Impact couplé des essais de fluage et des conditions climatiques sur des poutres entaillées de Pseudotsuga Menziesii et Abies Alba Mil

L'un des objectifs principaux du Projet français CLIMBOIS JCJC ANR N° ANR-13-JS09-0003-01, est de connaitre l'impact des variations climatiques sur le comportement mécanique des structures en bois. Pour atteindre cet objectif, un protocole expérimental a été mis en place. Il consiste à prendre en compte l'impact couplé des variations climatiques, du chargement différé (fluage) et de la variabilité spatiale des défauts initiaux (orientation des cernes, disposition des n?uds, gerces, ...) sur des poutres entaillées de Pseudotsuga Menziesii et Abies Alba Mil. Au préalable, les poutres entaillées testées, tout au long du projet, sont dimensionnées selon la norme Européenne EUROCODE 5. Puis elles sont chargées en fluage extérieur, en flexion 4 points. Les dispositions des entailles sont faites de telle sorte que, juste après le chargement, il y ait apparition des fissures au droit des entailles. L'apparition de ces fissures entraine un suivi quotidien et régulier de leur propagation (longueur, ouverture) en fonction des paramètres climatiques (température T, humidité relative HR), jusqu'à la rupture de la poutre. Le dépouillement des données issues des premiers essais montre un impact certain des variations climatiques (T, HR) sur la propagation (longueur et ouverture) de la fissure et à fortiori sur la durabilité des structures en bois. Ceux en cours consistent à prendre en considération l'effet du fluage couplé aux variations climatiques et à la disposition spatiale des défauts initiaux sur la durabilité de la structure. Les résultats expérimentaux issus de ces essais, permettrons de caler un modèle numérique sur le logiciel CAST3M prenant en compte le caractère mécanosorptif du bois en climat ambiant et les paramètres (intensité du chargement, défauts initiaux du bois,...) précédemment énumérés. Remerciements: Les auteurs voudraient par cette occasion remercier l'Agence Nationale de la Recherche (ANR) Française pour le support financier apporté tout au long du projet CLIMBOIS ANR-13-JS09-0003-01 ainsi que le label du pôle Français ViaMéca

The mean state and variability of the North Atlantic circulation: a perspective from ocean reanalyses

The observational network around the North Atlantic has improved significantly over the last few decades with subsurface profiling floats and satellite observations, and the recent efforts to monitor the Atlantic Meridional Overturning Circulation (AMOC). These have shown decadal timescale changes across the North Atlantic including in heat content, heat transport and the circulation. However there are still significant gaps in the observational coverage. Ocean reanalyses integrate the observations with a dynamically consistent ocean model and can be used to understand the observed changes. However the ability of the reanalyses to represent the dynamics must also be assessed. We use an ensemble of global ocean reanalyses to examine the time mean state and interannual‐decadal variability of the North Atlantic ocean since 1993. We assess how well the reanalyses are able to capture processes and whether any understanding can be gained. In particular we examine aspects of the circulation including convection, AMOC and gyre strengths, and transports. We find that reanalyses show some consistency, in particular showing a weakening of the subpolar gyre and AMOC at 50oN from the mid‐90s until at least 2009 (related to decadal variability in previous studies), a strengthening and then weakening of the AMOC at 26.5oN since 2000, and impacts of circulation changes on transports. These results agree with model studies and the AMOC observations at 26.5oN since 2005. We also see less spread across the ensemble in AMOC strength and mixed layer depth, suggesting improvements as the observational coverage has improved

Brain Health Services: organization, structure, and challenges for implementation. A user manual for Brain Health Services—part 1 of 6

Dementia has a devastating impact on the quality of life of patients and families and comes with a huge cost to society. Dementia prevention is considered a public health priority by the World Health Organization. Delaying the onset of dementia by treating associated risk factors will bring huge individual and societal benefit. Empirical evidence suggests that, in higher-income countries, dementia incidence is decreasing as a result of healthier lifestyles. This observation supports the notion that preventing dementia is possible and that a certain degree of prevention is already in action. Further reduction of dementia incidence through deliberate prevention plans is needed to counteract its growing prevalence due to increasing life expectancy. An increasing number of individuals with normal cognitive performance seek help in the current memory clinics asking an evaluation of their dementia risk, preventive interventions, or interventions to ameliorate their cognitive performance. Consistent evidence suggests that some of these individuals are indeed at increased risk of dementia. This new health demand asks for a shift of target population, from patients with cognitive impairment to worried but cognitively unimpaired individuals. However, current memory clinics do not have the programs and protocols in place to deal with this new population. We envision the development of new services, henceforth called Brain Health Services, devoted to respond to demands from cognitively unimpaired individuals concerned about their risk of dementia. The missions of Brain Health Services will be (i) dementia risk profiling, (ii) dementia risk communication, (iii) dementia risk reduction, and (iv) cognitive enhancement. In this paper, we present the organizational and structural challenges associated with the set-up of Brain Health Services

Modifiable risk factors for dementia and dementia risk profiling. A user manual for Brain Health Services—part 2 of 6

Abstract: We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39–64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues