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The Metabolic Effects of Natural Sugars, Refined Sugars and Low-Calorie Sweeteners
No full textThis thesis evaluated the metabolic effects of natural sugars, refined sugars and low-calorie sweeteners in healthy individuals. Two narrative reviews, one comprehensive critical review and one experimental study were conducted. The first narrative review examined the metabolic health effects associated with the consumption of both sugar-sweetened beverages and natural fruit juices. Specifically, it summarized the physiology of glucose and fructose metabolism and their distinct impacts on metabolic health, with particular emphasis on blood lipid profiles. However, the limited evidence on metabolic effects beyond systemic low-grade inflammation, combined with significant discrepancies in study designs and measured outcomes, prevents the formulation of evidence-based recommendations regarding whether fruit juices represent healthier alternatives to sugar-sweetened beverages. The second article reviewed the potential metabolic health effects associated with low-calorie sweetener consumption, also an alternative to sugar-sweetened beverages. Aimed at informing physicians and clinicians, it provided a concise overview of the available evidence in French, thereby contributing to knowledge dissemination and enhancing scientific accessibility within francophone communities. Since the publication of this narrative review, substantial new evidence has emerged examining the effects of low-calorie sweeteners, particularly sucralose, on glucose homeostasis and gut microbiota. To contextualize and deepen these findings, the third article presents a comprehensive and critical synthesis of current evidence specifically addressing the cumulative effects of sucralose consumption on postprandial glycemic responses in humans. Furthermore, it explores the potential role of gut microbiota composition and functionality in mediating metabolic outcomes. Building on the mechanistic insights and study limitations synthesized in this critical review, the fourth article presents a randomized controlled trial designed under real-world conditions to evaluate the cumulative effects of sucralose consumption on postprandial glycemic responses and related physiological mechanisms in healthy adults (NARELO study). These potential mechanisms included alterations in gut microbiota profiles, intestinal barrier permeability and systemic low-grade inflammation. In this study, we demonstrated that the realistic consumption of sucralose-sweetened beverages for 21 days impairs postprandial glycemic responses in healthy adults compared to sugar-sweetened beverages (P_Bonf = 0.040), in the absence of significant changes in insulin concentrations, body composition, gut microbiota composition, fecal concentrations of SCFAs and BCFAs, and plasmatic biomarkers of intestinal permeability and systemic low-grade inflammation. Clinically, postprandial glycemic responses were 8.4% higher following the three-week consumption of sucralose-sweetened beverages, based on estimated marginal means (baseline: 5.00 mmol/L, 95% CI 4.36–5.64; post-intervention: 5.42 mmol/L, 95% CI 4.78–6.06). Further, we also explored whether free sugars derived from natural sources elicit distinct metabolic responses compared with refined sugars. To this end, 100% natural fruit juice was included as an exploratory comparator. No meaningful differences were observed in glucose tolerance when comparing natural fruit juice to sugar-sweetened beverages. Collectively, the findings of this thesis challenge the prevailing assumption that low-calorie sweeteners are physiologically inert, emphasizing the need for compound-specific evaluation as the food industry advances toward the next generation of sweeteners. Although a definitive mechanistic explanation remains elusive, the work presented herein considerably advances our understanding of the potential long-term effects of low-calorie sweeteners on glucose homeostasis. Overall, this thesis provides critical evidence on the metabolic impacts of natural sugars, refined sugars, and low-calorie sweeteners, offering valuable insights to inform public health guidelines
Implementation strategies for embedding patient-reported outcome and experience measures (PROMs/PREMs) in routine care: secondary analysis of an umbrella review
No full textAbstract Background Routine capture of patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) is championed as core infrastructure for learning health systems and value-based care. Yet, the guidance on how to implement these measures is scattered. We synthesised evidence on implementation strategies used to introduce and sustain PROMs and PREMs, and examined how these strategies align with common barriers and stages of implementation. Methods We conducted a secondary analysis of an umbrella review (25 reviews; 1086 primary studies, 2014–2023) that catalogued implementation determinants and processes of PROMs and PREMs. Two reviewers independently coded implementation strategies using the 73-item Expert Recommendations for Implementing Change (ERIC) taxonomy. Strategies were temporally mapped to the phases of the Exploration–Preparation–Implementation–Sustainment (EPIS) framework, and onto the barriers identified in the parent review using the CFIR × ERIC matching tool. Results Twenty of 25 reviews reported at least one implementation strategy, yielding 152 instances coded to 43 of 73 ERIC strategies. Pre-implementation strategies (74 instances) focused on local consensus building, readiness and barrier assessments, early IT integration, and front-loaded education and champion preparation. During implementation and sustainment (78 instances), the strategies most often used were audit and feedback, real-time data feedback to clinicians, reminders, facilitation, technical assistance, refresher training, and patient onboarding and prompts. Mapping strategies to key barriers showed reasonable coverage for workflow, staff capability, and organisational fit, but gaps for patient capability, long-term financing, data analytics, and equity. Thirty ERIC strategies were not identified, most relating to policy, financing, or market-shaping. Conclusion Implementing PROMs and PREMs in routine care requires coordinated changes in relationships, workflows, technology, and incentives. This study organises existing evidence into practical tools that health system teams and researchers can use to select, sequence, and resource implementation strategies for PROM and PREM programmes
Background Deletion: The Syntax of Clausal Ellipsis in Hindi/Urdu
No full textThis thesis explores the syntax of subsententials in Hindi/Urdu (H/U), with an empirical focus on sluicing and fragment answers. Such phenomena represent instances where all clausal material is unpronounced, except for a (wh-)phrase (e.g., A: Who did John see? B: Mary.). With evidence from various connectivity effects, I argue that a non-structuralist analysis of such configurations, which does not assume the presence of tacit material, is untenable. Rather, subsententials in this language warrant a structuralist solution, according to which the surfacing remnant base-generates in an underlying clause whose morpho-syntax is reduced at PF. Most structuralist proposals of clausal ellipsis, including scant proposals of sluicing in H/U, assume PF-deletion targets a syntactic constituent (TP), forcing the remnant to escape the ellipsis site it is born in (e.g., A: Who did John see? B: Mary ., where material in angled brackets = PF-deletion). I argue against this conventional view, given the conceptual and empirical issues it raises (chiefly, exceptional movement). I alternatively suggest that non-pronunciation freely and maximally affects morpho-syntactic material surrounding the remnant, allowing it to remain in situ (e.g., A: Who did John see? B: Mary.), as has been argued elsewhere (Morgan 1973; Kimura 2010, 2013; Bruening 2015; Abe 2015; Ott and Struckmeier 2018; Sato et al. 2018; Griffiths 2019; among others). Although PF-deletion is not sensitive to syntactic constituency from this perspective, morpho-syntactic material that does PF-delete must constitute the propositional background of the elided clause to ensure recoverability of unspoken content, reducing clausal ellipsis in H/U to background deletion. I then propose to extend this analysis to correlativization in H/U, wherein a left-peripheral relative clause is associated with a correlate in the host clause (HC) (e.g., The girl who is standing, she is tall). Correlatives (CRs) in this language bear discordant characteristics: on the one hand, CRs display properties that point to their connectivity with the HC (e.g., reconstruction effects) and, on the other, features that point to their extra-sentential status (e.g., the lack of a gap in the HC and prosodic separation of CR–HC). Following recent work on Romance/Germanic left-dislocation (Ott 2014, 2015), which presents a similar paradox, I propose that CRs are not syntactically dependent on their HC; conversely, they are relatives that are part of a separate root clause which is juxtaposed in discourse with the HC and is reduced at PF under identity with it (e.g., The girl who is standing . She is tall.). Connectivity effects of CRs are argued to be ellipsis-mediated, given that such effects are likewise observed in sluicing and fragment answers. In reconciling the contradictory properties of CRs, this novel proposal has an explanatory edge over existing accounts that assume syntactic integration of CR–HC and that rely on either movement or base-generation
Surface Functionalization of Lanthanide-Doped Nanoparticles for Targeted Biomedical Applications
No full textLa causalité concourante en noétique : étude de la q. 2, d. 17, du livre II des Sentences de Jacques de Metz
No full textLe présent mémoire de maîtrise s’intéresse à la théorie noétique des causes concourantes du théologien et philosophe dominicain Jacques de Metz (†1301?). Cette théorie est présentée à la question deux, distinction dix-sept, du livre deux de son Commentaire des Sentences. Dans cette question, l’auteur se demande si la faculté active de l’intellect – l’intellect agent – laisse quelque chose de lui-même dans l’objet présent dans l’âme – le phantasme – pour que ce dernier puisse actualiser la faculté passive de l’intellect, l’intellect possible. Dans cette optique, nous commençons (chapitre 1) par contextualiser la noétique médiévale et le problème de l’interaction entre deux agents ontologiquement hétérogènes : l’intellect et le phantasme. Ensuite (chapitre 2), nous présentons et discutons en détail de la noétique de Jacques. Selon ce dernier, l’intellect agent et le phantasme agissent de concours pour actualiser l’intellect possible, de sorte qu’ils sont tous deux causes de l’acte cognitif. Comme nous le verrons au chapitre 3, cette position se rapproche de celle du franciscain Jean Duns Scot (c. 1266-1308) qui est lui aussi connu pour avoir défendu la théorie des causes concourantes en noétique. C’est pourquoi nous faisons une étude comparative de la position des deux auteurs afin d’en tirer les points communs et les points divergents. Cela nous permet, enfin, de discuter du statut historique de la théorie noétique des causes concourantes. En ce sens, l’objectif général du présent travail est de dresser un portrait compréhensif de la noétique de Jacques de Metz et du contexte dans laquelle elle s’insère
Assessing Changes in Sexual Attractions
No full textSexual attraction is an important component of sexual orientation and is linked to people’s sexual identity and behaviour. Emerging research, typically with samples of women, finds that people experience changes over time in the genders to which they are sexually attracted. Theories and clinical applications related to sexual fluidity continue to be developed based on findings that describe changes in gender-based sexual attractions. But people are sexually attracted to targets/acts beyond men and women. The extent of change in sexual attraction over time to targets/acts beyond gender has not been studied. The goal of this research program is to describe the extent of such changes by developing and using a measure of self-reported sexual attraction (i.e., the Sexual Attractions Inventory; SAI) toward diverse targets/acts over multiple time points. The research questions addressed are (1) how much change is observed in sexual attractions over time, (2) is the SAI a reliable and valid measure of sexual attraction, and (3) what is the extent of change to diverse targets/acts generally and between biographic groups? A three-part sequential research program was conducted. This program began with a systematic review of the literature on changes in sexual attractions, finding that among 15 unique samples, sexual attractions change for almost a fifth of participants. Following this, a measure development and psychometric evaluation study was conducted with a sample of 670 university students, resulting in the use of the SAI to detect change in sexual attraction to 40 items over six months. Finally, a one-year longitudinal study was conducted using an online sample of 2,000 international participants. Effect sizes of change, reliable change indices, and group-based trajectory modeling were used to analyze the data at three time points. The results of this dissertation indicate that some people experience changes in their sexual attractions over time, but stability is common. When people experienced a change, its magnitude varied by target/act (i.e., different changes between normophilic and paraphilic targets/acts) and biographic factors (i.e., gender, age, and sexual orientation of the rater). These findings have both theoretical and clinical implications, which are further discussed
Des sciences forensiques à la science forensique : Implications conceptuelles d'une redéfinition au singulier
No full textLa science forensique, souvent présentée comme une science infaillible capable de révéler la vérité lorsque celle-ci semble inaccessible, est en réalité un champ complexe et en pleine mutation. Ce mémoire plonge au coeur d'une transformation majeure : le passage de multiples "sciences forensiques" à une "science forensique" unifiée. Comment cette quête d'unité peut-elle composer avec une notion de vérité qui se montre complexe, plurielle, voire construite ? En examinant les propositions de la Déclaration de Sydney, les analyses des Critical Forensic Studies et les perspectives de la Contre-Forensique, ce travail explore comment chaque courant épistémologique, en redéfinissant la discipline, engage un rapport distinct à la vérité. Au-delà des mots, se (re)définir c'est s'inscrire dans une certaine construction du savoir. Cette étude met ainsi en lumière les tensions et les implications conceptuelles qui animent ce champ en pleine redéfinition
Weighted Limits in Categories Graded by Monoidal Categories
No full textCategories graded by a monoidal category generalize both -actegories and -enriched categories without requiring additional properties of . However, -graded categories are themselves enriched in the monoidal category of presheaves on . In this text, we define a notion of weighted limit for -graded categories, and show that -graded weighted limits are precisely the -enriched weighted limits whose weights take on representable values. When is biclosed and the -graded categories involved are -enriched, we recover precisely the familiar notion of -enriched weighted limit. We use -graded structure to define weighted limits in -actegories and in -categories for a non-biclosed monoidal . We develop both a convenient concrete formulation and an equivalent abstract description as -graded representations, and explore examples including -graded powers and conical limits
Development of New Bone Substitutes Supporting Vascularization and Mineralization Using 3D Bioprinting
No full textCritical-size bone defects (CBD) remain a major clinical challenge, and their rising incidence has intensified the need for effective and customizable bone substitutes. Successful repair of CBD requires the coordinated establishment of a functional vascular network along with mineralized matrix formation. By enabling precise spatial organization of materials, cells, and growth factors, 3D bioprinting provides a powerful platform for bone regeneration through the fabrication of customized, biomimetic scaffolds. Accordingly, the overall objective of this thesis was to develop new bone substitutes capable of supporting both vascularization and mineralization using 3D bioprinting. The specific objectives were to: 1. develop and characterize a new fibrinogen/gelatin methacryloyl (GelMA)-based bioink with vasculogenic and osteogenic potential; and 2. fabricate scaffolds using the newly developed bioink, either as a stand-alone system or by injecting the bioink into 3D-printed cylindrical polycaprolactone (PCL) grids serving as a reinforcement phase, and compare their physicochemical, mechanical, and biological properties. Three fibrinogen/gelatin methacryloyl (GelMA) ink formulations (with different fibrinogen concentrations) were evaluated for their rheological properties and printability. Following this characterization, the inks were supplemented with vascular endothelial growth factor (VEGF165) and bone morphogenetic protein 2 (BMP 2), and assessed for their ability to enable sustained growth factor release from 3D-printed disk-shaped scaffolds. All inks exhibited suitable rheological properties, including shear-thinning behavior, demonstrated good printability, and enabled sustained growth factor release from scaffolds. To evaluate cell viability, vasculogenic and osteogenic responses, disk-shaped scaffolds were printed with the newly developed bioink containing a mid-range concentration of fibrinogen, supplemented with growth factors, and laden with human bone marrow-derived mesenchymal stem cells (hBM-MSC) and human umbilical vein endothelial cells (HUVEC). Cell viability remained high throughout 21 days of in vitro culture. Immunohistochemical analysis revealed progressive alignment and sprouting of CD31 positive cells, indicative of early vasculogenesis, alongside early osteogenic differentiation, as confirmed by histochemical analysis of alkaline phosphatase (ALP) activity. In parallel, scaffolds were fabricated by printing cylindrical PCL grids that served as a reinforcement phase, into which the bioink was injected. The compressive modulus of these scaffolds under unconfined compression was comparable to values reported for trabecular bone. Finally, an alginate-heparinized alginate/collagen-based ink containing hydroxyapatite nanopowder (HAnp) and supplemented with BMP-2 was developed to fabricate acellular scaffolds. Sustained BMP-2 release from 3D-printed disk-shaped scaffolds was observed over 21 days, likely due in part to the conjugation of alginate to heparin. The released BMP-2 remained biologically active, as evidenced by early osteogenic differentiation of hBM-MSC cultured in 2D with supernatants from BMP-2-supplemented scaffolds. In conclusion, this work demonstrated the potential of a fibrinogen/GelMA-based bioink, supplemented with VEGF165 and BMP-2, to enable vascularization and mineralization in 3D-printed scaffolds for bone regeneration in non-load-bearing applications. When the bioink was injected into a cylindrical PCL grid, the resulting scaffold was mechanically reinforced, supporting its use in load-bearing applications. Additionally, the alginate/collagen-based acellular ink containing heparinized alginate enabled sustained release of bioactive BMP 2 from scaffolds, which could facilitate the recruitment of endogenous cells and promote their osteogenic differentiation in vivo. Together, these findings highlight the potential of the newly developed inks for the fabrication of scaffolds supporting bone regeneration in a broad range of applications
Formation of Ruthenium-Oxo Complexes: An End, and a Beginning for Stereoretentive Olefin Metathesis
No full textOlefin metathesis is a central methodology in modern synthetic chemistry, offering unmatched versatility in the formation of carbon-carbon bonds. Its utility is illustrated by its long-standing use in petrochemical applications, over a period now spanning decades. In synthetic contexts, ruthenium catalysts have been widely adopted owing to their ease of handling relative to the group 6 catalysts. Improvements in catalyst reliability have come with the recognition that the "robust" Ru catalysts are in fact readily degraded by Brønsted and Lewis bases. Oxygen is generally presumed to be relatively unimportant. This study challenges that assumption, setting out contexts in which oxygen sensitivity must be considered.
Much recent attention has focused on stereocontrolled metathesis. Ruthenium dithiocatecholate catalysts, in particular, have been employed in leading contexts, including stereoselective macrocyclization. Their productivity is strikingly low; however, suggesting rapid decomposition during operating conditions. This thesis work investigated the pathways involved. The dithiocatecholate catalysts Ru(S₂C₆H₂-3,6-Cl₂)(NHC)(=CHAr) (where Ar = C₆H₄-2-OiPr; NHC = H₂IPr or H₂IMes) were shown to decompose rapidly in solution in air. Quantitative formation of aldehydes ArCHO was confirmed by NMR spectroscopy, with co-formation of four-coordinate oxo complexes Ru(O)(S₂C₆H₂-3,6-Cl₂)(NHC), the structure of which was confirmed by single crystal X-ray diffraction of the H₂IPr complex. Additional experiments involving olefin metathesis in air indicated that the oxo complexes do not function as isomerization catalysts, in contrast to many of the common ruthenium decomposition products. Neither positional nor geometric isomerization of the C=C bonds was detected.
Additional work explored synthetic routes to these Ru-oxo complexes, following the discovery in parallel work that the metathesis catalyst can be regenerated by treating the H₂IPr oxo complex with the ylide Ph₃P=CHAr. With the idea of leveraging this discovery to investigate alkylidene-free entry points to olefin metathesis catalysts, routes to the oxo complexes from conventional ruthenium precursors were explored. Synthesis of the piano-stool complex Ru(S₂C₆H₂-3,6-Cl₂)(p-cymene)(PPh₃), followed by reaction with H₂IPr, yielded four-coordinate Ru(S₂C₆H₂-3,6-Cl₂)(PPh₃)(H₂IPr). Upon exposure to air, the latter afforded the target dithiocatecholate oxo complex. Attempts to expand this chemistry to the more widely used dichloride catalysts were less successful, but the oxo complex Ru(O)Cl₂(IMes)(NMe₃) was synthesized using trimethylamine N-oxide as an oxidant. These findings highlight the dual importance of oxidative degradation pathways even in Ru-catalyzed olefin metathesis, but also of Ru-oxo species as a new entry point to metathesis catalysts