Sensitivity kernels for time-distance helioseismology: efficient computation for spherically-symmetric solar models

The interpretation of helioseismic measurements, such as wave travel-time, is based on the computation of kernels that give the sensitivity of the measurements to localized changes in the solar interior. These are computed using the ray or the Born approximation. The Born approximation is preferable as it takes finite-wavelength effects into account, but can be computationally expensive. We propose a fast algorithm to compute travel-time sensitivity kernels under the assumption that the background solar medium is spherically symmetric. Kernels are typically expressed as products of Green's functions that depend upon depth, latitude and longitude. Here, we compute the spherical harmonic decomposition of the kernels and show that the integrals in latitude and longitude can be performed analytically. In particular, the integrals of the product of three associated Legendre polynomials can be computed thanks to the algorithm of Dong and Lemus (2002). The computations are fast and accurate and only require the knowledge of the Green's function where the source is at the pole. The computation time is reduced by two orders of magnitude compared to other recent computational frameworks. This new method allows for flexible and computationally efficient calculations of a large number of kernels, required in addressing key helioseismic problems. For example, the computation of all the kernels required for meridional flow inversion takes less than two hours on 100 cores

Economie solidaire et espaces fragilisés auvergnats : une participation à la dynamique des territoires ? (Ambert, Saugues)

National audienceL'Auvergne rurale et l'Auvergne des petites villes apparaît comme un espace perdu, oublié, sans perspective de développement possible. Certes, la réalité tend parfois à confirmer une telle approche mais la nuance territoriale est fortement présente. De fait, l'économie sociale et solidaire est perçue fort différemment dans l'Ambertois et le Saugain. La première région, celle d'Ambert, présente une véritable dynamique liée à l'ESS ; celle-ci est un apport aux problématiques de développement local. L'ESS est considérée comme un outil généré par une citoyenneté active ou impulsé par les politiques locales. Cette citoyenneté s'inspire de l'attachement au local (histoire, enclavement, pérennité nécessaire...). Sur le second site, celui de la Margeride saugaine, l'ESS est davantage perçue comme un élément extérieur à la communauté locale ; élément qui risquerait de déstabiliser cette micro-société. Toutefois, une dynamique existe, bien qu'elle ait peine à s'exprimer, et l'avenir devrait se révéler porteur. En effet, cet espace connaît une mutation sociale où les pouvoirs vont être redistribués

Diagnostic Value of (18)F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography in Prosthetic Pulmonary Valve Infective Endocarditis

OBJECTIVES: The aim of this study was to assess the diagnostic performances of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) in congenital heart disease (CHD) patients with pulmonary prosthetic valve or conduit endocarditis (PPVE) suspicion. BACKGROUND: PPVE is a major issue in the growing CHD population. Diagnosis is challenging, and usual imaging tools are not always efficient or validated in this specific population. Particularly, the diagnostic yield of (18)F-FDG PET/CT remains poorly studied in PPVE. METHODS: A retrospective multicenter study was conducted in 8 French tertiary centers. Children and adult CHD patients who underwent (18)F-FDG PET/CT in the setting of PPVE suspicion between January 2010 and May 2020 were included. The cases were initially classified as definite, possible, or rejected PPVE regarding the modified Duke criteria and finally by the Endocarditis Team consensus. The result of (18)F-FDG PET/CT had been compared with final diagnosis consensus used as gold-standard in our study. RESULTS: A total of 66 cases of PPVE suspicion involving 59 patients (median age 23 years, 73% men) were included. Sensitivity, specificity, positive predictive value, and negative predictive value of (18)F-FDG PET/CT in PPVE suspicion were respectively: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%). (18)F-FDG PET/CT findings would help to correctly reclassify 57% (4 of 7) of possible PPVE to definite PPVE. CONCLUSIONS: Using (18)F-FDG PET/CT improves the diagnostic accuracy of the Duke criteria in CHD patients with suspected PPVE. Its high positive predictive value could be helpful in routine to shorten diagnosis and treatment delays and improve clinical outcomes.L'Institut de Rythmologie et modélisation Cardiaqu

Meta-Analysis for Genome-Wide Association Study Identifies Multiple Variants at the BIN1 Locus Associated with Late-Onset Alzheimer's Disease

Recent GWAS studies focused on uncovering novel genetic loci related to AD have revealed associations with variants near CLU, CR1, PICALM and BIN1. In this study, we conducted a genome-wide association study in an independent set of 1034 cases and 1186 controls using the Illumina genotyping platforms. By coupling our data with available GWAS datasets from the ADNI and GenADA, we replicated the original associations in both PICALM (rs3851179) and CR1 (rs3818361). The PICALM variant seems to be non-significant after we adjusted for APOE e4 status. We further tested our top markers in 751 independent cases and 751 matched controls. Besides the markers close to the APOE locus, a marker (rs12989701) upstream of BIN1 locus was replicated and the combined analysis reached genome-wide significance level (p = 5E-08). We combined our data with the published Harold et al. study and meta-analysis with all available 6521 cases and 10360 controls at the BIN1 locus revealed two significant variants (rs12989701, p = 1.32E-10 and rs744373, p = 3.16E-10) in limited linkage disequilibrium (r2 = 0.05) with each other. The independent contribution of both SNPs was supported by haplotype conditional analysis. We also conducted multivariate analysis in canonical pathways and identified a consistent signal in the downstream pathways targeted by Gleevec (P = 0.004 in Pfizer; P = 0.028 in ADNI and P = 0.04 in GenADA). We further tested variants in CLU, PICALM, BIN1 and CR1 for association with disease progression in 597 AD patients where longitudinal cognitive measures are sufficient. Both the PICALM and CLU variants showed nominal significant association with cognitive decline as measured by change in Clinical Dementia Rating-sum of boxes (CDR-SB) score from the baseline but did not pass multiple-test correction. Future experiments will help us better understand potential roles of these genetic loci in AD pathology

Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and risk of in situ breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BACKGROUND: Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle factors and BCIS risk are lacking. Thus, we investigated the association between lifestyle and BCIS risk within the European Prospective Investigation into Cancer and Nutrition cohort. METHODS: Lifestyle was operationalized by a score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. The recommendations utilized in these analyses were the ones pertinent to healthy body weight, physical activity, consumption of plant-based foods, energy-dense foods, red and processed meat, and sugary drinks and alcohol, as well as the recommendation on breastfeeding. Cox proportional hazards regression was used to assess the association between lifestyle score and BCIS risk. The results were presented as hazard ratios (HR) and corresponding 95% confidence intervals (CI). RESULTS: After an overall median follow-up time of 14.9 years, 1277 BCIS cases were diagnosed. Greater adherence to the WCRF/AICR cancer prevention recommendations was not associated with BCIS risk (HR = 0.98, 95% CI 0.93-1.03; per one unit of increase; multivariable model). An inverse association between the lifestyle score and BCIS risk was observed in study centers, where participants were recruited mainly via mammographic screening and attended additional screening throughout follow-up (HR = 0.85, 95% CI 0.73-0.99), but not in the remaining ones (HR = 0.99, 95% CI 0.94-1.05). CONCLUSIONS: While we did not observe an overall association between lifestyle and BCIS risk, our results indicate that lifestyle is associated with BCIS risk among women recruited via screening programs and with regular screening participation. This suggests that a true inverse association between lifestyle habits and BCIS risk in the overall cohort may have been masked by a lack of information on screening attendance. The potential inverse association between lifestyle and BCIS risk in our analyses is consistent with the inverse associations between lifestyle scores and breast cancer risk reported from previous studies

A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.

BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.journal articleresearch support, non-u.s. gov't2016 Feb2015 10 26importe

The nature of task representation by novice multimedia authors /

The continuing importance of literacy and the emergence of electronic text forms have incited interest in the use of technology in a number of domains, among them writing and multimedia authoring. The expectation is that technology will facilitate the writing process by supporting cognitive processes and align school instruction with real-world tasks by providing more meaningful learning environments. This study tracked middle school students' task representation as they participated in protracted multimedia design and writing tasks. Students were engaged in the creation of a literary magazine over several weeks, with both written and media products linked to a particular theme. Cognitive strategies and behaviours associated with problem solving and communication are described through joint design activities. Students' working activities and their competencies in English Language Arts and Computer Science were identified, and cognitive processes tracked in negotiating and defining the boundaries of the task. Teachers' task representations were also examined in terms of their ability to address student variability; strengths and weaknesses between members of a group as well as their inherent dynamics are brought to the fore. Results point to the need for a better understanding of complex cognitive activities in developing new and more sophisticated repertoires of practice to realize the vision of children 'constructing' their own knowledge. Consequently, educators will gain new insights into what students can achieve when given the opportunities and the tools to do so. The role of educators is seen as instrumental in providing structure and mechanisms for supporting students' engagement in complex tasks. Findings underscore the importance of adopting a broader framework for thinking about the impact of students' participation in literacy projects. Limitations of the study are addressed as well as the key variables in the research on writte

Researching the design and development of a Personal Learning Environment

After speculation in the literature about the nature of Personal Learning Environments, research in the design and development of PLEs is now in progress. This paper will report on the first phase of research in a PLE, the identification process, of what potential users would find important components, applications and tools on a PLE. The methodology includes surveying \u201csuper-users\u201d on their use of existing tools, applications and systems and their preferences in learning, in order to enhance the development of a PLE and reach a specification that potential learners will find useful and empowering in their learning.Peer reviewed: YesNRC publication: Ye