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

Eumelanin Pigment for Green Organic Electronics : Band Structure, Nanoscale, and Magnetic Properties

RÉSUMÉ: Nous vivons dans une époque où les déchets d'équipements électriques et électroniques (DEEE) représentent des déchets solides dont la quantité est en croissance rapide, contribuant à la pollution environnementale. Cette thèse de doctorat s'est focalisée sur le bio-pigment « eumélanine », un candidat potentiel pour le développement d'électronique organique verte, qui vise à atténuer les problèmes liés aux DEEE. L'eumélanine présente une conductivité ionique-électronique mixte qui dépend de l'humidité, prometteuse pour les applications basées sur la transduction ioniqueélectronique dans les signaux biologiques et les applications de semi-conducteurs organiques. Explorer cette propriété nécessite encore des études approfondies sur les structures électroniques et morphologiques du bio-pigment. À cet égard, nous avons étudié sa structure de bandes d’énergie, ses nanostructures et ses propriétés magnétiques pour éclairer son comportement semi-conducteur. Premièrement, nous avons localisé les plus hautes orbitales moléculaires occupées et les plus basses orbitales moléculaires non occupées (HOMO et LUMO) des couches produites à partir des monomères d'eumélanine chimiquement contrôlées (DHI et DHICA). Différentes méthodes de production de couches ont été utilisées, à savoir le revêtement par rotation de la solution et l'évaporation thermique, tout en considérant différentes atmosphères lors de la formation des couches après la déposition, (c'est-à-dire une atmosphère riche en ammoniac, une atmosphère où l'oxygène et l'humidité sont contrôlés, et une évaporation thermique sous vide). Les méthodes de photoémission inverse et directe ont montré que les emplacements des niveaux d’énergie HOMO et LUMO se situent dans les marges de 5,34-5,80 eV et 3,80-4,0 eV, respectivement par rapport au niveau du vide. Les résultats ont montré une forte dépendance de la structure des bandes d’énergie des couches d'eumélanine sur la méthode de déposition ainsi que la structure moléculaire des monomères. Deuxièmement, nous avons utilisé la microscopie à force atomique (AFM) et l'AFM conductrice pour élucider la structure nanométrique et la réponse électrique de Sepia eumélanine. Les images d'AFM ont montré des granules quasi-sphériques comportant des protubérances à leur surface, avec une largeur moyenne d'environ 18,5 ± 6,4 nm et une hauteur moyenne d'environ 3,0 ± 1,6 nm. Les protubérances sont compatibles avec les sous-unités de granule considérées dans le développement hiérarchique de Sepia eumélanine, tel que proposé dans la littérature. ABSTRACT: We live in an age where waste electrical et electronic equipment (WEEE or e-waste) is the fastestgrowing solid-state stream waste, leading to environmental pollution. This PhD thesis focused on eumelanin pigment, a potential candidate for the development of organic green electronics, which aims to alleviate the e-waste issues. Eumelanin features mixed ionic-electronic conduction that depends on humidity, promising for both ion-to-electronic transduction in biological signals and semiconductor-based applications. Exploring this property still requires further studies on the electronic and morphological structures of the pigment. In this regard, we studied its band structure, nanostructure, and magnetic properties to shed light on its semiconducting behaviour. First, we located the highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO) of films produced from chemically controlled eumelanin building blocks (DHI and DHICA). Different film production methods were used, which are solution spin-coating and thermal evaporation (considering different atmospheres during film formation i.e. ammonia atmosphere, oxygen- and humidity-controlled atmosphere, and thermal evaporation in vacuum). The ultraviolet and inverse photoemission spectroscopy methods showed that the locations of HOMO and LUMO are in the ranges of 5.34-5.80 eV and 3.80-4.0 eV, respectively reference to the vacuum level. The results showed a strong dependence of the band structure of eumelanin films on the processing protocols and the molecular structure of the monomers. Second, we used atomic force microscopy (AFM) and conductive AFM to elucidate the nanoscale structure and electrical response of Sepia eumelanin. AFM images showed quasi-spherical granules featuring protrusions on their surfaces, with a width average of about 18.5±6.4 nm and a height average of about 3.0±1.6 nm. The protrusions are compatible with granule subunits considered in the hierarchical development of Sepia eumelanin, as proposed in the literature. C-AFM revealed for the first time a nanoscale electrical response of films formulated from Sepia eumelanin ink, indicating a charge carrier transport through intra- and inter-granular conduction paths. The results related to the band structure and nanostructures pave the way toward defining suitable eumelaninmetal electrode interfaces for efficient charge carrier injection and charge transport, owing to similarities between the supramolecular structure of DHI/DHICA synthetic films and that of Sepia at the protrusions length scale