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Using Fisher Information Matrix to predict uncertainty in covariate effects and power to detect their relevance in Non-Linear Mixed Effect Models in pharmacometrics
No full textInternational audienceThis work focuses on design of experiments for Pharmacokinetic (PK) and Pharmacodynamic (PD) studies. Non-Linear Mixed Effects Models (NLMEM) modelling allows the identification and quantification of covariates that explain inter-individual variability (IIV). The Fisher Information Matrix (FIM), computed by linearization, has already been used to predict uncertainty on covariate parameters and power of test to detect statistical significance. A covariate effect is deemed statistically significant if it is different from 0 according to a Wald comparison test and clinically relevant if the ratio of change it causes in the parameter is relevant according to a test inspired by the two one-sided tests (TOST) as in bioequivalence studies. FIM calculation was extended by computing its expectation on the joint distribution of the covariates, discrete and continuous. Three methods were proposed: using a provided sample of covariate vectors, simulating covariate vectors, based on provided independent distributions or on estimated copulas. Thereafter, CI of ratios, power of tests and number of subjects needed to achieve desired confidence were derived. Methods were implemented in a working version of the R package PFIM6.1. A simulation study was conducted under various scenarios, including different sample sizes, sampling points, and IIV. Overall, uncertainty on covariate effects and power of tests were accurately predicted. The method was applied to a population PK model of the drug cabozantinib including 27 covariate relationships. Despite numerous relationships, limited representation of certain covariates, FIM correctly predicted uncertainty, and is therefore suitable for rapidly computing number of subjects needed to achieve given powers.</div
Overcoming the Strength-Plasticity Trade-Off in Metallic Thin Films through Atomic and Microstructural Design Strategies
No full textInternational audienceThe current trend toward miniaturization in devices components in key technologies such as microelectronics, energy production, sensors and wear protection requires the development of high-performance thin films (TFs) with superior mechanical properties combining mutually excluding mechanical properties such as high yield strength and plastic deformation. Achieving such performance, relies on leveraging TF’s atomic composition and microstructure (nanointerfaces, grain size etc.) exploiting nanoengineering design concepts. Here, I will present recent results for several class of advanced TF materials including nanostructured metallic glasses (ZrCu, ZrCuAl) [1, 2] high entropy alloys (CoCuCrFeNi, AlxCoCuCrFeNi) and nanolaminates (fully amorphous, amorphous/crystalline, FCC/BCC) [3, 4], highlighting how the control of the microstructure affect the and micro-scale mechanical behavior and enable ultimate overcoming the strength-plasticity paradigm. Among the main results, I will show the fabrication of fully amorphous Zr24Cu76/Zr61Cu39 nanolaminates with controlled nanoscale periodicity (Λ, down to 5 nm), local chemistry and glass-glass interfaces [3]. I will show how the shear band instability can be mitigated when Λ ≤ 50 nm, reaching remarkably large elastic/plastic deformation (16%) and yield strength (~2GPa) by micro-pillar compression [3]. Then, I will present the synthesis nanostructured metallic glass and High Entropy Alloy TFs. I will show how nanogranular ZrCu metallic glass can reach ultimate yield strength (>3 GPa) and ductility (>6 %). Then, I will focus on the synthesis of crystal/glass ultrafine nanolaminates [4] in which ∼4 nm Al (crystalline) separate 6 and 9 nm-thick Zr50Cu50 metallic glass nanolayers, showing high yield strength (3.4 GPa) in combination with enhanced elastoplastic deformation (>6%, in compression), while managing to effectively block the percolation of shear bands even at >15% deformation [4]. Finally, I will present, the synthesis of CoCrCuFeNi High Entropy Alloys TFs with nanosized grains, enabling strong Hall-Petch strengthening, plastic deformably and thermal stability.In the last part of the seminar, I will present recent developments within my group at LSPM, highlighting new research activities dealing with the synthesis of nanostructured metallic films and the development of a new platform for in situ SEM mechanical characterization.Figure: Synthesis of nanostructured metallic films with high strength and plasticity product.References[1] M. Ghidelli et al., Novel class of nanostructured metallic glass films with superior and tunable mechanical properties, Acta Mater. 213 (2021) 116955.[2] C. Poltronieri et al., Mechanical properties and thermal stability of ZrCuAlx thin film metallic glasses: Experiments and first-principle calculations, Acta Mater. 258 (2023) 119226.[3] A. Brognara et al., Tailoring Mechanical Properties and Shear Band Propagation in ZrCu Metallic Glass Nanolaminates Through Chemical Heterogeneities and Interface Density, Small Struct. (2024) 2400011.[4] F. Bignoli et al., Novel class of crystal/glass ultrafine nanolaminates with large and tunable mechanical properties, ACS Appl. Mater. Inter. 16(27) (2024) 35686-35696
Covid, chikungunya : à La Réunion, une gestion des crises sanitaires entre héritages coloniaux et volonté de participation citoyenne
No full textAdvanced Thin Film High Entropy Alloys with Tailorable Microstructure and Mechanical Properties
No full textInternational audienceHigh entropy alloy thin films (HEAs-TF) have recently gained attention due to their possibility to combine mutually exclusive properties, such as high yield strength, ductility and thermal stability, while offering a wide range of chemical compositions. For this reason, HEAs-TF have potential applications for microscale electrical devices or high-performance coatings [1]. However, microstructural control for advanced HEAs-TF (nanocrystalline films, nanolaminates) is often limited by traditional thin film deposition techniques such as magnetron sputtering, hindering the formation of HEAs-TF with large mechanical properties (yield strength, ductility). In this regard, pulsed laser deposition (PLD) was used to prepare advanced HEAs-TF allowing to easily control the nanoarchitecture of nanocrystalline films and ultrafine nanolaminates.In this context, firstly I will focus on the synthesis of nanocrystalline CoCrCuFeNi HEA-TFs by PLD with a wide range of microstructures (grain size and morphology) obtained simply by controlling the background gas pressure, while comparing with sputter-deposited counterparts. A transition from compact to nanogranular morphology was observed for deposition pressures >1 Pa, leading to a decrease in mass density and grain size (6.81 g/cm3 and 11 nm, respectively) compared to the compact counterpart (7.72 g/cm3 and 40 nm, respectively). These films by PLD show increased hardness (≈11 GPa) compared to sputter-deposited films (≈8.3 GPa) due to their ultrafine grain structure leading to Hall-Petch strengthening. Micropillar compression tests show high yield strength of 1.9 GPa with high plastic deformability (30% strain). Post-thermal annealing treatments reveal grain coarsening and segregation of a secondary BCC phase starting at 400°C for both compact and nanogranular films. However, nanogranular films maintain a lower grain size during annealing (< 20nm), thus retaining higher hardness of 8.5 GPa (Hall-Petch strengthening). Secondly, I will focus on Al/HEA nanolaminates (NLs) by PLD and magnetron sputtering, aiming to block the propagation of dislocations by controlling the interface density to improve hardness and yield strength [2]. Nanolaminates with different atomic compositions have been fabricated by magnetron sputtering, involving semi-coherent (FCC/FCC Al/CoCrCuFeNi) and incoherent (FCC/BCC Al/Al25(CoCrCuFeNi)75) interfaces to further hinder cross-layer dislocation propagation and boost mechanical properties. Among the main results, in situ micropillar compression test shows that incoherent interfaces have greater capability to improve yield strength (up to 2.2 GPa), while still showing great plastic deformability with no appearance of cracks even at 30% deformation. Using PLD, a wide range of bilayer periods (Λ) was explored, allowing to prepare ultrafine NLs with a bilayer period as low as 2.5 nm up until 400 nm. These NLs show high hardness, with a maximum of 9.8 GPa for Λ = 25 nm due to the high interface density, despite having a 50% volume fraction of Al. Our results show how PLD and sputtering can be used to control the nano-engineering of TF-HEAs, resulting in improved and tunable mechanical properties with key implications for industry applications.[1] N. I. M. Nadzri et al. ‘High-Entropy Alloy for Thin Film Application: A Review’, Coatings, 12, 2022[2] A. Sàenz-Trevizo et al., Nanomaterials by design: a review of nanoscale metallic multilayers Nanotechnology, 31, 202
What factors shape an individual’s probability to be enrolled in a professionally-managed community-based health insurance? Results from a cross-sectional case-control study in two districts in Mali
No full textInternational audienceAcross West Africa, countries are promoting new models of community-based health insurance (CBHI) to overcome the challenges faced by existing schemes. We investigated factors associated with an individual’s probability to be enrolled in one of two professionally-managed CBHI in Mali. We carried out a case-control methodology and used multi-stage sampling to select CBHI members and non-members. The primary outcome variable was being enrolled or not in the CBHI. Three-level mixed-effects logistic regression model was used to estimate the association between individual enrolment and series of individual, household, and wider community factors. Of the 1,270 people surveyed 847 and 423 were non-members and members respectively. Respondents with primary education (AOR = 1.6, P = 0,035), secondary education (AOR = 2.31, P = 0,001) or higher school/University (AOR = 5.5, P < 0,001); who were economically active (AOR = 1.52, P = 0,05) and considered themselves wealthy (AOR = 1.94, P < 0,001) were more likely to subscribe to CBHI. Those who reported having a good perception of their health (AOR = 0.68, P = 0,038) were less likely to subscribe to CBHI. Albeit substantially higher than what experienced by community-based schemes, membership in these professionally-managed CBHI remains low and the determinants of participation do not differ substantially from what reported in the general literature. Targeting the needs of poor vulnerable people and more pervasive communication strategies are urgently needed to enhance enrolment in these new CBHI and ensure the way to UHC
Sociologie
No full textInternational audienceLa sociologie de l’alimentation analyse la diversité des pratiques alimentaires en les rapportant aux contextes sociaux, économiques, genrés et biographiques qui les façonnent. En mobilisant des approches qualitatives et quantitatives, elle met en lumière les inégalités sociales face à l’alimentation et la réception différenciée des normes et politiques publiques
Modulation mécanosensible des interactions vWF/GPIb par le désassemblage du cytosquelette d'actine induit par MICAL1
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Assessment of Age at Death in Perinatal Individuals from Dental Histology Analysis. An Exploratory Study
No full textInternational audienceAge estimation is one of the main data used in the study of child skeletal remains in forensic and bioarchaeological investigations. Objective: Our aim was to assess the age at death attributed through methods based on bone development and by analysing the microstructure of tooth enamel. Methods: Age at death was estimated using femur length and dental histology in 9 perinatal individuals of known age. Two methods were selected for the estimation of age at death from femur length. Previous work has reported that these two methods produce the best estimations of the age at death of individuals. For the dental histology analysis, longitudinal ground sections of 6 deciduous incisors from 5 individuals were examined. Incremental lines in the tooth enamel (striae of Retzius and the neonatal line) were used to estimate the age at death, assuming a daily secretion rate of 3.23 μm. Results: The ages estimated by the two methods based on femur length differ, except for those concerning the last stage of gestation. It is interesting to note that the accuracy of the estimation depends on whether the method was established with prenatal or postnatal individuals. Estimated ages based on dental histology (N=3 individuals) are consistent with the recorded data. Conclusion: The study of dental histology based on the analysis of enamel microanatomy has some limitations but allows the age at death in to be established very accurately. The quality and quantity of data that this technique provides is of prime importance for forensic studies and for analyses of historical populations and archaeological remains
Les infrastructures numériques du vote en Afrique. Biométrie, machines à voter et marchands de démocratie au Kenya et au Sénégal
No full textDigital infrastructures of African Elections. Biometrics, voting machines and the democracy industries in Kenya and SenegalVoting machines have become prominent features of public life in Africa. Parliamentary majorities advocate their use to support modernization policies, while opposition parties accuse them of hacking election databases to favor a « computer-generated » president. Citizens, now well-versed in voting technology, are demanding that servers be opened to reveal the truth about election results. They criticize the selection of technology providers and question whether operators respect their digital privacy and sovereignty. In Kenya, Senegal, and other countries across the continent, the election of the head of state unfolds within the context of a unique technical democracy -largely uncharted by Science and Technology Studies (STS) -characterized by the integration of computing technology debates within parliamentary democracy. What does the proliferation of digital tools, professions, and industries tell us about political authority, its relationship with technical authority, and the exercise of power in the postcolony? At the intersection of STS, African Studies, and the sociology of voting, this dissertation examines the close relationship between postcolonial practices of democracy and the development of digital and biometric industries. Far from being the product of administration evolution, digital voting developed alongside the expansion of citizenship and electoral practices after the 1960s Independence, through market creation and the industrial valorization of postcolonial popular participation. The thesis draws on a comparative investigation conducted from 2017 to 2022 on the digitization of voting in Kenya and Senegal. It is based on: a) Two ethnographic field studies during the presidential elections of 2017 (Kenya) and 2019 (Senegal), observing the articulation between public political debates (the stage, the interface) and the behind-the-scenes work of electoral institutions on the production of voting technologies (the infrastructure, the back office); b) A corpus of interviews with seventy-three individuals involved in the organization of voting and electoral biometrics in Africa since the 1970s: African and Western computer engineers, actors in the biometrics industry, and officials from development and democratization cooperation agencies; c) A collection of documentation (electoral laws, print and online media, industrial documents) covering the industrial history of electoral technologies in the two countries studied, from 1977 to 2022. The thesis presents three findings that contribute to the literature in political anthropology, anthropology of the state, sociology of development and democracy, and the sociology of voting. The first concerns the longue durée of computer governance in Kenya and Senegal. Far from being an innovation of our century, IT governance was established with the worldwide introduction of computers in public administrations during the 1960s and 1970s. Emerging in parallel with African independences from the colonial rule, IT governance exists in continuity with the transnational forms of governance initiated during the colonial era. The second finding reveals how electoral problems, often viewed as striclty national and local, are on the contrary closely linked to practices of international intervention through computing. Biometrics in Senegal and the electronic transmission of election results in Kenya are two market products and two travelling and hegemonics models of democracy, developed between the local electoral field and the international development and democracy sphere. The third finding shows that, contrary to viewing computing as a tool for politica pacification, it is a key dimension of political violence. Already used in the most controversial elections in the history of the two countries (1980s-1990s) and present before Kenya's violent post-election riots in 2007, electoral computing emerges as an instrument for governing political opposition and perpetuating power, both nationally and transnationally.Les machines à voter, ou urnes électroniques sont désormais des figures proéminentes de la vie publique en Afrique : les majorités parlementaires les invoquent pour promouvoir des politiques modernistes ; les oppositions les accusent de s'en servir pour pirater les bases de données électorales au profit de chefs d'État élus par ordinateur ; les citoyens, désormais experts en ingénierie du vote, réclament l'ouverture des serveurs pour dévoiler « la vérité électorale », critiquent les choix des fournisseurs, tout en se demandant si les opérateurs respectent leur souveraineté numérique. Au Kenya, au Sénégal, l'élection du chef de l'État se déroule dans le contexte d'une démocratie technique singulière, inexplorée par les études sociales des sciences (STS), dont la spécificité est d'inscrire les débats sur les technologies de l'informatique dans le cadre de la fabrique de la démocratie parlementaire. Que nous apprend l'inflation des outils, des métiers et des industries numériques sur l'autorité politique, sur sa relation à l'autorité technique, et sur l'exercice du pouvoir en postcolonie ? À l'intersection entre les STS, les études africaines et de la sociologie du vote, cette thèse rend compte d'une relation étroite entre les pratiques de la démocratie postcoloniale et le développement des industries numériques mondiales. Loin de n'être que le produit exogène d'une évolution de l'administration du vote, les technologies électorales numériques se construisent parallèlement à la massification de la citoyenneté et des pratiques de vote après les Indépendances, à travers une valorisation industrielle de la participation populaire. La thèse s'appuie sur une enquête comparative conduite de 2017 à 2022 et portant sur la numérisation du vote au Kenya et au Sénégal. Je me base sur a) deux terrains de recherche au cours des élections présidentielles de 2017 (Kenya) et de 2019 (Sénégal), observant aussi bien la scène du débat politique que les coulisses du travail de production technique des institutions électorales ; b) un corpus d'entretiens avec soixante-treize personnes impliquées dans l'organisation du vote et de la biométrie électorale en Afrique depuis les années 1970 : ingénieurs-informaticiens africains et occidentaux, acteurs d'entreprises de biométrie, responsables d'agences de coopération au développement ; sur une collecte de documentation (lois électorales, presse, documents industriels) couvrant l'histoire industrielle des technologies. La thèse apporte trois résultats principaux : le premier illustre la longue durée de la gouvernance informatique au Kenya et au Sénégal. Loin d'être une innovation de notre siècle, elle a émergé dans les années 1960 et 1970, avec l'arrivée des ordinateurs dans les administrations publiques du monde entier. Apparue en même temps que les Indépendances, la gouvernance informatique s'inscrit dans la continuité des formes transnationales de gouvernance de l'État postcolonial, des populations et du politique. Le deuxième résultat montre comment les « problèmes électoraux » au Kenya et au Sénégalsouvent considérés comme des enjeux locaux et nationaux -sont en réalité étroitement liés aux pratiques d'intervention internationale par le biais de l'informatique. La biométrie au Sénégal et la transmission électronique des résultats électoraux au Kenya sont deux produits du marché et deux modèles de démocratiehégémoniques et voyageurs - élaborés entre le champ électoral local et la sphère internationale de l'aide au développement (de la France) et à la démocratisation (des États-Unis). Le troisième résultat montre que, loin d'être un instrument de pacification électorale, l'informatique constitue une dimension clé des violences politiques. Déjà mobilisée lors des élections les plus controversées de l'histoire des pays étudiés (années 1980-1990) et présents lors des violentes émeutes postélectorales de 2007 au Kenya, l'informatique dans le vote apparaît comme un outil de centralisation du pouvoir, de contrôle des partis à l'opposition et de pérennisation du pouvoir, tant au niveau national qu'au niveau transnational
