Chasing ambiguity: critical reflections on working with dance graduates

This paper questions whether are we able to foster uncertainty and ambiguity within higher education arts programmes, specifically alongside current institutional demands and embedded pedagogies. If not, then what effect does this have on current dance graduates? I attend to these questions through critical reflections upon my work as a pedagogue, specifically reflecting upon a series of artistic choreographic projects working in collaboration with recent dance graduates. During these choreographic projects, my interactions with the graduates illuminated their struggle to operate within ambiguous creative spaces outside of institutional environments. This struggle manifest in turbulent working relationships and highlighted perceived contradictions or ‘gaps’ between what creative arts education attempts to teach, how it is taught within the institution, and what graduates demonstrate within professional creative practice. Through a recognition and critique of these ‘gaps’, I question whether it is possible to actively work within these ‘messy’ spaces, to chase the ambiguities present, in order to foster sustainable dance graduates that can work more visibly alongside academics and professionals to shape the current dance landscape

Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease

Behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) dementia are characterised by progressive brain atrophy. Longitudinal MRI volumetry may help to characterise ongoing structural degeneration and support the differential diagnosis of dementia subtypes. Automated, observer-independent atlas-based MRI volumetry was applied to analyse 102 MRI data sets from 15 bvFTD, 14 AD, and 10 healthy elderly control participants with consecutive scans over at least 12 months. Anatomically defined targets were chosen a priori as brain structures of interest. Groups were compared regarding volumes at clinic presentation and annual change rates. Baseline volumes, especially of grey matter compartments, were significantly reduced in bvFTD and AD patients. Grey matter volumes of the caudate and the gyrus rectus were significantly smaller in bvFTD than AD. The bvFTD group could be separated from AD on the basis of caudate volume with high accuracy (79% cases correct). Annual volume decline was markedly larger in bvFTD and AD than controls, predominantly in white matter of temporal structures. Decline in grey matter volume of the lateral orbitofrontal gyrus separated bvFTD from AD and controls. Automated longitudinal MRI volumetry discriminates bvFTD from AD. In particular, greater reduction of orbitofrontal grey matter and temporal white matter structures after 12 months is indicative of bvFTD

Genome- and epigenome-wide association study of hypertriglyceridemic waist in Mexican American families

This file contains Supplementary Table 1. (XLSX 782 MB

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

Diagnostic accuracy of consensus diagnostic criteria for frontotemporal dementia in a memory clinic population

Background/Aims: The goal of the present study was to evaluate the diagnostic accuracy of the core diagnostic criteria for frontotemporal dementia (FTD) [Neary D, et al: Neurology 1998;51:1546-1554] within a memory clinic population. Methods: The 5 core diagnostic criteria for FTD were operationalised in an informant-based written questionnaire. For a diagnosis of FTD the total clinical picture was weighted with findings on additional investigations and possible exclusion criteria, with follow-up of at least 1 year. Results: The operationalised core criteria for FTD had a sensitivity of 79% (95% CI = 57-92) and a specificity of 90% (95% CI = 85-94). Conclusion: The core diagnostic criteria for FTD applied in a caregiver questionnaire have good diagnostic accuracy among subjects without advanced dementia attending a memory clinic. This stresses the importance of the informant-based history in the differential diagnosis of dementia. Copyrigh

Implementation determinants and strategies in integration of PrEP into maternal and child health and family planning services: experiences of frontline healthcare workers in Kenya

BackgroundDelivery of PrEP to adolescent girls and young women (AGYW) and to pregnant women through maternal and child health (MCH) and family planning (FP) clinics is scaling up in Kenya. Evaluation of implementation challenges and strategies is critical to optimize delivery.MethodsWe conducted focus group discussions (FGDs) with healthcare workers (HCWs) in MCH and FP clinics offering PrEP in a large implementation project in Kisumu, Kenya. Discussion guides were based on the Consolidated Framework for Implementation Research (CFIR). FGDs were audio recorded and transcribed. Directed content analysis was used to identify implementation challenges and strategies to overcome them.ResultsFifty HCWs from 26 facilities participated in 8 FGDs. HCWs believed PrEP integration was appropriate because it met the needs of AGYW and pregnant women by providing a female-controlled prevention strategy and aligned with policy priorities of elimination of vertical HIV transmission. They were universally accepting of PrEP provision, especially through MCH clinics, noting the relative advantage of this approach because it: (1) enabled high coverage, (2) harmonized PrEP and MCH visits, and (3) minimized stigma compared to PrEP offered through HIV care clinics. However, HCWs noted implementation challenges affecting feasibility and adoption including: (1) increased workload and documentation burden amid workforce shortages, (2) insufficient health care worker knowledge (3) multiple implementing partners with competing priorities (4) drug and documentation form stockouts. HCWs employed various implementation strategies to overcome challenges, including task shifting from nurses to HIV testing providers, patient flow modifications (e.g., fast-tracking PrEP clients to reduce wait times), PrEP demand generation and myth clarification during health talks, provider education, dedicated PrEP delivery rooms, and coordination with adolescent-friendly services. Additional suggested strategies to improve PrEP integration included community education to increase broader PrEP awareness and enable shorter counseling sessions, and task-shifting data entry and client risk assessments.ConclusionsHCWs were enthusiastic about the appropriateness and acceptability of integrating PrEP services into MCH and FP clinics but noted challenges to adoption and feasibility. Strategies to address challenges focused on improving provider time and space constraints, and increasing provider and client knowledge

Roles of P2 receptors in glial cells: focus on astrocytes

Central nervous system glial cells release and respond to nucleotides under both physiological and pathological conditions, suggesting that these molecules play key roles in both normal brain function and in repair after damage. In particular, ATP released from astrocytes activates P2 receptors on astrocytes and other brain cells, allowing a form of homotypic and heterotypic signalling, which also involves microglia, neurons and oligodendrocytes. Multiple P2X and P2Y receptors are expressed by both astrocytes and microglia; however, these receptors are differentially recruited by nucleotides, depending upon specific pathophysiological conditions, and also mediate the long-term trophic changes of these cells during inflammatory gliosis. In astrocytes, P2-receptor-induced gliosis occurs via activation of the extracellular-regulated kinases (ERK) and protein kinase B/Akt pathways and involves induction of inflammatory and anti-inflammatory genes, cyclins, adhesion and antiapoptotic molecules. While astrocytic P2Y1 and P2Y2,4 are primarily involved in short-term calcium-dependent signalling, multiple P2 receptor subtypes seem to cooperate to astrocytic long-term changes. Conversely, in microglia, exposure to inflammatory and immunological stimuli results in differential functional changes of distinct P2 receptors, suggesting highly specific roles in acquisition of the activated phenotype. We believe that nucleotide-induced activation of astrocytes and microglia may originally start as a defence mechanism to protect neurons from cytotoxic and ischaemic insults; dysregulation of this process in chronic inflammatory diseases eventually results in neuronal cell damage and loss. On this basis, full elucidation of the specific roles of P2 receptors in these cells may help exploit the beneficial neuroprotective features of activated glia while attenuating their harmful properties and thus provide the basis for novel neuroprotective strategies that specifically target the purinergic system

Longitudinal evaluation of quality of life in 288 patients with Neurofibromatosis 2

Advances in molecular biology have resulted in novel therapy for neurofibromatosis 2-related (NF2) tumours, highlighting the need for robust outcome measures. The disease-focused NF2 impact on quality of life (NFTI-QOL) patient questionnaire was assessed as an outcome measure for treatment in a multi-centre study. NFTI-QOL was related to clinician-rated severity (ClinSev) and genetic severity (GenSev) over repeated visits. Data were evaluated for 288 NF2 patients (n = 464 visits) attending the English national NF2 clinics from 2010 to 2012. The male-to-female ratio was equal and the mean age was 42.2 (SD 17.8) years. The analysis included NFTI-QOL eight-item score, ClinSev graded as mild, moderate, or severe, and GenSev as a rank order of the number of NF2 mutations (graded as mild, moderate, severe). The mean (SD) 8.7 (5.4) score for NFTI-QOL for either a first visit or all visits 9.2 (5.4) was similar to the published norm of 9.4 (5.5), with no significant relationships with age or gender. NFTI-QOL internal reliability was good, with a Cronbach’s alpha score of 0.85 and test re-test reliability r = 0.84. NFTI related to ClinSev (r = 0.41, p < 0.001; r = 0.46 for all visits), but weakly to GenSev (r = 0.16, p < 0.05; r = 0.15 for all visits). ClinSev related to GenSev (r = 0.41, p < 0.001; r = 0.42 for all visits). NFTI-QOL showed a good reliability and ability to detect significant longitudinal changes in the QOL of individuals. The moderate relationships of NFTI-QOL with clinician- and genetic-rated severity suggest that NFTI-QOL taps into NF2 patient experiences that are not encompassed by ClinSev rating or genotype

Comprehensive mRNA Expression Profiling Distinguishes Tauopathies and Identifies Shared Molecular Pathways

Background: Understanding the aetiologies of neurodegenerative diseases such as Alzheimer's disease (AD), Pick's disease (PiD), Progressive Supranuclear Palsy (PSP) and Frontotemporal dementia (FTD) is often hampered by the considerable clinical and molecular overlap between these diseases and normal ageing. The development of high throughput genomic technologies such as microarrays provide a new molecular tool to gain insight in the complexity and relationships between diseases, as they provide data on the simultaneous activity of multiple genes, gene networks and cellular pathways. Methodology/Principal Findings: We have constructed genome wide expression profiles from snap frozen post-mortem tissue from the medial temporal lobe of patients with four neurodegenerative disorders (5 AD, 5 PSP, 5 PiD and 5 FTD patients) and 5 control subjects. All patients were matched for age, gender, ApoE-e and MAPT (tau) haplotype. From all groups a total of 790 probes were shown to be differently expressed when compared to control individuals. The results from these experiments were then used to investigate the correlations between clinical, pathological and molecular findings. From the 790 identified probes we extracted a gene set of 166 probes whose expression could discriminate between these disorders and normal ageing. Conclusions/Significance: From genome wide expression profiles we extracted a gene set of 166 probes whose expression could discriminate between neurological disorders and normal ageing. This gene set can be further developed into an accurate microarray-based classification test. Furthermore, from this dataset we extracted a disease specific set of genes and identified two aging related transcription factors (FOXO1A and FOXO3A) as possible drug targets related to neurodegenerative disease