OBJECTIVE To study the macrostructural and microstructural MRI correlates of brain astrocytosis, measured with 11C-deuterium-L-deprenyl (11C-DED)-PET, in familial autosomal dominant Alzheimer disease (ADAD). METHODS The total sample (n = 31) comprised ADAD mutation carriers (n = 10 presymptomatic, 39.2 ± 10.6 years old; n = 3 symptomatic, 55.5 ± 2.0 years old) and noncarriers (n = 18, 44.0 ± 13.7 years old) belonging to families with mutations in either the presenilin-1 or amyloid precursor protein genes. All participants underwent structural and diffusion MRI and neuropsychological assessment, and 20 participants (6 presymptomatic and 3 symptomatic mutation carriers and 11 noncarriers) also underwent 11C-DED-PET. RESULTS Vertex-wise interaction analyses revealed a differential relationship between carriers and noncarriers in the association between 11C-DED binding and estimated years to onset (EYO) and between cortical mean diffusivity (MD) and EYO. These differences were due to higher 11C-DED binding in presymptomatic carriers, with lower binding in symptomatic carriers compared to noncarriers, and to lower cortical MD in presymptomatic carriers, with higher MD in symptomatic carriers compared to noncarriers. see more Using a vertex-wise local correlation approach, 11C-DED binding was negatively correlated with cortical MD and positively correlated with cortical thickness. CONCLUSIONS Our proof-of-concept study is the first to show that microstructural and macrostructural changes can reflect underlying neuroinflammatory mechanisms in early stages of Alzheimer disease (AD). The findings support a role for neuroinflammation in AD pathogenesis, with potential implications for the correct interpretation of neuroimaging biomarkers as surrogate endpoints in clinical trials. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.OBJECTIVE To test the hypothesis that markers of coagulation and hemostatic activation (MOCHA) help identify causes of cryptogenic stroke, we obtained serum measurements on 132 patients and followed them up to identify causes of stroke. METHODS Consecutive patients with cryptogenic stroke who met embolic stroke of undetermined source (ESUS) criteria from January 1, 2017, to October 31, 2018, underwent outpatient cardiac monitoring and the MOCHA profile (serum D-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) obtained ≥2 weeks after the index stroke; abnormal MOCHA profile was defined as ≥2 elevated markers. Prespecified endpoints monitored during routine clinical visits included new atrial fibrillation (AF), malignancy, venous thromboembolism (VTE), or other defined hypercoagulable states (HS). RESULTS Overall, 132 patients with ESUS (mean age 64 ± 15 years, 61% female, 51% nonwhite) met study criteria. During a median follow-up of 10 (interquartile range 7-14) months, AF, malignancy, VTE, or HS was identified in 31 (23%) patients; the 53 (40%) patients with ESUS with abnormal MOCHA were significantly more likely than patients with normal levels to have subsequent new diagnoses of malignancy (21% vs 0%, p less then 0.001), VTE (9% vs 0%, p = 0.009), or HS (11% vs 0%, p = 0.004) but not AF (8% vs 9%, p = 0.79). The combination of 4 normal MOCHA and normal left atrial size (n = 30) had 100% sensitivity for ruling out the prespecified endpoints. CONCLUSION The MOCHA profile identified patients with cryptogenic stroke more likely to have new malignancy, VTE, or HS during short-term follow-up and may be useful in direct evaluation for underlying causes of cryptogenic stroke. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.We consider the problem of interpreting negative maximum likelihood estimates of heritability that sometimes arise from popular statistical models of additive genetic variation. These may result from random noise acting on estimates of genuinely positive heritability, but we argue that they may also arise from misspecification of the standard additive mechanism that is supposed to justify the statistical procedure. Researchers should be open to the possibility that negative heritability estimates could reflect a real physical feature of the biological process from which the data were sampled. Copyright © 2020, Genetics.OBJECTIVES Common mental disorders (CMDs) are among the main causes of sickness absence and can lead to suffering and high costs for individuals, employers and the society. The occupational health service (OHS) can offer work-directed interventions to support employers and employees. The aim of this study was to evaluate the effect on sickness absence and health of a work-directed intervention given by the OHS to employees with CMDs or stress-related symptoms. METHODS Randomisation was conducted at the OHS consultant level and each consultant was allocated into either giving a brief problem-solving intervention (PSI) or care as usual (CAU). The study group consisted of 100 employees with stress symptoms or CMDs. PSI was highly structured and used a participatory approach, involving both the employee and the employee’s manager. CAU was also work-directed but not based on the same theoretical concepts as PSI. Outcomes were assessed at baseline, at 6 and at 12 months. Primary outcome was registered sickness absence during the 1-year follow-up period. Among the secondary outcomes were self-registered sickness absence, return to work (RTW) and mental health. RESULTS A statistical interaction for group × time was found on the primary outcome (p=0.033) and PSI had almost 15 days less sickness absence during follow-up compared with CAU. Concerning the secondary outcomes, PSI showed an earlier partial RTW and the mental health improved in both groups without significant group differences. CONCLUSION PSI was effective in reducing sickness absence which was the primary outcome in this study. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.CRISPR/Cas9 has become the preferred gene-editing technology to obtain loss-of-function mutants in plants, and hence a valuable tool to study gene function. This is mainly due to the easy reprogramming of Cas9 specificity using customizable small non-coding RNAs, and to the possibility of editing several independent genes simultaneously. Despite these advances, the identification of CRISPR-edited plants remains time and resource-intensive. Here, based on the premise that one editing event in one locus is a good predictor of editing event/s in other locus/loci, we developed a CRISPR co-editing selection strategy that greatly facilitates the identification of CRISPR-mutagenized Arabidopsis thaliana plants. This strategy is based on targeting the gene/s of interest simultaneously with a proxy of CRISPR-Cas9-directed mutagenesis. The proxy is an endogenous gene whose loss-of-function produces an easy-to-detect visible phenotype that is unrelated to the expected phenotype of the gene/s under study. We tested this strategy via assessing the frequency of co-editing of three functionally unrelated proxy genes.