Search

Posterior cortical atrophy (PCA), usually an atypical clinical syndrome of Alzheimer’s disease, has well-characterized patterns of cortical atrophy and tau deposition that are distinct from typical amnestic presentations of Alzheimer’s disease. However, the mechanisms underlying the cortical spread of tau in PCA remain unclear. Here, in a sample of 17 biomarker-confirmed (A+/T+/N+) individuals with PCA, we sought to identify functional networks with heightened vulnerability to tau pathology by examining the cortical distribution of elevated tau as measured by 18F-flortaucipir (FTP) PET. We then assessed the relationship between network-specific FTP uptake and visuospatial cognitive task performance. As predicted, we found consistent and prominent localization of tau pathology in the dorsal attention network and visual network of the cerebral cortex. Elevated FTP uptake within the dorsal attention network (particularly the ratio of FTP uptake between the anterior and posterior nodes) was associated with poorer visuospatial attention in PCA; associations were also identified in other functional networks, although to a weaker degree. Furthermore, using functional MRI data collected from each patient at wakeful rest, we found that a greater anterior-to-posterior ratio in FTP uptake was associated with stronger intrinsic functional connectivity between anterior and posterior nodes of the dorsal attention network. Taken together, we conclude that our cross-sectional marker of anterior-to-posterior FTP ratio could indicate tau propagation from posterior to anterior dorsal attention network nodes, and that this anterior progression occurs in relation to intrinsic functional connectivity within this network critical for visuospatial attention. Our findings help to clarify the spatiotemporal pattern of tau propagation in relation to visuospatial cognitive decline and highlight the key role of the dorsal attention network in the disease progression of PCA.

Frontotemporal dementia (FTD) therapy development is hamstrung by a lack of susceptibility, diagnostic, and prognostic biomarkers. Blood neurofilament light (NfL) shows promise as a biomarker, but studies have largely focused only on core FTD syndromes, often grouping patients with different diagnoses. To expedite the clinical translation of NfL, we avail ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources and conduct a comprehensive investigation of plasma NfL across FTD syndromes and in presymptomatic FTD mutation carriers. We find plasma NfL is elevated in all studied syndromes, including mild cases; increases in presymptomatic mutation carriers prior to phenoconversion; and associates with indicators of disease severity. By facilitating the identification of individuals at risk of phenoconversion, and the early diagnosis of FTD, plasma NfL can aid in participant selection for prevention or early treatment trials. Moreover, its prognostic utility would improve patient care, clinical trial efficiency, and treatment outcome estimations.

Although successful on many fronts, solid organ transplantation fails patients who die on waitlists. Too few organ donors beget this failure. Dispelling misperceptions associated with donation and transplantation would expectedly increase donation and decrease waitlist mortality; recipients would also receive transplants earlier in their disease process, leading to better post-transplantation outcomes.Survey responses to 7 questions pertaining to organ donation and transplantation were analyzed to determine their association with willingness to donate. Subgroup analyses according to race, residence status (rural vs nonrural), and education level were performed.There were 766 respondents; 84.6% were willing to be a donor, 76.2% were female, 79.7% were Caucasian, and 16.5% were African-American. Having concerns about getting inadequate medical care if registered as a donor was the strongest independent predictor of willingness to donate overall (odds ratio 0.21; 95% CI 0.13 to 0.36) and in each subgroup; African Americans were more likely than Caucasians to have this concern (20.2% vs 9.5%; p 0.001). Race (odds ratio 0.41; 95% CI 0.22 to 0.75 for African Americans) and age were also predictive overall, but less so. Willingness to donate a family member's organs depended on whether a discussion about donation had hypothetically occurred: 61.0% would donate if there had been no discussion; 95.2% would donate if the family member had said "yes" to donation; and 11.0% would donate if the family member had said "no" (p0.001). If there was no prior discussion, having concerns about getting less-aggressive medical care predicted willingness to donate a family member's organs (odds ratio 0.40; 95% CI 0.25 to 0.65).The strongest deterrent of willingness to donate one's own or a family member's organs is a misperception that should be correctable. Race and age are less predictive. Efforts to dispel misperceptions and increase donation remain desperately needed to improve waitlist mortality and post-transplantation outcomes.

265 Background: A recent study ( Fossati et al, 2018) found that higher lymph node count at radical prostatectomy was associated with improved outcomes in patients treated with salvage radiation for elevated prostate-specific antigen (PSA) after surgery. We sought to validate these results in NRG/RTOG 9601, a randomized controlled trial of men with pT2/T3 disease who underwent either radiation (RT) alone or RT+antiandrogen (bicalutamide) therapy for PSA elevation following radical prostatectomy from 1998-2003. Methods: We reviewed available pathology reports for all patients in NRG/RTOG 9601 to determine the nodal count at radical prostatectomy. Clinical data was as of 11/5/2015, same as the primary endpoint for the trial. Cox proportional hazards models were used to assess the effect of number of positive lymph nodes, treatment arm (RT alone or RT+bicalutamide), Gleason score, positive margins, and seminal vesicle invasion on the following endpoints: times to local and distant failure and overall and disease specific survival. Results: Out of the 760 patients originally eligible in the trial, 552 (73%, 276 in each arm) had complete data available. Median node count in the entire cohort was 6 (range 0-33, Q1-Q3 3-9). There were no significant differences between treatment arms in terms of patient demographic or clinical characteristics, including total lymph nodes removed in either arm (RT alone vs RT+bicalutamide median 5 vs 6, p = 0.11). There was no significant association between total lymph nodes and overall survival with both arms combined (HR = 1.00, 95% CI:0.97-1.03, p = 0.87) or in the individual arms alone (RT+Casodex: HR = 1.01, 95% CI:0.97-1.05, p = 0.65; RT+Placebo: HR = 0.98, 95% CI: 0.94-1.03, p = 0.45). There was also no significant association between total lymph nodes and disease-specific survival with both arms combined (HR = 1.00, 95% CI:0.95-1.04, p = 0.84) and in the arms alone (RT+Casodex: HR = 1.00, 95% CI:0.95-1.05, p = 0.92; RT+Placebo: HR = 0.99, 95% CI: 0.92-1.07, p = 0.86). In multivariable analysis performed on the two arms, Gleason score was the only feature associated with worse overall and disease-specific survival, seen only in the RT alone arm. Similar findings were seen when evaluating times to local and distant failure. Conclusions: Lymph node yield in NRG/RTOG 9601 did not show any association with adverse outcomes in the entire cohort, or in either treatment arm alone. The therapeutic benefit of an extensive lymph node dissection in this population remains uncertain. Clinical trial information: NCT00002874.

INTRODUCTION: We created global rating scoring rules for the CDR® plus NACC FTLD to detect and track early frontotemporal lobar degeneration (FTLD) and to conduct clinical trials in FTLD. METHODS: The CDR plus NACC FTLD rating was applied to 970 sporadic and familial participants from the baseline visit of Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL)/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS). Each of the eight domains of the CDR plus NACC FTLD was equally weighed in determining the global score. An interrater reliability study was completed for 40 participants. RESULTS: The CDR plus NACC FTLD showed very good interrater reliability. It was especially useful in detecting clinical features of mild non‐fluent/agrammatic variant primary progressive aphasia participants. DISCUSSION: The global CDR plus NACC FTLD score could be an attractive outcome measure for clinical trials in symptomatic FTLD, and may be useful in natural history studies and clinical trials in FTLD spectrum disorders.

The article reviews the book "Teaching and Learning Chinese in Global Contexts" edited by Linda Tsung and Ken Cruickshank.

This article examines the pedagogical challenges and value of using objectionable texts in the classroom by way of two case studies: Martin Luther’s writings on Jews and two works by J.S. Bach. The use of morally or otherwise offensive materials in the classroom has the potential to degrade the learning environment or even produce harm if not carefully managed. On the other hand, historically informed instructors can use difficult works to model good scholarly methodology and offer useful contexts for investigating of contemporary issues. Moral judgments about historical actors and events are inevitable, the authors argue, so the instructor’s responsibility is to seize the opportunity for constructive dialogue.

This study presents results from a 2-year investigation of the comparative efficacy of tonal spelling and diacritics in the teaching of Mandarin Chinese pronunciation.1 The research site was the elementary level Chinese language course at the University of Oregon. During the 1991-92 academic year, the course was taught using a romanization system with diacritics, hanyū pinyin (PY); during the 1992-93 academic year, the course was taught using a tonal spelling system, gwoyeu romatzyh (GR). The analytical mechanism of this study calculates student tonal error rates in identical (save for the romanization system used) reading tasks at identical points in each year's course. Native speakers of Chinese served as assessors. The results clearly indicated that GR did not lead to significantly greater accuracy in tonal production. Indeed, the use of GR reflected slightly lower rates of tonal production accuracy for native speakers of both American English and Japanese.

The Renaissance saw the reemergence of the dialogue as one of the most popular forms of writing across nearly every field of learning. Humanist approaches to education, particularly dialectical and rhetorical strategies that sought to involve the audience as a means of per-suasion, were particularly congruent with the dialogue format. For religious writers in an age of censorship, the dialogue was rich with possibilities. Controversial opinions could be expressed without being claimed, theological reasoning and biblical interpretation could be modeled for eager learners rather than simply theorized, and pastoral practice could be explored. Along with the printed sermon, dialogues helped meet part of the tremendous demand for Protestant devotional literature.1 And, while some dialogues moved toward a definitive conclusion, the genre also was capable of an indeterminacy that appealed to certain English Protestants seeking to work out a distinct religious identity within the broader English church and to explore methods of pastoral care or “practical divinity.”2

The usage of authentic texts to develop cultural understanding extends to at least three types of culture—functional, informational and achievement. Even seemingly survival (functional) oriented texts such as transportation time schedules embody a great deal of informational culture. The present project describes how to utilize two timetables (one boat, one train) from the People's Republic of China to enhance students' understanding of elements of the informational culture on the mainland, as well as their performative ability with respect to the functional culture. Specifics of both pre-reading and reading activities are provided, as well as a suggestion for a post-reading activity which may serve as an effective language game either within or outside of the formal language classroom.

The article reviews the book "Teaching Chinese as a Foreign Language: Theories and Applications," edited by Michael E. Everson and Yun Xiao.

George Gifford, Elizabethan minister and puritan activist, was among the earliest English writers to address the witch-hunts of the latter sixteenth century. Though not as influential as the works of his contemporaries Reginald Scot and William Perkins, Gifford's Dialogue Concerning Witches and Witchcraftes (1593) is notable for its attention to the ministerial challenges posed by witch belief as well as for its entertaining dialogue designed to appeal to a wide audience. Gifford understood witch belief primarily as a pastoral problem, and this led him to discount the power of witches and to reject witch-hunts as spiritually distracting for the common sort of Christian. His approach contrasts with that of other writers, both skeptics and believers, who understood witchcraft primarily as an intellectual or theological problem.