Drawing from name in semantic dementia reveals graded object knowledge representations in anterior temporal lobe.

Semantic dementia (SD) is characterized by progressive impairment in conceptual knowledge due to anterior temporal lobe (ATL) neurodegeneration. Extended neuropsychological assessments can quantitatively demonstrate the semantic impairment, but this graded loss of knowledge can also be readily observed in the qualitative observation of patients' recall of single concepts. Here, we present the results of a simple task of object drawing-from-name, by patients with SD (N = 19), who have isolated atrophy of the ATL bilaterally. Both cross-sectionally and longitudinally, patient drawings demonstrated a pattern of degradation in which rare and distinctive features (such as the hump on a camel) were lost earliest in disease course, and there was an increase in the intrusion of prototypical features (such as the typical small ears of most mammals on an elephant) with more advanced disease. Crucially, patient drawings showed a continuum of conceptual knowledge loss rather than a binary 'present' or 'absent' state. Overall, we demonstrate that qualitative evaluation of line drawings of animals and objects provides fascinating insights into the transmodal semantic deficit in SD. Our results are consistent with a distributed-plus-hub model of semantic memory. The graded nature of the deficit in semantic performance observed in our subset of longitudinally observed patients suggests that the temporal lobe binds feature-based semantic attributes in its central convergence zone.

Socioeconomic and gendered inequities in travel behaviour in Africa: Mixed-method systematic review and meta-ethnography.

Travel has individual, societal and planetary health implications. We explored socioeconomic and gendered differences in travel behaviour in Africa, to develop an understanding of travel-related inequity. We conducted a mixed-methods systematic review (PROSPERO CRD42019124802). In 2019, we searched MEDLINE, TRID, SCOPUS, Web of Science, LILACS, SciELO, Global Health, Africa Index Medicus, CINAHL and MediCarib for studies examining travel behaviour by socioeconomic status and gender in Africa. We appraised study quality using Critical Appraisal Skills Programme checklists. We synthesised qualitative data using meta-ethnography, followed by a narrative synthesis of quantitative data, and integrated qualitative and quantitative strands using pattern matching principles. We retrieved 103 studies (20 qualitative, 24 mixed-methods, 59 quantitative). From the meta-ethnography, we observed that travel is: intertwined with social mobility; necessary to access resources; associated with cost and safety barriers; typified by long distances and slow modes; and dictated by gendered social expectations. We also observed that: motorised transport is needed in cities; walking is an unsafe, 'captive' mode; and urban and transport planning are uncoordinated. From these observations, we derived hypothesised patterns that were tested using the quantitative data, and found support for these overall. In lower socioeconomic individuals, travel inequity entailed reliance on walking and paratransit (informal public transport), being unable to afford travel, travelling less overall, and travelling long distances in hazardous conditions. In women and girls, travel inequity entailed reliance on walking and lack of access to private vehicles, risk of personal violence, societally-imposed travel constraints, and household duties shaping travel. Limitations included lack of analytical rigour in qualitative studies and a preponderance of cross-sectional quantitative studies (offering a static view of an evolving process). Overall, we found that travel inequity in Africa perpetuates socioeconomic and gendered disadvantage. Proposed solutions focus on improving the safety, efficiency and affordability of public transport and walking.

Resolving mechanisms of immune-mediated disease in primary CD4 T cells.

Deriving mechanisms of immune-mediated disease from GWAS data remains a formidable challenge, with attempts to identify causal variants being frequently hampered by strong linkage disequilibrium. To determine whether causal variants could be identified from their functional effects, we adapted a massively parallel reporter assay for use in primary CD4 T cells, the cell type whose regulatory DNA is most enriched for immune-mediated disease SNPs. This enabled the effects of candidate SNPs to be examined in a relevant cellular context and generated testable hypotheses into disease mechanisms. To illustrate the power of this approach, we investigated a locus that has been linked to six immune-mediated diseases but cannot be fine-mapped. By studying the lead expression-modulating SNP, we uncovered an NF-κB-driven regulatory circuit which constrains T-cell activation through the dynamic formation of a super-enhancer that upregulates TNFAIP3 (A20), a key NF-κB inhibitor. In activated T cells, this feedback circuit is disrupted-and super-enhancer formation prevented-by the risk variant at the lead SNP, leading to unrestrained T-cell activation via a molecular mechanism that appears to broadly predispose to human autoimmunity.