1,720,959 research outputs found
Mathematical modelling and inference for Alzheimer’s Disease
Full text linkAlzheimer’s disease is a devastating neurological condition characterised by the accumulation of two toxic proteins, amyloid-beta and tau, resulting in neurodegen- eration and cognitive decline. The aetiology of Alzheimer’s disease is multifaceted and complex, and there remain a limited number of treatment options available for patients. The mechanisms of Alzheimer’s are particularly challenging to probe due to the numerous difficulties in observing disease mechanisms in vivo in the human brain. Instead, researchers must investigate from afar, relying on macro-scale neuroimaging methods and animal models of disease mechanisms. In this work, we address these obstacles by employing physics-based models of Alzheimer’s pathology that can be paired with neuroimaging data to investigate disease mechanisms.
In Chapter 2, we introduce the two components necessary for modelling tau pathol- ogy: transport through axonal connections and production via prion-like replication. We show that a simple network-based reaction-diffusion model of tau and neurodegen- eration can be usefully applied to human neuroimaging data to identify mechanisms of disease propagation, namely accelerated production of tau. In Chapter 3, we intro- duce a novel model of tau progression that accounts for the regional heterogeneity in vulnerability to tau pathology. We show that regionally specific production rates of tau are necessary for the accurate prediction of regional tau data and that the model can identify differences in transport and production dynamics across the Alzheimer’s disease continuum. In Chapter 4, we use results from previous chapters to develop the first mechanistic model of the amyloid-tau-neurodegeneration pathway and apply it to multimodal longitudinal neuroimaging data. The model explains and predicts several aspects of Alzheimer’s disease, including the necessity of amyloid for the ac- celeration of tau pathology, amyloid-induced regional heterogeneity of tau deposition, and tau-induced atrophy progression. Furthermore, we show that the spatial depo- sition of amyloid imparts a particular vulnerability to the entorhinal cortex for the deposition of tau seeds, providing a novel theory of amyloid-induced tau seeding.
Overall, we provide a framework for how mechanism-based modelling of Alzheimer’s disease can aid investigation into Alzheimer’s disease pathology and provide valuable tools for application in clinical research
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Braiding Braak and Braak: staging patterns and model selection in network neurodegeneration
Full text linkA hallmark of Alzheimer’s disease is the aggregation of insoluble amyloid-beta plaques and tau protein neurofibrillary tangles. A key histopathological observation is that tau protein aggregates follow a structured progression pattern through the brain. Mathematical network models of prion-like propagation have the ability to capture such patterns but a number of factors impact the observed staging result, thus introducing questions regarding model selection. Here, we introduce a novel approach, based on braid diagrams, for studying the structured progression of a marker evolving on a network. We apply this approach to a six-stage ‘Braak pattern’ of tau proteins, in Alzheimer’s disease, motivated by a recent observation that seed-competent tau precedes tau aggregation. We show that the different modeling choices, from the model parameters to the connectome resolution, play a significant role in the landscape of observable staging patterns. Our approach provides a systematic way to approach model selection for network propagation of neurodegenerative diseases that ensures both reproducibility and optimal parameter fitting
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