Center for Diagnosis and Research on Alzheimer's Disease

Abstract BackgroundMetabolic biomarkers can potentially be used for early diagnosis, prognostic risk stratification and/or early treatment and prevention of individuals at risk to develop Alzheimer’s disease (AD).ObjectiveOur goal is to evaluate changes in metabolite concentration levels associated with AD to identify biomarkers that could support early and accurate diagnosis and therapeutic interventions by using targeted mass spectrometry and machine learning approaches.MethodsSerum samples collected from a total of 107 individuals, including 55 individuals diagnosed with AD and 52 healthy controls (HC) enrolled previously to ADDIA cohort were analyzed using the Biocrates®400 metabolite panel. Several machine learning models including Lasso, Random Forest, and XGBoost were trained to classify AD and HC. Repeated cross-validation was used to ensure performance evaluation.ResultsWe identified 18 metabolites with nominal differences (p<0.05; AUC>0.60) between AD and HC. These included alterations in acylcarnitines, phosphatidylcholines, sphingomyelins, triglycerides, and amino acids, suggesting disruptions in lipid metabolism, mitochondrial function, and oxidative stress. The best model achieved an average AUC of 0.88 on the train set and 0.73 on the test set. Classification performance was further improved by combining multiple metabolites in a single panel and addingAPOEgenotyping (AUC=0.902).ConclusionsThese results highlight important metabolic signatures that could help to reduce misdiagnosis and support the development of metabolomic panels to detect AD. The combination of multiple serum metabolic biomarkers andAPOEgenotyping can significantly improve classification accuracy and potentially assist in making non-invasive, cost-effective diagnostic approach.

Due to the continuing interest of the French Navy (DCN & DRET), signi cant improvements have been made to magnetostrictive transducers to produce low-frequency, high-power sonar sources.Much progress has been made in the eld of Tonpilz transducers as a result of these improvements.The previous Quadripode transducer was built in two versions, Quadripode I and II.They had acoustic power of 1.0 and 1.6 kW, respectively.Next, an attempt to design a third version of the Quadripode led to a new Tonpilz transducer called the Tripode.Its purpose is to reach an acoustic power of at least 3 kW.It bene ts from magnetic circuit design results and from the giant dynamic strain capability of Terfenol-D (Peak-to-Peak strain higher than 2400ppm) discovered in 90-91.In this paper, the modelling results are reminded, and the results obtained from the rst series of inwater measurements of the Tripode are analyzed.These results tend to con rm expectations. of nding shading coef cients for any arbitrary array geometry and a given set of beampattern requirements.

Midlife hypercholesterolemia is a well-known risk factor for sporadic Alzheimer’s disease (AD), and like AD, it is highly influenced by genetics with heritability estimates of 32–63%. We thus hypothesized that genetics underlying peripheral blood total cholesterol (TC) levels could influence the risk of developing AD. We created a weighted polygenic score (TC-PGS) using summary data from a meta-analysis of TC genome-wide association studies for evaluation in three independent AD-related cohorts spanning pre-clinical, clinical, and pathophysiologically proved AD. APOE-ε4 variant was purposely included in the analysis as it represents an already well-established genetic risk factor for both AD and circulating TC. We could vastly improve the performance of the score when considering p-value thresholds for inclusion in the score, sex, and statin use. This optimized score (p-value threshold of 1 × 10−6 for inclusion in the score) explained 18.2% of the variance in TC levels in statin free females compared to 6.9% in the entire sample and improved prediction of hypercholesterolemia (receiver operator characteristics analysis revealed area under the curve increase from 70.8% to 80.5%). The TC-PGS was further evaluated for association with AD risk and pathology. We found no association between the TC-PGS and either of the AD hallmark pathologies, assessed by cerebrospinal fluid levels of Aβ-42, p-Tau, and t-Tau, and 18F-NAV4694 and 18F-AV-1451 positron emission tomography. Similarly, we found no association with the risk of developing amyloid pathology or becoming cognitively impaired in individuals with amyloid pathology.

On s’attend à ce que le nombre de personnes vivant avec la démence atteigne près du double au Canada[1][1] et dans le monde[2][2] d’ici 2030, ce qui fait de la condition une priorité de santé publique[2][2]. En 2012, l’Organisation mondiale de la Santé recommandait que les gouvernements

This paper studies the influence of the magnetic nonlinear frames in the detection of the short-circuit faults based on the investigation of the magnetic field in the induction motors neighboring. The conclusions are based on the comparison of the finite element results obtained with three models: without frame, an ideal closed frame with very important shielding effect, and a frame with two opposite windows, whose radiative behavior is not so different than in the case of real frames.

Queda prohibida la reproduccin, distribucin, comercializacin, transformacin, y en general, cualquier otra forma de explotacin, por cualquier procedimiento, de todo o parte de los contenidos de esta obra sin autorizacin expresa y por escrito de sus autores.

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A la fin du siecle dernier, il existait entre l’ecrivain et le critique un face-a-face intellectuel beaucoup plus direct et plus violent que ce que nous pouvons connaitre aujourd’hui. La joute s’exercait sur une scene qui ne ressemblait guere a celle de l’epoque presente. Elle avait pour cadre une multitude de petits journaux qui s’opposaient entre eux selon de subtils partages ideologiques. Chacun cherchait a y imposer son autorite par des moyens qui lui etaient propres. Le combat etait commande par une rhetorique minutieusement reglee, qui gouvernait les manieres d’ecrire comme les facons de penser. C’est cet affrontement que ce livre entend decrire, en se replacant a l’epoque de Germinal, il y a un peu plus de cent ans. Dans l’espace du journal ou de la revue, les acteurs de la bataille litteraire se nomment, s’interpellent, mesurent avec adresse les coups qu’ils vont se porter. Ils se connaissent tous, se detestent et se menagent en meme temps. Chaque ouvrage qui parait, chaque evenement d’importance est pour eux l’occasion d’une partie qu’ils engagent. Pour le plus grand plaisir de leurs lecteurs, complices bienveillants… Date de premiere edition : 1989.