Targeted T1 Magnetic Resonance Imaging Contrast Enhancement with Extraordinarily Small CoFe2O4 Nanoparticles

Extraordinarily small (2.4 nm) cobalt ferrite nanoparticles (ESCIoNs) were synthesized by a one-pot thermal decomposition approach to study their potential as magnetic resonance imaging (MRI) contrast agents. Fine size control was achieved using oleylamine alone, and annular dark-field scanning transmission electron microscopy revealed highly crystalline cubic spinel particles with atomic resolution. Ligand exchange with dimercaptosuccinic acid rendered the particles stable in physiological conditions with a hydrodynamic diameter of 12 nm. The particles displayed superparamagnetic properties and a low r2/r1 ratio suitable for a T1 contrast agent. The particles were functionalized with bile acid, which improved biocompatibility by significant reduction of reactive oxygen species generation and is a first step toward liver-targeted T1 MRI. Our study demonstrates the potential of ESCIoNs as T1 MRI contrast agents

The Transcriptome of Human Epicardial, Mediastinal and Subcutaneous Adipose Tissues in Men with Coronary Artery Disease

The biological functions of epicardial adipose tissue (EAT) remain largely unknown. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). The objectives of this study were to identify genes differentially regulated among three adipose tissues, namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases.Samples were collected from subjects undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in the three adipose depots of six men using the Illumina® HumanWG-6 v3.0 expression BeadChips. Twenty-three and 73 genes were differentially up-regulated in EAT compared to MAT and SAT, respectively. Ninety-four genes were down-regulated in EAT compared to SAT. However, none were significantly down-regulated in EAT compared to MAT. More specifically, the expression of the adenosine A1 receptor (ADORA1), involved in myocardial ischemia, was significantly up-regulated in EAT. Levels of the prostaglandin D2 synthase (PTGDS) gene, recently associated with the progression of atherosclerosis, were significantly different in the three pairwise comparisons (EAT>MAT>SAT). The results of ADORA1 and PTGDS were confirmed by quantitative real-time PCR in 25 independent subjects.Overall, the transcriptional profiles of EAT and MAT were similar compared to the SAT. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were differentially up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Génération de base de connaissance à partir de données hétérogènes dans le monde culturel

RÉSUMÉ RÉSUMÉ : Le monde culturel québécois est riche et varié, et ceci se concrétise par l’importante quantité de métadonnées sur les mondes du livre et du cinéma que les acteurs gouvernementaux, aca- démiques et commerciaux ont accumulé. Cependant, ces données sont actuellement en bonne partie indisponibles au public, et sont encodées dans des bases de données dont les modèles, parfois complexes et généralement incompatibles d’une institution à l’autre, rendent l’exploi- tation difficile. De plus, sauf certaines exceptions, elles ne sont pas reliées aux métadonnées diffusées librement ailleurs sur le web, que ce soit par l’entremise de projets collaboratifs publics tels que Wikidata, ou par des acteurs tels que certaines bibliothèques nationales européennes. La création de bases de connaissances sous forme de graphes peut permettre la démocratisa- tion de ces métadonnées, en simplifiant leur exploitation et en les liant vers d’autres bases de connaissances existantes. Ce mémoire résume notre travail de création de bases de connais- sances pour les mondes du cinéma et de la littérature québécois, en particulier la modélisation de modèles ontologiques et la population des graphes à partir de sources relationnelles. Nous présentons d’abord une base de connaissances pour le domaine du cinéma québécois, qui utilise un jeu de métadonnées fourni par la Cinémathèque québécoise. À partir de scénarios d’utilisation fournis par des experts du milieu, nous développons un modèle ontologique pour ce domaine, et décrivons la conversion des données sources de leur format original vers la base de connaissances finale. ---------- ABSTRACT : Quebec’s cultural world is rich and full of variety, as is illustrated through the imposing amount of cultural heritage metadata that exists. Governmental, academic and commer- cial players have accumulated a large amount of data relating to literary and film works. However, this data is currently largely unavailable to the greater public, and are held in datastores whose underlying datamodels, which are often complex and incompatible between institutions, complicate their use. On top of this, except for rare exceptions, this data is not interlinked with other linked open data sources available elsewhere on the web, whether they be public collaborative projects such as Wikidata or knowledge bases published by national librairies. The development of knowledge bases in graph form can aid in democratising this metadata, by simplifying its exploitation and allowing it to be linked with existing, open knowledge bases. This memoir summarizes our work, which is the creation of knowledge bases for Quebec’s cinema and literature data. In particular, our work focuses on modelling and populating such knowledge bases from existing relational databases. We first model a knowledge base for Quebec’s film world, which uses a dataset provided by the Cinémathèque québécoise. Our use cases, provided by domain experts, guide our development of an ontological model for this domain. We describe the translation of this source data from its original format towards the final knowledge base

Tailored synthesis of ultra-small nanoparticles for biomedical applications

Accurate and early diagnosis of disease is a critical worldwide challenge in healthcare. The emergence of nanomaterials has opened up the possibility of engineering new and improved diagnostic and therapeutic tools which can interact on a sub-cellular level. Ultra-small (&lt; 3 nm) metal-oxide nanoparticles (NPs) have been highlighted as particularly strong candidates for enhancing positive T1 image contrast in magnetic resonance imaging (MRI), an important and powerful diagnostic imaging tool. Current T1 gadolinium contrast agents are limited by long-term toxicity issues, and cannot be given to patients with kidney disease, which represents 16% of the UK population. Metal-oxide NPs, such as iron oxide, are more biocompatible, and below 3 nm, they present the ideal magnetic properties to enhance T1 image contrast, offering a potential alternative to current gadolinium-based agents. However, several roadblocks must be overcome to reach clinical application of ultra-small NPs. The primary challenge lies in the development of suitable synthesis methods that offer the exquisite control over particle size and composition that is required to produce ultra-small NPs. Furthermore, their properties need fine-tuning in order to achieve T1-weighted contrast that is more comparable with gadolinium. An additional important consideration is that the NPs are designed with core and surface features that enable excellent stability, performance and biocompatibility in vivo. This thesis details the synthesis, characterisation, and functionalisation of ultra-small iron oxide and cobalt ferrite NPs for application as T1 MRI contrast agents. The main findings of this thesis concern the investigation of 2.4 nm cobalt ferrite NPs for T1 MRI. Cobalt ferrite NPs may be excellent candidates for T1-weighted contrast as they offer beneficial properties in comparison to iron oxide, such as lower magnetisation and greater chemical stability. Size-controlled synthesis of ultra-small NPs was addressed with a simple and fast thermal decomposition approach using oleylamine and acetylacetonate precursors. Sub-nm size control in the range of 2.4-5 nm was achieved by tailoring the oleylamine-to-precursor ratio. Annular dark-field scanning transmission electron microscopy revealed highly-crystalline cubic spinel particles 2.4 nm in size with atomic-resolution. Both iron oxide and cobalt ferrite NPs displayed size and coating-dependent superparamagnetic properties. In consideration for in vivo applications, two strategies were explored to obtain water-dispersible NPs. A novel phase transfer method with bovine serum albumin proved unsuitable as the NPs quickly flocculated. Ligand exchange with dimercaptosuccinic acid rendered the particles stable in physiological conditions with an average hydrodynamic diameter of ~12 nm. It was found that dialysing the particles prior to ligand exchange to remove excess oleylamine and alkalising the particles after ligand exchange were key steps to obtain reproducible results. The potential toxicity of the NPs was investigated with cytotoxicity and oxidative stress assays comparing the effect of particle size and metal composition. Neither iron oxide nor cobalt ferrite NPs of any size displayed cytotoxicity towards HepG2 liver cells. However, both NP types produced reactive oxygen species (ROS), and it was found that cobalt ferrite produced significantly more. Serendipitously, ROS generation was effectively alleviated through conjugation to a bile acid derivative, cholic acid. Conjugation was achieved by EDC-NHS coupling, following which the ROS levels reduced by 62% and 67% for iron oxide and cobalt ferrite NPs respectively. This new insight reveals the potential of cholic acid to mitigate ROS generation, a common issue encountered in metal-oxide NPs. Furthermore, the cholic acid coating could promote active liver-targeting in vivo. Finally, the MRI application of DMSA-coated iron oxide and cobalt ferrite NPs was assessed with phantom studies using 3.0 T and 9.4 T scanners. Cobalt ferrite NPs were found to have a low r2/r1 ratio suitable for a T1 contrast agent. The work described in this thesis demonstrates the potential of ultra-small ferrite NPs towards application as liver-targeted T1 MRI contrast agents. The synthesis and functionalisation methods described may open up the possibility of applying ultra-small ferrite NPs in other exciting areas of biomedicine.</p

MusX: Online Exploring and Visualizing Graph-Based Musical Adaptations

This paper introduces MusX, a visualization-based system that helps to search and explore a large multivariate bipartite graph of artists and songs. An additional tree structure for the song nodes is also inherited from the musical adaptation relations. In tight collaboration with a public national library and archives institution, we propose a novel artist-centered interactive set of representations, focusing on several identified user tasks. This online system is targeted towards laypersons, willing to quickly navigate artists' body of songs and explore their relationships to other artists through their implication in song creation. In this paper, we present a detailed description of MusX along with design and technical considerations, and the demonstration scenarios we intend to present to the audience