Cognitive function is associated with risk aversion in community-based older persons

<p>Abstract</p> <p>Background</p> <p>Emerging data from younger and middle-aged persons suggest that cognitive ability is negatively associated with risk aversion, but this association has not been studied among older persons who are at high risk of experiencing loss of cognitive function.</p> <p>Methods</p> <p>Using data from 369 community-dwelling older persons without dementia from the Rush Memory and Aging Project, an ongoing longitudinal epidemiologic study of aging, we examined the correlates of risk aversion and tested the hypothesis that cognition is negatively associated with risk aversion. Global cognition and five specific cognitive abilities were measured via detailed cognitive testing, and risk aversion was measured using standard behavioral economics questions in which participants were asked to choose between a certain monetary payment ($15) versus a gamble in which they could gain more than$15 or gain nothing; potential gamble gains ranged from $21.79 to$151.19 with the gain amounts varied randomly over questions. We first examined the bivariate associations of age, education, sex, income and cognition with risk aversion. Next, we examined the associations between cognition and risk aversion via mixed models adjusted for age, sex, education, and income. Finally, we conducted sensitivity analyses to ensure that our results were not driven by persons with preclinical cognitive impairment.</p> <p>Results</p> <p>In bivariate analyses, sex, education, income and global cognition were associated with risk aversion. However, in a mixed effect model, only sex (estimate = -1.49, standard error (SE) = 0.39, p < 0.001) and global cognitive function (estimate = -1.05, standard error (SE) = 0.34, p < 0.003) were significantly inversely associated with risk aversion. Thus, a lower level of global cognitive function and female sex were associated with greater risk aversion. Moreover, performance on four out of the five cognitive domains was negatively related to risk aversion (<it>i.e</it>., semantic memory, episodic memory, working memory, and perceptual speed); performance on visuospatial abilities was not.</p> <p>Conclusion</p> <p>A lower level of cognitive ability and female sex are associated with greater risk aversion in advanced age.</p

Cell-scale degradation of peritumoural extracellular matrix fibre network and its role within tissue-scale cancer invasion

Local cancer invasion of tissue is a complex, multiscale process which plays an essential role in tumour progression. Occurring over many different temporal and spatial scales, the first stage of invasion is the secretion of matrix degrading enzymes (MDEs) by the cancer cells that consequently degrade the surrounding extracellular matrix (ECM). This process is vital for creating space in which the cancer cells can progress and it is driven by the activities of specific matrix metalloproteinases (MMPs). In this paper, we consider the key role of two MMPs by developing further the novel two-part multiscale model introduced in [33] to better relate at micro-scale the two micro-scale activities that were considered there, namely, the micro-dynamics concerning the continuous rearrangement of the naturally oriented ECM fibres within the bulk of the tumour and MDEs proteolytic micro-dynamics that take place in an appropriate cell-scale neighbourhood of the tumour boundary. Focussing primarily on the activities of the membrane-tethered MT1-MMP and the soluble MMP-2 with the fibrous ECM phase, in this work we investigate the MT1-MMP/MMP-2 cascade and its overall effect on tumour progression. To that end, we will propose a new multiscale modelling framework by considering the degradation of the ECM fibres not only to take place at macro-scale in the bulk of the tumour but also explicitly in the micro-scale neighbourhood of the tumour interface as a consequence of the interactions with molecular fluxes of MDEs that exercise their spatial dynamics at the invasive edge of the tumour

A systematic review of physiological methods in rodent pharmacological MRI studies

Rationale: Pharmacological magnetic resonance imaging (phMRI) provides an approach to study effects of drug challenges on brain processes. Elucidating mechanisms of drug action helps us to better understand the workings of neurotransmitter systems, map brain function or facilitate drug development. phMRI is increasingly used in preclinical research employing rodent models; however, data interpretation and integration are complicated by the use of different experimental approaches between laboratories. In particular, the effects of different anaesthetic regimes upon neuronal and haemodynamic processes and baseline physiology could be problematic. Objectives: This paper investigates how differences in phMRI research methodologies are manifested and considers associated implications, placing particular emphasis on choice of anaesthetic regimes. Methods: A systematic review of rodent phMRI studies was conducted. Factors such as those describing anaesthetic regimes (e.g. agent, dosage) and parameters relating to physiological maintenance (e.g. ventilatory gases) and MRI method were recorded. Results: We identified 126 eligible studies and found that the volatile agents isoflurane (43.7 %) and halothane (33.3 %) were most commonly used for anaesthesia, but dosage and mixture of ventilatory gases varied substantially between laboratories. Relevant physiological parameters were usually recorded, although 32 % of studies did not provide cardiovascular measures. Conclusions: Anaesthesia and animal preparation can influence phMRI data profoundly. The variation of anaesthetic type, dosage regime and ventilatory gases makes consolidation of research findings (e.g. within a specific neurotransmitter system) difficult. Standardisation of a small(er) number of preclinical phMRI research methodologies and/or increased consideration of approaches that do not require anaesthesia is necessary to address these challenges

A cluster randomised controlled trial of the clinical and cost-effectiveness of a 'whole systems' model of self-management support for the management of long- term conditions in primary care: trial protocol

BackgroundPatients with long-term conditions are increasingly the focus of quality improvement activities in health services to reduce the impact of these conditions on quality of life and to reduce the burden on care utilisation. There is significant interest in the potential for self-management support to improve health and reduce utilisation in these patient populations, but little consensus concerning the optimal model that would best provide such support. We describe the implementation and evaluation of self-management support through an evidence-based 'whole systems' model involving patient support, training for primary care teams, and service re-organisation, all integrated into routine delivery within primary care.MethodsThe evaluation involves a large-scale, multi-site study of the implementation, effectiveness, and cost-effectiveness of this model of self-management support using a cluster randomised controlled trial in patients with three long-term conditions of diabetes, chronic obstructive pulmonary disease (COPD), and irritable bowel syndrome (IBS). The outcome measures include healthcare utilisation and quality of life. We describe the methods of the cluster randomised trial.DiscussionIf the 'whole systems' model proves effective and cost-effective, it will provide decision-makers with a model for the delivery of self-management support for populations with long-term conditions that can be implemented widely to maximise 'reach' across the wider patient population.Trial registration numberISRCTN: ISRCTN9094004