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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
Over the past several years there has been considerable interest in the relation between emotion dysregulation and non-suicidal self-injury (NSSI), particularly given that rates of NSSI have been increasing and NSSI is a critical risk factor for suicidal behavior. To date, however, no synthesis of empirical findings exists.
The present study presents a comprehensive meta-analytic review of the literature on the association between NSSI and emotion dysregulation. A total of 48 publications, including 49 independent samples, were included in this analysis.
Overall, a significant association was found between emotion dysregulation and NSSI (pooled OR = 3.03 [95% CI = 2.56–3.59]). This association was reduced but remained significant (OR = 2.40 [95% CI = 2.01–2.86]) after adjustment for publication bias. Emotion dysregulation subscales most strongly associated with NSSI included limited access to regulation strategies, non-acceptance of emotional responses, impulse control difficulties, and difficulties engaging goal-directed behavior. Lack of emotional awareness/clarity and cognitive aspects of dysregulation yielded weaker, yet significant, positive associations with NSSI.
Findings support the notion that greater emotion dysregulation is associated with higher risk for NSSI among individuals across settings, regardless of age or sex. Furthermore, findings reveal facets of dysregulation that may have unique implications for NSSI. This meta-analysis highlights the importance of better understanding emotion dysregulation as a treatment target for preventing NSSI.
Texture-engineered ceramics enable access to a vast array of novel texture-property relations leading to property values ranging between those of single crystals and isotropic bulk ceramics. Recently developed templated grain growth and magnetic alignment texturing methods yield high quality crystallographic texture, and thus significant advances in achievable texture-engineered properties in magnetic, piezoelectric, electronic, optical, thermoelectric, and structural ceramics. In this paper, we outline the fundamental basis for these texture-engineered properties and review recent contributions to the field of texture-engineered ceramics with an update on the properties of textured lead-free and lead-based piezoelectrics. We propose that further property improvements can be realized through development of processes that improve crystallographic alignment of the grain structure, create biaxial texture, and explore a wider array of crystallographic orientations. There is a critical need to model the physics of texture-engineered ceramics, and more comprehensively characterize texture, thus enabling testing of texture orientation-property relations and materials performance. We believe that in situ measurements of texture evolution can lead to a more fundamental and comprehensive understanding of the mechanisms of texture development.
Background: Hyperacute stroke is a time-sensitive emergency for which outcomes improve with faster treatment. When stroke systems are accessed via emergency medical services (EMS), patients are routed to hyperacute stroke centres and are treated faster. But over a third of patients with strokes do not come to the hospital by EMS, and may inadvertently arrive at centres that do not provide acute stroke services. We developed and studied the impact of protocols to quickly identify and move “walk-in” patients from non-hyperacute hospitals to regional stroke centres (RSCs). Methods and Results: Protocols were developed by a multi-disciplinary and multi-institutional working group and implemented across 14 acute hospital sites within the Greater Toronto Area in December of 2012. Key metrics were recorded 18 months pre- and post-implementation. The teams regularly reviewed incident reports of protocol non-adherence and patient flow data. Transports increased by 80% from 103 to 185. The number of patients receiving tissue plasminogen activator (tPA) increased by 68% from 34 to 57. Total EMS transport time decreased 17 minutes (mean time of 54.46 to 37.86 minutes, p<0.0001). Calls responded to within 9 minutes increased from 34 to 59%. Conclusions: A systems-based approach that included a multi-organizational collaboration and consensus-based protocols to move patients from non-hyperacute hospitals to RSCs resulted in more patients receiving hyperacute stroke interventions and improvements in EMS response and transport times. As hyperacute stroke care becomes more centralized and endovascular therapy becomes more broadly implemented, the protocols developed here can be employed by other regions organizing patient flow across systems of stroke care.
St Andrews was of tremendous significance in medieval Scotland. Its importance remains readily apparent in the buildings which cluster the rocky promontory jutting out into the North Sea: the towers and walls of cathedral, castle and university provide reminders of the status and wealth of the city in the Middle Ages. As a centre of earthly and spiritual government, as the place of veneration forScotland's patron saint and as an ancient seat of learning, St Andrews was the ecclesiastical capital of Scotland. This volume provides the first full study of this special and multi-faceted centre throughout its golden age. The fourteen chapters use St Andrews as a focus for the discussion of multiple aspects of medieval life in Scotland. They examine church, spirituality, urban society andlearning in a specific context from the seventh to the sixteenth century, allowing for the consideration of St Andrews alongside other great religious and political centres of medieval Europe.
Michael Brown is Professor of Medieval Scottish History, University of St Andrews; Katie Stevenson is Keeper of Scottish History and Archaeology, National Museums Scotland and Senior Lecturer in Late Medieval History, University of St Andrews.
Contributors: Michael Brown, Ian Campbell, David Ditchburn, Elizabeth Ewan, Richard Fawcett, Derek Hall, Matthew Hammond, Julian Luxford, Roger Mason, Norman Reid, Bess Rhodes, Catherine Smith, Katie Stevenson, Simon Taylor, Tom Turpie.
Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.