Visual short-term memory relates to tau and amyloid burdens in preclinical autosomal dominant Alzheimer's disease

Background: Over the past decade, visual short-term memory (VSTM) binding tests have been shown to be one of the most sensitive behavioral indicators of Alzheimer’s disease (AD), especially when they require the binding of multiple features (e.g., color and shape). Recently, it has become possible to directly measure amyloid and tau levels in vivo via positron emission tomography (PET). To this point, these behavioral and neurochemical markers have not been compared in humans with AD or at risk for it. Methods: In a cross-sectional study, we compared VSTM performance to tau and amyloid concentrations, measured by PET, in individuals certain to develop AD by virtue of their inheritance of the presenilin-1 E280A mutation. These included 21 clinically unimpaired subjects and 7 subjects with early mild cognitive impairment (MCI), as well as 30 family members who were not carriers of the mutation. Results: We found that VSTM performance correlated strongly with tau in entorhinal cortex and inferior temporal lobe, and also with amyloid when examining asymptomatic carriers only. The condition requiring binding was not preferentially linked to tau—in fact, the non-binding “shape only” condition showed a stronger relationship. Conclusions: The results confirm VSTM’s status as an early marker of AD pathology, and raise interesting questions as to the course of binding-specific versus non-binding aspects of VSTM in early AD

An Ontological Approach to Inform HMI Designs for Minimizing Driver Distractions with ADAS

ADAS (Advanced Driver Assistance Systems) are in-vehicle systems designed to enhance driving safety and efficiency as well as comfort for drivers in the driving process. Recent studies have noticed that when Human Machine Interface (HMI) is not designed properly, an ADAS can cause distraction which would affect its usage and even lead to safety issues. Current understanding of these issues is limited to the context-dependent nature of such systems. This paper reports the development of a holistic conceptualisation of how drivers interact with ADAS and how such interaction could lead to potential distraction. This is done taking an ontological approach to contextualise the potential distraction, driving tasks and user interactions centred on the use of ADAS. Example scenarios are also given to demonstrate how the developed ontology can be used to deduce rules for identifying distraction from ADAS and informing future designs

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Longitudinal amyloid and tau accumulation in autosomal dominant Alzheimer's disease: findings from the Colombia-Boston (COLBOS) biomarker study

Background: Neuroimaging studies of autosomal dominant Alzheimer's disease (ADAD) enable characterization of the trajectories of cerebral amyloid-beta (A beta) and tau accumulation in the decades prior to clinical symptom onset. Longitudinal rates of regional tau accumulation measured with positron emission tomography (PET) and their relationship with other biomarker and cognitive changes remain to be fully characterized in ADAD.Methods: Fourteen ADAD mutation carriers (Presenilin-1 E280A) and 15 age-matched non-carriers from the Colombian kindred underwent 2-3 sessions of A beta (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET, structural magnetic resonance imaging, and neuropsychological evaluation over a 2-4-year follow-up period. Annualized rates of change for imaging and cognitive variables were compared between carriers and non-carriers, and relationships among baseline measurements and rates of change were assessed within carriers.Results: Longitudinal measurements were consistent with a sequence of ADAD-related changes beginning with A beta accumulation (16 years prior to expected symptom onset, EYO), followed by entorhinal cortex (EC) tau (9 EYO), neocortical tau (6 EYO), hippocampal atrophy (6 EYO), and cognitive decline (4 EYO). Rates of tau accumulation among carriers were most rapid in parietal neocortex (similar to 9%/year). EC tau PET signal at baseline was a significant predictor of subsequent neocortical tau accumulation and cognitive decline within carriers.Conclusions: Our results are consistent with the sequence of biological changes in ADAD implied by cross-sectional studies and highlight the importance of EC tau as an early biomarker and a potential link between A beta burden and neocortical tau accumulation in ADAD

Cortical thickness across the lifespan in a Colombian cohort with autosomal-dominant Alzheimer's disease: A cross-sectional study

Introduction Cortical thinning is a marker of neurodegeneration in Alzheimer's disease (AD). We investigated the age-related trajectory of cortical thickness across the lifespan (9-59 years) in a Colombian kindred with autosomal dominant AD (ADAD). Methods Two hundred eleven participants (105 presenilin-1 [PSEN1] E280A mutation carriers, 16 with cognitive impairment; 106 non-carriers) underwent magnetic resonance imaging. A piecewise linear regression identified change-points in the age-related trajectory of cortical thickness in carriers and non-carriers. Results Unimpaired carriers exhibited elevated cortical thickness compared to non-carriers, and thickness more negatively correlated with age and cognition in carriers relative to non-carriers. We found increased cortical thickness in child carriers, after which thickness steadied compared to non-carriers prior to a rapid reduction in the decade leading up to the expected age at cognitive impairment in carriers. Discussion Findings suggest that cortical thickness may fluctuate across the ADAD lifespan, from early-life increased thickness to atrophy proximal to clinical onset