Characterising pandemic severity and transmissibility from data collected during first few hundred studies

Early estimation of the probable impact of a pandemic influenza outbreak can assist public health authorities to ensure that response measures are proportionate to the scale of the threat. Recently, frameworks based on transmissibility and severity have been proposed for initial characterization of pandemic impact. Data requirements to inform this assessment may be provided by "First Few Hundred" (FF100) studies, which involve surveillance-possibly in person, or via telephone-of household members of confirmed cases. This process of enhanced case finding enables detection of cases across the full spectrum of clinical severity, including the date of symptom onset. Such surveillance is continued until data for a few hundred cases, or satisfactory characterization of the pandemic strain, has been achieved. We present a method for analysing these data, at the household level, to provide a posterior distribution for the parameters of a model that can be interpreted in terms of severity and transmissibility of a pandemic strain. We account for imperfect case detection, where individuals are only observed with some probability that can increase after a first case is detected. Furthermore, we test this methodology using simulated data generated by an independent model, developed for a different purpose and incorporating more complex disease and social dynamics. Our method recovers transmissibility and severity parameters to a high degree of accuracy and provides a computationally efficient approach to estimating the impact of an outbreak in its early stages.Andrew J. Black, Nicholas Gear, James M. McCaw, Jodie McVernon, Joshua V. Ros

Three Preventative Interventions to Address the Fake News Phenomenon on Social Media

Fake news on social media undermines democracies and civil society. To date the research response has been message centric and reactive. This does not address the problem of fake news contaminating social media populations with disinformation, nor address the fake news producers and disseminators who are predominantly human social media users. Our research proposes three preventative interventions - two that empower social media users and one social media structural change to reduce the spread of fake news. Specifically, we investigate how i) psychological inoculation; ii) digital media literacy and iii) Transaction Cost Economy safeguarding through reputation ranking could elicit greater cognitive elaboration from social media users. Our research provides digital scalable preventative interventions to empower social media users with the aim to reduce the population size exposed to fake news

A Qualitative Exploration of the Impact of Social Media Disinformation on Social Media Use

Social media disinformation continues to increase and negatively affect the digital and physical world. Disinformation often has negative consequences on individuals, social groups, organizations, societies and governments. The introduction of platform and regulator policies addressing disinformation has had nominal and sometimes negative effect. Users keep being exposed and in response adapt their views, practices and behaviours. In this study we interviewed fifteen active social media users about disinformation’s impact on their social media behaviours. Studying user’s behavioural responses to disinformation may provide strategies for effective platform rules and governance. We find participants adapting and maladapting behaviours, and that disinformation receives critical evaluation when negative language or exaggerated claims are made. We also find strong topic interest drives user engagement. Finally, we propose a model of Social Media Disinformation Processing that provides a conceptual framework to explain social media user’s adapted behaviours in response to disinformation

Testing a model of successful aging in a cohort of masters swimmers

Geard, DE ORCiD: 0000-0002-4292-9278; Rebar, A ORCiD: 0000-0003-3164-993XDue to their high physical functioning, masters athletes are regularly proposed to exemplify successful aging. However, successful aging research on masters athletes has never been undertaken using a multidimensional successful aging model. To determine the best model for future successful aging research on masters athletes, we had masters swimmers (N = 169, M age = 57.4 years, 61% women) self-report subjective successful aging, and physical, psychological, cognitive, and social functioning. Using this data we tested one hypothesized and three alternative successful aging models. The hypothesized model fit the data best (-2LL = 2052.32, AIC = 1717) with physical (β = 0.31, SE = 0.11), psychological (β = 0.25, SE = 0.11), and social (β = 1.20, SE = 0.63) functioning factors significantly loading onto a higher order successful aging latent factor. Successful aging should be conceptualized as a multidimensional phenomenon in future masters athlete research. © 2018 Human Kinetics, Inc

Effects of a 12-Week Cycling Intervention on Successful Aging Measures in Mid-Aged Adults

Purpose: To compare the effect of 12-weeks of cycling training and competition versus recreational cycling on successful aging across physical, psychological, cognitive, and social functioning domains in mid-aged adults. Methods: Recreational cyclists were randomly assigned to an intervention (n = 13, M age = 47.18 years) and comparison (n = 13, M age = 46.91 years) group. Analysis of Covariance was used on self-reported pre-post data to determine changes across time and differences between groups on outcomes. Results: The intervention group scored higher on the role limitation due to physical problems measure of physical functioning (p = .045) and the social activity measure of social functioning (p = .008) with large effect sizes (ηp2 > .14). The remaining physical, psychological, cognitive, and social functioning measures were not significantly different (p > .05) between groups with small to medium effect sizes (ηp2 > .01 to ≤ .06). Conclusion: Cycling training and competition promotes better physical and social functioning than recreational cycling. This finding indicates that an intervention that incorporates the training and competition aspects of sport may promote positive outcomes that are above and beyond those that can be gained from participation in recreational physical activity. Objective measurements on larger samples across a broader range of sports are required to confirm and extend these findings

Integrating BDI agents with Agent-based simulation platforms

Agent-Based Models (ABMs) is increasingly being used for exploring and supporting decision making about social science scenarios involving modelling of human agents. However existing agent-based simulation platforms (e.g., SWARM, Repast) provide limited support for the simulation of more complex cognitive agents required by such scenarios. We present a framework that allows Belief-Desire Intention (BDI) cognitive agents to be embedded in an ABM system. Architecturally, this means that the "brains" of an agent can be modelled in the BDI system in the usual way, while the "body" exists in the ABM system. The architecture is exible in that the ABM can still have non-BDI agents in the simulation, and the BDI-side can have agents that do not have a physical counterpart (such as an organisation). The framework addresses a key integration challenge of coupling event-based BDI systems, with time-stepped ABM systems. Our framework is modular and supports integration off-the-shelf BDI systems with off-the-shelf ABM systems. The framework is Open Source, and all integrations and applications are available for use by the modelling community

Diabetes drugs activate neuroprotective pathways in models of neonatal hypoxic-ischemic encephalopathy

Hypoxic-ischaemic encephalopathy (HIE) arises from diminished blood flow and oxygen to the neonatal brain during labor, leading to infant mortality or severe brain damage, with a global incidence of 1.5 per 1000 live births. Glucagon-like Peptide 1 Receptor (GLP1-R) agonists, used in type 2 diabetes treatment, exhibit neuroprotective effects in various brain injury models, including HIE. In this study, we observed enhanced neurological outcomes in post-natal day 10 mice with surgically induced hypoxic-ischaemic (HI) brain injury after immediate systemic administration of exendin-4 or semaglutide. Short- and long-term assessments revealed improved neuropathology, survival rates, and locomotor function. We explored the mechanisms by which GLP1-R agonists trigger neuroprotection and reduce inflammation following oxygen-glucose deprivation and HI in neonatal mice, highlighting the upregulation of the PI3/AKT signalling pathway and increased cAMP levels. These findings shed light on the neuroprotective and anti-inflammatory effects of GLP1-R agonists in HIE, potentially extending to other neurological conditions, supporting their potential clinical use in treating infants with HIE

Continual Conscious Bioluminescent Imaging in Freely Moving Mice

In vivo bioluminescent imaging allows the detection of reporter gene expression in rodents in real time. Here we describe a novel technology whereby we can generate somatotransgenic rodents with the use of a viral vector carrying a luciferase transgene. We are able to achieve long term luciferase expression by a single injection of lentiviral or adeno-associated virus vectors to newborn mice. Further, we describe whole body bioluminescence imaging of conscious mice in a noninvasive manner, thus enforcing the 3R’s (replacement, reduction, and refinement) of biomedical animal research

A GLP1 receptor agonist diabetes drug ameliorates neurodegeneration in a mouse model of infantile neurometabolic disease

Infantile neuroaxonal dystrophy (INAD) is a rare paediatric neurodegenerative condition caused by mutations in the PLA2G6 gene, which is also the causative gene for PARK14-linked young adult-onset dystonia parkinsonism. INAD patients usually die within their first decade of life, and there are currently no effective treatments available. GLP1 receptor (GLP-1R) agonists are licensed for treating type 2 diabetes mellitus but have also demonstrated neuroprotective properties in a clinical trial for Parkinson's disease. Therefore, we evaluated the therapeutic efficacy of a new recently licensed GLP-1R agonist diabetes drug in a mouse model of INAD. Systemically administered high-dose semaglutide delivered weekly to juvenile INAD mice improved locomotor function and extended the lifespan. An investigation into the mechanisms underlying these therapeutic effects revealed that semaglutide significantly increased levels of key neuroprotective molecules while decreasing those involved in pro-neurodegenerative pathways. The expression of mediators in both the apoptotic and necroptotic pathways were also significantly reduced in semaglutide treated mice. A reduction of neuronal loss and neuroinflammation was observed. Finally, there was no obvious inflammatory response in wild-type mice associated with the repeated high doses of semaglutide used in this study

Comparison of different promoters to improve AAV vector-mediated gene therapy for neuronopathic Gaucher disease

Gaucher Disease (GD) is an inherited metabolic disorder caused by mutations in the GBA1 gene. It can manifest with severe neurodegeneration and visceral pathology. The most acute neuronopathic form (nGD), for which there are no curative therapeutic options, is characterised by devastating neuropathology and death during infancy. In this study, we investigated the therapeutic benefit of systemically delivered AAV9 vectors expressing the human GBA1 gene at two different doses comparing a neuronal-selective promoter with ubiquitous promoters. Our results highlight the importance of a careful evaluation of the promoter sequence used in gene delivery vectors, suggesting a neuron-targeted therapy leading to high levels of enzymatic activity in the brain but lower GCase expression in the viscera, might be the optimal therapeutic strategy for nGD