Chemical Imaging on Liver Steatosis Using Synchrotron Infrared and ToF-SIMS Microspectroscopies

Fatty liver or steatosis is a frequent histopathological change. It is a precursor for steatohepatitis that may progress to cirrhosis and in some cases to hepatocellular carcinoma. In this study we addressed the in situ composition and distribution of biochemical compounds on tissue sections of steatotic liver using both synchrotron FTIR (Fourier transform infrared) and ToF-SIMS (time of flight secondary ion mass spectrometry) microspectroscopies. FTIR is a vibrational spectroscopy that allows investigating the global biochemical composition and ToF-SIMS lead to identify molecular species in particular lipids. Synchrotron FTIR microspectroscopy demonstrated that bands linked to lipid contribution such as -CH3 and -CH2 as well as esters were highly intense in steatotic vesicles. Moreover, a careful analysis of the -CH2 symmetric and anti-symmetric stretching modes revealed a slight downward shift in spectra recorded inside steatotic vesicles when compared to spectra recorded outside, suggesting a different lipid environment inside the steatotic vesicles. ToF-SIMS analysis of such steatotic vesicles disclosed a selective enrichment in cholesterol as well as in diacylglycerol (DAG) species carrying long alkyl chains. Indeed, DAG C36 species were selectively localized inside the steatotic vesicles whereas DAG C30 species were detected mostly outside. Furthermore, FTIR detected a signal corresponding to olefin (C = C, 3000-3060 cm−1) and revealed a selective localization of unsaturated lipids inside the steatotic vesicles. ToF-SIMS analysis definitely demonstrated that DAG species C30, C32, C34 and C36 carrying at least one unsaturated alkyl chain were selectively concentrated into the steatotic vesicles. On the other hand, investigations performed on the non-steatotic part of the fatty livers have revealed important changes when compared to the normal liver. Although the non-steatotic regions of fatty livers exhibited normal histological aspect, IR spectra demonstrated an increase in the lipid content and ToF-SIMS detected small lipid droplets corresponding most likely to the first steps of lipid accretion

Nitrogen partitioning and remobilization in relation to leaf senescence, grain yield and grain nitrogen concentration in wheat cultivars

Our objective was to investigate the determinants of genetic variation in N accumulation, N partitioning and N remobilization to the grain post-flowering and associations with flag-leaf senescence, grain yield and grain N% in 16 wheat cultivars grown under high N (HN) and low N (LN) conditions in the UK and France. Overall, cultivars ranged in leaf lamina N accumulation at anthesis from 5.32 to 8.03 g N m−2 at HN and from 2.69 to 3.62 g N m−2 at LN, and for the stem-and leaf-sheath from 5.45 to 7.25 g N m−2 at HN and from 2.55 to 3.41 g N m−2 at LN (P < 0.001). Cultivars ranged in N partitioning index (proportion of above-ground N in the crop component) at anthesis for the leaf lamina from 0.37 to 0.42 at HN and 0.34 to 0.40 at LN; and for the stem-and leaf-sheath from 0.39 to 0.43 at HN and from 0.35 to 0.41 at LN (P < 0.001). The amount of leaf lamina N remobilized post-anthesis was negatively associated with the duration of post-anthesis flag-leaf senescence amongst cultivars in all experiments under HN. In general, it was difficult to separate genetic differences in lamina N remobilization from those in lamina N accumulation at anthesis. Genetic variation in grain yield and grain N% (through N dilution effects) appeared to be mainly influenced by pre-anthesis N accumulation rather than post-anthesis N remobilization under high N conditions and under milder N stress (Sutton Bonington LN). Where N stress was increased (Clermont Ferrand LN), there was some evidence that lamina N remobilization was a determinant of genetic variation in grain N% although not of grain yield. Our results suggested that selection for lamina N accumulation at anthesis and lamina N remobilization post-anthesis may have value in breeding programmes aimed at optimizing senescence duration and improving grain yield, N-use efficiency and grain N% of wheat

Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study

AIMS/HYPOTHESIS: This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). METHODS: The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. RESULTS: We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th-75th percentile) 28.4 (25.0-32.4) kg/m(2). Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5-14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. CONCLUSIONS/INTERPRETATION: In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04324736

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

Rétines courbes : une approche bio-inspirée de simplification et miniaturisation des systèmes infrarouge

In natural world, plane retina, on which are based our cameras does not exist. The focal plane is either concave for human beings or convex in insects' eyes. Both curvatures offer novel solution to miniaturize and simplify the optical design, and both of them have been studied in this work.The concave curving of the focal plane suppresses one aberration, the field curvature, on which depends the image quality of large field of view instruments. Advantages in image quality and optical design have been studied by theoretical analysis and by real cases of instruments. The convex curvature results in a miniaturization achieved by reproducing the compound eye of small invertebrates. This design, which is composed of several groups of pixels interconnected by metallic lines, has been realized with cooled infrared detecting device. The performed detectors are still electrically functional with a comparable behaviour than conventional sensors. The originality of this work is the spherical curvature of monocrystalline and monolithic components; the active layer is not modified for this purpose. The process of curvature has been developed on thinned square silicon bare dies and then transferred to thinned functional devices: Si-CMOS and micro-bolometers. The concave curvature of bolometers leads to the realization of two cameras. The first one, composed of two commercial lenses, was dedicated to the comparison between a planar traditional camera and a curved detector system. Optical advantages, and especially the response uniformity, have been proved thanks to measures of the contrast modulation function (CMF). Finally, I have realized an infrared eye composed of a unique lens and a curved concave bolometer. Both the image quality obtained and CMF experiments proved the interest of the curved focal plane in miniaturized optical systems.Si dans les caméras actuelles, les matrices de photodétection sont planes, dans la nature, aucune surface focale n'est plane : la rétine est soit concave (œil humain), soit convexe (œil d'insecte). Ces architectures offrent deux solutions de miniaturisation et de simplification des systèmes de détection, qui ont fait l'objet des travaux de cette thèse. La courbure concave du détecteur permet de supprimer l'aberration de courbure de champ qui est particulièrement présente dans les instruments grand champ. L'étude théorique de cette solution, étayée par des applications concrètes, a permis de démontrer la simplification des architectures accessibles par cette approche, ainsi que les améliorations en termes de performances optiques. La courbure convexe permet quant à elle de miniaturiser les systèmes grand champ, en s'inspirant de l'œil composé des petits invertébrés. Cette architecture, constituée de groupes de pixels reliés par une métallisation souple, a été réalisée sur une matrice de détecteurs infrarouge en CdHgTe. Les composants obtenus sont fonctionnels et comparables en termes de performances aux valeurs standard. Ils ouvrent à la voie à des architectures grand champ extrêmement compactes. L'originalité du travail a porté sur la mise en forme sphérique de composants monolithiques, dont la couche active n'est pas modifiée, permettant ainsi de produire des systèmes avec un taux de remplissage de 100%. Après une étude de la souplesse d'échantillons de silicium aminci, le procédé de courbure a été transféré sur des composants fonctionnels: circuit de lecture Si-CMOS et matrice de micro-bolomètres infrarouge. La courbure concave des matrices de détection infrarouge de type micro-bolomètres, a mené à la réalisation de deux caméras. La première, constituée de deux lentilles du commerce, a permis de comparer les systèmes composés des détecteurs plan et courbe. Le gain lié à la courbure sphérique de la rétine sur l'uniformité de la réponse impulsionnelle a été prouvé grâce aux mesures de la fonction de transfert de contrastes (FTC). Enfin, à l'image d'un œil humain, un œil infrarouge composé d'une seule lentille et d'une matrice de micro-bolomètres courbée en concave a été réalisée. La qualité des images obtenues, ainsi que la FTC mesurée, ont mis en évidence le potentiel des plans focaux courbés pour des systèmes ultra-compacts, inenvisageables jusqu'à ce jour

Curved retina : a bio-inspired approach to simplify and miniaturize infrared systems

Si dans les caméras actuelles, les matrices de photodétection sont planes, dans la nature, aucune surface focale n'est plane : la rétine est soit concave (œil humain), soit convexe (œil d'insecte). Ces architectures offrent deux solutions de miniaturisation et de simplification des systèmes de détection, qui ont fait l'objet des travaux de cette thèse. La courbure concave du détecteur permet de supprimer l'aberration de courbure de champ qui est particulièrement présente dans les instruments grand champ. L'étude théorique de cette solution, étayée par des applications concrètes, a permis de démontrer la simplification des architectures accessibles par cette approche, ainsi que les améliorations en termes de performances optiques. La courbure convexe permet quant à elle de miniaturiser les systèmes grand champ, en s'inspirant de l'œil composé des petits invertébrés. Cette architecture, constituée de groupes de pixels reliés par une métallisation souple, a été réalisée sur une matrice de détecteurs infrarouge en CdHgTe. Les composants obtenus sont fonctionnels et comparables en termes de performances aux valeurs standard. Ils ouvrent à la voie à des architectures grand champ extrêmement compactes. L'originalité du travail a porté sur la mise en forme sphérique de composants monolithiques, dont la couche active n'est pas modifiée, permettant ainsi de produire des systèmes avec un taux de remplissage de 100%. Après une étude de la souplesse d'échantillons de silicium aminci, le procédé de courbure a été transféré sur des composants fonctionnels: circuit de lecture Si-CMOS et matrice de micro-bolomètres infrarouge. La courbure concave des matrices de détection infrarouge de type micro-bolomètres, a mené à la réalisation de deux caméras. La première, constituée de deux lentilles du commerce, a permis de comparer les systèmes composés des détecteurs plan et courbe. Le gain lié à la courbure sphérique de la rétine sur l'uniformité de la réponse impulsionnelle a été prouvé grâce aux mesures de la fonction de transfert de contrastes (FTC). Enfin, à l'image d'un œil humain, un œil infrarouge composé d'une seule lentille et d'une matrice de micro-bolomètres courbée en concave a été réalisée. La qualité des images obtenues, ainsi que la FTC mesurée, ont mis en évidence le potentiel des plans focaux courbés pour des systèmes ultra-compacts, inenvisageables jusqu'à ce jour.In natural world, plane retina, on which are based our cameras does not exist. The focal plane is either concave for human beings or convex in insects' eyes. Both curvatures offer novel solution to miniaturize and simplify the optical design, and both of them have been studied in this work.The concave curving of the focal plane suppresses one aberration, the field curvature, on which depends the image quality of large field of view instruments. Advantages in image quality and optical design have been studied by theoretical analysis and by real cases of instruments. The convex curvature results in a miniaturization achieved by reproducing the compound eye of small invertebrates. This design, which is composed of several groups of pixels interconnected by metallic lines, has been realized with cooled infrared detecting device. The performed detectors are still electrically functional with a comparable behaviour than conventional sensors. The originality of this work is the spherical curvature of monocrystalline and monolithic components; the active layer is not modified for this purpose. The process of curvature has been developed on thinned square silicon bare dies and then transferred to thinned functional devices: Si-CMOS and micro-bolometers. The concave curvature of bolometers leads to the realization of two cameras. The first one, composed of two commercial lenses, was dedicated to the comparison between a planar traditional camera and a curved detector system. Optical advantages, and especially the response uniformity, have been proved thanks to measures of the contrast modulation function (CMF). Finally, I have realized an infrared eye composed of a unique lens and a curved concave bolometer. Both the image quality obtained and CMF experiments proved the interest of the curved focal plane in miniaturized optical systems

Audits et inspections dans l'industrie pharmaceutique

CLERMONT FD-BCIU-Santé (631132104) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Qui se plaint aux urgences et pourquoi ?

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF