Discovery of new biomarkers of mild cognitive impairment and Alzheimer\u27s disease risk in buccal cells using laser scanning cytometry

Previous studies have shown that mild cognitive impairment (MCI) may reflect the early stages of more pronounced neurodegenerative disorders such as Alzheimer’s disease (AD). In clinical practice, patients with AD are not usually identified until the disease has progressed to a stage when primary prevention is no longer possible. Therefore there is a need for a minimally invasive and inexpensive diagnostic to identify those who exhibit cellular pathology indicative of MCI and AD risk so that they can be prioritised for primary prevention. Human buccal cells are accessible in a minimally invasive manner, and exhibit cytological and nuclear morphologies that may be indicative of accelerated ageing or neurodegenerative disorders such as AD. The hypothesis that a minimally invasive approach using isolated buccal mucosa cells can be used to identify individuals diagnosed with MCI or AD was therefore tested using laser scanning cytometry (LSC). LSC combines the principles of flow cytometry, quantitative imaging and immunohistochemistry with high-content, multi-color fluorescence analysis, and can be used to identify specific cells in a heterogeneous population as well as scoring unique molecular events within them. This study aimed at investigating buccal cell types (buccal cell cytome) by the use of high-content LSC analysis and to detect potential biomarkers of MCI and AD risk i.e. buccal cell types, nuclear DNA content, intracellular neutral lipids, Tau protein and amyloid-β (Aβ) protein. Buccal cells were sampled from the South Australian Alzheimer’s Nutrition & DNA Damage study (SAND) or the The Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL), fixed and stained with labelled fluorescent antibodies (for detection of Aβ and Tau) and/or DAPI, Fast Green and Oil Red O dyes. In an initial study an LSC protocol was developed to identify and measure differences in buccal cell types and nuclear DNA content as well as a significant increase in micronuclei measured in AD (n=10) and Down’s syndrome (n=10) compared to their respective controls (n=20). Another LSC protocol measured a significant increase in DNA content and hyperdiploidy (as measured by DAPI fluorescence) as well as a significant decrease in neutral lipid content (measured by Oil Red O staining) in buccal cells of MCI (n=22) and AD (n=15) compared to controls (n=37) from the SAND study. Using another novel LSC protocol a significant increase in Aβ was measured in buccal cells from AD (n=20) compared to controls (n=20) from the AIBL study. Immunocytochemistry and ELISA experiments showed no significant differences in putative buccal cell Tau protein. The diagnostic value of parameters examined in these studies, individually or in combination was assessed and reported as specificity and sensitivity scores. In these studies, LSC has proven to be an efficient and useful technology for high-content analysis of buccal cells. Moreover, the changes in the buccal cell cytome observed using LSC may reflect alterations in the metabolism, cellular kinetics, gene expression, genome stability or structural profile of the buccal mucosa, and may prove useful as potential biomarkers in identifying individuals with a high risk of developing MCI and eventually AD

Consumption-Savings Trade-Off in the Allocation of Migrants; Remittances and Economic Growth: The Cases of Burkina Faso and Senegal

The objective of this research is to assess the impact on growth of reallocating migrant remittances for savings investment purposes It focuses on two countries in the West African Economic and Monetary Union WAEMU zone Burkina Faso and Senegal The methodological approach adopted is dynamic Computable General Equilibrium CGE modeling that integrates a procedure for reallocating remittances Simulation results show that an increase in the propensity to save as a result of reallocation of remittances received by households for savings purposes leads to an increase in economic growt

Quels besoins techniques en arboriculture biologique en Europe ? Exemple des ravageurs du pommier

Le projet européen BIOFRUITNET (2019-2022) a pour objectif d'identifier les réseaux de producteurs de fruits biologiques, rassembler les connaissances pratiques existantes et recenser les difficultés dans la production biologique de fruits à pépins, de fruits à noyau et d'agrumes en Europe. Afin de mieux connaître les besoins techniques et les pratiques concernant la production de pomme, poire, abricot, pêche, prune, cerise et orange en agriculture biologique, une enquête a été réalisé auprès de 149 agriculteurs et 100 conseillers techniques dans 26 pays. Le poster présente des résultats concernant la pomme

A Microscopic Lattice for Two-dimensional Dipolar Excitons

We report a two-dimensional artificial lattice for dipolar excitons confined in a GaAs double quantum well. Exploring the regime of large fillings per lattice site, we verify that the lattice depth competes with the magnitude of excitons repulsive dipolar interactions to control the degree of localisation in the lattice potential. Moreover, we show that dipolar excitons radiate a narrow-band photoluminescence, with a spectral width of a few hundreds of micro-eV at 340 mK, in both localised and delocalised regimes. This makes our device suitable for explorations of dipolar excitons quasi-condensation in a periodic potential.Comment: 5 pages, 4 figure

Enabling lock-free concurrent workers over temporal graphs composed of multiple time-series

Time series are commonly used to store temporal data, e.g., sensor measurements. However, when it comes to complex analytics and learning tasks, these measurements have to be combined with structural context data. Temporal graphs, connecting multiple time- series, have proven to be very suitable to organize such data and ultimately empower analytic algorithms. Computationally intensive tasks often need to be distributed and parallelized among different workers. For tasks that cannot be split into independent parts, several workers have to concurrently read and update these shared temporal graphs. This leads to inconsistency risks, especially in the case of frequent updates. Distributed locks can mitigate these risks but come with a very high-performance cost. In this paper, we present a lock-free approach allowing to concurrently modify temporal graphs. Our approach is based on a composition operator able to do online reconciliation of concurrent modifications of temporal graphs. We evaluate the efficiency and scalability of our approach compared to lock-based approaches

107 Care management of heart failure in elderly patients in France. Results from the DEVENIR study

RationaleThe part of elderly patients (pts) in heart failure (HF) population is growing. They might pose specific problems due to the greater proportion of HF with preserved LVEF, more frequent comorbidities or contra-indications to recommended HF treatment.Objectivesto describe the care management of pts > 80-year treated for HF in France.MethodsCross sectional observational survey with retrospective collection of data at hospital discharge. Pts must have been diagnosed with CHF and have been hospitalised for CHF within the previous 18 months. Pts are classified according to the LVEF at hospital discharge.Results412 French outhospital cardiologists entered 1 452 pts meeting the inclusion criteria. FEVG at hospital discharge was known for 1408 pts. 355 (25%) were more than 80-year-old. Management care at hospital discharge according to age and LVEF is detailed below.LVEF < 40%LVEF 40-50%LVEF > 50%TotalAge>80ACEI/ARB84%81%80%82%*BB71%67%40%†,‡62%*Loop diuretics92%85%85%88%Spironolactone/eplerenone26%20%18%22%*Digoxin20%15%29%21%*Calcium antagonists10%14%37%†,‡18%Anticoagulants49%45%51%49%*Age≤80ACEI/ARB93%93%85%†,‡92%BB79%78%76%79%Loop diuretics90%82%79%†,§86%Spironolactone/eplerenone35%21%25%†,§30%Digoxin16%15%16%15%Calcium antagonists9%19%21%†,§13%Anticoagulants42%39%39%41%†p<0.05 for comparisons between LVEF > 50% and LVEF<40%;‡p<0.05 for comparisons between LVEF>50% and LVEF between 40% and 50%;§: p<0.05 for comparisons between LVEF<40% and LVEF between 40% and 50%;*p<0.05 for comparisons between > 80 and ≤ 80 years old adjusted for LVEF.ConclusionBB, ACEI/ARB, spironolactone/eplerenone are less often prescribed in elderly patients contrasting with digoxin and anticoagulants prescription. These differences persist after adjustment on LVEF

088 Prescription of beta blockers at hospital discharge and beyond, in patients with heart failure. Results from the DEVENIR study

RationaleBeta blockers are a corner stone treatment of heart failure (HF) in patients with altered systolic function (LVEF<40%). Guidelines are less clear for HF patients with preserved systolic function (LVEF>50%) or for patients belonging to the “grey zone” (LVEF 40-50%).Objectivesto describe the prescription rate of beta-blockers in HF patients.MethodsCross sectional observational survey with retrospective collection of data at hospital discharge. Patients must have been diagnosed with CHF and have been hospitalised for CHF within the previous 18 months. Patients are classified according to the LVEF at hospital discharge.Results1 452 patients were included by 412 French outhospital cardiologists. 1137 with known LVEF at hospital discharge have had at least one visit by the cardiologist between hospital discharge (mean delay 5.76±4.51 months). In a multivariate model, BB prescription was more frequent in HF from ischemic origin (OR=1.39) or with dilated cardiomyopathy (OR=1.44) and less frequent in older patients (OR=0.97 per year) and in case of asthma/COPD (OR=0.31 and if FEVG was >50% (OR=0.62).LVEF < 40% N=661LVEF 40-50% N=282LVEF > 50% N=194Total N=1137At hospital discharge/at entry in the surveyBB78%/83%78%/85%62%/70%76%/82%Recommended BB†75%/77%72%/74%54%/62%71%/74%Reaching the target dose8%/16%7%/16%7%/13%7%/15%Changes since dischargeBB added*28%34%25%28%BB stopped**1%1%2%1%BB dose increased*27%27%17%25%BB dose decreased4%1%3%3%†metoprolol, nebivolol, bisoprolol, carvedilol ;*percentage calculated in patients without BB at hospital discharge (N=278);**percentage calculated in patients with BB at hospital discharge (N=859).ConclusionRate of betablockers prescription is high at hospital discharge. Outhospital cardiologists not only pursue but also amplify the care strategies defined during hospitalisation increasing the proportion of patients receiving BB and the percentage reaching the target dose

Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs

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