ED Sciences Physiques et de l'Ingénieur
Parametric Design and Manufacturing
by Alexandre PREVOT (I2M - Institut de Mécanique et d'Ingénierie de Bordeaux)
The defense will take place at 10h00 - Amphithéâtre La Rochefoucauld Liancourt Arts et Métiers de Bordeaux Esplanade des Arts et Métiers, 33400, Talence
in front of the jury composed of
- Denis TEISSANDIER - Professeur des universités - Université de Bordeaux - Directeur de these
- Yann LEDOUX - Professeur des universités - Grenoble INP - CoDirecteur de these
- Jean-Marc LINARES - Professeur des universités - Aix-Marseille Université - Examinateur
- François THIEBAUT - Maître de conférences - Université Paris-Saclay - Rapporteur
- Jean-Yves DANTAN - Professeur des universités - Arts et Métiers de Metz - Rapporteur
Tolerancing, at the design stage, consists of transferring a functional requirement, defined at the product level, to geometric specifications of individual parts. At the production stage, these specifications are transferred to the control of the processes implemented in the manufacturing range. In an aeronautical context of small series of high value-added parts, with specifications with tight tolerance intervals that are difficult to control in production, it is common to find non-conformities with some specifications. An important economic issue is, nevertheless, the use of the parts. Indeed, a part that does not conform to one (or more) specification(s) can sometimes satisfy the functional requirements at the part or product level. Currently, the decision to retain or reject these parts is left to the tolerance analysis experts, who have few tools to quantify the impact of part non-conformities. They are therefore sometimes forced to rely on feedback to make such a decision. The objective of this thesis project is to respond to this problem by developing an innovative approach, known as Parametric Design and Manufacturing (PDM). This approach consists of actively adapting the parameterisation and estimation of the admissible defects of parts from the design phase to the manufacturing phase. This is based on measurements made on parts and sub-assemblies already produced. This approach involves: - Ensuring the functional traceability of specifications in a digital chain, integrating the design and manufacturing stages. - Estimating the conformity of the product despite one or more parts that do not comply with the geometric specifications, without modifying the production parameters. - To propose modifications to the geometric parameters of a part, in the case where it is unlikely that the functional requirements of the product will be met. Thus the production parameters of this part would be modified. This type of action consists of pairing the parts. In this way, it would be possible to propose a qualification and decision tool in the face of non-conformities. One consequence of this approach is that the interchangeability of parts challengend, when pairing is used. The PDM will therefore be limited to permanent assemblies (e.g. welded assemblies) that do not require regular maintenance.
ED Sciences et environnements
Arcy-sur-Cure Neandertals (Yonne, France): Morphological variability, dental wear and behavioral insights
by Juliette HENRION (De la Préhistoire à l'Actuel : Culture, Environnement, Anthropologie)
The defense will take place at 14h00 - Amphitheatre B6 Université de Bordeaux, bâtiment B6, Allée Geoffroy Saint-Hilaire CS 50023, 33615 Pessac Cedex, France
in front of the jury composed of
- Bruno MAUREILLE - Directeur de recherche - Université de Bordeaux - Directeur de these
- Sireen EL-ZAATARI - Professeure - Universitat Tübingen - Rapporteur
- Emma POMEROY - Associate Professor - Cambridge University - Rapporteur
- Jean-Jacques HUBLIN - Professeur - Collège de France - CoDirecteur de these
- Priscilla BAYLE - Maîtresse de conférences - Université de Bordeaux - Examinateur
- Sandrine PRAT - Directrice de recherche - UMR7194 HNHP - Examinateur
- Shara BAILEY - Professeure - New York University - Examinateur
The prehistoric caves of Arcy-sur-Cure provide a unique archaeological record, contributing to the study of Neanderthal populations from the Middle to Late Paleolithic for over 75 years. Five caves have yielded 147 remains spanning the Mousterian to Châtelperronian techno-complexes. A single tooth is found in the Grotte du Loup, while the Grotte du Bison present the highest number of dental remains (n = 42/49), representing a minimum of 12 individuals across all age groups. The Grotte du Renne yielded 74 remains from a minimum of nine individuals, mostly juveniles (in utero to pubescent). The Schoepflin Galerie, associated to the Grotte du Renne, contains five remains from at least three individuals. The Grotte de l'Hyène (n = 18) yields at least six individuals, ranging from late childhood to old age. The dental collection displays morphological traits frequently seen in Neanderthal and apomorphies. Consistent grooves and pits on the crown apex of unworn teeth (33/48) suggest a relatively homogenous sample. Inter-individual variation is also evident, particularly in the crown diameters of the Grotte du Renne and Grotte du Bison specimens, which can align with pre-Neanderthal variability. Premolars exhibit extensive root variability both between and within specimens. Morphometric analyses place the premolars and molars within Neanderthal variability, though the Grotte du Bison M1, the Grotte du Renne M1 and P4, and the P4 are projected between early and late Neanderthals. Three specimens fall morphometrically between Neanderthal and anatomically modern human variability, indicating morphological diversity among late Neanderthals at Arcy-sur-Cure. Dental wear patterns suggest heavy mastication of hard materials, with pronounced occlusal pitting, enamel fractures, and advanced hypercementosis together with strong occlusal relief reduction. The occlusal topography and microwear of the Grotte de l'Hyène specimens indicate a right-side preference in both dental arches. The important occlusal wear of the Grotte de l'Hyène maxilla, characterized by marked wear basins, particularly distally, aligns with prolonged processing of hard materials. This mechanic is also observed in a younger individual from the Grotte du Bison. The mandible from the Grotte de l'Hyène exhibits pronounced scrapings on the buccal surfaces of postcanine teeth and a central incisor, suggesting non-masticatory use. These findings imply similar dental behaviors across age groups and between the Mousterian units of the Grotte du Bison and Grotte de l'Hyène.
ED Sociétés, Politique, Santé Publique
Evaluation of trastuzumab safety profile: analysis of ADRs occurred in the EU countries during years 2018-2024 after the availability of biosimilars
by Andrea OLIVA (Bordeaux Population Health Research Center)
The defense will take place at 11h00 - En visioconférence
in front of the jury composed of
- Francesco SALVO - Professeur des universités - Université de Bordeaux - Directeur de these
- Armando GENAZZANI - Professeur des universités - Università di Torino - Rapporteur
- Annamaria DE LUCA - Professeure des universités - Università degli Studi di Bari Aldo Moro - Rapporteur
- Paola MINGHETTI - Professeure des universités - Università degli studi di Milano - Examinateur
- Marco TUCCORI - Associate Professor - Università di Verona - Examinateur
- Cristina SCAVONE - Associate Professor - Link Campus University - CoDirecteur de these
In the last decade, cancer therapies have increasingly taken the form of combination treatments in which biologic agents play a crucial role. In breast cancer, the treatment strategy is adjusted to intrinsic subtypes such as human epidermal growth factor receptor-2(HER2)-positive. With the introduction of trastuzumab, a monoclonal antibody against HER2, survival has significantly improved in early and metastatic breast cancer. Considering that Herceptin has been on the European market for over twenty years and its biosimilars have also been available since 2018, through the evaluation of the scientific literature and safety information from post-marketing reports we want to carry out an updated evaluation of the safety profile of trastuzumab, with a secondary focus on the differences between the originator and the biosimilars. Specifically, two analyses were conducted: a meta-analysis of phase three randomized trials and an evaluation of Individual Case of Safety Reports (ICSRs) from EudraVigilance in the period 2018-2024. Through the literature screening were been identified 199 records then 42 articles were considered eligible according to inclusion criteria therefor analysed as full text. At the end 14 records are included for the meta-analysis; the outcome of our analysis showed that no significant difference in death-related adverse events was found for trastuzumab biosimilar and originator when evaluated for an early breast cancer in the neoadjuvant phase (Risk Ratio [RR], 1.30; 95% confidence interval [CI], 0.47-3.59; I2 = 0%; p = 0.57) and overall (RR, 0.43; 95%CI, 0.11-1.66; I2 = 20%; p = 0.26), and for metastatic breast cancer (RR, 0.61; 95%CI, 0.30-1.26; I2 = 0%; p = 0.85). From post-marketing analysis 11,951 ICSRs were collected, covering 29,726 PTs, related to trastuzumab products; during the study period, the majority of ICSRs reported trastuzumab originator as suspected drug. ICSRs were mainly classified as serious, especially for trastuzumab originator, and that the outcome was mostly reported as favorable, especially for biosimilars-related ADRs. For the SOC "Cardiac Disorders", originator trastuzumab was most frequently reported as a suspect drug, while for the SOC "Respiratory Disorders", originator was less frequently reported compared to biosimilars, as well as for infusion reactions. Analysis of data from the literature and post-marketing data confirmed the safety profile of trastuzumab, with no significant differences emerging between the originator and biosimilars.