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1. General vacuum stability of orbifold gauge breaking and application to asymptotic grand unification

Author

Cacciapaglia, Giacomo, Cornell, Alan S., Deandrea, Aldo, Isnard, Wanda, Pasechnik, Roman, Preda, Anca, and Wang, Zhi-Wei

Subjects
High Energy Physics - Phenomenology, High Energy Physics - Theory
Abstract

We examine the vacuum stability of gauge symmetry breaking in five dimensions, compactified on the $S_1/(\mathbb{Z}_2 \times \mathbb{Z}'_2)$ orbifold. We consider $SU(N)$, $Sp(N)$, $SO(2N)$ and $SO(2N+1)$ theories in the bulk, and provide an exhaustive classification of possible parity assignments that lead to stable orbifolds and of the corresponding symmetry breaking patterns. We use these results in the search for viable asymptotic grand unification theories (aGUT), testing the stability criteria on models based on $SU(6)$ and $SU(8)$. As a result, we identify two viable aGUTs: a unique $SU(6)$ pathway down to the Standard Model, and one $SU(8)$ model leading to an intermediate Pati-Salam partial unification., Comment: 44 pages, 4 figures

Published
2024

6. Advancing Wavefront Shaping with Resonant Nonlocal Metasurfaces: Beyond the Limitations of Lookup Tables

Author

Isnard, Enzo, Héron, Sébastien, Lanteri, Stéphane, and Elsawy, Mahmoud

Subjects
Physics - Optics, Physics - Applied Physics
Abstract

Resonant metasurfaces are of paramount importance in addressing the growing demand for reduced thickness and complexity, while ensuring high optical efficiency. This becomes particularly crucial in overcoming fabrication challenges associated with high aspect ratio structures, thereby enabling seamless integration of metasurfaces with electronic components at an advanced level. However, traditional design approaches relying on lookup tables and local field approximations often fail to achieve optimal performance, especially for nonlocal resonant metasurfaces. In this study, we investigate the use of statistical learning optimization techniques for nonlocal resonant metasurfaces, with a specific emphasis on the role of near-field coupling in wavefront shaping beyond single unit cell simulations. Our study achieves significant advancements in the design of resonant metasurfaces. For transmission-based metasurfaces, a beam steering design outperforms the classical design by achieving an impressive efficiency of 80\% compared to the previous 23%. Additionally, our optimized extended depth-of-focus (EDOF) metalens yields a remarkable five-fold increase in focal depth, a four-fold enhancement in focusing power compared to conventional designs and an optical resolution superior to 600 cycle/mm across the focus region. Moreover, our study demonstrates remarkable performance with a wavelength-selected beam steering metagrating in reflection, achieving exceptional efficiency surpassing 85\%. This far outperforms classical gradient phase distribution approaches, emphasizing the immense potential for groundbreaking applications in the field of resonant metasurfaces.

Published
2023

7. MMS19 and IFIH1 Host Genetic Variants Associate with SARS-CoV-2 Infection in Elderly Residents of Long-Term Care Facilities

Author

Sandra Franco, Macedonia Trigueros, Dolors Palacín, Josep Maria Bonet-Simó, Maria del Mar Isnard, Nemesio Moreno, Lourdes Mateu, Nuria Prat, Marta Massanella, and Miguel Angel Martinez

Subjects
SARS-CoV-2, infection susceptibility, host genetics, elderly, COVID-19, Specialties of internal medicine, RC581-951
Abstract

The coronavirus disease 2019 (COVID-19) pandemic has significantly affected older adults. Identifying host COVID-19 susceptibility genes in elderly populations remains a challenge. Here, we aimed to identify host genetic factors influencing the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We genotyped 12 single-nucleotide polymorphisms (SNPs) previously associated with the innate immune response in a total of 97 elderly (age > 65 years) residents of three long-term care facilities located in Barcelona, Spain. Individuals were PCR-tested during the SARS-CoV-2 outbreaks between September and November 2020. SARS-CoV-2 PCR tests revealed infections in 81 residents. Importantly, the 16 uninfected residents remained SARS-CoV-2 seronegative until vaccination (January and February 2021). After adjusting for sex and age, we found that two SNPs were significantly associated with SARS-CoV-2 infection susceptibility—MMS19 nucleotide excision repair protein homolog (MMS19)/rs2236575 (p = 0.029) and interferon-induced helicase C domain-containing 1 (IFIH1)/rs1990760 (p = 0.034). No association with SARS-CoV-2 infection was found for 10 additional genotyped SNPs, which included 4 SNPs on chromosome 12 in the gene encoding oligoadenylate synthetase (OAS). Our results indicate that MMS19/rs2236575_A and IFIH1/rs1990760_TC genetic variants were associated with a resistance to SARS-CoV-2 infection in a cohort of institutionalized seniors.

Published
2024
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8. Composite Hybrid Inflation: Dilaton and Waterfall Pions

Author

Cacciapaglia, Giacomo, Cheong, Dhong Yeon, Deandrea, Aldo, Isnard, Wanda, and Park, Seong Chan

Subjects
High Energy Physics - Phenomenology, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We investigate the possibility that inflation originates from a composite field theory, in terms of an effective chiral Lagrangian involving a dilaton and pions. The walking dynamics of the theory constrain the potential in a specific way, where the anomalous dimensions of operators involving pions play a crucial role. For realistic values of the anomalous dimensions, we find a successful hybrid inflation occurring via the dilaton-inflaton, with the pions acting as waterfall fields. Compositeness consistency strongly constrain the model, predicting a dilaton scale $f_\chi \sim \mathcal{O} (1)$ in unit of the Planck scale, an inflation scale $H_\text{inf} \sim 10^{10}$ GeV, and the pion scale around $10^{14}$ GeV. We further discuss possible phenomenological consequences of this theory., Comment: 14 pages, 4 figures

Published
2023

9. Influence of high pressure on the remarkable itinerant electron behaviour in Y$_{0.7}$Er$_{0.3}$Fe$_2$D$_{4.2}$ compounds

Author

Arnold, Z., Isnard, O., and Paul-Boncour, V.

Subjects
Condensed Matter - Materials Science
Abstract

Monoclinic Y$_{0.7}$Er$_{0.3}$Fe$_2$D$_{4.2}$ compound exhibits unusual magnetic properties with different field induced magnetic transitions. The deuteride is ferrimagnetic at low temperature and the Er and Fe sublattices present magnetic transitions at different temperatures. The Er moments are ordered below T$_{Er}$=55 K, whereas the Fe moments remain ferromagnetically coupled up to T$_{M0}$ = 66 K. At T$_{M0}$ the Fe moments display a sharp ferromagnetic-antiferromagnetic transition (FM-AFM) through an itinerant electron metamagnetic (IEM) behaviour very sensitive to any volume change. Y$_{0.7}$Er$_{0.3}$Fe$_2$D$_{4.2}$ becomes paramagnetic above T$_N$=125 K. The pressure dependence of T$_{Er}$ and T$_{M0}$ have been extracted from magnetic measurements under hydrostatic pressure up to 0.49 GPa. Both temperatures decrease linearly upon applied pressure with dT$_{Er}$/dP=-126 and dTM0/dP=-140 K.GPa$^{-1}$ for a field of B=0.03 T. Both magnetic Er and ferromagnetic Fe order disappear at P=0.44(4) GPa. However, under a larger applied field B=5 T, dT$_{M0}$/dP=-156 K.GPa$^{-1}$ whereas dT$_{Er}$/dP=-134 K.GPa$^{-1}$ showing a weaker sensitivity to pressure and magnetic field. At 2 K the decrease of the saturation magnetization under pressure can be attributed to a reduction of the mean Er moment due to canting and/or crystal field effect. Above T$_{M0}$ the magnetization curves display a metamagnetic behaviour from AFM to FM state, which is also very sensitive to the applied pressure. The transition field B$_{trans}$, which increases linearly upon heating, is shifted to lower temperature upon applied pressure with dT=-17 K between 0 and 0.11 GPa. These results show a strong decoupling of the Er and Fe magnetic sublattices versus temperature, applied field and pressure., Comment: 24 pages, 10 figures, 1 tables

Published
2023
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10. Male genitourinary schistosomiasis-related symptoms among long-term Western African migrants in Spain: a prospective population-based screening study

Author

Roure, Sílvia, Vallès, Xavier, Pérez-Quílez, Olga, López-Muñoz, Israel, Chamorro, Anna, Abad, Elena, Valerio, Lluís, Soldevila, Laura, España, Sergio, Hegazy, Alaa H. A., Fernández-Rivas, Gema, Gorriz, Ester, Herena, Dolores, Oliveira, Mário, Miralles, Maria Carme, Conde, Carmen, Montero-Alia, Juan José, Fernández-Pedregal, Elia, Miranda-Sánchez, Jose, Llibre, Josep M., Isnard, Mar, Bonet, Josep Maria, Estrada, Oriol, Prat, Núria, and Clotet, Bonaventura

Published
2024
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12. Hidden Supersymmetric Dark Sectors

Author

Cacciapaglia, Giacomo, Deandrea, Aldo, and Isnard, Wanda

Subjects
High Energy Physics - Phenomenology, High Energy Physics - Theory
Abstract

The attractive feature of supersymmetry is predictive power, due to the large number of calculable properties and to coupling non-renormalisation. This power can be fully expressed in hidden sectors where supersymmetry may be exact, as these sectors are secluded from the visible one where instead supersymmetry must be broken. This suggests a new paradigm for supersymmetric dark sectors, where supersymmetry is exact at the dark matter scale, implying that many properties of hidden supersymmetric dark sectors can be fully computed. As a proof of concept we discuss a concrete example based on $\mathcal{N}=1$ super Yang-Mills., Comment: 4 pages, 3 figures. Supplementary material appended to the main text

Published
2023

13. On Computing Large Temporal (Unilateral) Connected Components

Author

Costa, Isnard Lopes, Lopes, Raul, Marino, Andrea, and Silva, Ana

Subjects
Mathematics - Combinatorics
Abstract

A temporal (directed) graph is a graph whose edges are available only at specific times during its lifetime, $\tau$. Paths are sequences of adjacent edges whose appearing times are either strictly increasing or non-strictly increasingly (i.e., non-decreasing) depending on the scenario. Then, the classical concept of connected components and also of unilateral connected components in static graphs and digraphs naturally extends to the temporal setting. In this paper, we answer to the following fundamental questions in temporal graphs. (i) What is the complexity of deciding the existence of a component of size $k$, parameterized by $\tau$, by $k$, and by $k+\tau$? We show that this question has a different answer depending on the considered definition of component and whether the temporal graph is directed or undirected. (ii) What is the minimum running time required to check whether a subset of vertices are pairwise reachable? A quadratic algorithm is known but, contrary to the static case, we show that a better running time is unlikely unless SETH fails. (iii) Is it possible to verify whether a subset of vertices is a component in polynomial time? We show that depending on the definition of temporal component this test is NP-complete.

Published
2023

14. Diet at birth is critical for healthy growth, independent of effects on the gut microbiota

Author

Lieke J. W. van den Elsen, Akila Rekima, Miriam A. Lynn, Charlotte Isnard, Savannah Machado, Nivedithaa Divakara, Diana Patalwala, Alana Middleton, Natalie Stevens, Florence Servant, Remy Burcelin, David J. Lynn, and Valerie Verhasselt

Subjects
Growth hormone resistance, Neonatal microbiota, Growth failure, Breast milk, Colostrum, Microbial ecology, QR100-130
Abstract

Abstract Background Colostrum is the first milk for a newborn. Its high content in microbiota shaping compounds and its intake at the time of gut microbiota seeding suggests colostrum may be critical in the establishment of a healthy microbiota. There is also accumulating evidence on the importance of the gut microbiota for healthy growth. Here, we aimed to investigate the contribution of colostrum, and colostrum-induced microbiota to growth promotion. Addressing this question is highly significant because (1) globally, less than half of the newborns are fully colostrum fed (2) the evidence for the importance of the microbiota for the prevention of undernutrition has only been demonstrated in juvenile or adult pre-clinical models while stunting already starts before weaning. Results To address the importance of diet at birth in growth failure, we developed a unique mouse model in which neonates are breastfed by mothers at an advanced stage of lactation who no longer provide colostrum. Feeding newborn mice with mature milk instead of colostrum resulted in significant growth retardation associated with the biological features of chronic undernutrition, such as low leptin levels, dyslipidemia, systemic inflammation, and growth hormone resistance. We next investigated the role of colostrum in microbiota shaping. At the end of the lactation period, we found a major difference in gut microbiota alpha diversity, beta diversity, and taxa distribution in control and colostrum-deprived mice. To determine the causal relationship between changes in microbiota and growth trajectories, we repeated our experiment in germ-free mice. The beneficial effect of colostrum on growth remained in the absence of microbiota. Conclusion Our data suggest that colostrum may play an important role in the prevention of growth failure. They highlight that the interplay between neonatal gut microbiome assembly and diet may not be as crucial for growth control in the developing newborn as described in young adults. This opens a paradigm shift that will foster research for colostrum’s bioactives that may exert a similar effect to microbiota-derived ligands in promoting growth and lead to new avenues of translational research for newborn-tailored prevention of stunting. Video Abstract

Published
2024
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15. Pregnancy and cardiac maternal outcomes in women with inherited cardiomyopathy: interest of the CARPREG II risk score

Author

Thomas Wallet, Lise Legrand, Richard Isnard, Estelle Gandjbakhch, Françoise Pousset, Julie Proukhnitzky, Marc Dommergues, Jacky Nizard, and Philippe Charron

Subjects
Cardiomyopathy, Pregnancy, Prognosis, Risk score, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aims Inherited cardiomyopathies are relatively rare but carry a high risk of cardiac maternal morbidity and mortality during pregnancy and postpartum. However, data for risk stratification are scarce. The new CARPREG II score improves prediction of prognosis in pregnancies associated with heart disease, though its role in inherited cardiomyopathies is unclear. We aim to describe characteristics and cardiac maternal outcomes in patients with inherited cardiomyopathy during pregnancy, and to evaluate the interest of the CARPREG II risk score in this population. Methods and results In this retrospective single‐centre study, 90 consecutive pregnancies in 74 patients were included (mean age 32 ± 5 years), including 28 cases of dilated cardiomyopathy (DCM), 46 of hypertrophic cardiomyopathy, 11 of arrhythmogenic right ventricular cardiomyopathy and 5 of left ventricular noncompaction, excluding peripartum cardiomyopathy. The discriminatory power of several risk scores was assessed by the area under the receiver‐operating characteristic curve (AUC). Median CARPREG II score was 2 [0;3] and was higher in the DCM subgroup. A severe cardiac maternal complication was observed in 18 (20%) pregnancies, mainly driven by arrhythmia and heart failure (each event in 10 pregnancies), with 3 cardiovascular deaths. Forty‐three pregnancies (48%) presented foetal/neonatal complications (18 premature delivery, 3 foetal/neonatal death). CARPREG II was significantly associated with cardiac maternal complications (P

Published
2024
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16. Development and validation of algorithms to predict left ventricular ejection fraction class from healthcare claims data

Author

Damien Logeart, Maxime Doublet, Margaux Gouysse, Thibaud Damy, Richard Isnard, and François Roubille

Subjects
Machine learning, Heart failure, Left ventricular ejection fraction, Claims database, Registry records, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aims The use of large medical or healthcare claims databases is very useful for population‐based studies on the burden of heart failure (HF). Clinical characteristics and management of HF patients differ according to categories of left ventricular ejection fraction (LVEF), but this information is often missing in such databases. We aimed to develop and validate algorithms to identify LVEF in healthcare databases where the information is lacking. Methods and results Algorithms were built by machine learning with a random forest approach. Algorithms were trained and reinforced using the French national claims database [Système National des Données de Santé (SNDS)] and a French HF registry. Variables were age, gender, and comorbidities, which could be identified by medico‐administrative code‐based proxies, Anatomical Therapeutic Chemical codes for drug delivery, International Classification of Diseases (Tenth Revision) coding for hospitalizations, and administrative codes for any other type of reimbursed care. The algorithms were validated by cross‐validation and against a subset of the SNDS that includes LVEF information. The areas under the receiver operating characteristic curve were 0.84 for the algorithm identifying LVEF ≤ 40% and 0.79 for the algorithms identifying LVEF

Published
2024
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17. Male genitourinary schistosomiasis-related symptoms among long-term Western African migrants in Spain: a prospective population-based screening study

Author

Sílvia Roure, Xavier Vallès, Olga Pérez-Quílez, Israel López-Muñoz, Anna Chamorro, Elena Abad, Lluís Valerio, Laura Soldevila, Sergio España, Alaa H. A. Hegazy, Gema Fernández-Rivas, Ester Gorriz, Dolores Herena, Mário Oliveira, Maria Carme Miralles, Carmen Conde, Juan José Montero-Alia, Elia Fernández-Pedregal, Jose Miranda-Sánchez, Josep M. Llibre, Mar Isnard, Josep Maria Bonet, Oriol Estrada, Núria Prat, Bonaventura Clotet, and The Schisto-Stop study group

Subjects
Schistosomiasis, Chronic schistosomiasis, Urogenital schistosomiasis, Male genital schistosomiasis, Long-term migrant, Infectious and parasitic diseases, RC109-216, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Schistosomiasis is highly endemic in sub-Saharan Africa and frequently imported to Europe. Male urogenital manifestations are often neglected. We aimed to ascertain the prevalence of genitourinary clinical signs and symptoms among long-term African migrants in a non-endemic European country using a serology test. Methods We carried out a prospective, community-based cross-sectional study of adult male migrants from sub-Saharan Africa living in Spain. Schistosoma serology tests and microscopic urine examinations were carried out, and clinical data were obtained from an electronic medical record search and a structured questionnaire. Results We included 388 adult males, mean age 43.5 years [Standard Deviation (SD) = 12.0, range: 18–76]. The median time since migration to the European Union was 17 [Interquartile range (IQR): 11–21] years. The most frequent country of origin was Senegal (N = 179, 46.1%). Of the 338, 147 (37.6%) tested positive for Schistosoma. Parasite eggs were present in the urine of only 1.3%. Nine genitourinary clinical items were significantly associated with positive Schistosoma serology results: pelvic pain (45.2%; OR = 1.57, 95% CI: 1.0–2.4), pain on ejaculation (14.5%; OR = 1.85, 95% CI: 1.0–3.5), dyspareunia (12.4%; OR = 2.45, 95% CI: 1.2–5.2), erectile dysfunction (9.5%; OR = 3.10, 95% CI: 1.3–7.6), self-reported episodes of infertility (32.1%; OR = 1.69, 95% CI: 1.0–2.8), haematuria (55.2%; OR = 2.37, 95% CI: 1.5–3.6), dysuria (52.1%; OR = 2.01, 95% CI: 1.3–3.1), undiagnosed syndromic STIs (5.4%), and orchitis (20.7%; OR = 1.81, 95% CI: 1.0–3.1). Clinical signs tended to cluster. Conclusions Urogenital clinical signs and symptoms are prevalent among male African long-term migrants with a positive Schistosoma serology results. Genital involvement can be frequent even among those with long periods of non-residence in their sub-Saharan African countries of origin. Further research is needed to develop diagnostic tools and validate therapeutic approaches to chronic schistosomiasis. Graphical Abstract

Published
2024
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19. Public perception vs ecological quality status: Examining the ecological restoration of the Congost River's Environment

Author

Quim Zaldo-Aubanell, Antoni Mas-Ponce, Guiu Asbert, Berta Clota, Manel Isnard, Lorenzo Proia, Albert Bach, and Sònia Sànchez Mateo

Subjects
Ecological indicators, Public perception, Sociodemographic groups, Survey analysis, Environmental restoration strategies, Environmental attitudes, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

This study examines the public's perceptions of the ecological restoration of the Congost River over the past thirty years, focusing on the period between 2010 and 2022. We conducted a survey of 112 river users across five key zones identified through a pilot study for their high pedestrian density, aiming to analyse how different sociodemographic groups perceive the river's ecological state. A structured questionnaire was distributed along both sides of the river to engage a diverse range of individuals typically utilizing the river environment. The collected data were analysed using regression models and Mann-Whitney U tests to assess differences between groups, with Bonferroni adjustments applied to control for multiple comparisons.The results reveal a broad increase in appreciation for the river since 2010, alongside measurable ecological improvements supported by scientific data. Despite these positive changes, a majority of surveyed users remain sceptical about the river's recovery, with less pronounced scepticism among older respondents, those with higher education, and environmental volunteers. These groups' perceptions align more closely with empirical evidence, highlighting the influence of sociodemographic factors on environmental awareness.Individuals living closer to natural settings and frequent river visitors were found to be more attuned to changes in the river's environment, particularly in aesthetic and sensory aspects. The study underscores the persistence of a perceptual gap between scientific assessments of ecological health and public sentiment, emphasizing the complex relationship between community perceptions and objective environmental indicators. These insights underline the complex relationship between community perceptions and objective environmental indicators, reflecting a broader trend in environmental awareness and the importance of factual communication in ecological issues.

Published
2024
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20. Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Author

Barbara Wanjiru Citarella, Christiana Kartsonaki, Elsa D. Ibáñez-Prada, Bronner P. Gonçalves, Joaquin Baruch, Martina Escher, Mark G. Pritchard, Jia Wei, Fred Philippy, Andrew Dagens, Matthew Hall, James Lee, Demetrios James Kutsogiannis, Evert-Jan Wils, Marília Andreia Fernandes, Bharath Kumar Tirupakuzhi Vijayaraghavan, Prasan Kumar Panda, Ignacio Martin-Loeches, Shinichiro Ohshimo, Arie Zainul Fatoni, Peter Horby, Jake Dunning, Jordi Rello, Laura Merson, Amanda Rojek, Michel Vaillant, Piero Olliaro, Luis Felipe Reyes, S.A. Moharam, Sabriya Abdalasalam, Alaa Abdalfattah Abdalhadi, Naana Reyam Abdalla, Walaa Abdalla, Almthani Hamza Abdalrheem, Ashraf Abdalsalam, Saedah Abdeewi, Esraa Hassan Abdelgaum, Mohamed Abdelhalim, Mohammed Abdelkabir, Israa Abdelrahman, Sheryl Ann Abdukahil, Lamees Adil Abdulbaqi, Salaheddin Abdulhamid, Widyan Abdulhamid, Nurul Najmee Abdulkadir, Eman Abdulwahed, Rawad Abdunabi, Ryuzo Abe, Laurent Abel, Ahmed Mohammed Abodina, Amal Abrous, Lara Absil, Kamal Abu Jabal, Nashat Abu Salah, Abdurraouf Abusalama, Tareg Abdallah Abuzaid, Subhash Acharya, Andrew Acker, Elisabeth Adam, Safia Adem, Manuella Ademnou, Francisca Adewhajah, Diana Adrião, Anthony Afum-Adjei Awuah, Melvin Agbogbatey, Saleh Al Ageel, Aya Mustafa Ahmed, Musaab Mohammed Ahmed, Shakeel Ahmed, Zainab Ahmed Alaraji, Abdulrahman Ahmed Elhefnawy Enan, Reham Abdelhamid Ahmed Khalil, Ali Mostafa Ahmed Mohamed Abdelaziz, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Aisha, Bugila Aisha, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Chika Akwani, Eman Al Qasim, Ahmed Alajeeli, Ahmed Alali, Razi Alalqam, Aliya Mohammed Alameen, Mohammed Al-Aquily, Zinah A. Alaraji, Khalid Albakry, Safa Albatni, Angela Alberti, Osama Aldabbourosama, Tala Al-dabbous, Amer Aldhalia, Abdulkarim Aldoukali, Senthilkumar Alegesan, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Asil Alflite, Huda Alfoudri, Qamrah Alhadad, Hoda Salem Alhaddad, Maali Khalid Mohamed Abdalla Alhasan, Ahmad Nabil Alhouri, Hasan Alhouri, Adam Ali, Imran Ali, Maha TagElser Mohammed Ali, Syed Ali Abbas, Yomna Ali Abdelghafar, Naseem Ali Sheikh, Kazali Enagnon Alidjnou, Mahmoud Aljadi, Sarah Aljamal, Mohammed Alkahlout, Akram Alkaseek, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Lana Almasri, Abdulrahman Almjersah, Raja Ahmed Alqandouz, Walaa Alrfaea, Moayad Alrifaee, Rawan Alsaadi, Yousef Al-Saba'a, Entisar Alshareea, Eslam Alshenawy, Aneela Altaf, João Melo Alves, João Alves, Rita Alves, Joana Alves Cabrita, Maria Amaral, Amro Essam Amer, Nur Amira, Amos Amoako Adusei, John Amuasi, Roberto Andini, Claire Andrejak, Andrea Angheben, François Angoulvant, Sophia Ankrah, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Elizabeth A. Ashley, Muhammad Ashraf, Muhammad Sheharyar Ashraf, Abir Ben Ashur, Franklin Asiedu-Bekoe, Namra Asif, Mohammad Asim, Grace Assi, Jean Baptiste Assie, Amirul Asyraf, Fouda Atangana, Ahmed Atia, Minahel Atif, Asia Atif Abdelrhman Abdallahrs, Anika Atique, Moad Atlowly, AM Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Abdelmalek Awad Ali Mohammed, Eyvind W. Axelsen, Ared Ayad, Ahmed Ayman Hassan Helmi, Laurène Azemar, Mohammed Azizeldin, Cecile Azoulay, Hakeem Babatunde, Benjamin Bach, Delphine Bachelet, Claudine Badr, Roar Bævre-Jensen, Nadia Baig, John Kenneth Baillie, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Hibah Bileid Bakeer, Ashraf Bakri, Andriy Bal, Mohanaprasanth Balakrishnan, Irene Bandoh, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S. Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Cleide Barrigoto, Marie Bartoli, Joaquín Baruch, Romain Basmaci, Muhammad Fadhli Hassin Basri, AbdAlkarim Batool, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Abigail Beane, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Lamis Berdeweel, Delphine Bergeaud, Hazel Bergin, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Isabella Bianchi, Claudia Bianco, Sandra Bichoka, Farah Nadiah Bidin, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, Muhannud Binnawara, Zeno Bisoffi, Patrick Biston, Laurent Bitker, Mustapha Bittaye, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Debby Bogaert, Anne-Hélène Boivin, Ariel Bolanga, Isabela Bolaños, Pierre-Adrien Bolze, François Bompart, Aurelius Bonifasius, Joe Bonney, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Latsaniphone Bountthasavong, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Marielle Boyer-Besseyre, Maria Boylan, Fernando Augusto Bozza, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Dorothy Breen, Patrick Breen, David Brewster, Kathy Brickell, Tessa Broadley, Helen Brotherton, Alex Browne, Nicolas Brozzi, Sonja Hjellegjerde Brunvoll, Marjolein Brusse-Keizer, Petra Bryda, Nina Buchtele, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Donald Buri, Aidan Burrell, Ingrid G. Bustos, Denis Butnaru, André Cabie, Susana Cabral, Joana Cabrita, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Janice Caoili, Pauline Caraux-Paz, Sheila Cárcel, Filipa Cardoso, Filipe Cardoso, Nelson Cardoso, Sofia Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Gail Carson, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Masaneh Ceesay, Shelby Cerkovnik, Minerva Cervantes-Gonzalez, Muge Cevik, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Jean-Marc Chapplain, Charlotte Charpentier, Julie Chas, Muhammad Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Léo Chenard, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Danoy Chommanam, Marie-Charlotte Chopin, Yock Ping Chow, Ting Soo Chow, Nathaniel Christy, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Rolando Claure-Del Granado, Sara Clohisey, Cassidy Codan, Caitriona Cody, Jennifer Coles, Megan Coles, Gwenhaël Colin, Michael Collins, Pamela Combs, Jennifer Connolly, Marie Connor, Anne Conrad, Elaine Conway, Graham S. Cooke, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Juthaporn Cowan, Rachel Cregan, Gloria Crowl, Jonathan Crump, Claudina Cruz, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, John Arne Dahl, Darren Dahly, Umberto D'Alessandro, Peter Daley, Zaina Dalloul, Heidi Dalton, Jo Dalton, Seamus Daly, Juliana Damas, Joycelyn Dame, Cammandji Damien, Nick Daneman, Jorge Dantas, Frédérick D'Aragon, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Bianca DeBenedictis, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Romain Decours, Eve Defous, Isabelle Delacroix, Alexandre Delamou, Eric Delaveuve, Karen Delavigne, Nathalie M. Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhangar, Alpha Diallo, Souleymane Taran Diallo, Sylvain Diamantis, André Dias, Fernanda Dias Da Silva, Rodrigo Diaz, Juan Jose Diaz, Priscila Diaz, Bakary K. Dibba, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Cedric Djadda, Félix Djossou, Annemarie B. Docherty, Helen Doherty, Arjen M. Dondorp, Christl A. Donnelly, Yoann Donohue, Sean Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, Yash Doshi, Phouvieng Douangdala, James Joshua Douglas, Renee Douma, Nathalie Dournon, Joanne Downey, Mark Downing, Thomas Drake, Aoife Driscoll, Ibrahim Kwaku Duah, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Audrey Dubot-Pérès, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, III, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Ada Ebo, Marco Echeverria-Villalobos, Michael Edelstein, Siobhan Egan, Linn Margrete Eggesbø, Khadeja Ehzaz, Carla Eira, Mohammed El Sanharawi, Marwan El Sayed, Mohammed Elabid, Mohamed Bashir Elagili, Subbarao Elapavaluru, Mohammad Elbahnasawy, Sohail Elboshra, Brigitte Elharrar, Jacobien Ellerbroek, Merete Ellingjord-Dale, Hamida ELMagrahi, Mohammad Muatasm Elmubark, Loubna Elotmani, Lauren Eloundou, Philippine Eloy, Basma Elshaikhy, Tarek Elshazly, Wafa Elsokni, Aml Ahmed Eltayeb, Iqbal Elyazar, Zarief Kamel Emad, Hussein Embarek, Isabelle Enderle, Tomoyuki Endo, Gervais Eneli, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Haneen Esaadi, Mariano Esperatti, Hélène Esperou, Catarina Espírito Santo, Marina Esposito-Farese, Rachel Essaka, Lorinda Essuman, João Estevão, Manuel Etienne, Anna Greti Everding, Mirjam Evers, Isabelle Fabre, Marc Fabre, Ismaila Fadera, Asgad Osman Abdalla Fadlalla, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Mohamed Fathi, Salem Fatima, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Jorge Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Benigno Ferreira, Isabel Ferreira, Bernardo Ferreira, Sílvia Ferreira, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Thomas Flament, Tom Fletcher, Aline-Marie Florence, Letizia Lucia Florio, Brigid Flynn, Deirdre Flynn, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Karen Forrest, Simon Forsyth, Denise Foster, Giuseppe Foti, Berline Fotso, Erwan Fourn, Robert A. Fowler, Marianne Fraher, Diego Franch-Llasat, Christophe Fraser, John F. Fraser, Marcela Vieira Freire, Ana Freitas Ribeiro, Craig French, Caren Friedrich, Ricardo Fritz, Stéphanie Fry, Nora Fuentes, Masahiro Fukuda, G. Argin, Valérie Gaborieau, Rostane Gaci, Massimo Gagliardi, Jean-Charles Gagnard, Amandine Gagneux-Brunon, Abdou Gai, Sérgio Gaião, Linda Gail Skeie, Adham Mohamed Galal Mohamed Ramadan, Phil Gallagher, Carrol Gamble, Yasmin Gani, Arthur Garan, Rebekha Garcia, Julia Garcia-Diaz, Esteban Garcia-Gallo, Navya Garimella, Denis Garot, Valérie Garrait, Basanta Gauli, Anatoliy Gavrylov, Alexandre Gaymard, Johannes Gebauer, Eva Geraud, Louis Gerbaud Morlaes, Nuno Germano, Malak Ghemmeid, Praveen Kumar Ghisulal, Jade Ghosn, Marco Giani, Tristan Gigante, Elaine Gilroy, Guillermo Giordano, Michelle Girvan, Valérie Gissot, Gezy Giwangkancana, Daniel Glikman, Petr Glybochko, Eric Gnall, Geraldine Goco, François Goehringer, Siri Goepel, Jean-Christophe Goffard, Jin Yi Goh, Brigitta Golács, Jonathan Golob, Kyle Gomez, Joan Gómez-Junyent, Marie Gominet, Alicia Gonzalez, Patricia Gordon, Isabelle Gorenne, Laure Goubert, Cécile Goujard, Tiphaine Goulenok, Margarite Grable, Jeronimo Graf, Edward Wilson Grandin, Pascal Granier, Giacomo Grasselli, Lorenzo Grazioli, Christopher A. Green, Courtney Greene, William Greenhalf, Segolène Greffe, Domenico Luca Grieco, Matthew Griffee, Fiona Griffiths, Ioana Grigoras, Albert Groenendijk, Fassou Mathias Grovogui, Heidi Gruner, Yusing Gu, Jérémie Guedj, Martin Guego, Anne-Marie Guerguerian, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Maisa Guimarães de Castro, Thomas Guimard, Marieke Haalboom, Daniel Haber, Ali Hachemi, Abdurrahman Haddud, Nadir Hadri, Wael Hafez, Fakhir Raza Haidri, Fatima Mhd Rida Hajij, Sheeba Hakak, Adam Hall, Sophie Halpin, Shaher Hamdan, Abdelhafeez Hamdi, Jawad Hameed, Ansley Hamer, Raph L. Hamers, Rebecca Hamidfar, Bato Hammarström, Naomi Hammond, Terese Hammond, Lim Yuen Han, Matly Hanan, Rashan Haniffa, Kok Wei Hao, Hayley Hardwick, Ewen M. Harrison, Janet Harrison, Samuel Bernard Ekow Harrison, Alan Hartman, Sulieman Hasan, Mohammad Ali Nabil Hasan, Mohd Shahnaz Hasan, Junaid Hashmi, Madiha Hashmi, Amoni Hassan, Ebtisam Hassanin, Muhammad Hayat, Ailbhe Hayes, Leanne Hays, Jan Heerman, Lars Heggelund, Ahmed Helmi, Ross Hendry, Martina Hennessy, Aquiles Rodrigo Henriquez-Trujillo, Maxime Hentzien, Diana Hernandez, Andrew Hershey, Liv Hesstvedt, Astarini Hidayah, Eibhlin Higgins, Rupert Higgins, Samuel Hinton, Hiroaki Hiraiwa, Haider Hirkani, Hikombo Hitoto, Antonia Ho, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Oscar Hoiting, Rebecca Holt, Jan Cato Holter, Juan Pablo Horcajada, Ikram Houas, Mabrouka Houderi, Catherine L. Hough, Stuart Houltham, Jimmy Ming-Yang Hsu, Jean-Sébastien Hulot, Abby Hurd, Iqbal Hussain, Aliae Mohamed Hussein, Mahmood Hussein, Fatima Ibrahim, Bashir Ibran, Samreen Ijaz, M. Arfan Ikram, Carlos Cañada Illana, Patrick Imbert, Muhammad Imran Ansari, Rana Imran Sikander, Hugo Inácio, Carmen Infante Dominguez, Yun Sii Ing, Mariachiara Ippolito, Vera Irawany, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Mette Stausland Istre, Junji Itai, Daniel Ivulich, Danielle Jaafar, Salma Jaafoura, Hamza Jaber, Julien Jabot, Clare Jackson, Abubacarr Jagne, Stéphane Jaureguiberry, Denise Jaworsky, Florence Jego, Anilawati Mat Jelani, Synne Jenum, Ruth Jimbo-Sotomayor, Ong Yiaw Joe, Ruth Noemí Jorge García, Silje Bakken Jørgensen, Cédric Joseph, Mark Joseph, Swosti Joshi, Mercé Jourdain, Philippe Jouvet, Anna Jung, Hanna Jung, Dafsah Juzar, Ouifiya Kafif, Florentia Kaguelidou, Neerusha Kaisbain, Thavamany Kaleesvran, Sabina Kali, Karl Trygve Kalleberg, Smaragdi Kalomoiri, Muhammad Aisar Ayadi Kamaluddin, Armand Saloun Kamano, Zul Amali Che Kamaruddin, Nadiah Kamarudin, Kavita Kamineni, Darshana Hewa Kandamby, Kong Yeow Kang, Darakhshan Kanwal, Dyah Kanyawati, Mohamed Karghul, Pratap Karpayah, Todd Karsies, Daisuke Kasugai, Kevin Katz, Christy Kay, Lamees Kayyali, Seán Keating, Pulak Kedia, Andrea Kelly, Aoife Kelly, Claire Kelly, Niamh Kelly, Sadie Kelly, Yvelynne Kelly, Maeve Kelsey, Kalynn Kennon, Sommay Keomany, Maeve Kernan, Younes Kerroumi, Sharma Keshav, Shams Khail, Sarah Khaled, Imrana Khalid, Antoine Khalil, Irfan Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Krish Kherajani, Michelle E. Kho, Denisa Khoo, Ryan Khoo, Saye Khoo, Muhammad Nasir Khoso, Amin Khuwaja, Khor How Kiat, Yuri Kida, Peter Kiiza, Beathe Kiland Granerud, Anders Benjamin Kildal, Jae Burm Kim, Antoine Kimmoun, Detlef Kindgen-Milles, Nobuya Kitamura, Eyrun Floerecke Kjetland Kjetland, Paul Klenerman, Rob Klont, Gry Kloumann Bekken, Stephen R. Knight, Robin Kobbe, Paa Kobina Forson, Chamira Kodippily, Malte Kohns Vasconcelos, Sabin Koirala, Mamoru Komatsu, Franklina Korkor Abebrese, Volkan Korten, Stephanie Kouba, Mohamed Lamine Kourouma, Karifa Kourouma, Arsène Kpangon, Karolina Krawczyk, Ali Kredan, Vinothini Krishnan, Sudhir Krishnan, Oksana Kruglova, Anneli Krund, Pei Xuan Kuan, Ashok Kumar, Deepali Kumar, Ganesh Kumar, Mukesh Kumar, Dinesh Kuriakose, Ethan Kurtzman, Demetrios Kutsogiannis, Galyna Kutsyna, Ama Kwakyewaa Bedu-Addo, Sylvie Kwedi, Konstantinos Kyriakoulis, Marie Lachatre, Marie Lacoste, John G. Laffey, Nadhem Lafhej, Marie Lagrange, Fabrice Laine, Olivier Lairez, Sanjay Lakhey, Marc Lambert, François Lamontagne, Marie Langelot-Richard, Vincent Langlois, Eka Yudha Lantang, Marina Lanza, Cédric Laouénan, Samira Laribi, Delphine Lariviere, Stéphane Lasry, Sakshi Lath, Naveed Latif, Youssef Latifeh, Odile Launay, Didier Laureillard, Yoan Lavie-Badie, Andy Law, Cassie Lawrence, Teresa Lawrence, Minh Le, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Ema Leal, Marta Leal Santos, Biing Horng Lee, Heng Gee Lee, Su Hwan Lee, Jennifer Lee, Todd C. Lee, Yi Lin Lee, Gary Leeming, Bénédicte Lefebvre, Laurent Lefebvre, Benjamin Lefèvre, Sylvie LeGac, Merili-Helen Lehiste, Jean-Daniel Lelievre, François Lellouche, Adrien Lemaignen, Véronique Lemee, Anthony Lemeur, Gretchen Lemmink, Ha Sha Lene, Jenny Lennon, Rafael León, Marc Leone, Tanel Lepik, Quentin Lepiller, François-Xavier Lescure, Olivier Lesens, Mathieu Lesouhaitier, Amy Lester-Grant, Andrew Letizia, Sophie Letrou, Bruno Levy, Yves Levy, Claire Levy-Marchal, Katarzyna Lewandowska, Erwan L'Her, Gianluigi Li Bassi, Janet Liang, Ali Liaquat, Geoffrey Liegeon, Kah Chuan Lim, Wei Shen Lim, Chantre Lima, Bruno Lina, Lim Lina, Andreas Lind, Maja Katherine Lingad, Guillaume Lingas, Sylvie Lion-Daolio, Keibun Liu, Marine Livrozet, Patricia Lizotte, Antonio Loforte, Navy Lolong, Leong Chee Loon, Diogo Lopes, Dalia Lopez-Colon, Anthony L. Loschner, Paul Loubet, Bouchra Loufti, Guillame Louis, Silvia Lourenco, Lara Lovelace-Macon, Lee Lee Low, Marije Lowik, Jia Shyi Loy, Jean Christophe Lucet, Carlos M. Luna, Olguta Lungu, Miles Lunn, Liem Luong, Nestor Luque, Dominique Luton, Olavi Maasikas, Moïse Machado, Sara Machado, Gabriel Macheda, Mustafa Magzoub, Rafael Mahieu, Sophie Mahy, Ana Raquel Maia, Lars S. Maier, Oumou Maiga Ascofare, Mylène Maillet, Thomas Maitre, Nimisha Abdul Majeed, Maximilian Malfertheiner, Nadia Malik, Paddy Mallon, Fernando Maltez, Denis Malvy, Victoria Manda, Laurent Mandelbrot, Frank Manetta, Julie Mankikian, Edmund Manning, Aldric Manuel, Veronika Maráczi, Ceila Maria Sant′Ana Malaque, Flávio Marino, Samuel Markowicz, Ana Marques, Catherine Marquis, Laura Marsh, Brian Marsh, Megan Marshal, John Marshall, Celina Turchi Martelli, Dori-Ann Martin, Emily Martin, Guillaume Martin-Blondel, Alessandra Martinelli, F. Eduardo Martinez, Martin Martinot, Alejandro Martín-Quiros, Ana Martins, João Martins, Nuno Martins, Caroline Martins Rego, Gennaro Martucci, Olga Martynenko, Eva Miranda Marwali, Marsilla Marzukie, David Maslove, Sabina Mason, Sobia Masood, Fatma Masoud, Moise Massoma, Palmer Masumbe, Mohd Basri Mat Nor, Moshe Matan, Henrique Mateus Fernandes, Meghena Mathew, Christina Mathew, Mathieu Mattei, Laurence Maulin, Juergen May, Javier Maynar, Mayfong Mayxay, Thierry Mazzoni, Lisa Mc Sweeney, Colin McArthur, Naina McCann, Peter McCanny, Aine McCarthy, Anne McCarthy, Colin McCloskey, Rachael McConnochie, Sherry McDermott, Sarah E. McDonald, Aine McElroy, Samuel McElwee, Natalie McEvoy, Allison McGeer, Kenneth A. McLean, Paul McNally, Bairbre McNicholas, Edel Meaney, Cécile Mear-Passard, Maggie Mechlin, Nastia Medombou, Omar Mehkri, Ferruccio Mele, Luis Melo, Kashif Ali Memon, João João Mendes, Ogechukwu Menkiti, Kusum Menon, France Mentré, Alexander J. Mentzer, Emmanuelle Mercier, Noémie Mercier, Antoine Merckx, Mayka Mergeay-Fabre, Blake Mergler, António Mesquita, Roberta Meta, Osama Metwally, Agnès Meybeck, Dan Meyer, Alison M. Meynert, Vanina Meysonnier, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Efstathia Mihelis, Vladislav Mihnovit, Duha Milad Abdullah, Jennene Miller, Hugo Miranda-Maldonado, Nor Arisah Misnan, Nik Nur Eliza Mohamed, Nouralsabah Mohamed, Tahira Jamal Mohamed, Alaa Mohamed Ads, Ahmed Reda Mohamed Elsayed Abdelhalim, Libya Mohammed, Shrouk Fawze Mohammed Mostafa, Manahil Omer Abdelrahman Mohammedahmed, Omer Abdullah Mohammedelhassan, Asma Moin, Walaa Mokhtar, Elena Molinos, Brenda Molloy, Mary Mone, Agostinho Monteiro, Claudia Montes, Giorgia Montrucchio, Sarah Moore, Shona C. Moore, Lina Morales Cely, Marwa Morgom, Lucia Moro, Catherine Motherway, Ana Motos, Hugo Mouquet, Clara Mouton Perrot, Julien Moyet, Suleiman Haitham Mualla, Mohamed Muftah, Aisha Kalsoom Mufti, Ng Yong Muh, Mo'nes Muhaisen, Dzawani Muhamad, Jimmy Mullaert, Fredrik Müller, Karl Erik Müller, Daniel Munblit, Syed Muneeb Ali, Nadeem Munir, Laveena Munshi, Aisling Murphy, Patrick Murray, Marlène Murris, Srinivas Murthy, Himed Musaab, Alamin Mustafa, Mus'ab Mustafa, Dana Mustafa, Himasha Muvindi, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Behzad Nadjm, Dave Nagpal, Alex Nagrebetsky, Blanka Nagybányai-Nagy, Herwin Nanda Boudoin, Mangala Narasimhan, Nageswaran Narayanan, Prashant Nasa, Rashid Nasim Khan, Ahmad Nasrallah, Adel Gerges Nassif Metri, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Nikita Nekliudov, Matthew Nelder, Erni Nelwan, Raul Neto, Emily Neumann, Wing Yiu Ng, Pauline Yeung Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Nerissa Niba, Alistair D. Nichol, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Nurul Faten Izzati Norharizam, Anita North, Alessandra Notari, Mahdad Noursadeghi, Adam Nowinski, Saad Nseir, Leonard Numfor, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Anders Benteson Nygaard, Fionnuala O. Brien, Annmarie O. Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Lawrence Ofori-Boadu, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Sally-Ann Ohene, João Oliveira, Larissa Oliveira, Piero L. Olliaro, Cinderella Omar Rageh Elnaggar, Alsarrah Ali Mohammed Omer, Pierre Ondobo, David S.Y. Ong, Jee Yan Ong, Wilna Oosthuyzen, Anne Opavsky, Peter Openshaw, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Jamel Ortoleva, Mohamed Osama Elsayed Soliman, Javier Osatnik, Linda O'Shea, Miriam O'Sullivan, Eman Othman, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Micheal Owusu, Ama Akyampomaa Owusu-Asare, Eric Oziol, Maïder Pagadoy, Justine Pages, Amanda Palacios, Massimo Palmarini, Giovanna Panarello, Hem Paneru, Lai Hui Pang, Mauro Panigada, Nathalie Pansu, Aurélie Papadopoulos, Rachael Parke, Melissa Parker, Jérémie Pasquier, Bruno Pastene, Fabian Patauner, Drashti Patel, Mohan Dass Pathmanathan, Luís Patrão, Patricia Patricio, Lisa Patterson, Rajyabardhan Pattnaik, Christelle Paul, Mical Paul, Jorge Paulos, William A. Paxton, Jean-François Payen, Sandra L. Peake, Kalaiarasu Peariasamy, Giles J. Peek, Florent Peelman, Nathan Peiffer-Smadja, Vincent Peigne, Mare Pejkovska, Paolo Pelosi, Ithan D. Peltan, Rui Pereira, Daniel Perez, Thomas Perpoint, Antonio Pesenti, Vincent Pestre, Lenka Petrou, Michele Petrovic, Ventzislava Petrov-Sanchez, Frank Olav Pettersen, Gilles Peytavin, Richard Odame Philips, Ooyanong Phonemixay, Soulichanya Phoutthavong, Michael Piagnerelli, Walter Picard, Olivier Picone, Maria de Piero, Djura Piersma, Carlos Pimentel, Raquel Pinto, Catarina Pires, Lionel Piroth, Ayodhia Pitaloka, Chiara Piubelli, Riinu Pius, Simone Piva, Laurent Plantier, Hon Shen Png, Julien Poissy, Ryadh Pokeerbux, Sergio Poli, Georgios Pollakis, Diane Ponscarme, Diego Bastos Porto, Andra-Maris Post, Douwe F. Postma, Pedro Povoa, Diana Póvoas, Jeff Powis, Sofia Prapa, Viladeth Praphasiri, Sébastien Preau, Christian Prebensen, Jean-Charles Preiser, Anton Prinssen, Gamage Dona Dilanthi Priyadarshani, Lucia Proença, Sravya Pudota, Bambang Pujo Semedi, Mathew Pulicken, Peter Puplampu, Gregory Purcell, Luisa Quesada, Vilmaris Quinones-Cardona, Else Quist-Paulsen, Mohammed Quraishi, Fadi Qutishat, Maia Rabaa, Christian Rabaud, Ebenezer Rabindrarajan, Aldo Rafael, Marie Rafiq, Abdelrahman Ragab, Mutia Rahardjani, Arslan Rahat Ullah, Ahmad Kashfi Haji Ab Rahman, Rozanah Abd Rahman, Fernando Rainieri, Giri Shan Rajahram, Pratheema Ramachandran, Nagarajan Ramakrishnan, José Ramalho, Ahmad Afiq Ramli, Blandine Rammaert, Grazielle Viana Ramos, Asim Rana, Rajavardhan Rangappa, Ritika Ranjan, Christophe Rapp, Aasiyah Rashan, Thalha Rashan, Ghulam Rasheed, Menaldi Rasmin, Indrek Rätsep, Cornelius Rau, Tharmini Ravi, Ali Raza, Andre Real, Stanislas Rebaudet, Sarah Redl, Brenda Reeve, Attaur Rehman, Muhammad Osama Rehman Khalid, Dag Henrik Reikvam, Renato Reis, Jonathan Remppis, Martine Remy, Hongru Ren, Hanna Renk, Anne-Sophie Resseguier, Matthieu Revest, Oleksa Rewa, Maria Ines Ribeiro, Antonia Ricchiuto, David Richardson, Denise Richardson, Laurent Richier, Siti Nurul Atikah Ahmad Ridzuan, Ana L. Rios, Asgar Rishu, Patrick Rispal, Karine Risso, Maria Angelica Rivera Nuñez, Chiara Robba, André Roberto, Stephanie Roberts, Charles Roberts, David L. Robertson, Olivier Robineau, Anna Roca, Ferran Roche-Campo, Paola Rodari, Simão Rodeia, Bernhard Roessler, Claire Roger, Pierre-Marie Roger, Roberto Roncon-Albuquerque, Jr., Mélanie Roriz, Manuel Rosa-Calatrava, Michael Rose, Dorothea Rosenberger, Andrea Rossanese, Matteo Rossetti, Patrick Rossignol, Carine Roy, Benoît Roze, Desy Rusmawatiningtyas, Clark D. Russell, Maeve Ryan, Steffi Ryckaert, Aleksander Rygh Holten, Isabela Saba, Sairah Sadaf, Musharaf Sadat, Valla Sahraei, Abdurraouf Said, Nadia Saidani, Pranya Sakiyalak, Fodé Bangaly Sako, Moamen Salah, Ali Alaa Salah Eldin Mohamed Abbas, Nawal Salahuddin, Leonardo Salazar, Jodat Saleem, Mohammed Saleh Alyasiri, Talat Ahmed Abu Salem, Gabriele Sales, Charlotte Salmon Gandonniere, Hélène Salvator, Dana Samardali, Shaden Samardali, Yehia Samir Shaaban Aly Orabi, Emely Sanchez, Olivier Sanchez, Kizy Sanchez de Oliveira, Angel Sanchez-Miralles, Vanessa Sancho-Shimizu, Gyan Sandhu, Zulfiqar Sandhu, Pierre-François Sandrine, Oana Săndulescu, Marlene Santos, Shirley Sarfo-Mensah, Bruno Sarmento Banheiro, Iam Claire E. Sarmiento, Benjamine Sarton, Ankana Satya, Sree Satyapriya, Rumaisah Satyawati, Egle Saviciute, Yen Tsen Saw, Justin Schaffer, Tjard Schermer, Arnaud Scherpereel, Marion Schneider, János Schnur, Stephan Schroll, Michael Schwameis, Gary Schwartz, Janet T. Scott, James Scott-Brown, Nicholas Sedillot, Tamara Seitz, Jaganathan Selvanayagam, Mageswari Selvarajoo, Malcolm G. Semple, Rasidah Bt Senian, Eric Senneville, Claudia Sepulveda, Filipa Sequeira, Tânia Sequeira, Ary Serpa Neto, Ellen Shadowitz, Syamin Asyraf Shahidan, Hamza Shahla, Laila Shalabi, Haitam Shames, Anuraj Shankar, Shaikh Sharjeel, Pratima Sharma, Catherine A. Shaw, Victoria Shaw, John Robert Sheenan, Dr. Rajesh Mohan Shetty, Rohan Shetty, Mohiuddin Shiekh, Nobuaki Shime, Keiki Shimizu, Sally Shrapnel, Shubha Kalyan Shrestha, Pramesh Sundar Shrestha, Hoi Ping Shum, Nassima Si Mohammed, Ng Yong Siang, Moses Siaw-Frimpong, Jeanne Sibiude, Bountoy Sibounheuang, Nidhal Siddig, Atif Siddiqui, Maqsood Ahmed Siddiqui, Louise Sigfrid, Fatoumata Sillah, Piret Sillaots, Catarina Silva, Maria Joao Silva, Rogério Silva, Benedict Sim Lim Heng, Wai Ching Sin, Dario Sinatti, Mahendra Singh, Punam Singh, Pompini Agustina Sitompul, Karisha Sivam, Vegard Skogen, Sue Smith, Benjamin Smood, Coilin Smyth, Morgane Snacken, Dominic So, Tze Vee Soh, Lene Bergendal Solberg, Joshua Solomon, Tom Solomon, Emily Somers, Agnès Sommet, Myung Jin Song, Rima Song, Tae Song, Jack Song Chia, Arne Søraas, Albert Sotto, Edouard Soum, Ana Chora Sousa, Marta Sousa, Maria Sousa Uva, Vicente Souza-Dantas, Mamadou Saliou Sow, Alexandra Sperry, Elisabetta Spinuzza, B. P. Sanka Ruwan Sri Darshana, Shiranee Sriskandan, Sarah Stabler, Thomas Staudinger, Stephanie-Susanne Stecher, Trude Steinsvik, Ymkje Stienstra, Birgitte Stiksrud, Eva Stolz, Amy Stone, Anca Streinu-Cercel, Adrian Streinu-Cercel, Geoff Strong, Ami Stuart, David Stuart, Richa Su, Decy Subekti, Gabriel Suen, Jacky Y. Suen, Prasanth Sukumar, Asfia Sultana, Charlotte Summers, Dubravka Supic, Deepashankari Suppiah, Magdalena Surovcová, Atie Suwarti, Andrey Svistunov, Sarah Syahrin, Augustina Sylverken, Konstantinos Syrigos, Jaques Sztajnbok, Konstanty Szuldrzynski, Shirin Tabrizi, Fabio S. Taccone, Lysa Tagherset, Shahdattul Mawarni Taib, Sara Taleb, Cheikh Talla, Jelmer Talsma, Renaud Tamisier, Maria Lawrensia Tampubolon, Kim Keat Tan, Yan Chyi Tan, Hiroyuki Tanaka, Taku Tanaka, Hayato Taniguchi, Huda Taqdees, Arshad Taqi, Coralie Tardivon, Yousef Tarek Kamal Mostafa, Ali Tarhabat, Pierre Tattevin, M Azhari Taufik, Hassan Tawfik, Tze Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Elmi Theron, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Niamh Thompson, Shaun Thompson, Emma C. Thomson, David Thomson, Mathew Thorpe, Surain Raaj Thanga Thurai, Ryan S. Thwaites, Paul Tierney, Vadim Tieroshyn, Peter S. Timashev, Jean-François Timsit, Noémie Tissot, Fiona Toal, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Marta Torre, Antoni Torres, Margarida Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Aboubacar Tounkara, Michael Towers, Fodé Amara Traoré, Tony Trapani, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Alexis F. Turgeon, Jean-Marie Turmel, Lance C.W. Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, PG Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Effua Usuf, Timothy M. Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Stijn Van de Velde, Marcel van den Berge, Machteld van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Ilonka van Veen, Noémie Vanel, Henk Vanoverschelde, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Pavan Kumar Vecham, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, José Ernesto Vidal, César Vieira, Deepak Vijayan, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Manivanh Vongsouvath, Harald Vonkeman, Fanny Vuotto, Suhaila Abdul Wahab, Noor Hidayu Wahab, Nadirah Abdul Wahid, Marina Wainstein, Laura Walsh, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Katharina Weil, Tan Pei Wen, Hassi Wesam, Sanne Wesselius, T. Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Sue Willems, Bailey Williams, Patricia J. Williams, Virginie Williams, Jessica Wittman, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Lim Saio Xian, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Elizabeth Yarad, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Abdelrahman Yehia Mahmoud Abdelaal, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Touxiong Yiaye, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Gustavo E. Zabert, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, and David Zucman

Subjects
COVID-19, Non-respiratory symptoms, Respiratory symptoms, Risk factors, Mortality, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Published
2024
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21. Advancing wavefront shaping with resonant nonlocal metasurfaces: beyond the limitations of lookup tables

Author

Enzo Isnard, Sébastien Héron, Stéphane Lanteri, and Mahmoud Elsawy

Subjects
Medicine, Science
Abstract

Abstract Resonant metasurfaces are of paramount importance in addressing the growing demand for reduced thickness and complexity, while ensuring high optical efficiency. This becomes particularly crucial in overcoming fabrication challenges associated with high aspect ratio structures, thereby enabling seamless integration of metasurfaces with electronic components at an advanced level. However, traditional design approaches relying on lookup tables and local field approximations often fail to achieve optimal performance, especially for nonlocal resonant metasurfaces. In this study, we investigate the use of statistical learning optimization techniques for nonlocal resonant metasurfaces, with a specific emphasis on the role of near-field coupling in wavefront shaping beyond single unit cell simulations. Our study achieves significant advancements in the design theoretical conception of resonant metasurfaces. For transmission-based metasurfaces, a beam steering design outperforms the classical design by achieving an impressive efficiency of 80% compared to the previous 23%. Additionally, our optimized extended depth-of-focus (EDOF) metalens yields a remarkable five-fold increase in focal depth, a four-fold enhancement in focusing power compared to conventional designs and an optical resolution superior to 600 cycle/mm across the focus region. Moreover, our study demonstrates remarkable performance with a wavelength-selected beam steering metagrating in reflection, achieving exceptional efficiency surpassing 85%. This far outperforms classical gradient phase distribution approaches, emphasizing the immense potential for groundbreaking applications in the field of resonant metasurfaces.

Published
2024
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24. The AMPK-Sirtuin 1-YAP axis is regulated by fluid flow intensity and controls autophagy flux in kidney epithelial cells

Author

Aurore Claude-Taupin, Pierre Isnard, Alessia Bagattin, Nicolas Kuperwasser, Federica Roccio, Biagina Ruscica, Nicolas Goudin, Meriem Garfa-Traoré, Alice Regnier, Lisa Turinsky, Martine Burtin, Marc Foretz, Marco Pontoglio, Etienne Morel, Benoit Viollet, Fabiola Terzi, Patrice Codogno, and Nicolas Dupont

Subjects
Science
Abstract

Abstract Shear stress generated by urinary fluid flow is an important regulator of renal function. Its dysregulation is observed in various chronic and acute kidney diseases. Previously, we demonstrated that primary cilium-dependent autophagy allows kidney epithelial cells to adapt their metabolism in response to fluid flow. Here, we show that nuclear YAP/TAZ negatively regulates autophagy flux in kidney epithelial cells subjected to fluid flow. This crosstalk is supported by a primary cilium-dependent activation of AMPK and SIRT1, independently of the Hippo pathway. We confirm the relevance of the YAP/TAZ-autophagy molecular dialog in vivo using a zebrafish model of kidney development and a unilateral ureteral obstruction mouse model. In addition, an in vitro assay simulating pathological accelerated flow observed at early stages of chronic kidney disease (CKD) activates YAP, leading to a primary cilium-dependent inhibition of autophagic flux. We confirm this YAP/autophagy relationship in renal biopsies from patients suffering from diabetic kidney disease (DKD), the leading cause of CKD. Our findings demonstrate the importance of YAP/TAZ and autophagy in the translation of fluid flow into cellular and physiological responses. Dysregulation of this pathway is associated with the early onset of CKD.

Published
2023
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25. Chronic Myelomonocytic Leukemia Patients With Lysozyme Nephropathy and Renal Infiltration Display Markers of Severe Disease

Author

Marie-Camille Lafargue, Mickaël Bobot, Helmut G. Rennke, Marie Essig, Martin Carre, Lucile Mercadal, Jonathan Farhi, Hamza Sakhi, Thibault Comont, Léonard Golbin, Pierre Isnard, Jonathan Chemouny, Nathalie Cambier, Kamel Laribi, Umut Selamet, Leonardo V. Riella, Olivier Fain, Lionel Adès, Pierre Fenaux, Camille Cohen, and Arsène Mekinian

Subjects
acute kidney injury, chronic myelomonocytic leukemia, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Introduction: Chronic myelomonocytic leukemia (CMML) is a hematologic disorder that is an overlap syndrome between myelodysplastic syndromes and myeloproliferative neoplasms, and can be associated with autoimmune and inflammatory diseases. This study aimed to describe kidney involvement in patients with CMML, their treatments, and outcomes. Methods: We conducted a French and American multicenter retrospective study in 15 centers, identifying patients with CMML with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results: Sixteen patients (males, n = 14; median age 76.5 years [71.9–83]) developed a kidney disease 6 months [1.6–25.6] after the diagnosis of CMML. At the time of kidney disease diagnosis, median urinary protein-to-creatinine ratio was 2 g/g [1.25–3.4], and median serum creatinine was 2.26 mg/dl [1.46–2.68]. Fourteen patients (87.5%) underwent a kidney biopsy, and the 2 main pathological findings were lysozyme nephropathy (56%) and renal infiltration by the CMML (37.5%). Ten patients received a new treatment following the CMML-associated kidney injury. Among patients with monitored kidney function, and after a median follow-up of 15 months [9.9–34.9], 4 patients had CKD stage 3, 4 had CKD stage 4, 1 had an end-stage kidney disease. In our patient series, 2 patients evolved to an acute myeloid leukemia (AML), and 5 died. Compared with 116 CMML controls, patients who had a kidney involvement had a higher monocyte count (P < 0.001), had more CMML-1 (P = 0.005), were more susceptible to develop an AML (P = 0.02), and were more eligible to receive a specific hematologic treatment, with hydroxyurea, or hypomethylating agents (P < 0.001), but no survival difference was seen between the 2 groups (P = 0.6978). Conclusion: In this cohort of patients with CMML with a kidney injury, the 2 most frequent renal complications were lysozyme-induced nephropathy and renal infiltration by the CMML. Kidney involvement should be closely monitored in patients with CMML.

Published
2023
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29. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

Author

Andrikopoulos, Petros, Aron-Wisnewsky, Judith, Chakaroun, Rima, Myridakis, Antonis, Forslund, Sofia K., Nielsen, Trine, Adriouch, Solia, Holmes, Bridget, Chilloux, Julien, Vieira-Silva, Sara, Falony, Gwen, Salem, Joe-Elie, Andreelli, Fabrizio, Belda, Eugeni, Kieswich, Julius, Chechi, Kanta, Puig-Castellvi, Francesc, Chevalier, Mickael, Le Chatelier, Emmanuelle, Olanipekun, Michael T., Hoyles, Lesley, Alves, Renato, Helft, Gerard, Isnard, Richard, Køber, Lars, Coelho, Luis Pedro, Rouault, Christine, Gauguier, Dominique, Gøtze, Jens Peter, Prifti, Edi, Froguel, Philippe, Zucker, Jean-Daniel, Bäckhed, Fredrik, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean-Michel, Blüher, Matthias, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Yaqoob, Muhammad M., Stumvoll, Michael, Pedersen, Oluf, Ehrlich, S. Dusko, Clément, Karine, and Dumas, Marc-Emmanuel

Published
2023
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31. Proteomics validate circulating GDF-15 as an independent biomarker for COVID-19 severity

Author

Simeng Bu, Léna Royston, Tsoarello Mabanga, Carolina A. Berini, Cécile Tremblay, Bertrand Lebouché, Joseph Cox, Cecilia T. Costiniuk, Madeleine Durand, Stephane Isnard, and Jean-Pierre Routy

Subjects
GDF-15, COVID-19, SARS-CoV-2, proteomics, BQC19, severity, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionGrowth differentiation factor 15 (GDF-15) was originally described as a stress-induced cytokine, and a biomarker of aging and cardiovascular diseases. We hypothesized that circulating GDF-15 would be associated with COVID-19 disease severity. Herein, we explored this hypothesis in a large cohort of COVID-19 patients.MethodsBlood samples were collected from 926 COVID-19 adult patients and from 285 hospitalized controls from the Biobanque Québécoise de la COVID-19 (BQC19). COVID-19 severity was graded according to the WHO criteria. SOMAscan proteomics assay was performed on 50µL of plasma. ELISA were performed on 46 selected participants with left-over plasma to validate differences in plasma GDF-15 levels. Statistical analyses were conducted using GraphPad Prism 9.0 and SPSS. P values < 0.01 were considered significant.ResultsProteomics showed that plasma GDF-15 levels were higher in COVID-19 patients compared to hospitalized controls. GDF-15 levels increased with COVID-19 severity. COVID-19 patients presenting with comorbidities including diabetes, cancer, chronic obstructive pulmonary disease (COPD) and cardiovascular disease had higher GDF-15 levels. ELISA revealed significant elevation of GDF-15 until 30 days after hospitalization. Plasma GDF-15 elevation was correlated with older age. Moreover, GDF-15 levels correlated with pro-inflammatory cytokine interleukin-6 (IL-6) and inflammation marker C-reactive protein (CRP) as well as soluble levels of its putative receptor CD48. No association was established between anti-SARS-CoV-2 IgG levels and plasma GDF-15 levels.ConclusionsThis study confirms GDF-15 as a biomarker for COVID-19 severity. Clinical evaluation of GDF-15 levels could assist identification of persons at high-risk of progressing to severe disease, thus improving patient care.

Published
2024
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32. Non-myeloma light chain cast nephropathy: a multicenter retrospective study on clinicopathological characteristics

Author

Ana Cristina Martins, Jean-Baptiste Gibier, Charles Ronsin, Christine Kandel-Aznar, Anne Moreau, Marion Chapal, Diogo Francisco, Hamza Sakhi, Julie Oniszczuk, Lorraine Gueguen, Anne Grunenwald, Mathilde Devaux, Alexandre Karras, Virginie Royal, Marion Rabant, Viviane Gnemmi, Jérôme Olagne, Jean-Paul Duong Van Huyen, and Pierre Isnard

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Not available.

Published
2024
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33. Haemophagocytic lymphohistiocytosis following the anti-PD-1 nivolumab in a patient with gastric cancer and ankylosing spondylitis

Author

Clara Long, Abdulrahman Al-Abdulmalek, Jonathan Lai, David G. Haegert, Stephane Isnard, Denis Cournoyer, and Jean-Pierre Routy

Subjects
hemophagocytic lymphohistiocytosis, immunotherapy, anti-pd1, gastric cancer, ankylosing spondylitis, Medicine
Abstract

Background: Autoimmune diseases are not contraindications for immune checkpoint inhibitors (ICI) therapy in patients with cancer. However, immune-related adverse events (irAEs) are frequently observed in patients receiving ICIs including dermatitis, thyroiditis, colitis, and pneumonitis. Thrombocytopenic purpura, aplasia, and haemophagocytic lymphohistiocytosis (HLH) are rarely observed during ICIs. Case description: We report the case of a male patient with pre-existing untreated HLA B27 and ankylosing spondylitis with gastric cancer and liver metastases. The 79-year-old man was treated with anti-HER2 trastuzumab and anti-PD-1 nivolumab. Seventeen days after the seventh cycle of treatment, he presented at the emergency department with acute fever, confusion, and hypotension. Laboratory results showed pancytopenia, and elevation of ferritin and triglyceride. No infections were detected. Although not seen in a bone marrow biopsy, clinical presentation, and absence of infection, together with an H-score of 263, indicated HLH. The patient was treated with dexamethasone for four days and discharged on a tapering dose of steroids. At the two-month follow-up, clinical presentation was normal and blood test almost normalised. At 8 months, no liver metastases were observed. Conclusions: In a patient with a pre-existing autoimmune condition, immunotherapy led to the development of HLH, which was controlled by glucocorticoid. Absence of the feature of haemophagocytosis in the bone marrow biopsy did not exclude the diagnosis, as HLH can occur in the spleen or in the liver. Glucocorticoid therapy did not prevent the anti-cancer effect of ICIs, and liver metastases disappeared 8 months post-HLH. This case warrants further research on the interplay between autoimmunity and ICI response, as well as ICI-induced irAEs.

Published
2024
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34. Development, psychometric evaluation, and factor analysis of an instrument measuring quality of life in autistic preschoolers

Author

Jérôme Lichtlé, Emmanuel Devouche, Isaora Zefania Dialahy, Aude deGaulmyn, Anouck Amestoy, Romain Coutelle, Pascale Isnard, Jean‐Louis Monestès, Laurent Mottron, and Emilie Cappe

Subjects
acceptance, autism spectrum disorder, preschoolers, psychometric validation, quality of life, temperament, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Introduction Early interventions for autistic children should target their quality of life (QoL) but require adapted measures. The association of a child's temperament and parental characteristics with the QoL of autistic children remains unknown. Methods We constructed an autism module based on a thematic analysis, a Delphi survey with experts, and a pre‐test with parents to be completed alongside the proxy version of the PedsQL 4.0. We explored compliance, responsiveness, internal consistency, convergent validity, and factor structure with 157 parents of autistic preschool children. We examined the association between child and parental characteristics with the QoL of autistic children using correlation analysis, principal component analysis, hierarchical ascending classification, and linear regression. Sociodemographic information was collected via multiple choice questions, autism severity via Autism Diagnostic Observation Schedule (ADOS) scores, and parental acceptance and child's temperament via the Acceptance and Action Questionnaire and the Emotionality, Activity, and Sociability. Results An autism module comprised of 27 items emerged. Psychometric evaluation resulted in a 24‐item autism module with good internal consistency and significant convergent validity. ADOS total score was not significantly related to QoL, contrary to children's sleep issues, children's emotionality, and parental acceptance. Conclusions The autism module is a reliable QoL proxy measure for autistic preschool children. Results suggest parental interventions targeting children's QoL.

Published
2024
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35. Bi-specific autoantigen-T cell engagers as targeted immunotherapy for autoreactive B cell depletion in autoimmune diseases

Author

Luca Perico, Federica Casiraghi, Fabiane Sônego, Marta Todeschini, Daniela Corna, Domenico Cerullo, Anna Pezzotta, Patricia Isnard-Petit, Silvia Faravelli, Federico Forneris, Kader Thiam, Ariela Benigni, and Giuseppe Remuzzi

Subjects
autoimmune diseases, membranous nephropathy, anti-PLA2R antibodies, autoreactive B cell, targeted immunotherapies, bi-specific autoantigen-T cell engagers, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionIn autoimmune diseases, autoreactive B cells comprise only the 0.1-0.5% of total circulating B cells. However, current first-line treatments rely on non-specific and general suppression of the immune system, exposing patients to severe side effects. For this reason, identification of targeted therapies for autoimmune diseases is an unmet clinical need.MethodsHere, we designed a novel class of immunotherapeutic molecules, Bi-specific AutoAntigen-T cell Engagers (BiAATEs), as a potential approach for targeting the small subset of autoreactive B cells. To test this approach, we focused on a prototype autoimmune disease of the kidney, membranous nephropathy (MN), in which phospholipase A2 receptor (PLA2R) serves as primary nephritogenic antigen. Specifically, we developed a BiAATE consisting of the immunodominant Cysteine-Rich (CysR) domain of PLA2R and the single-chain variable fragment (scFv) of an antibody against the T cell antigen CD3, connected by a small flexible linker.ResultsBiAATE creates an immunological synapse between autoreactive B cells bearing an CysR-specific surface Ig+ and T cells. Ex vivo, the BiAATE successfully induced T cell-dependent depletion of PLA2R-specific B cells isolated form MN patients, sparing normal B cells. Systemic administration of BiAATE to mice transgenic for human CD3 reduced anti-PLA2R antibody levels following active immunization with PLA2R.DiscussionShould this approach be confirmed for other autoimmune diseases, BiAATEs could represent a promising off-the-shelf therapy for precision medicine in virtually all antibody-mediated autoimmune diseases for which the pathogenic autoantigen is known, leading to a paradigm shift in the treatment of these diseases.

Published
2024
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36. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

Author

Petros Andrikopoulos, Judith Aron-Wisnewsky, Rima Chakaroun, Antonis Myridakis, Sofia K. Forslund, Trine Nielsen, Solia Adriouch, Bridget Holmes, Julien Chilloux, Sara Vieira-Silva, Gwen Falony, Joe-Elie Salem, Fabrizio Andreelli, Eugeni Belda, Julius Kieswich, Kanta Chechi, Francesc Puig-Castellvi, Mickael Chevalier, Emmanuelle Le Chatelier, Michael T. Olanipekun, Lesley Hoyles, Renato Alves, Gerard Helft, Richard Isnard, Lars Køber, Luis Pedro Coelho, Christine Rouault, Dominique Gauguier, Jens Peter Gøtze, Edi Prifti, Philippe Froguel, The MetaCardis Consortium, Jean-Daniel Zucker, Fredrik Bäckhed, Henrik Vestergaard, Torben Hansen, Jean-Michel Oppert, Matthias Blüher, Jens Nielsen, Jeroen Raes, Peer Bork, Muhammad M. Yaqoob, Michael Stumvoll, Oluf Pedersen, S. Dusko Ehrlich, Karine Clément, and Marc-Emmanuel Dumas

Subjects
Science
Abstract

Abstract The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied “explainable” machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.

Published
2023
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37. Theoretical Study of the Magnetic Properties of the SmFe12−xMox (x = 1, 2) and SmFe10Mo2H Compounds

Author

Diana Benea, Eduard Barna, Viorel Pop, and Olivier Isnard

Subjects
ab initio calculations, magneto-crystalline anisotropy, Curie temperature, permanent magnets, Crystallography, QD901-999
Abstract

We present theoretical investigations examining the electronic and magnetic properties of the SmFe12−xMox (x = 1, 2) and SmFe10Mo2H compounds, including magneto-crystalline anisotropy, magnetic moments, exchange-coupling parameters, and Curie temperatures. The spin-polarized fully relativistic Korringa–Kohn–Rostoker (SPR-KKR) band structure method has been employed, using the coherent potential approximation (CPA) to deal with substitutional disorder. Hubbard-U correction was applied to the local spin density approximation (LSDA+U) in order to account for the significant correlation effects arising from the 4f electronic states of Sm. According to our calculations, the total magnetic moments increases with H addition, in agreement with experimental data. Adding one H atom in the near-neighbor environment of the Fe 8j site reduces the magnetic moments of Fe 8j and enhances the magnetic moment of Fe 8f. For every investigated alloy, the site-resolved spin magnetic moments of Fe on the 8i, 8j, and 8f sites exhibit the same magnitude sequence, with msFe (8i) > msFe (8j) > msFe (8f). While the addition of H has a positive impact on magneto-crystalline anisotropy energy (MAE), the increase in Mo concentration is detrimental to MAE. The computed exchange-coupling parameters reveal the highest values between the closest Fe 8i spins, followed by Fe 8i and Fe 8j spins, for all investigated alloys. The Curie temperature of the alloys under investigation is increased by decreasing the Mo concentration or by H addition, which is qualitatively consistent with experimental findings.

Published
2024
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38. Predictors of Speech-in-Noise Understanding in a Population of Occupationally Noise-Exposed Individuals

Author

Guillaume Andéol, Nihaad Paraouty, Fabrice Giraudet, Nicolas Wallaert, Vincent Isnard, Annie Moulin, and Clara Suied

Subjects
extended high frequency, speech in noise, amplitude modulation detection, frequency modulation detection, distortion products of otoacoustic emissions, electrocochleography, Biology (General), QH301-705.5
Abstract

Understanding speech in noise is particularly difficult for individuals occupationally exposed to noise due to a mix of noise-induced auditory lesions and the energetic masking of speech signals. For years, the monitoring of conventional audiometric thresholds has been the usual method to check and preserve auditory function. Recently, suprathreshold deficits, notably, difficulties in understanding speech in noise, has pointed out the need for new monitoring tools. The present study aims to identify the most important variables that predict speech in noise understanding in order to suggest a new method of hearing status monitoring. Physiological (distortion products of otoacoustic emissions, electrocochleography) and behavioral (amplitude and frequency modulation detection thresholds, conventional and extended high-frequency audiometric thresholds) variables were collected in a population of individuals presenting a relatively homogeneous occupational noise exposure. Those variables were used as predictors in a statistical model (random forest) to predict the scores of three different speech-in-noise tests and a self-report of speech-in-noise ability. The extended high-frequency threshold appears to be the best predictor and therefore an interesting candidate for a new way of monitoring noise-exposed professionals.

Published
2024
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39. Acute kidney injury in patients treated with immune checkpoint inhibitors

Author

Gupta, Shruti, Short, Samuel AP, Sise, Meghan E, Prosek, Jason M, Madhavan, Sethu M, Soler, Maria Jose, Ostermann, Marlies, Herrmann, Sandra M, Abudayyeh, Ala, Anand, Shuchi, Glezerman, Ilya, Motwani, Shveta S, Murakami, Naoka, Wanchoo, Rimda, Ortiz-Melo, David I, Rashidi, Arash, Sprangers, Ben, Aggarwal, Vikram, Malik, A Bilal, Loew, Sebastian, Carlos, Christopher A, Chang, Wei-Ting, Beckerman, Pazit, Mithani, Zain, Shah, Chintan V, Renaghan, Amanda D, De Seigneux, Sophie, Campedel, Luca, Kitchlu, Abhijat, Shin, Daniel Sanghoon, Rangarajan, Sunil, Deshpande, Priya, Coppock, Gaia, Eijgelsheim, Mark, Seethapathy, Harish, Lee, Meghan D, Strohbehn, Ian A, Owen, Dwight H, Husain, Marium, Garcia-Carro, Clara, Bermejo, Sheila, Lumlertgul, Nuttha, Seylanova, Nina, Flanders, Lucy, Isik, Busra, Mamlouk, Omar, Lin, Jamie S, Garcia, Pablo, Kaghazchi, Aydin, Khanin, Yuriy, Kansal, Sheru K, Wauters, Els, Chandra, Sunandana, Schmidt-Ott, Kai M, Hsu, Raymond K, Tio, Maria C, Mothi, Suraj Sarvode, Singh, Harkarandeep, Schrag, Deborah, Jhaveri, Kenar D, Reynolds, Kerry L, Cortazar, Frank B, Leaf, David E, Salem, Joe-Elie, Bagnis, Corinne Isnard, Rahma, Osama E, Mothi, Suraj S, Selamet, Umut, Chang, Weiting, Hirsch, Jamie S, Sakhiya, Vipulbhai, Stalbow, Daniel, Wu, Sylvia, Cennamo, Armando, Papa, Sophie, Rigg, Anne, Shaunak, Nisha, Kibbelaar, Zoe A, and Benesova, Karolina

Subjects
Kidney Disease, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Renal and urogenital, Good Health and Well Being, Acute Kidney Injury, Aged, Cohort Studies, Female, Humans, Immune Checkpoint Inhibitors, Immunotherapy, Male, Middle Aged, Risk Factors, immunotherapy, CTLA-4 antigen, programmed cell death 1 receptor, ICPi-AKI Consortium Investigators
Abstract

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Published
2021

40. Translocation of bacterial LPS is associated with self-reported cognitive abilities in men living with HIV receiving antiretroviral therapy

Author

Stéphane Isnard, Léna Royston, Susan C. Scott, Tsoarello Mabanga, John Lin, Brandon Fombuena, Simeng Bu, Carolina A. Berini, Mark S. Goldberg, Malcolm Finkelman, Marie-Josée Brouillette, Lesley K. Fellows, Nancy E. Mayo, and Jean-Pierre Routy

Subjects
People living with HIV, Cognition, Gut, Microbial translocation, LPS, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Gut damage allows translocation of bacterial lipopolysaccharide (LPS) and fungal β-D-glucan (BDG) into the blood. This microbial translocation contributes to systemic inflammation and risk of non-AIDS comorbidities in people living with HIV, including those receiving antiretroviral therapy (ART). We assessed whether markers of gut damage and microbial translocation were associated with cognition in ART-treated PLWH. Methods Eighty ART-treated men living with HIV from the Positive Brain Health Now Canadian cohort were included. Brief cognitive ability measure (B-CAM) and 20-item patient deficit questionnaire (PDQ) were administered to all participants. Three groups were selected based on their B-CAM levels. We excluded participants who received proton pump inhibitors or antiacids in the past 3 months. Cannabis users were also excluded. Plasma levels of intestinal fatty acid binding protein (I-FABP), regenerating islet-derived protein 3 α (REG3α), and lipopolysaccharides (LPS = were quantified by ELISA, while 1–3-β-D-glucan BDG) levels were assessed using the Fungitell assay. Univariable, multivariable, and splines analyses were performed. Results Plasma levels of I-FABP, REG3α, LPS and BDG were not different between groups of low, intermediate and high B-CAM levels. However, LPS and REG3α levels were higher in participants with PDQ higher than the median. Multivariable analyses showed that LPS association with PDQ, but not B-CAM, was independent of age and level of education. I-FABP, REG3α, and BDG levels were not associated with B-CAM nor PDQ levels in multivariable analyses. Conclusion In this well characterized cohort of ART-treated men living with HIV, bacterial but not fungal translocation was associated with presence of cognitive difficulties. These results need replication in larger samples.

Published
2023
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42. Description of a new low-cost and open-source audiometer and its validation with normal-hearing listeners: The Aupiometer.

Author

Vincent Isnard, Véronique Chastres, and Guillaume Andéol

Subjects
Medicine, Science
Abstract

Hearing loss is a major public health problem. In 2050, it could affect 2.5 billion people. It has therefore become necessary to prevent and diagnose them as early and as widely as possible. However, the costs of clinical equipment dedicated to the functional exploration of hearing remain high and hamper their distribution, while the technologies used are relatively basic. For example, the gold-standard pure-tone audiometry (PTA) essentially consists of emitting pure sounds. In addition, clinical audiometers are generally limited to PTA or few audiological tests, while hearing loss induce multiple functional deficits. Here, we present the Aupiometer, a low-cost audiometer implemented on a modular open-source system based on Raspberry Pi, and which integrates the entire technical framework necessary to carry out audiological measurements. Several hearing tests are already implemented (e.g. PTA, speech audiometry, questionnaires), while the clinical validity of the Aupiometer was verified on a panel of participants (N = 16) for an automated test of standard and extended high-frequency PTA, from 0.125 to 16 kHz, in comparison with a clinical audiometer. For this comparison between the two devices and over this wide frequency range, the difference is evaluated as less than ±10 dB for a 90% confidence interval, of the same order of magnitude as on test-retest differences on a single device. The interest of this device also extends to academic research as it should encourage the prototyping of innovative hearing tests by the community, in order to better understand the diversity of hearing problems in the population.

Published
2024
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43. The detection of solid phosphorus and fluorine in the dust from the coma of comet 67P/Churyumov-Gerasimenko

Author

Gardner, Esko, Lehto, Harry J., Lehto, Kirsi, Fray, Nicolas, Bardyn, Anaïs, Lönnberg, Tuomas, Merouane, Sihane, Isnard, Robin, Cottin, Hervé, and Hilchenbach, Martin

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

Here, we report the detection of phosphorus and fluorine in solid particles collected from the inner coma of comet 67P/Churyumov-Gerasimenko measured with the COmetary Secondary Ion Mass Analyser (COSIMA) instrument on-board the Rosetta spacecraft, only a few kilometers away from the comet nucleus. We have detected phosphorus-containing minerals from the presented COSIMA mass spectra, and can rule out e.g. apatite minerals as the source of phosphorus. This result completes the detection of life-necessary CHNOPS-elements in solid cometary matter, indicating cometary delivery as a potential source of these elements to the young Earth. Fluorine was also detected with CF$^+$ secondary ions originating from the cometary dust., Comment: 5 pages, 1 figure, 1 table, supplementary 2 tables and 2 figures

Published
2020
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44. Structural properties and Raman spectra of columbite-type NiNb$_{2-x}$V$_x$O$_6$ synthesized under high pressure

Author

Peña, Jully P., Bouvier, Pierre, and Isnard, Oliver

Subjects
Condensed Matter - Materials Science, Condensed Matter - Other Condensed Matter
Abstract

The complete set of structural parameters of the new series of compounds NiNb$_{2-x}$V$_x$O$_6$ ($0\leq x \leq 2$) with the unusual columbite-type structure is presented here. In the samples containing vanadium, this crystalline structure was stabilized by synthesis in conditions of high pressure and high temperature. Here we report here the first Raman spectrum for the NiV$_2$O$_6$-\textsl{Pbcn} polymorph and extend the list of the previously observed modes for the NiNb$_2$O$_6$. The evolution of the vibrational Raman spectrum produced when the vanadium is substituted for niobium along the series is also presented and discussed. This evolution is interpreted by taking into account the changes in the local structural environment of the niobium/vanadium atoms and its influence over the nickel-oxygen bonds around them. The presence of vanadium atoms favors an increase of the symmetry in the arrangement of oxygen atoms around the nickel-ones; in counterpart, the vanadium is in an octahedral environment which is more distorted than that of the niobium. Because of these apparently subtle differences, the homogeneous distribution of vanadium in the solid solution NiNb$_{2-x}$V$_x$O$_6$ is not possible.

Published
2020
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45. Origin of the metamagnetic transitions in Y1-xErxFe2(H,D)4.2 compounds

Author

Paul-Boncour, V., Isnard, O., Shtender, V., Skourski, Y., and Guillot, M.

Subjects
Condensed Matter - Materials Science
Abstract

The structural and magnetic properties of Y1-xErxFe2 intermetallic compounds and their hydrides and deuterides Y1-xErxFe2H(D)4.2 have been investigated using X-ray diffraction and magnetic measurements under static and pulsed magnetic field up to 60 T. The intermetallics crystallize in the C15 cubic structure , whereas corresponding hydrides and deuterides crystallize in a monoclinic structure. All compounds display a linear decrease of the unit cell volume versus Er concentration; the hydrides have a 0.8% larger cell volume compared to the deuterides with same Er content. They are ferrimagnetic at low field and temperature with a compensation point at x = 0.33 for the intermetallics and x = 0.57 for the hydrides and deuterides. A sharp first order ferromagnetic-antiferromagnetic (FM-AFM) transition is observed upon heating at TFM-AFM for both hydrides and deuterides. These compounds show two different types of field induced transitions, which have different physical origin. At low temperature (T < 50 K), a forced ferri-ferromagnetic metamagnetic transition with Btrans1 = 8 T, related to the change of the Er moments orientation from antiparallel to parallel Fe moment, is observed. Btrans1 is not sensitive to Er concentration, temperature and isotope effect. A second metamagnetic transition resulting from antiferromagnetic to ferrimagnetic state is also observed. The transition field Btrans2 increases linearly versus temperature and relates to the itinerant electron metamagnetic behavior of the Fe sublattice. An onset temperature TM0 is obtained by extrapolating TFM-AFM (B) at zero field. TM0 decreases linearly versus the Er content and is 45(5) K higher for the hydrides compared to the corresponding deuteride. The evolution of TM0 versus cell volume shows that it cannot be attributed exclusively to a pure volume effect and that electronic effects should also be considered., Comment: 22 pages, 10 figures

Published
2020
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46. Candida albicans can foster gut dysbiosis and systemic inflammation during HIV infection

Author

Silvere D Zaongo, Jing Ouyang, Stéphane Isnard, Xin Zhou, Vijay Harypursat, Hongjuan Cui, Jean-Pierre Routy, and Yaokai Chen

Subjects
Candida albicans, HIV, gut microbiota, dysbiosis, systemic infections, microbial translocation, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

ABSTRACTCandida albicans (C. albicans) is a ubiquitous fungal commensal component of the human microbiota, and under certain circumstances, such as during an immunocompromised state, it may initiate different types of infection. Moreover, C. albicans continuously and reciprocally interacts with the host immune system as well as with other elements of the gut microbiota, thus contributing significantly to both gut homeostasis and host immunity. People living with HIV (PLWH), including those receiving antiretroviral therapy, are characterized by a depletion of CD4 + T-cells and dysbiosis in their gut. C. albicans colonization is frequent in PLWH, causing both a high prevalence and high morbidity. Gut barrier damage and elevated levels of microbial translocation are also fairly common in this population. Herein, we take a closer look at the reciprocity among C. albicans, gut microbiota, HIV, and the host immune system, thus throwing some light on this complex interplay.

Published
2023
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47. Long-term tolerance and efficacy of siltuximab (anti-IL-6) in a young adult with idiopathic multicentric Castleman disease during COVID-19

Author

Helbies Bedier, Stéphane Isnard, Chelsea Maedler-Kron, and Jean-Pierre Routy

Subjects
lymphoproliferative disorders, multicentric castleman disease, siltuximab, il-6, covid-19, Medicine
Abstract

Background: Castleman disease (CD) is a rare lymphoproliferative disorder with various subtypes, including the HHV-8-negative/idiopathic multicentric CD (iMCD). The diagnosis of iMCD remains challenging due to its non-specific presentation, in the form of generalised lymphadenopathies and inflammation. Two clinical presentations have been recently defined: a severe form iMCD-TAFRO and a milder form of iMCD not otherwise specified (iMCD-NOS). identification of interleukin-6 (IL-6) as a major culprit of inflammatory symptoms led to the development of anti-IL-6 therapies, with siltuximab being the approved first-line treatment. Case description: A 16-year-old male presented with recurrent fever, night sweats and several other non-specific symptoms. After extensive evaluations, an excisional lymph node biopsy confirmed the iMCD-NOS diagnosis. The patient received high-dose steroid therapy followed by siltuximab for four years. This treatment was well tolerated with only mild neutropenia not leading to dose adjustment. On siltuximab, the patient developed two mild COVID-19 episodes. His response to siltuximab remained effective throughout four years. Discussion: The absence of biomarker or causal agent identification poses a diagnostic challenge requiring lymph node histopathology for a definitive diagnosis of iMCD. Anti-IL 6 (siltuximab) is the recommended frontline therapy, suppressing inflammation and halting disease progression. Intravenous administration every 3 to 6 weeks can impact patient quality of life, prompting further research for alternative treatments. High-dose steroids, rituximab, cyclosporine, tacrolimus, lenalidomide or combined chemotherapy such as rituximab-bortezomib-dexamethasone are among the considered options according to disease severity. Conclusion: Overall, long-term siltuximab effectively controlled iMCD symptoms and was well tolerated by this young adult, who endured two mild COVID-19 episodes.

Published
2023
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48. Predictors of outcomes after surgery for medically intractable insular epilepsy: A systematic review and individual participant data meta‐analysis

Author

Sami Obaid, Jia‐Shu Chen, George M. Ibrahim, Alain Bouthillier, Evan Dimentberg, Werner Surbeck, Elena Guadagno, Tristan Brunette‐Clément, Nathan A. Shlobin, Aidan Shulkin, Andrew T. Hale, Luke D. Tomycz, Marec Von Lehe, Michael Scott Perry, Francine Chassoux, Viviane Bouilleret, Delphine Taussig, Martine Fohlen, Georg Dorfmuller, Koichi Hagiwara, Jean Isnard, Chima O. Oluigbo, Naoki Ikegaya, Dang K. Nguyen, Aria Fallah, and Alexander G. Weil

Subjects
epilepsy, epilepsy surgery, insula, insular epilepsy, insulectomy, surgical outcome, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Insular epilepsy (IE) is an increasingly recognized cause of drug‐resistant epilepsy amenable to surgery. However, concerns of suboptimal seizure control and permanent neurological morbidity hamper widespread adoption of surgery for IE. We performed a systematic review and individual participant data meta‐analysis to determine the efficacy and safety profile of surgery for IE and identify predictors of outcomes. Of 2483 unique citations, 24 retrospective studies reporting on 312 participants were eligible for inclusion. The median follow‐up duration was 2.58 years (range, 0‐17 years), and 206 (66.7%) patients were seizure‐free at last follow‐up. Younger age at surgery (≤18 years; HR = 1.70, 95% CI = 1.09‐2.66, P = .022) and invasive EEG monitoring (HR = 1.97, 95% CI = 1.04‐3.74, P = .039) were significantly associated with shorter time to seizure recurrence. Performing MR‐guided laser ablation or radiofrequency ablation instead of open resection (OR = 2.05, 95% CI = 1.08‐3.89, P = .028) was independently associated with suboptimal or poor seizure outcome (Engel II‐IV) at last follow‐up. Postoperative neurological complications occurred in 42.5% of patients, most commonly motor deficits (29.9%). Permanent neurological complications occurred in 7.8% of surgeries, including 5% and 1.4% rate of permanent motor deficits and dysphasia, respectively. Resection of the frontal operculum was independently associated with greater odds of motor deficits (OR = 2.75, 95% CI = 1.46‐5.15, P = .002). Dominant‐hemisphere resections were independently associated with dysphasia (OR = 13.09, 95% CI = 2.22‐77.14, P = .005) albeit none of the observed language deficits were permanent. Surgery for IE is associated with a good efficacy/safety profile. Most patients experience seizure freedom, and neurological deficits are predominantly transient. Pediatric patients and those requiring invasive monitoring or undergoing stereotactic ablation procedures experience lower rates of seizure freedom. Transgression of the frontal operculum should be avoided if it is not deemed part of the epileptogenic zone. Well‐selected candidates undergoing dominant‐hemisphere resection are more likely to exhibit transient language deficits; however, the risk of permanent deficit is very low.

Published
2023
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49. Evaluation of ceftolozane-tazobactam susceptibility on a French nationwide collection of Enterobacterales

Author

Agnès B. Jousset, Sandrine Bernabeu, Cécile Emeraud, Rémy A. Bonnin, Alexandra Lomont, Jean Ralph Zahar, Audrey Merens, Christophe Isnard, Nathalie Soismier, Eric Farfour, Vincent Fihman, Nicolas Yin, Olivier Barraud, Hervé Jacquier, Anne-Gaëlle Ranc, Frédéric Laurent, Stéphane Corvec, Louise Ruffier d'Epenoux, Emmanuelle Bille, Nicolas Degand, Chloé Plouzeau, Thomas Guillard, Vincent Cattoir, Asaf Mizrahi, Antoine Grillon, Frédéric Janvier, Cécile Le Brun, Marlène Amara, Mathilda Bastide, Alban Lemonnier, and Laurent Dortet

Subjects
Ceftolozane-tazobactam, ESBL, Carbapenemase, Enterobacterales, Epidemiology, France, Microbiology, QR1-502
Abstract

ABSTRACT: Objectives: Ceftolozane-tazobactam (C/T) proved its efficacy for the treatment of infections caused by non-carbapenemase producing Pseudomonas aeruginosa and Enterobacterales. Here, we aimed to provide susceptibility data on a large series of Enterobacterales since the revision of EUCAST categorization breakpoints in 2020. Methods: First, C/T susceptibility was determined on characterized Enterobacterales resistant to third generation cephalosporins (3GCs) (extended spectrum β-lactamase [ESBL] production or different levels of AmpC overexpression) (n = 213) and carbapenem-resistant Enterobacterales (CRE) (n = 259), including 170 carbapenemase producers (CPE). Then, 1632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by E-test® (biomérieux) and broth microdilution (BMD) (Sensititre™, Thermo Scientific) to perform method comparison. Results: Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with important variation depending on the resistance mechanism: 93% vs. 13% susceptibility for CTX-M and SHV-ESBL producers, respectively. Only 20% of the CRE were susceptible to C/T. Among CPE, 80% of OXA-48-like producers were susceptible to C/T, whereas all metallo-β-lactamase producers were resistant. The prospective study revealed that 95.6% of clinical isolates were susceptible to C/T. Method comparison performed on these 1632 clinical isolates demonstrated 99% of categorization agreement between MIC to C/T determined by E-test® in comparison with the BMD (reference) and only 74% of essential agreement. Conclusion: Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers, and ESBL-producing Escherichia coli but is less active against ESBL-producing Klebsiella pneumoniae, and CRE. E-test® led to an underestimation of the MICs in comparison to the BMD reference.

Published
2023
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50. Glucan rich nutrition does not increase gut translocation of beta‐glucan

Author

Hoenigl, Martin, Lin, John, Finkelman, Malcolm, Zhang, Yonglong, Karris, Maile Y, Letendre, Scott L, Ellis, Ronald J, Burke, Leah, Richard, Byron, Gaufin, Thaidra, Isnard, Stéphane, Routy, Jean‐Pierre, and Gianella, Sara

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Liver Disease, Clinical Research, Chronic Liver Disease and Cirrhosis, HIV/AIDS, Infectious Diseases, Infection, Oral and gastrointestinal, Adult, Biomarkers, Female, Glucans, HIV Infections, Humans, Invasive Fungal Infections, Liver Cirrhosis, Male, Middle Aged, Pilot Projects, Young Adult, beta-Glucans, 1&#8208, 3&#8208, beta&#8208, D&#8208, glucan, fungal translocation, healthy controls, liver cirrhosis, microbial translocation, non&#8208, AIDS events, plasma, 1-3-beta-D-glucan, non-AIDS events, Microbiology, Clinical sciences
Abstract

Background(1-3)-b-D-glucan (BDG) is a fungal cell wall component and, in the absence of invasive fungal infection, a novel biomarker for microbial translocation of endogenous fungal products from the gastrointestinal tract into systemic circulation. However, its value as a marker of fungal translocation is limited by a concern that plant BDG-rich food influences blood BDG levels.MethodsWe conducted a pilot clinical trial to evaluate the impact of a standardised oral BDG challenge on blood BDG levels in participants with and without elevated microbial translocation. We enrolled 14 participants including 8 with HIV infection, 2 with advanced liver cirrhosis, and 4 healthy controls. After obtaining a baseline blood sample, participants received a standardised milkshake containing high levels of BDG followed by serial blood samples up to 8 hours after intake.ResultsThe standardised oral BDG challenge approach did not change the blood BDG levels over time in all participants. We found consistently elevated blood BDG levels in one participant with advanced liver cirrhosis and a single person with HIV with a low CD4 count of 201 cells/mm3 .ConclusionOur findings indicate that BDG blood levels were not influenced by plant origin BDG-rich nutrition in PWH, people with advanced liver cirrhosis, or healthy controls. Future studies are needed to analyse gut mycobiota populations in individuals with elevated blood BDG levels.

Published
2021

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