of the W boson polarization in top quark decays performed by the ATLAS and CMS collaborations is presented. The measurements are based on proton-proton collision data produced at the LHC at a centre-of-mass energy of 8 TeV, and corresponding to an integrated luminosity of about 20 fb −1 for each experiment. The measurements used events containing one lepton and having different jet multiplicities in the final state. The results are quoted as fractions of W bosons with longitudinal (F 0), left-handed (F L), or right-handed (F R) polarizations. The resulting combined measurements of the polarization fractions are F 0 = 0.693 ± 0.014 and F L = 0.315 ± 0.011. The fraction F R is calculated from the unitarity constraint to be F R = −0.008 ± 0.007. These results are in agreement with the standard model predictions at next-to-next-to-leading order in perturbative quantum chromodynamics and represent an improvement in precision of 25 (29)% for F 0 (F L) with respect to the most precise single measurement. A limit on anomalous right-handed vector (V R), and left- and right-handed tensor (g L , g R) tWb couplings is set while fixing all others to their standard model values. The allowed regions are [−0.11, 0.16] for V R, [−0.08, 0.05] for g L, and [−0.04, 0.02] for g R, at 95% confidence level. Limits on the corresponding Wilson coefficients are also derived.

Published
2020
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36. Validation of an algorithm based on administrative data to detect new onset of atrial fibrillation after cardiac surgery

Author

Jonathan Bourgon Labelle, Paul Farand, Christian Vincelette, Myriam Dumont, Mathilde Le Blanc, and Christian M. Rochefort

Subjects
Validation study, Administrative databases, Postoperative atrial fibrillation, Cardiac surgery, Canadian version of the international classification of diseases., Medicine (General), R5-920
Abstract

Abstract Introduction Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery associated with important morbidity, mortality, and costs. To assess the effectiveness of preventive interventions, an important prerequisite is to have access to accurate measures of POAF incidence. The aim of this study was to develop and validate such a measure. Methods A validation study was conducted at two large Canadian university health centers. First, a random sample of 976 (10.4%) patients who had cardiac surgery at these sites between 2010 and 2016 was generated. Then, a reference standard assessment of their medical records was performed to determine their true POAF status on discharge (positive/negative). The accuracy of various algorithms combining diagnostic and procedure codes from: 1) the current hospitalization, and 2) hospitalizations up to 6 years before the current hospitalization was assessed in comparison with the reference standard. Overall and site-specific estimates of sensitivity, specificity, positive (PPV), and negative (NPV) predictive values were generated, along with their 95%CIs. Results Upon manual review, 324 (33.2%) patients were POAF-positive. Our best-performing algorithm combining data from both sites used a look-back window of 6 years to exclude patients previously known for AF. This algorithm achieved 70.4% sensitivity (95%CI: 65.1–75.3), 86.0% specificity (95%CI: 83.1–88.6), 71.5% PPV (95%CI: 66.2–76.4), and 85.4% NPV (95%CI: 82.5–88.0). However, significant site-specific differences in sensitivity and NPV were observed. Conclusion An algorithm based on administrative data can identify POAF patients with moderate accuracy. However, site-specific variations in coding practices have significant impact on accuracy.

Published
2020
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37. Translation and Cultural Adaptation of PROactive Instruments for COPD in French and Influence of Weather and Pollution on Its Difficulty Score

Author

Vaidya T, Thomas-Ollivier V, Hug F, Bernady A, Le Blanc C, de Bisschop C, and Chambellan A

Subjects
copd, physical activity, questionnaire, reliability, Diseases of the respiratory system, RC705-779
Abstract

Trija Vaidya,1 Véronique Thomas-Ollivier,2 François Hug,2,3 Alain Bernady,4 Camille Le Blanc,5 Claire de Bisschop,1 Arnaud Chambellan2,6 1Laboratory MOVE (EA6314), Université de Poitiers, Faculty of Sport Sciences, Poitiers, France; 2Faculty of Sport Sciences, Movement–Interactions–Performance, MIP, EA 4334, Université de Nantes, Nantes F-4000, France; 3Institut Universitaire de France (IUF), Paris, France; 4Toki-Eder Centre Médical Cardio-Respiratoire, Cambo-Les-Bains, France; 5Physical Medicine and Rehabilitation Department, University Hospital of Nantes, Nantes, France; 6L’institut du Thorax, Laboratory MIP, UNIV Nantes, University Hospital of Nantes, Nantes, FranceCorrespondence: Arnaud ChambellanExplorations fonctionnelles, l’institut du thorax, CHU de Nantes, Bd Jacques Monod, Nantes Cedex 1 44093, FranceTel +33 240 165 511Fax +33 240 165 391Email arnaud.chambellan@chu-nantes.frIntroduction: The recently developed daily and clinical visit PROactive physical activity in COPD (PPAC) instruments are hybrid tools to objectively quantify the level of physical activity and the difficulties experienced in everyday life. Our aim was to translate these instruments for the French-speaking chronic obstructive pulmonary disease (COPD) community worldwide and evaluate the influence of weather and pollution on difficulty score.Methods: The translation procedure was conducted following the guidelines for cross-cultural adaptation process. The translated clinical visit (C-PPAC) was tested among COPD patients in France. A retest was conducted after an interval of at least 2 weeks. The C-PPAC difficulty score was then tested to see how sensitive it was to the influence of weather and outdoor pollution.Results: One hundred and seventeen COPD patients (age 65± 9 years; FEV1: 51± 20%) from 9 regions in France were included. The French version of C-PPAC was found comprehensible by the patients with an average score of 4.8/5 on a Likert-scale. It showed good internal consistency with Cronbach’s α> 0.90 and a good test retest reliability with an intraclass correlation coefficient of ≥ 0.80. The difficulty score was negatively correlated with duration of daylight (ρ=− 0.266; p< 0.01) and influenced by the intensity of rainfall (light vs. heavy rainfall: 68± 16 vs. 76± 14 respectively, p=0.045). The score was lower in patients receiving long term oxygen therapy (60± 15 vs. 71± 15, p< 0.01), but not correlated with the pollution indices.Conclusion: The French versions of the questionnaires of the PPAC instruments are accepted and comprehensible to COPD patients. The difficulty score of C-PPAC is sensitive to duration of daylight and rainfall. Such weather factors must be taken into consideration when evaluating the physical activity behavior using these tools in COPD.Keywords: COPD, physical activity, questionnaire, reliability

Published
2020

38. Lecture et typologie textuelle: la traduction des formes brèves

Author

Charles Le Blanc

Subjects
aphorism, fragment, proverb, short forms, translation, typology, Anthropology, GN1-890, Language. Linguistic theory. Comparative grammar, P101-410
Abstract

This article focuses on the translation of short forms. It starts from the idea that any translator is a double translator, since he must be able to render both the natural language and the artistic language of the text (s)he has to translate. Once this premise is acquired, typology – understood as the form through which the text manifests itself – comes into play. The author focuses on a genre typically associated with Romanticism, the fragment; its translation does not require the application of a method, but the concrete exercise of an art: the fragment imposes and, as it were, directs its own translation. A similar link between typology and way of translating can be found in all short forms. In order to prove it, the text analyses various short forms, ranging from a minimum to a maximum of authorial presence: from the total absence of the author (as in proverbs) we come to the exclusive presence, to the solitude, of the author (as in aphorisms, when they are written without thinking about a future publication).

Published
2020
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39. Evaluating the Impact of Adaptive Personalized Goal Setting on Engagement Levels of Government Staff With a Gamified mHealth Tool: Results From a 2-Month Randomized Controlled Trial

Author

Raoul Nuijten, Pieter Van Gorp, Alireza Khanshan, Pascale Le Blanc, Pauline van den Berg, Astrid Kemperman, and Monique Simons

Subjects
Information technology, T58.5-58.64, Public aspects of medicine, RA1-1270
Abstract

BackgroundAlthough the health benefits of physical activity are well established, it remains challenging for people to adopt a more active lifestyle. Mobile health (mHealth) interventions can be effective tools to promote physical activity and reduce sedentary behavior. Promising results have been obtained by using gamification techniques as behavior change strategies, especially when they were tailored toward an individual’s preferences and goals; yet, it remains unclear how goals could be personalized to effectively promote health behaviors. ObjectiveIn this study, we aim to evaluate the impact of personalized goal setting in the context of gamified mHealth interventions. We hypothesize that interventions suggesting health goals that are tailored based on end users’ (self-reported) current and desired capabilities will be more engaging than interventions with generic goals. MethodsThe study was designed as a 2-arm randomized intervention trial. Participants were recruited among staff members of 7 governmental organizations. They participated in an 8-week digital health promotion campaign that was especially designed to promote walks, bike rides, and sports sessions. Using an mHealth app, participants could track their performance on two social leaderboards: a leaderboard displaying the individual scores of participants and a leaderboard displaying the average scores per organizational department. The mHealth app also provided a news feed that showed when other participants had scored points. Points could be collected by performing any of the 6 assigned tasks (eg, walk for at least 2000 m). The level of complexity of 3 of these 6 tasks was updated every 2 weeks by changing either the suggested task intensity or the suggested frequency of the task. The 2 intervention arms—with participants randomly assigned—consisted of a personalized treatment that tailored the complexity parameters based on participants’ self-reported capabilities and goals and a control treatment where the complexity parameters were set generically based on national guidelines. Measures were collected from the mHealth app as well as from intake and posttest surveys and analyzed using hierarchical linear models. ResultsThe results indicated that engagement with the program inevitably dropped over time. However, engagement was higher for participants who had set themselves a goal in the intake survey. The impact of personalization was especially observed for frequency parameters because the personalization of sports session frequency did foster higher engagement levels, especially when participants set a goal to improve their capabilities. In addition, the personalization of suggested ride duration had a positive effect on self-perceived biking performance. ConclusionsPersonalization seems particularly promising for promoting the frequency of physical activity (eg, promoting the number of suggested sports sessions per week), as opposed to the intensity of the physical activity (eg, distance or duration). Replications and variations of our study setup are critical for consolidating and explaining (or refuting) these effects. Trial RegistrationClinicalTrials.gov NCT05264155; https://clinicaltrials.gov/ct2/show/NCT05264155

Published
2022
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40. Diversity of respiratory parameters and metabolic adaptation to low oxygen tension in mesenchymal stromal cells

Author

Kim Olesen, Noah Moruzzi, Ivana Bulatovic, Clifford Folmes, Ryounghoon Jeon, Ulrika Felldin, Andre Terzic, Oscar E. Simonson, Katarina Le Blanc, Cecilia Österholm, Per-Olof Berggren, Tomas Schiffer, Sergey Rodin, Andreas Tilevik, and Karl-Henrik Grinnemo

Subjects
Mesenchymal stromal cells, Development, Aerobic glycolysis, Hypoxia, Mitochondria, Metabolism, Physiology, QP1-981, Biochemistry, QD415-436
Abstract

Objective: Cell metabolism has been shown to play an active role in regulation of stemness and fate decision. In order to identify favorable culture conditions for mesenchymal stromal cells (MSCs) prior to transplantation, this study aimed to characterize the metabolic function of MSCs from different developmental stages in response to different oxygen tension during expansion. Materials and methods: We cultured human fetal cardiac MSCs and human adult bone-marrow MSCs for a week under hypoxia (3% O2) and normoxia (20% O2). We performed mitochondrial characterization and assessed oxygen consumption- and extracellular acidification-rates (OCR and ECAR) in addition to oxygen-sensitive respiration and mitochondrial complex activities, using both the Seahorse and Oroboros systems. Results: Adult and fetal MSCs displayed similar basal respiration and mitochondrial amount, however fetal MSCs had lower spare respiratory capacity and apparent coupling efficiency. Fetal MSCs expanded in either hypoxia or normoxia demonstrated similar acidification rates, while adult MSCs downregulated their aerobic glycolysis in normoxia. Acute decrease in oxygen tension caused a higher respiratory inhibition in adult compared to fetal MSCs. In both sources of MSCs, minor changes in complex activities in normoxic and hypoxic cultures were found. Conclusions: In contrast to adult MSCs, fetal MSCs displayed similar respiration and aerobic glycolysis at different O2 culture concentrations during expansion. Adult MSCs adjusted their respiration to glycolytic activities, depending on the culture conditions thus displaying a more mature metabolic function. These findings are relevant for establishing optimal in vitro culturing conditions, with the aim to maximize engraftment and therapeutic outcome.

Published
2022
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41. Pilot Evaluation of the Impact of Lottery-Based Incentives on Engagement Levels of Male Low SES Vocational Students With an mHealth App

Author

Raoul Nuijten, Pieter Van Gorp, Juup Hietbrink, Pascale Le Blanc, Astrid Kemperman, Pauline van den Berg, and Monique Simons

Subjects
lottery-based incentive, regret lottery, anticipated regret, low SES, vocational students, health promotion, Medicine, Public aspects of medicine, RA1-1270, Electronic computers. Computer science, QA75.5-76.95
Abstract

In general, individuals with lower socioeconomic status (SES) are less physically active and adhere to poorer diets than higher SES individuals. To promote healthier lifestyles in lower SES populations, we hosted a digital health promotion program among male vocational students at a school in The Netherlands. In a pilot study, we evaluated whether this target audience could be engaged with an mHealth app using lottery-based incentives that trigger feelings of anticipated regret. Especially, we studied the social and interpersonal aspects of regret lotteries in a within-subject experimental design. In this design, subjects either participated in a social variant (i.e., with students competing against their peers for a chance at a regret lottery), or an individual variant (i.e., with subjects solely individually engaged in a lottery). Additionally, we studied the impact of different payout schedules in a between-subject experimental design. In this design, participants were assigned to either a short-term, low-value payout schedule, or a long-term, high-value payout schedule. From a population of 72 male students, only half voluntarily participated in our 10-week program. From interviews, we learned that the main reason for neglecting the program was not related to the lottery-based incentives, nor to the prizes that were awarded. Instead, non-enrolled subjects did not join the program, because their peers were not joining. Paradoxically, it was suggested that students withheld their active participation until a larger portion of the sample was actively participating. From the subjects that enrolled in the program (N = 36, males, between 15 and 25 years of age), we found that a large proportion stopped interacting with the program over time (e.g., after roughly 4 weeks). Our results also indicated that students performed significantly more health-related activities when assigned to the social regret lottery, as opposed to the individual variant. This result was supported by interview responses from active participants: They mainly participated to compete against their peers, and not so much for the prizes. Hence, from this study, we obtained initial evidence on the impact of social and competitive aspects in lottery-based incentives to stimulate engagement levels in lower SES students with an mHealth app.

Published
2022
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42. EuPRAXIA Conceptual Design Report

Author

Assmann, R. W., Weikum, M. K., Akhter, T., Alesini, D., Alexandrova, A. S., Anania, M. P., Andreev, N. E., Andriyash, I., Artioli, M., Aschikhin, A., Audet, T., Bacci, A., Barna, I. F., Bartocci, S., Bayramian, A., Beaton, A., Beck, A., Bellaveglia, M., Beluze, A., Bernhard, A., Biagioni, A., Bielawski, S., Bisesto, F. G., Bonatto, A., Boulton, L., Brandi, F., Brinkmann, R., Briquez, F., Brottier, F., Bründermann, E., Büscher, M., Buonomo, B., Bussmann, M. H., Bussolino, G., Campana, P., Cantarella, S., Cassou, K., Chancé, A., Chen, M., Chiadroni, E., Cianchi, A., Cioeta, F., Clarke, J. A., Cole, J. M., Costa, G., Couprie, M. -E., Cowley, J., Croia, M., Cros, B., Crump, P. A., D’Arcy, R., Dattoli, G., Del Dotto, A., Delerue, N., Del Franco, M., Delinikolas, P., De Nicola, S., Dias, J. M., Di Giovenale, D., Diomede, M., Di Pasquale, E., Di Pirro, G., Di Raddo, G., Dorda, U., Erlandson, A. C., Ertel, K., Esposito, A., Falcoz, F., Falone, A., Fedele, R., Ferran Pousa, A., Ferrario, M., Filippi, F., Fils, J., Fiore, G., Fiorito, R., Fonseca, R. A., Franzini, G., Galimberti, M., Gallo, A., Galvin, T. C., Ghaith, A., Ghigo, A., Giove, D., Giribono, A., Gizzi, L. A., Grüner, F. J., Habib, A. F., Haefner, C., Heinemann, T., Helm, A., Hidding, B., Holzer, B. J., Hooker, S. M., Hosokai, T., Hübner, M., Ibison, M., Incremona, S., Irman, A., Iungo, F., Jafarinia, F. J., Jakobsson, O., Jaroszynski, D. A., Jaster-Merz, S., Joshi, C., Kaluza, M., Kando, M., Karger, O. S., Karsch, S., Khazanov, E., Khikhlukha, D., Kirchen, M., Kirwan, G., Kitégi, C., Knetsch, A., Kocon, D., Koester, P., Kononenko, O. S., Korn, G., Kostyukov, I., Kruchinin, K. O., Labate, L., Le Blanc, C., Lechner, C., Lee, P., Leemans, W., Lehrach, A., Li, X., Li, Y., Libov, V., Lifschitz, A., Lindstrøm, C. A., Litvinenko, V., Lu, W., Lundh, O., Maier, A. R., Malka, V., Manahan, G. G., Mangles, S. P. D., Marcelli, A., Marchetti, B., Marcouillé, O., Marocchino, A., Marteau, F., Martinez de la Ossa, A., Martins, J. L., Mason, P. D., Massimo, F., Mathieu, F., Maynard, G., Mazzotta, Z., Mironov, S., Molodozhentsev, A. Y., Morante, S., Mosnier, A., Mostacci, A., Müller, A. -S., Murphy, C. D., Najmudin, Z., Nghiem, P. A. P., Nguyen, F., Niknejadi, P., Nutter, A., Osterhoff, J., Oumbarek Espinos, D., Paillard, J. -L., Papadopoulos, D. N., Patrizi, B., Pattathil, R., Pellegrino, L., Petralia, A., Petrillo, V., Piersanti, L., Pocsai, M. A., Poder, K., Pompili, R., Pribyl, L., Pugacheva, D., Reagan, B. A., Resta-Lopez, J., Ricci, R., Romeo, S., Rossetti Conti, M., Rossi, A. R., Rossmanith, R., Rotundo, U., Roussel, E., Sabbatini, L., Santangelo, P., Sarri, G., Schaper, L., Scherkl, P., Schramm, U., Schroeder, C. B., Scifo, J., Serafini, L., Sharma, G., Sheng, Z. M., Shpakov, V., Siders, C. W., Silva, L. O., Silva, T., Simon, C., Simon-Boisson, C., Sinha, U., Sistrunk, E., Specka, A., Spinka, T. M., Stecchi, A., Stella, A., Stellato, F., Streeter, M. J. V., Sutherland, A., Svystun, E. N., Symes, D., Szwaj, C., Tauscher, G. E., Terzani, D., Toci, G., Tomassini, P., Torres, R., Ullmann, D., Vaccarezza, C., Valléau, M., Vannini, M., Vannozzi, A., Vescovi, S., Vieira, J. M., Villa, F., Wahlström, C. -G., Walczak, R., Walker, P. A., Wang, K., Welsch, A., Welsch, C. P., Weng, S. M., Wiggins, S. M., Wolfenden, J., Xia, G., Yabashi, M., Zhang, H., Zhao, Y., Zhu, J., and Zigler, A.

Published
2020
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43. Erratum to: EuPRAXIA Conceptual Design Report: Eur. Phys. J. Special Topics 229, 3675-4284 (2020), https://doi.org/10.1140/epjst/e2020-000127-8

Author

Assmann, R. W., Weikum, M. K., Akhter, T., Alesini, D., Alexandrova, A. S., Anania, M. P., Andreev, N. E., Andriyash, I., Artioli, M., Aschikhin, A., Audet, T., Bacci, A., Barna, I. F., Bartocci, S., Bayramian, A., Beaton, A., Beck, A., Bellaveglia, M., Beluze, A., Bernhard, A., Biagioni, A., Bielawski, S., Bisesto, F. G., Bonatto, A., Boulton, L., Brandi, F., Brinkmann, R., Briquez, F., Brottier, F., Bründermann, E., Büscher, M., Buonomo, B., Bussmann, M. H., Bussolino, G., Campana, P., Cantarella, S., Cassou, K., Chancé, A., Chen, M., Chiadroni, E., Cianchi, A., Cioeta, F., Clarke, J. A., Cole, J. M., Costa, G., Couprie, M. -E., Cowley, J., Croia, M., Cros, B., Crump, P. A., D’Arcy, R., Dattoli, G., Del Dotto, A., Delerue, N., Del Franco, M., Delinikolas, P., De Nicola, S., Dias, J. M., Di Giovenale, D., Diomede, M., Di Pasquale, E., Di Pirro, G., Di Raddo, G., Dorda, U., Erlandson, A. C., Ertel, K., Esposito, A., Falcoz, F., Falone, A., Fedele, R., Ferran Pousa, A., Ferrario, M., Filippi, F., Fils, J., Fiore, G., Fiorito, R., Fonseca, R. A., Franzini, G., Galimberti, M., Gallo, A., Galvin, T. C., Ghaith, A., Ghigo, A., Giove, D., Giribono, A., Gizzi, L. A., Grüner, F. J., Habib, A. F., Haefner, C., Heinemann, T., Helm, A., Hidding, B., Holzer, B. J., Hooker, S. M., Hosokai, T., Hübner, M., Ibison, M., Incremona, S., Irman, A., Iungo, F., Jafarinia, F. J., Jakobsson, O., Jaroszynski, D. A., Jaster-Merz, S., Joshi, C., Kaluza, M., Kando, M., Karger, O. S., Karsch, S., Khazanov, E., Khikhlukha, D., Kirchen, M., Kirwan, G., Kitégi, C., Knetsch, A., Kocon, D., Koester, P., Kononenko, O. S., Korn, G., Kostyukov, I., Kruchinin, K. O., Labate, L., Le Blanc, C., Lechner, C., Lee, P., Leemans, W., Lehrach, A., Li, X., Li, Y., Libov, V., Lifschitz, A., Lindstrøm, C. A., Litvinenko, V., Lu, W., Lundh, O., Maier, A. R., Malka, V., Manahan, G. G., Mangles, S. P. D., Marcelli, A., Marchetti, B., Marcouillé, O., Marocchino, A., Marteau, F., Martinez de la Ossa, A., Martins, J. L., Mason, P. D., Massimo, F., Mathieu, F., Maynard, G., Mazzotta, Z., Mironov, S., Molodozhentsev, A. Y., Morante, S., Mosnier, A., Mostacci, A., Müller, A. -S., Murphy, C. D., Najmudin, Z., Nghiem, P. A. P., Nguyen, F., Niknejadi, P., Nutter, A., Osterhoff, J., Oumbarek Espinos, D., Paillard, J. -L., Papadopoulos, D. N., Patrizi, B., Pattathil, R., Pellegrino, L., Petralia, A., Petrillo, V., Piersanti, L., Pocsai, M. A., Poder, K., Pompili, R., Pribyl, L., Pugacheva, D., Reagan, B. A., Resta-Lopez, J., Ricci, R., Romeo, S., Rossetti Conti, M., Rossi, A. R., Rossmanith, R., Rotundo, U., Roussel, E., Sabbatini, L., Santangelo, P., Sarri, G., Schaper, L., Scherkl, P., Schramm, U., Schroeder, C. B., Scifo, J., Serafini, L., Sharma, G., Sheng, Z. M., Shpakov, V., Siders, C. W., Silva, L. O., Silva, T., Simon, C., Simon-Boisson, C., Sinha, U., Sistrunk, E., Specka, A., Spinka, T. M., Stecchi, A., Stella, A., Stellato, F., Streeter, M. J. V., Sutherland, A., Svystun, E. N., Symes, D., Szwaj, C., Tauscher, G. E., Terzani, D., Toci, G., Tomassini, P., Torres, R., Ullmann, D., Vaccarezza, C., Valléau, M., Vannini, M., Vannozzi, A., Vescovi, S., Vieira, J. M., Villa, F., Wahlström, C. -G., Walczak, R., Walker, P. A., Wang, K., Welsch, A., Welsch, C. P., Weng, S. M., Wiggins, S. M., Wolfenden, J., Xia, G., Yabashi, M., Zhang, H., Zhao, Y., Zhu, J., and Zigler, A.

Published
2020
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45. Temporal Behavior in Auditory Fear Conditioning: Stimulus Property Matters

Author

Boulanger Bertolus, Julie, Knippenberg, Jeroen, Verschueren, Anna, Le Blanc, Pascale, Brown, Bruce L., Mouly, Anne-Marie, and Doyère, Valérie

Subjects
Time perception, Tone frequency, Duration discrimination, Conditioned suppression, Rat, Auditory fear conditioning, Auditory threat conditioning
Abstract

The accuracy of time judgments depends upon many factors, including the sensory properties of the to-be-timed stimulus. In auditory Pavlovian fear conditioning, an initially neutral tone (conditioned stimulus, CS) predicts the arrival of an aversive event (unconditioned stimulus, US) at a fixed time interval. The temporal relation between the CS and US events is encoded, leading to the development of a temporal pattern of responding. Little attention has been paid to the potential impact of the characteristics of the CS tone on the development of this temporal pattern. Here we compared the acquisition of the temporal pattern of conditioned responses of rats to different CS tone frequencies. Rats were first conditioned to lever press for food. Then, while lever pressing for food, they were presented with 60-s tones  of two very different frequencies 1kHz or 11kHz, each paired with a foot-shock given 30s after tone onset. This fear conditioning led to the appearance of conditioned suppression of the lever pressing. On probe trials the tone duration was 60 s, and the reinforcer was omitted. With training, a pattern of suppression evolved during the probe trials, showing a maximum of suppression near the programmed time of the shock US, however the 11kHz CS tone yielded better temporal control than did the 1kHz tone. A second experiment investigated rats’ abilities to discriminate between two times of shock arrival (10s or 30s) predicted by the different tone frequencies (1kHz or 11kHz), In this experiment, rats showed poorer discriminative timing performance when the lower frequency (1kHz) was associated with the longer duration (30s). Our results suggest a strong impact of the CS sensory properties on the expression of temporal learning within the context of auditory fear conditioning in rats.

Published
2015

46. Using Drama for Learning to Foster Positive Attitudes and Increase Motivation: Global Simulation in French Second Language Classes

Author

Dicks, Joseph E. and Le Blanc, Barbara

Abstract

Drama has been effectively used in many learning contexts including English as a second language classes. However, it has received less attention in foreign/second contexts. This article explores how drama for learning can impact upon the relationships among attitudes, motivation and learning in French second language (FSL) classrooms. The authors describe a second language research project done in grade 9 and 10 classrooms based on the principles of drama for learning including play and make believe, learning in context, and ownership of learning. Global simulation, the particular form of drama for learning used in the project, involves a voyage of discovery undertaken by a group involving a final destination and an itinerary. During this second language journey, students act, react and interact to create meaningful individual and group experiences and incorporate cooperative learning principles. The approach also allows the facilitators to draw on Gardner's multiple intelligence theory in order to structure activities that maximize students' individual strengths. The research project included development and piloting of the global simulation module, assessment of the pilot as well as assessment of implications for its future use. Data gathered for assessment included student questionnaires and teacher interviews. Results of the project indicated that there were improvements in the learning environments, including an increased level of motivation on the part of the learners involved. The teachers also expressed a high degree of satisfaction with the approach, especially because of their involvement in the development and implementation of the material from the beginning, which appeared to give them a sense of ownership and empowered them in their professional growth. Students also appeared to become more active and engaged in their learning as a result of a sense of ownership over their drama productions. In general, the results suggest that drama for learning and specifically global simulation are viable approaches for grade 9 and 10 FSL classes. This research lays the groundwork and provides direction and concrete resource materials for those who would like to experiment with global simulation in enhancing motivation among students in second language classrooms.

Published
2009

47. Les gemmes acquises par Gaston d’Orléans : nouvelles hypothèses sur le corpus

Author

Marianne Cojannot-Le Blanc and Évelyne Prioux

Subjects
cameos, collections, Orléans (Gaston d’), Villiers (George), images of power, intaglios, Fine Arts, History of the arts, NX440-632, History of France, DC1-947
Abstract

A fresh study of the available documentation makes it possible to identify between thirty-five and forty-one gems that initially belonged to Peter Paul Rubens and, later on, to the 1st Duke of Buckingham and to Gaston, Duke of Orléans. This paper thus argues that Gaston acquired about a fourth of the Duke of Buckingham’s collection of ancient gems and that he did so in Paris, during the Fronde. It also appears that Gaston selected the gems according to topics of interest. Many of the gems he acquired pertain (or might pertain) to political iconography (e.g. royal and imperial portraits featuring, in particular, Alexander the Great, as well as mythological scenes involving Hercules and Apollo). Such scenes are often engraved on prestigious and sizeable cameos. These images of power may reflect Gaston’s political ambitions at the time he bought his collection. Other gems selected by the duke include ‘erotic’ scenes and references to the pleasures of wine (e.g. depictions of female nudes and children’s bacchanalia). Finally, a third group of scenes show an interest in pagan religions (e.g. representations of Egyptian gods and scenes of sacrifice).

Published
2021
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48. To be is to be perceived, not to be is not to be perceived

Author

Guillaume Le Blanc

Subjects
visibility, invisibility, audibility, inaudibility, voice, ethics, Arts in general, NX1-820, English language, PE1-3729, English literature, PR1-9680
Abstract

Can we say that to be is to be perceived? Or that not to be is not to be perceived? Who decides who is to be visible or not? My contention is that invisibility is a social construction related to norms of apprehension, recognition and justification. Not seeing a person makes them absent, and precipitates them into social death. What happens when one is thus made invisible? Can one’s voice bring one back to life? And under what conditions is a silent voice still a living voice? Why is invisibility always attached to inaudibility? If losing one’s voice means losing one’s face, then keeping one’s voice, even when it is lost, allows an inner face to appear, a face that escapes from the eyes of others and is yet present. What is the future of this face?

Published
2021
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