Following spatial Aβ aggregation dynamics in evolving Alzheimer's disease pathology by imaging stable isotope labeling kinetics.

β-Amyloid (Aβ) plaque formation is the major pathological hallmark of Alzheimer’s disease (AD) and constitutes a potentially critical, early inducer driving AD pathogenesis as it precedes other pathological events and cognitive symptoms by decades. It is therefore critical to understand how Aβ pathology is initiated and where and when distinct Aβ species aggregate. Here, we used metabolic isotope labeling in APPNL-G-F knock-in mice together with mass spectrometry imaging to monitor the earliest seeds of Aβ deposition through ongoing plaque development. This allowed visualizing Aβ aggregation dynamics within single plaques across different brain regions. We show that formation of structurally distinct plaques is associated with differential Aβ peptide deposition. Specifically, Aβ1-42 is forming an initial core structure followed by radial outgrowth and late secretion and deposition of Aβ1-38. These data describe a detailed picture of the earliest events of precipitating amyloid pathology at scales not previously possible

Designing and Piloting a Tool for the Measurement of the Use of Pronunciation Learning Strategies

What appears to be indispensable to drive the field forward and ensure that research findings will be comparable across studies and provide a sound basis for feasible pedagogic proposals is to draw up a classification of PLS and design on that basis a valid and reliable data collection tool which could be employed to measure the use of these strategies in different groups of learners, correlate it with individual and contextual variables, and appraise the effects of training programs. In accordance with this rationale, the present paper represents an attempt to propose a tentative categorization of pronunciation learning strategies, adopting as a point of reference the existing taxonomies of strategic devices (i.e. O'Malley and Chamot 1990; Oxford 1990) and the instructional options teachers have at their disposal when dealing with elements of this language subsystem (e.g. Kelly 2000; Goodwin 2001). It also introduces a research instrument designed on the basis of the classification that shares a number of characteristics with Oxford's (1990) Strategy Inventory for Language Learning but, in contrast to it, includes both Likert-scale and open-ended items. The findings of a pilot study which involved 80 English Department students demonstrate that although the tool requires considerable refinement, it provides a useful point of departure for future research into PLS

Narratives As Zones Of Dialogic Constructions: A Bakhtinian Approach To Data In Qualitative Research

Narratives have become increasingly important in the field of applied linguistics, as recent publications have illustrated, yet narrative analysis could still be considered undertheorized. This article outlines a specific, dialogical approach to the narrative analysis of data in qualitative research. Building on Bakhtin\u27s notion of dialogue, it claims that personal narratives are uniquely positioned to capture the interplay between humans\u27 individual and autobiographic experiences on the one hand, and larger, socio-cultural discourses on the other. Narrators can actively construct relations with others and reposition themselves on the planes of both textual and visual media. The article illuminates that through strategies such as double-voicing, narratives function as a tool for repositioning, resistance, and agency. © 2013 Copyright © Taylor & Francis Group, LLC

Validation of a modified ETDRS chart for European-wide use in populations that use the Cyrillic, Latin or Greek alphabet

Purpose: To validate a modified ETDRS visual acuity (VA) chart developed for European-wide use, in populations that use the Cyrillic, Latin or Greek alphabet. Methods: The charts were validated in three groups: 310 school children in Bulgaria (mean age 13 ± 1 years), 227 school children in Greece (mean age 14 ± 1 years) and 85 patients with no ocular pathology in Belgium (mean age 26 ± 5 years). VA was assessed with the habitual refractive correction, using the standard ETDRS charts and the modified European-wide charts. The intra-class correlation coefficient (ICC) was used to assess the test–retest reliability of the European-wide chart. The Bland–Altman comparison method was used to assess agreement between the two different versions of the new chart, as well as to compare these to the standard ETDRS-charts. Limits of agreement were calculated for differences in VA scores (test–retest variability (TRV)) between measurement sessions for the European-wide charts. Results: The TRV of the European-wide charts was found to be ±0.10 logMAR, corresponding to 5 ETDRS letters, for both chart 1 and chart 2. The ICC was estimated to be 0.968 for the RE and 0.961 for the LE. The European-wide charts generated on average slightly higher logMAR scores compared to the standard ETDRS charts in all three groups. Conclusions: The “European-wide” charts appear to be a valid alternative to the standard ETDRS acuity charts, offering the advantage of containing letters readable by all European citizens

Intraoperative haemoadsorption for antithrombotic drug removal during cardiac surgery: initial report of the international safe and timely antithrombotic removal (STAR) registry

Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2 h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0 min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6 h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4 min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period