Objective C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD). We examined aging trajectories of cortical thickness (CTh) and surface area in C9orf72 expansion adult carriers compared to healthy controls to characterize preclinical cerebral changes leading to symptoms. Methods Data were obtained from the Genetic Frontotemporal Dementia Initiative. T1‐weighted magnetic resonance imaging scans were processed with CIVET 2.1 to extract vertex‐wide CTh and cortical surface area (CSA). Symptomatic and presymptomatic subjects were compared to age‐matched controls using mixed‐effects models, controlling for demographic variables. Aging trajectories were compared between carriers and noncarriers by testing the “age by genetic status” interaction. False discovery rate corrections were applied to all vertex‐wide analyses. Results The sample included 640 scans from 386 subjects, including 54 symptomatic C9orf72 carriers (72.2% behavioral variant FTD), 83 asymptomatic carriers, and 249 controls (age range = 18–86 years). Symptomatic carriers showed fairly symmetric reduction in CTh/CSA in most of the frontal lobes, in addition to large temporoparietal areas. Presymptomatic subjects had reduced CTh/CSA in more restricted areas of the medial frontoparietal lobes, in addition to scattered lateral frontal, parietal, and temporal areas. These differences were explained by faster cortical thinning linearly throughout adulthood in a similar anatomical distribution, with differences emerging in the early 30s. CSA reduction was also faster in mutation carriers predominantly in the ventrofrontal regions. Interpretation C9orf72 mutation carriers have faster cortical thinning and surface loss throughout adulthood in regions that show atrophy in symptomatic subjects. This suggests that the pathogenic effects of the mutation lead to structural cerebral changes decades prior to symptoms. ANN NEUROL 2020 ANN NEUROL 2020;88:113–122

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Primary Subject area Neonatal-Perinatal Medicine Background Organizational factors in neonatal intensive care units (NICUs) can increase the risk of adverse events, such as unplanned extubations (UPEs). UPE is the premature and unanticipated removal of an endotracheal tube. UPE and subsequent reintubation may increase the risk for lung injury and bronchopulmonary dysplasia (BPD) among preterm infants. Objectives First, we aimed to assess the association between daily nursing overtime and UPEs in the NICU. Second, we aimed to evaluate the association between UPE, re-intubation after UPE, and BPD in the sub-group of infants born < 29 weeks’ gestational age (GA). Design/Methods We conducted a retrospective cohort study including infants admitted to a tertiary care NICU between 2016-2019. Daily nursing hours were obtained from local administrative databases. Patient data was collected from the local Canadian Neonatal Network database. Association between ratio of daily nursing overtime hours/total nursing hours (OTR) was compared between days with and without UPEs, using logistic regression analyses. Associations between UPE and BPD among infants born <29 weeks requiring mechanical ventilation was evaluated in a 1:1 propensity-score matched (PSM) cohort. Infants were matched based on GA ± 2 weeks, mechanical ventilation days at time of UPE ± 5 days and SNAPII>20. Results There were 108/1370 (7.8%) days with ≥ 1 UPE, for a total of 116 UPE events from 87 patients (23-42 weeks GA). Higher median OTR was observed on days with UPE compared to days without (3.3% vs. 2.5%, p=0.01). OTR was associated with higher adjusted odds of UPE (aOR 1.09, 95% CI 1.01-1.18), while other organizational variables were not (Table 1). Among ventilated infants <29 weeks’ GA (n=XX), UPE rate was 31% (59), BPD rate was 42% (81) and re-intubation rate after UPE was 59% (35). In the PSM cohort of infants <29 weeks, re-intubation after UPE, was associated with increased length of mechanical ventilation (aOR 16.45; CI 6.18, 26.72) as well as increased odds of BPD, when compared to infants not requiring re-intubation (aOR 4.97, 95% CI 1.54-18.27) (Table 2). Conclusion Higher nursing overtime was associated with increased UPEs in the NICU. Re-intubation was frequently required after a UPE. Among the infants born < 29 weeks’ GA, UPE requiring reintubation was associated with increased total length of mechanical ventilation and increased risk of BPD. Our findings highlight the role of workforce management in improving outcomes in the NICU, through reducing the incidence of UPEs.