Application of Diffusion Tensor Imaging Parameters to Detect Change in Longitudinal Studies in Cerebral Small Vessel Disease.

Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI's potential as surrogate marker for SVD

Social representations and the politics of participation

Recent work has called for the integration of different perspectives into the field of political psychology (Haste, 2012). This chapter suggests that one possible direction that such efforts can take is studying the role that social representations theory (SRT) can play in understanding political participation and social change. Social representations are systems of common-sense knowledge and social practice; they provide the lens through which to view and create social and political realities, mediate people's relations with these sociopolitical worlds and defend cultural and political identities. Social representations are therefore key for conceptualising participation as the activity that locates individuals and social groups in their sociopolitical world. Political participation is generally seen as conditional to membership of sociopolitical groups and therefore is often linked to citizenship. To be a citizen of a society or a member of any social group one has to participate as such. Often political participation is defined as the ability to communicate one's views to the political elite or to the political establishment (Uhlaner, 2001), or simply explicit involvement in politics and electoral processes (Milbrath, 1965). However, following scholars on ideology (Eagleton, 1991; Thompson, 1990) and social knowledge (Jovchelovitch, 2007), we extend our understanding of political participation to all social relations and also develop a more agentic model where individuals and groups construct, develop and resist their own views, ideas and beliefs. We thus adopt a broader approach to participation in comparison to other political-psychological approaches, such as personality approaches (e.g. Mondak and Halperin, 2008) and cognitive approaches or, more recently, neuropsychological approaches (Hatemi and McDermott, 2012). We move away from a focus on the individual's political behaviour and its antecedents and outline an approach that focuses on the interaction between psychological and political phenomena (Deutsch and Kinnvall, 2002) through examining the politics of social knowledge

Perfusion by Arterial Spin Labelling following Single Dose Tadalafil in Small Vessel Disease (PASTIS): study protocol for a randomized controlled trial

Background Cerebral small vessel disease is a common cause of vascular cognitive impairment in older people, with no licensed treatment. Cerebral blood flow is reduced in small vessel disease. Tadalafil is a widely prescribed phosphodiesterase-5 inhibitor that increases blood flow in other vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. Methods/design Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. Sample size: 54 participants are required to detect a 15% increase in cerebral blood flow in subcortical white matter (p < 0.05, 90% power). Primary outcomes are cerebral blood flow in subcortical white matter and deep grey nuclei. Secondary outcomes are cortical grey matter cerebral blood flow and performance on cognitive tests (reaction time, information processing speed, digit span forwards and backwards, semantic fluency). Discussion Recruitment started on 4th September 2015 and 36 participants have completed to date (19th April 2017). No serious adverse events have occurred. All participants have been recruited from one centre, St George’s University Hospitals NHS Foundation Trust. Trial registration European Union Clinical Trials Register: EudraCT number 2015-001235-20. Registered on 13 May 2015

Teaching Feedback to First-year Medical Students: Long-term Skill Retention and Accuracy of Student Self-assessment

Giving and receiving feedback are critical skills and should be taught early in the process of medical education, yet few studies discuss the effect of feedback curricula for first-year medical students. To study short-term and long-term skills and attitudes of first-year medical students after a multidisciplinary feedback curriculum. Prospective pre- vs. post-course evaluation using mixed-methods data analysis. First-year students at a public university medical school. We collected anonymous student feedback to faculty before, immediately after, and 8 months after the curriculum and classified comments by recommendation (reinforcing/corrective) and specificity (global/specific). Students also self-rated their comfort with and quality of feedback. We assessed changes in comments (skills) and self-rated abilities (attitudes) across the three time points. Across the three time points, students’ evaluation contained more corrective specific comments per evaluation [pre-curriculum mean (SD) 0.48 (0.99); post-curriculum 1.20 (1.7); year-end 0.95 (1.5); p = 0.006]. Students reported increased skill and comfort in giving and receiving feedback and at providing constructive feedback (p &lt; 0.001). However, the number of specific comments on year-end evaluations declined [pre 3.35 (2.0); post 3.49 (2.3); year-end 2.8 (2.1)]; p = 0.008], as did students’ self-rated ability to give specific comments. Teaching feedback to early medical students resulted in improved skills of delivering corrective specific feedback and enhanced comfort with feedback. However, students’ overall ability to deliver specific feedback decreased over time

Acquisition of biologically relevant gene expression data by Affymetrix microarray analysis of archival formalin-fixed paraffin-embedded tumours

Robust protocols for microarray gene expression profiling of archival formalin-fixed paraffin-embedded tissue (FFPET) are needed to facilitate research when availability of fresh-frozen tissue is limited. Recent reports attest to the feasibility of this approach, but the clinical value of these data is poorly understood. We employed state-of-the-art RNA extraction and Affymetrix microarray technology to examine 34 archival FFPET primary extremity soft tissue sarcomas. Nineteen arrays met stringent QC criteria and were used to model prognostic signatures for metastatic recurrence. Arrays from two paired frozen and FFPET samples were compared: although FFPET sensitivity was low (∼50%), high specificity (95%) and positive predictive value (92%) suggest that transcript detection is reliable. Good agreement between arrays and real time (RT)–PCR was confirmed, especially for abundant transcripts, and RT–PCR validated the regulation pattern for 19 of 24 candidate genes (overall R(2)=0.4662). RT–PCR and immunohistochemistry on independent cases validated prognostic significance for several genes including RECQL4, FRRS1, CFH and MET – whose combined expression carried greater prognostic value than tumour grade – and cmet and TRKB proteins. These molecules warrant further evaluation in larger series. Reliable clinically relevant data can be obtained from archival FFPET, but protocol amendments are needed to improve the sensitivity and broad application of this approach

Interplay between n-3 and n-6 long-chain polyunsaturated fatty acids and the endocannabinoid system in brain protection and repair.

The brain is enriched in arachidonic acid (ARA) and docosahexaenoic acid (DHA), long-chain polyunsaturated fatty acids (LCPUFA) of the n-6 and n-3 series, respectively. Both are essential for optimal brain development and function. Dietary enrichment with DHA and other long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA) have shown beneficial effects on learning and memory, neuroinflammatory processes and synaptic plasticity and neurogenesis. ARA, DHA and EPA are precursors to a diverse repertoire of bioactive lipid mediators, including endocannabinoids. The endocannabinoid system comprises cannabinoid receptors, their endogenous ligands, the endocannabinoids, and their biosynthetic and degradation enzymes. Anandamide (AEA) and 2-archidonoylglycerol (2-AG) are the most widely studied endocannabinoids, and are both derived from phospholipid-bound ARA. The endocannabinoid system also has well established roles in neuroinflammation, synaptic plasticity and neurogenesis, suggesting an overlap in the neuroprotective effects observed with these different classes of lipids. Indeed, growing evidence suggests a complex interplay between n-3 and n-6 LCPUFA and the endocannabinoid system. For example, long-term DHA and EPA supplementation reduces AEA and 2-AG levels, with reciprocal increases in levels of the analogous endocannabinoid-like DHA and EPA-derived molecules. This review summarises current evidence of this interplay and discusses the therapeutic potential for brain protection and repair