Magnetic Resonance Spectroscopy discriminates the response to microglial stimulation of wild type and Alzheimer's disease models.

Microglia activation has emerged as a potential key factor in the pathogenesis of Alzheimers disease. Metabolite levels assessed by magnetic resonance spectroscopy (MRS) are used as markers of neuroinflammation in neurodegenerative diseases, but how they relate to microglial activation in health and chronic disease is incompletely understood. Using MRS, we monitored the brain metabolic response to lipopolysaccharides (LPS)-induced microglia activation in vivo in a transgenic mouse model of Alzheimers disease (APP/PS1) and healthy controls (wild-type (WT) littermates) over 4 hours. We assessed reactive gliosis by immunohistochemistry and correlated metabolic and histological measures. In WT mice, LPS induced a microglial phenotype consistent with activation, associated with a sustained increase in macromolecule and lipid levels (ML9). This effect was not seen in APP/PS1 mice, where LPS did not lead to a microglial response measured by histology, but induced a late increase in the putative inflammation marker myoinositol (mI) and metabolic changes in total creatine and taurine previously reported to be associated with amyloid load. We argue that ML9 and mI distinguish the response of WT and APP/PS1 mice to immune mediators. Lipid and macromolecule levels may represent a biomarker of activation of healthy microglia, while mI may not be a glial marker

Soluble pre-fibrillar tau and β-amyloid species emerge in early human Alzheimer’s disease and track disease progression and cognitive decline

Acknowledgments We would like to gratefully acknowledge all donors and their families for the tissue provided for this study. Human tissue samples were supplied by the Brains for Dementia Research programme, jointly funded by Alzheimer’s Research UK, the Alzheimer’s Society and the Medical Research Council, and sourced from the MRC London Neurodegenerative Diseases Brain Bank, the Manchester Brain Bank, the South West Dementia Brain Bank (SWDBB), the Newcastle Brain Tissue Resource and the Oxford Brain Bank. The Newcastle Brain Tissue Resource and Oxford Brain Bank are also supported by the National Institute for Health Research (NIHR) Units. The South West Dementia Brain Bank (SWDBB) receives additional support from BRACE (Bristol Research into Alzheimer’s and Care of the Elderly). Alz-50, CP13, MC-1 and PHF-1 antibodies were gifted from Dr. Peter Davies and brain lystates from BACE1−/−mice were obtained from Prof Mike Ashford. The work presented here was funded by Alzheimer’s Research UK (Grant refs: ARUKPPG2014A-21 and ARUK-NSG2015-1 to BP and DK and NIH/NIA grants NIH/NINDS R01 NS082730 and R01 AG044372 to NK)Peer reviewedPublisher PD

Lessons learned from evaluating eight password nudges in the wild

Background. The tension between security and convenience, when creating passwords, is well established. It is a tension that often leads users to create poor passwords. For security designers, three mitigation strategies exist: issuing passwords, mandating minimum strength levels or encouraging better passwords. The first strategy prompts recording, the second reuse, but the third merits further investigation. It seemed promising to explore whether users could be subtly nudged towards stronger passwords.Aim. The aim of the study was to investigate the influence of visual nudges on self-chosen password length and/or strength.Method. A university application, enabling students to check course dates and review grades, was used to support two consecutive empirical studies over the course of two academic years. In total, 497 and 776 participants, respectively, were randomly assigned either to a control or an experimental group. Whereas the control group received no intervention, the experimental groups were presented with different visual nudges on the registration page of the web application whenever passwords were created. The experimental groups’ password strengths and lengths were then compared that of the control group.Results. No impact of the visual nudges could be detected, neither in terms of password strength nor length. The ordinal score metric used to calculate password strength led to a decrease in variance and test power, so that the inability to detect an effect size does not definitively indicate that such an effect does not exist.Conclusion. We cannot conclude that the nudges had no effect on password strength. It might well be that an actual effect was not detected due to the experimental design choices. Another possible explanation for our result is that password choice is influenced by the user’s task, cognitive budget, goals and pre-existing routines. A simple visual nudge might not have the power to overcome these forces. Our lessons learned therefore recommend the use of a richer password strength quantification measure, and the acknowledgement of the user’s context, in future studies

CLERA: A Unified Model for Joint Cognitive Load and Eye Region Analysis in the Wild

Non-intrusive, real-time analysis of the dynamics of the eye region allows us to monitor humans' visual attention allocation and estimate their mental state during the performance of real-world tasks, which can potentially benefit a wide range of human-computer interaction (HCI) applications. While commercial eye-tracking devices have been frequently employed, the difficulty of customizing these devices places unnecessary constraints on the exploration of more efficient, end-to-end models of eye dynamics. In this work, we propose CLERA, a unified model for Cognitive Load and Eye Region Analysis, which achieves precise keypoint detection and spatiotemporal tracking in a joint-learning framework. Our method demonstrates significant efficiency and outperforms prior work on tasks including cognitive load estimation, eye landmark detection, and blink estimation. We also introduce a large-scale dataset of 30k human faces with joint pupil, eye-openness, and landmark annotation, which aims to support future HCI research on human factors and eye-related analysis.Comment: ACM Transactions on Computer-Human Interactio

Affect and Fairness

We investigate the role of affect and deliberation on social preferences. In our laboratory experiment subjects decide on a series of mini Dictator games while they are under varying degrees of cognitive load. The cognitive load is intended to decrease deliberation and therefore enhance the influence of affect on behavior. In each game subjects have two options: they can decide between a fair or an unfair allocation. We find that subjects in a high-load condition are more generous - they more often choose the fair allocation than subjects in a low-load condition. The series of mini Dictator games also allows us to investigate how subjects react to the gamesÕ varying levels of advantageous inequality. Low-load subjects react considerably more to the degree of advantageous inequality. Our results therefore underscore the importance of affect for basic altruistic behavior and deliberation in adjusting decisions to a given situation.social preferences, cognitive load, affect and emotion, lab experiment