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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.
A wide range of structural studies have been carried out in high pressure diamond anvil cells using x-rays. The most common experimental geometry is shown in Fig. 1a. The incident x-ray beam passes axially through the first diamond and enters the sample, typically 100-300 μm in diameter and 20-100 μm thick; the diffracted x-rays exit via the second diamond. Energy-dispersive detection techniques (EDXRD) have been used. However the intensity of diffracted radiation from the sample is weak, so that typical exposure times with a conventional, fixed anode, x-ray source are typically one to several days.Accordingly, higher intensity radiation from synchrotron sources has been used for these experiments.
To evaluate the psychometric properties of HEARTSMAP, an emergency psychosocial assessment and management tool, and its impact on patient care and flow measures.
We conducted the study in two phases: first validating the tool using extracted information from a retrospective cohort, then evaluating implementation on a prospective cohort of youth presenting with mental health complaints to a tertiary Pediatric Emergency Department (PED). In phase 1, six PED clinicians applied HEARTSMAP to extracted narratives and we calculated inter-rater agreement for referral recommendations using Cohen’s Kappa and the sensitivity and specificity for identifying youth requiring psychiatric consultation and hospitalization. In phase 2, PED clinicians prospectively used HEARTSMAP and we assessed the impact of the tool’s implementation on patient-related outcomes and Emergency department (ED) flow measures.
We found substantial agreement (κ=0.7) for cases requiring emergent psychiatric consultation and moderate agreement for cases requiring community urgent and non-urgent follow-up (κ=0.4 each). The sensitivity was 76% (95%CI: 63%, 90%) and specificity was 65% (95%CI: 55%, 71%) using retrospective cases. During pilot implementation, 62 patients received HEARTSMAP assessments: 46 (74%) of HEARTSMAP assessments triggered a recommendation for ED psychiatry assessment, 39 (63%) were evaluated by psychiatry and 13 (21%) were admitted. At follow-up, all patients with HEARTSMAP’s triggered recommendations had accessed community resources. For those hospitalized for further psychiatric care at their index or return visit within 30 days, 100% were initially identified by HEARTSMAP at the index visit as requiring ED psychiatric consultation.
HEARTSMAP has strong reliability, and when applied prospectively is a safe and effective management tool.
The World Alzheimer Report 2016 estimated that 47 million people are living with dementia worldwide (Alzheimer's Disease International, 2016). In the inaugural World Health Organization Ministerial Conference on Global Action against Dementia, six of the top ten research priorities were focused on prevention, identification, and reduction of dementia risk, and on delivery and quality of care for people with dementia and their carers (Shah et al., 2016). While the Lancet Neurology Commission has suggested that even minor advances to delay progression or ameliorate symptoms might have substantial financial and societal benefits (Winblad et al., 2016), advances have been slow.
Increasingly, ambulance services offer alternatives to transfer to the emergency department (ED), when this is better for patients. The introduction of electronic health records (EHR) in ambulance services is encouraged by national policy across the United Kingdom (UK) but roll-out has been variable and complex.
Electronic Records in Ambulances (ERA) is a two-year study which aims to investigate and describe the opportunities and challenges of implementing EHR and associated technology in ambulances to support a safe and effective shift to out of hospital care, including the implications for workforce in terms of training, role and clinical decision-making skills.
Our study includes a scoping review of relevant issues and a baseline assessment of progress in all UK ambulance services in implementing EHR. These will inform four in-depth case studies of services at different stages of implementation, assessing current usage, and examining context.
The scoping review identified themes including: there are many perceived potential benefits of EHR, such as improved safety and remote diagnostics, but as yet little evidence of them; technical challenges to implementation may inhibit uptake and lead to increased workload in the short term; staff implementing EHR may do so selectively or devise workarounds; and EHR may be perceived as a tool of staff surveillance.
Our scoping review identified some complex issues around the implementation of EHR and the relevant challenges, opportunities and workforce implications. These will help to inform our fieldwork and subsequent data analysis in the case study sites, to begin early in 2017. Lessons learned from the experience of implementing EHR so far should inform future development of information technology in ambulance services, and help service providers to understand how best to maximize the opportunities offered by EHR to redesign care.
Despite the transition from apartheid to democracy, South Africa is the most unequal country in the world. Its extremes of wealth and poverty undermine intensifying struggles for a better life for all. The wide-ranging essays in this sixth volume of the New South African Review demonstrate how the consequences of inequality extend throughout society and the political economy, crippling the quest for social justice, polarising the politics, skewing economic outcomes and bringing devastating environmental consequences in their wake. Contributors survey the extent and consequences of inequality across fields as diverse as education, disability, agrarian reform, nuclear geography and small towns, and tackle some of the most difficult social, political and economic issues. How has the quest for greater equality affected progressive political discourse? How has inequality reproduced itself, despite best intentions in social policy, to the detriment of the poor and the historically disadvantaged? How have shifts in mining and the financialisation of the economy reshaped the contours of inequality? How does inequality reach into the daily social life of South Africans, and shape the way in which they interact? How does the extent and shape of inequality in South Africa compare with that of other major countries of the global South which themselves are notorious for their extremes of wealth and poverty? South African extremes of inequality reflect increasing inequality globally, and The Crisis of Inequality will speak to all those – general readers, policy makers, researchers and students – who are demanding a more equal world.
Jacqui Ala, senior lecturer in International Relations at the University of the Witwatersrand, Johannesburg.,
David Black, Lester B Pearson professor of International Development Studies in the Department of Political Science at Dalhousie University, Canada
From a constructivist perspective the causes and manifestations of inequality are multidimensional. Different populations affected by systemic inequality are disadvantaged through a convergence of socio-economic, cultural and political factors that are also historically and contextually bound. Moreover, inequality is not experienced the same way either horizontally between different groups or vertically among people within the same group. Constructivism allows for a more nuanced understanding of the causes and consequences of inequality for particular groups within society.
Relatively little attention has been paid by development studies to issues concerning people with disabilities, in South Africa and elsewhere. In the transitional and immediately post-apartheid years of the 1990s, some progress was made by government in addressing the development needs of people with disabilities – indeed, South Africa was regarded internationally as a leader in addressing the rights of the disabled. However, this focus has waned. We will argue in this chapter that the accommodation of people with disabilities in the South African political economy was critically compromised by the country's post-apartheid embrace of several key policy choices. Most fundamentally, South Africa's initial vision of a society built on social democratic principles has been eroded by the awkward marriage of neoliberal economics to these ideals – a step initially marked by the abrupt abandonment of the Reconstruction and Development Programme (RDP) for the Growth, Employment and Redistribution (Gear) strategy in 1996 (see Naidoo 2010; Marais 2011). In this context, the adoption of a development framework based on human rights and social justice was unable to be effectively implemented, and the government's commitments to people with disabilities concomitantly waned. The steady spread of corruption and maladministration has only served to make the situation worse.
DISABILITY AND INEQUALITY IN SOUTH AFRICA
Despite variations and nuances in the manifestations of inequality, it can be firmly observed in South Africa – as elsewhere – that disabled people are typically the most disadvantaged within the various social categories of difference and inequity (Yeo and Moore 2003; Graham et al. 2013; Loeb et al. 2008; Leibbrandt et al. 2010). Despite wide-ranging constitutional and legislative provisions aiming to guarantee the rights of people with disabilities in South Africa, the disabled remain marginalised socially and economically.
Planetary systems appear to be one of the crucial links in the chain leading from simple molecules to living systems, particularly complex (intelligent?) living systems. Although there is currently no observational proof of the existence of any planetary system other than our own, techniques are now being developed which will permit a comprehensive search for other planetary systems. The scientific rationale for and methods used in such a search effort are reviewed here.
The aim of this analysis was to test if changes in insomnia symptoms and global sleep quality are associated with coinciding changes in depressed mood among older adults. We report on results yielded from secondary analysis of longitudinal data from a clinical trial of older adults (N = 49) aged 55 to 80 years who reported at least moderate levels of sleep problems. All measures were collected at baseline and after the trial ten weeks later. We computed change scores for two separate measures of disturbed sleep, the Athens Insomnia Scale (AIS) and the Pittsburgh Sleep Quality Index (PSQI), and tested their association with change in depressed mood (Beck Depression Inventory-II; BDI-II) in two separate linear regression models adjusted for biological covariates related to sleep (sex, age, body mass index, and NF-κB as a biological marker previously correlated with insomnia and depression). Change in AIS scores was associated with change in BDI-II scores (β = 0.38, p < 0.01). Change in PSQI scores was not significantly associated with change in BDI-II scores (β = 0.17, p = 0.26). Our findings suggest that improvements over ten weeks in insomnia symptoms rather than global sleep quality coincide with improvement in depressed mood among older adults.
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.