50 research outputs found
Insight Preparing for disease-modifying therapies in Alzheimer's disease
No full textChristopher R S Belder, Jonathan M Schott, Nick C Fo
The problematic syndrome of right temporal lobe atrophy: Unweaving the phenotypic rainbow
No full textChristopher R. S. Belder, Anthipa Chokesuwattanaskul, Charles R. Marshall, Chris J. D. Hardy, Jonathan D. Rohrer, and Jason D. Warre
Genetic testing in dementia
No full textFirst published September 17, 2024.There is growing public awareness and concern regarding dementia risk. In addition, genetic testing is increasingly accessible and is at the point of being integrated into routine clinical practice. As a result, there is a pressing need for treating clinicians to have the appropriate knowledge base to request and consent for diagnostic genetic testing in cognitive clinics. We outline our approach to genetic testing in patients with Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies and vascular cognitive impairment. We discuss when to consider testing, the consenting process, and the interpretation and communication of genetic test results.Antoinette O'Connor, Natalie S Ryan, Christopher R S Belder, David S Lynch, Nayana Lahiri, Henry Houlden, Jonathan D Rohrer, Nick C Fox, Sean O'Dow
Primary progressive aphasia: six questions in search of an answer
No full textHere, we review recent progress in the diagnosis and management of primary progressive aphasia—the language-led dementias. We pose six key unanswered questions that challenge current assumptions and highlight the unresolved difficulties that surround these diseases. How many syndromes of primary progressive aphasia are there—and is syndromic diagnosis even useful? Are these truly ‘language-led’ dementias? How can we diagnose (and track) primary progressive aphasia better? Can brain pathology be predicted in these diseases? What is their core pathophysiology? In addition, how can primary progressive aphasia best be treated? We propose that pathophysiological mechanisms linking proteinopathies to phenotypes may help resolve the clinical complexity of primary progressive aphasia, and may suggest novel diagnostic tools and markers and guide the deployment of effective therapies
The presenilin 1 mutation P436S causes familial Alzheimer's disease with elevated Aβ43 and atypical clinical manifestations
No full textINTRODUCTION: Familial Alzheimer’s disease (fAD) is heterogeneous in terms of age at onset and clinical presentation. A greater understanding of the pathogenicity of fAD variants and how these contribute to heterogeneitywill enhance our understanding of themechanisms of AD more widely. METHODS:To determine the pathogenicity of the unclassified PSEN1 P436S mutation, we studied an expanded kindred of eight affected individuals,withmagnetic resonance imaging (MRI) (two individuals), patient-derived induced pluripotent stem cell (iPSC) models (two donors), and post-mortem histology (one donor). RESULTS: An autosomal dominant pattern of inheritance of fAD was seen, with an average age at symptom onset of 46 years and atypical features. iPSC models and postmortem tissue supported high production of amyloid beta 43 (Aβ43). PSEN1 peptide maturation was unimpaired. DISCUSSION:We confirm that the P436S mutation in PSEN1 causes atypical fAD. The location of the mutation in the critical PSEN1 proline-alanine-leucine-proline (PALP) motif may explain the early age at onset despite appropriate protein maturation.Charles Arber, Christopher R. S. Belder, Filip Tomczuk, Rebecca Gabriele, Yazead Buhidma, Clíona Farrell, Antoinette O, Connor, Helen Rice, Tammaryn Lashley, Nick C. Fox, Natalie S. Ryan, SelinaWra
Investigating palettes used in the painting of Rembrandt’s Man with the red baret using X-ray fluorescence scanning and t-distributed stochastic neighbour embedding
No full textIt is assumed that 17th century paintings were painted by a very systematic approach which involved the use of very specific palettes. For every pictorial unit, such a skin, a very specific palette was created. In this case the palette would then only be used to paint the skin and nothing else. The result is that for each pictorial unit a separate palette is used. This assumption can be verified by characterizing the all the paint mixtures present in a painting. Paint derives it colour from the pigments present within them. Many pigments used in the 17th century contain characteristic heavy elements. The usage macro X-ray fluorescence (XRF) scanning is gaining popularity as a non-destructive method for determining elements present in a paintings. By the creation of elemental maps the pigments can be identified and localized in a painting. These maps already allow for visualizing many interesting features such as retouches, inpaintings and even hidden layers behind a painting. However the usage of the XRF data have never been used for identifying and visualizing the palettes used while painting.In this work it is attempted to identify and visualize the palettes used in the Man with the red baret by Rembrandt van Rijn, by an in-depth analysis of raw XRF data. The raw data was model fitted using a simulated annealing algorithm to retrieve spectral line intensities in each point of the painting. The fitted spectral intensities was then visualized using t-distributed stochastic neighbour embedding (t-SNE). With help of the t-SNE visualisation the painting is divided into 24 sections. The suggestion is that these 24 sections each contain a different and unique paint mixture. This suggestion is further investigated by the use of the two-sample χ²-test between the sections’ spectral composition. The combination of model fitting alongside with t-SNE on a XRF spectra can indeed visualize different paint mixtures and give strong suggestion of the different palettes used in Man with the red baret
060 A case report of myelin oligodendrocyte glycoprotein antibody positive encephalitis mimicking HaNDL syndrome with subsequent acute optic neuritis
No full textRoots and affixes : eliminating lexical categories from syntax
No full textRoots and Affixes is an investigation into the primitives of syntax. It focuses on the lexical projection and the categorial head. Accordingly, it consists of two parts. The first part argues that the features of lexical vocabulary items (such as light and kiss) are not an active part of the syntactic derivation. The author provides empirical support for the claim that vocabulary items are inserted post-syntactically, adopting the view that syntax operates on UG-features only. She argues that the root terminal node is a by-product of the operation Merge that is characterized by the mere absence of features. It is further shown that functional structure determines subcategories of lexical items. In the second part of the thesis it is argued that categorial heads do not exist. As a result, derivational affixes do not realize categorial heads. The author proposes instead that derivational affixes are lexical vocabulary items which realize root positions. It is shown that the abandonment of categorial heads does not lead to a loss of explanatory adequacy. The general conclusion is that lexical categorial features are not a primitive of syntax
A re-evaluation of ideas, interests and politics in repeal: the case of the Belgian Corn Laws, 1834-1873.
No full textEconomic interests, the influence of economic ideas and politics have been put forward in the literature as explanations for the British Repeal of the Corn Laws in 1846. In this paper, we will evaluate these competing explanations using the case of the liberalization of Belgian corn tariffs. The Belgian protectionist Corn Laws of 1834 were abolished in different steps between 1845 and 1873. The first part of this paper uses quantitative methods to assess the success of party affiliation, personal interests and the economic profile of the constituencies in predicting voting behavior. Thanks to the detailed censuses of 1846 on agriculture, industry and population, it is possible to typify the economic make-up of the electoral districts in much more detail than in the British case. However, the analysis of roll-call voting proves that party affiliation and personal and constituency economic interests are insufficient to explain the shift towards free trade. The second part of the paper then discusses the role played by political strategy and ideas in the liberalization of corn tariffs, using a qualitative analysis of the debates on tariff policy. The large number of votes over a forty year period allows us to document the relationship between ideas and interests in a new way.
