We performed a 15-year post-mortem neuropathological follow-up of patients in the first trial of amyloid-β immunotherapy for Alzheimer’s disease. Twenty-two participants of a clinical trial of active amyloid-β42 immunization (AN1792, Elan Pharmaceuticals) or placebo were studied. Comprehensive post-mortem neuropathological assessments were performed from 4 months to 15 years after the trial. We analysed the relationships between the topographical distribution of amyloid-β removal from the cerebral cortex and tau pathology, cerebrovascular territories, plasma anti-AN1792 antibody titres and late cognitive status. Seventeen of 22 (77%) participants had Alzheimer’s neuropathological change, whereas 5 of 22 (23%) had alternative causes for dementia (progressive supranuclear palsy = 1, Lewy body disease = 1, vascular brain injury = 1, and frontotemporal lobar degeneration = 2). Nineteen of the 22 participants had received the active agent, three the placebo. Fourteen of 16 (88%) patients with Alzheimer’s disease receiving the active agent had evidence of plaque removal (very extensive removal = 5, intermediate = 4, very limited = 5, no removal = 2). Of particular note, two Alzheimer’s patients who died 14 years after immunization had only very sparse or no detectable plaques in all regions examined. There was a significant inverse correlation between post-vaccination peripheral blood anti-AN1792 antibody titres and post-mortem plaque scores (ρ = − 0.664, P = 0.005). Cortical foci cleared of plaques contained less tau than did cortex with remaining plaques, but the overall distribution of tangles was extensive (Braak V/VI). In conclusion, patients with Alzheimer’s disease actively immunized against amyloid-β can remain virtually plaque-free for 14 years. The extent of plaque removal is related to the immune response. This long duration of efficacy is important in support of active immunization protocols as therapy for, or potentially prevention of, neurodegeneration-associated protein accumulations. Inclusion of patients without Alzheimer’s disease in Alzheimer’s therapy trials is a problem for assessing the efficacy of treatment. Despite modification of Alzheimer’s pathology, most patients had progressed to severe dementia, notably including the five with very extensive plaque removal, possibly due to continued tau propagation. Neuropathology follow-up of patients in therapeutic trials provides valuable information on the causes of dementia and effects of treatment.

Twenty-eight questionnaires were gathered (54.9% response rate), including 20 from Southampton and eight from BSMS. Long-term knowledge retention and better understanding of the material were rated 8.1 and 7.9 out of 10, respectively. Eight responses were from currently practising doctors, who rated how much they now use their teaching skills as doctors as 8.9 out of 10. Of the eight doctors, seven gained points for their foundation programme applications as a direct result of near-peer teaching. The most common motivator for engaging in teaching was to improve subject matter knowledge and the most common benefit was improved communication skills. There are numerous advantages to being a near-peer teacher in medical school DISCUSSION: There are numerous advantages to being a near-peer teacher in medical school, which include knowledge improvement, transferrable professional skills and employability. These initial results support the hypothesised benefits to the teachers and provide a foundation for further longitudinal studies.

This study explores the way in which consumers interpret and process the marketing and communication of sustainable forms of tourism in destinations, in order to inform policy makers about the appropriateness of different types of sustainability messages. Through a thematic analysis of focus group data, we explore the ways in which consumers engage with, and respond to, explicit discourses of sustainability in marketing a tourist destination. We find that overt discourses of sustainability are often rejected by consumers, thus suggesting that messages concerned with sustainability should place greater priority upon consumer experience and opportunities afforded by the purchase and consumption of the travel experience (that happens to be sustainable) they can expect at their chosen destination. As such, commitments to sustainability manifest within organisational philosophy and practice should not drive the principle, overt discourse communicated to consumers. Rather, as embedded within product and practice, such messages would have greater power and effect if they occupied a more subliminal position in destination marketing materials.

This study provides a framework for understanding pediatric staff perspectives on DCD programs in children. Results suggest several possible elements that may be helpful in framing interdisciplinary dialogue and informing institutional practices in the design of a pediatric DCD program.

BACKGROUND: Many polymorphisms in dopamine genes are reported to affect cognitive, imaging, or clinical phenotypes. It is often inferred or assumed that such associations are causal, mediated by a direct effect of the polymorphism on the gene product itself. However, the supporting evidence is not always clear. METHODS: We conducted systematic reviews and meta-analyses to assess the empirical evidence for functional polymorphisms in genes encoding dopaminergic enzymes (COMT, DBH, DDC, MAOA, MAOB, and TH), dopamine receptors (DRD1, DRD2, DRD3, DRD4, and DRD5), the dopamine transporter (DAT), and vesicular transporters (VMAT1 and VMAT2). We defined functionality as an effect of the polymorphism on the expression, abundance, activity, or affinity of the gene product. RESULTS: We screened 22,728 articles and identified 255 eligible studies. We found robust and medium to large effects for polymorphisms in 4 genes. For catechol-O-methyltransferase (COMT), the Val 158 Met polymorphism (rs4680) markedly affected enzyme activity, protein abundance, and protein stability. Dopamine b-hydroxylase (DBH) activity was associated with rs1611115, rs2519152, and the DBH-STR polymorphism. Monoamine oxidase A (MAOA) activity was associated with a 5 0 VNTR polymorphism. Dopamine D 2 receptor (DRD2) binding was influenced by the Taq1A (rs1800497) polymorphism, and rs1076560 affected DRD2 splicing. CONCLUSIONS: Some widely studied dopaminergic polymorphisms clearly and substantially affect the abundance or activity of the encoded gene product. However, for other polymorphisms, evidence of such an association is negative, inconclusive, or lacking. These findings are relevant when selecting polymorphisms as "markers" of dopamine function, and for interpreting the biological plausibility of associations between these polymorphisms and aspects of brain function or dysfunction.