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001), while those in the highest (versus lowest) organ failure score tertile exhibited less activity (22 fewer movements per epoch, p = 0.03). Significant inactivity/activity differences were not observed when evaluated based on age, sedation, or restraint status. CONCLUSIONS Actigraphy demonstrated that MICU patients are profoundly inactive, including those who are young, non-sedated and non-restrained. Hence, ICU-specific, non-patient-related factors may contribute to inactivity, an issue requiring further investigation. Published by Elsevier Inc.The choroid plexus (ChP) is a major source of cerebrospinal fluid (CSF) production, with a direct and indirect role in protein clearance, and pathogenesis of Alzheimer's disease (AD). Here, we tested the link between the ChP volume and levels of CSF proteins in 2 data sets of (i) healthy controls, mild cognitive impairment (MCI), and AD patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 509), and (ii) healthy controls and Parkinson's disease (PD) patients from the Parkinson's Progression Markers Initiative (N = 302). All patients had baseline CSF proteins (amyloid-β, total and phosphorylated-tau and α-synuclein (only in Parkinson's Progression Markers Initiative)). ChP was automatically segmented on 3T structural T1-weighted MRIs. We found negative associations between ChP volume and CSF proteins, which were stronger in healthy controls, early-MCI patients, and PD patients compared with late-MCI and AD patients. Further grouping of patients of ADNI dataset into amyloid-positive and amyloid-negative based on their florbetapir (AV45) PET imaging showed that the association between ChP volume and CSF proteins (t/p-tau) was lower in amyloid-positive group. Our findings support the possible role of ChP in the clearance of CSF proteins, provide evidence for ChP dysfunction in AD, and suggest the need to account for the ChP volume in future studies of CSF-based biomarkers. Several studies have investigated the differential vulnerability of hippocampal subfields during aging and Alzheimer's disease (AD). Results were often contradictory, mainly because these works were based on concatenations of cross-sectional measures in cohorts with different ages or stages of AD, in the absence of a longitudinal design. Here, we investigated 327 participants from a population-based cohort of nondemented older adults with a 14-year clinical follow-up. MRI at baseline and 4 years later were assessed to measure the annualized rates of hippocampal subfields atrophy in each participant using an automatic segmentation pipeline with subsequent quality control. On the one hand, CA4 dentate gyrus was significantly more affected than the other subfields in the whole population (CA1-3 -0.68%/year; subiculum -0.99%/year; and CA4-DG -1.39%/year; p less then 0.0001). On the other hand, the annualized rate of CA1-3 atrophy was associated with an increased risk of developing Alzheimer's clinical syndrome over time, independently of age, gender, educational level, and ApoE4 genotype (HR = 2.0; CI 95% 1.4-3.0). These results illustrate the natural history of hippocampal subfields atrophy during aging and AD by showing that the dentate gyrus is the most vulnerable subfield to the effects of aging while the cornu-ammonis is the primary target of AD pathophysiological processes, years before symptom onset. BACKGROUND New jurisdictionally-based vaccination programs were established providing free quadrivalent influenza vaccine (QIV) for preschool Australian children in 2018. This was in addition to the National Immunisation Program (NIP) funded QIV for Indigenous children and children with comorbid medical conditions. We assessed the impact of this policy change on influenza disease burden and vaccine coverage, as well as report on 2018 vaccine effectiveness in a hospital-based surveillance system. METHODS Subjects were recruited prospectively from twelve PAEDS-FluCAN sentinel hospital sites (April until October 2018). Children aged ≤16 years hospitalised with an acute respiratory illness (ARI) and laboratory-confirmed influenza were considered cases. Hospitalised children with ARI who tested negative for influenza were considered controls. VE estimates were calculated from the adjusted odds ratio of vaccination in cases and controls. RESULTS A total of 458 children were hospitalised with influenza 31.7% were lmortality. Whether to vaccinate or not is currently a hot topic in social discourse. Despite the majority view that childhood vaccination is safe and effective, websites and social media content opposing such vaccination are common. In this study, we searched the internet platforms Google, Facebook and YouTube for childhood vaccine information. We made every attempt to minimise selection bias generated by internet algorithms. We compared the displayed stances of vaccine information retrieved. Most of the information had a clearly stated stance on vaccines or made some sort of recommendation on whether or not to vaccinate. Despite our careful attempt to search comprehensively and systematically for vaccine information with as little bias as possible, this search yielded a sizeable minority of vaccine negative information. This research shows that negative vaccine information persists and is readily accessible online despite algorithm and policy changes in recent years, even when searching in the least biased way possible. It is important that vaccine-promoting entities and agencies continue to make every effort to maximize their presence online so that parents searching the internet to answer the question 'should I vaccinate my child?' continue to receive vaccine positive information. Despite a critical need for a respiratory syncytial virus (RSV) vaccine and decades of development efforts, a vaccine to protect infants, elderly, and other at-risk populations from RSV infection remains elusive. We have previously generated a new, live-attenuated vaccine candidate against RSV using rational, computer-aided gene design and chemical synthesis through a process termed viral gene "deoptimization." In this study, we assessed the attenuation, immunogenicity, and efficacy of this synthetic, live-attenuated RSV vaccine candidate, RSV-MinL4.0, in African Green Monkeys. Atglistatin RSV-MinL4.0 was produced under good-manufacturing-practice (GMP) in Vero cells. Vaccination with RSV-MinL4.0 resulted in minimal virus shedding after vaccination, generation of robust humoral and cellular immune responses (despite the presence of baseline RSV neutralizing antibodies in one animal) that were comparable to a wildtype infection, and protection from virus shedding post-challenge with wildtype RSV. These findings demonstrate the promise of RSV-MinL4.

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