SummaryBackgroundIdentification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy (CAA) is important because it is associated with a higher risk of recurrent intracerebral haemorrhage than arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a prediction model for the identification of CAA-associated lobar intracerebral haemorrhage using CT features and genotype.MethodsWe identified adults with first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology, Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population-based, inception cohort. We determined APOE genotype and radiologists rated CT imaging appearances. Radiologists were not aware of clinical, genetic, and histopathological features. A neuropathologist rated brain tissue for small vessel diseases, including CAA, and was masked to clinical, radiographic, and genetic features. We used CT and APOE genotype data in a logistic regression model, which we internally validated using bootstrapping, to predict the risk of CAA-associated lobar intracerebral haemorrhage, derive diagnostic criteria, and estimate diagnostic accuracy.FindingsAmong 110 adults (median age 83 years [IQR 76–87], 49 [45%] men) included in the LINCHPIN study between June 1, 2010 and Feb 10, 2016, intracerebral haemorrhage was lobar in 62 (56%) participants, deep in 41 (37%), and infratentorial in seven (6%). Of the 62 participants with lobar intracerebral haemorrhage, 36 (58%) were associated with moderate or severe CAA compared with 26 (42%) that were associated with absent or mild CAA, and were independently associated with subarachnoid haemorrhage (32 [89%] of 36 vs 11 [42%] of 26; p=0·014), intracerebral haemorrhage with finger-like projections (14 [39%] of 36 vs 0; p=0·043), and APOE ɛ4 possession (18 [50%] of 36 vs 2 [8%] of 26; p=0·0020). A prediction model for CAA-associated lobar intracerebral haemorrhage using these three variables had excellent discrimination (c statistic 0·92, 95% CI 0·86–0·98), confirmed by internal validation. For the rule-out criteria, neither subarachnoid haemorrhage nor APOE ɛ4 possession had 100% sensitivity (95% CI 88–100). For the rule-in criteria, subarachnoid haemorrhage and either APOE ɛ4 possession or finger-like projections had 96% specificity (95% CI 78–100).InterpretationThe CT and APOE genotype prediction model for CAA-associated lobar intracerebral haemorrhage shows excellent discrimination in this cohort, but requires external validation. The Edinburgh rule-in and rule-out diagnostic criteria might inform prognostic and therapeutic decisions that depend on identification of CAA-associated lobar intracerebral haemorrhage.FundingUK Medical Research Council, The Stroke Association, and The Wellcome Trust.

Ethics applications to conduct research with children who have experienced domestic violence will frequently raise a red flag to ethics committees about the potential for risk and retraumatization. On the other hand, such sensitive research can enable a hidden, marginalized population to have their voices heard. It can deliver findings about children's lives that can inform otherwise adult-centric research, policy and practice initiatives. The authors highlight ethical concerns and practical solutions using examples from domestic violence, family law and child abuse research with children. Ethical planning is explored according to methodologies, context and whether the violence has been named. Also discussed are consent procedures, confidentiality and the development of protocols for disclosure, distress, safety and risk assessment, which support ethical and safe research with children.

• Summary: Domestic violence often directly and indirectly undermines the relationship between mothers and their children. This paper describes ‘the tactics of abuse’ that are instrumental in this damaging process and draws on previous research by one of the authors which shows that a conspiracy of silence can ensue, precluding talk of the abuse that women and children have experienced. The first stage of a four-year action research process designed to address some of these issues is discussed. • Findings: Early findings show that those women and children living in refuges or using outreach services who chose to work together on activities have found the process beneficial. They have provided critical feedback about how the project and activities can be revised for the second action research cycle. The research also shows that not all women are ready to engage in this process when they enter a refuge, and it does require them to acknowledge that their children have been exposed to, and negatively affected by, domestic violence. • Applications: The implications for social workers and specifically the need to provide active support for the mother-child relationship in the aftermath of domestic violence are discussed.

Aims Sporadic human cerebral small vessel disease (SVD) commonly causes stroke and dementia but its pathogenesis is poorly understood. There are recognised neuroimaging and histopathological features. However, relatively few studies have examined the relationship between the radiological and pathological correlates of SVD; better correlation would promote greater insight into the underlying biological changes. Methods We performed a systematic review to collate and appraise the information derived from studies that correlated histological with neuroimaging‐defined SVD lesions. We searched for studies describing post‐mortem imaging and histological tissue examination in adults, extracted data from published studies, categorised the information and compiled this narrative. Results We identified 38 relevant studies, including at least 1146 subjects, 342 of these with SVD: 29 studies focussed on neuroradiological white matter lesions (WML), six on microinfarcts and three on dilated perivascular spaces (PVS) and lacunes. The histopathology terminology was diverse with few robust definitions. Reporting and methodology varied widely between studies, precluding formal meta‐analysis. PVS and ‘oedema’ were frequent findings in WML, being described in at least 94 and 18 radiological WML, respectively, in addition to myelin pallor. Histopathological changes extended beyond the radiological lesion margins in at least 33 radiological WML. At least 43 radiological lesions not seen pathologically and at least 178 histological lesions were not identified on imaging. Conclusions Histopathological assessment of human SVD is hindered by inconsistent methodological approaches and unstandardised definitions. The data from this systematic review will help to develop standardised definitions to promote consistency in human SVD research.

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