Is my configuration any good: checking usability in an interactive sensor-based activity monitor

We investigate formal analysis of two aspects of usability in a deployed interactive, configurable and context-aware system: an event-driven, sensor-based homecare activity monitor system. The system was not designed from formal requirements or specification: we model the system as it is in the context of an agile development process. Our aim was to determine if formal modelling and analysis can contribute to improving usability, and if so, which style of modelling is most suitable. The purpose of the analysis is to inform configurers about how to interact with the system, so the system is more usable for participants, and to guide future developments. We consider redundancies in configuration rules defined by carers and participants and the interaction modality of the output messages.Two approaches to modelling are considered: a deep embedding in which devices, sensors and rules are represented explicitly by data structures in the modelling language and non-determinism is employed to model all possible device and sensor states, and a shallow embedding in which the rules and device and sensor states are represented directly in propositional logic. The former requires a conventional machine and a model-checker for analysis, whereas the latter is implemented using a SAT solver directly on the activity monitor hardware. We draw conclusions about the role of formal models and reasoning in deployed systems and the need for clear semantics and ontologies for interaction modalities

Pros and Cons of Long-Chain Omega-3 Polyunsaturated Fatty Acids in Cardiovascular Health

The long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found in seafood, supplements, and concentrated pharmaceutical preparations. Prospective cohort studies demonstrate an association between higher intakes of EPA+DHA or higher levels of EPA and DHA in the body and lower risk of developing cardiovascular disease (CVD), especially coronary heart disease and myocardial infarction, and of cardiovascular mortality in the general population. The cardioprotective effect of EPA and DHA is due to the beneficial modulation of a number of risk factors for CVD. Some large trials support the use of EPA+DHA (or EPA alone) in high-risk patients, although the evidence is inconsistent. This review presents key studies of EPA and DHA in the primary and secondary prevention of CVD, briefly describes potential mechanisms of action, and discusses recently published RCTs and meta-analyses. Potential adverse aspects of long-chain omega-3 fatty acids in relation to CVD are discussed

Omega-3 (n-3) Fatty Acid-Statin Interaction: Evidence for a Novel Therapeutic Strategy for Atherosclerotic Cardiovascular Disease

Managing atherosclerotic cardiovascular disease (ASCVD) often involves a combination of lifestyle modifications and medications aiming to decrease the risk of cardiovascular outcomes, such as myocardial infarction and stroke. The aim of this article is to discuss possible omega-3 (n-3) fatty acid–statin interactions in the prevention and treatment of ASCVD and to provide evidence to consider for clinical practice, highlighting novel insights in this field. Statins and n-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) are commonly used to control cardiovascular risk factors in order to treat ASCVD. Statins are an important lipid-lowering therapy, primarily targeting low-density lipoprotein cholesterol (LDL-C) levels, while n-3 fatty acids address triglyceride (TG) concentrations. Both statins and n-3 fatty acids have pleiotropic actions which overlap, including improving endothelial function, modulation of inflammation, and stabilizing atherosclerotic plaques. Thus, both statins and n-3 fatty acids potentially mitigate the residual cardiovascular risk that remains beyond lipid lowering, such as persistent inflammation. EPA and DHA are both substrates for the synthesis of so-called specialized pro-resolving mediators (SPMs), a relatively recently recognized feature of their ability to combat inflammation. Interestingly, statins seem to have the ability to promote the production of some SPMs, suggesting a largely unrecognized interaction between statins and n-3 fatty acids with relevance to the control of inflammation. Although n-3 fatty acids are the major substrates for the production of SPMs, these signaling molecules may have additional therapeutic benefits beyond those provided by the precursor n-3 fatty acids themselves. In this article, we discuss the accumulating evidence that supports SPMs as a novel therapeutic tool and the possible statin–n-3 fatty acid interactions relevant to the prevention and treatment of ASCVD

Unsaturated fatty acids suppress interleukin-2 production and transferrin receptor expression by concanavalin A-stimulated rat Iymphocytes

The proliferation of T-lymphocytes is dependent upon their ability to synthesize and secrete the cytokine, interleukin-2, and to express cell surface receptors for interleukin-2 and transferrin. We have previously reported that certain fatty acids inhibit mitogen-stimulated T-lymphocyte proliferation. We now report that unsaturated fatty acids decrease the concentration of interleukin-2 in the culture medium of such cells by up to 45%. This suggests that unsaturated fatty acids inhibit lymphocyte proliferation by suppressing interleukin-2 production. However, lymphocyte proliferation was only partially restored by addition of exogenous interleukin-2 to cell culture medium in the presence of unsaturated fatty acids, indicating that these fatty acids also affect other processes involved in the control of proliferation. Saturated fatty acids, which also inhibit lymphocyte proliferation, did not affect the interleukin-2 concentration in the culture medium suggesting a different mechanism for their action. Neither saturated nor unsaturated fatty acids affected the expression of the interleukin-2 receptor by mitogenstimulated lymphocytes. In contrast, unsaturated fatty acids decreased expression of the transferrin receptor by up to 50%. These observations suggest that the mechanism by which unsaturated fatty acids inhibit lymphocyte proliferation involves suppression of interleukin-2 production and of transferrin receptor expression. The mechanism for the inhibitory action of saturated fatty acids is not clear

Diurnal rhythm of plasma EPA and DHA in healthy adults

Knowledge of the diurnal variation in circulating omega-3 polyunsaturated fatty acids (n-3 PUFAs) may be an important consideration for the development of dosing protocols designed to optimise tissue delivery of these fatty acids. The objective of the current study was to examine the variation in plasma concentrations of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) over a 24-h period in healthy adults under eating and sleeping conditions generally approximate to a free-living environment. Twenty-one healthy participants aged 25–44 years took part in a single laboratory visit encompassing an overnight stay. EPA and DHA were measured in plasma samples collected every two hours from 22:00 until 22:00 the following day, with all meals being provided at conventional times. Cosinor analysis was used to estimate the diurnal variation in each fatty acid from pooled data across all participants. A significant diurnal variation in the pooled plasma concentrations of both fatty acids was detected. However, evidence of distinct rhythmicity was strongest for DHA. The timing of the peak concentration of DHA was 17:43 with a corresponding nadir at 05:43. In comparison, the observed acrophase for EPA was delayed by three hours, occurring at 20:41, with a nadir at 08:41. This is the first time that the diurnal variation in these important bioactive fatty acids has been described in a sample of healthy adults following a normal pattern of eating and sleeping. In the absence of any dietary intake of EPA and DHA, circulating levels of these fatty acids fall during the overnight period and reach their lowest point in the morning. Consumption of n-3 PUFAs at night time, which counteracts this pattern, may have functional significance

Reply to "Overstated Claims of Efficacy and Safety. Comment On:Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients 2020, 12, 1181"

We thank Vorland et al [...

Dietary Docosahexaenoic Acid and Arachidonic Acid in Early Life:What Is the Best Evidence for Policymakers?

Background: A wealth of information on the functional roles of docosahexaenoic acid (DHA) and arachidonic acid (ARA) from cellular, animal, and human studies is available. Yet, there remains a lack of cohesion in policymaking for recommended dietary intakes of DHA and ARA in early life. This is predominantly driven by inconsistent findings from a relatively small number of randomised clinical trials (RCTs), which vary in design, methodology, and outcome measures, all of which were conducted in high-income countries. It is proposed that this selective evidence base may not fully represent the biological importance of DHA and ARA during early and later life and the aim of this paper is to consider a more inclusive and pragmatic approach to evidence assessment of DHA and ARA requirements in infants and young children, which will allow policymaking to reflect the marked diversity of need worldwide. Summary: Data from clinical RCTs is considered in the context of the extensive evidence from experimental, animal and human observational studies. Although the RCT data shows evidence of beneficial effects on visual function and in specific cognitive domains, early methodological approaches do not reflect current thinking and this undermines the strength of evidence. An outline of a framework for an inclusive and pragmatic approach to policy development on dietary DHA and ARA in early life is described. Conclusion: High-quality RCTs that will determine long-term health outcomes in appropriate real-world settings need to be undertaken. In the meantime, a collective pragmatic approach to evidence assessment, may allow public health policymakers to make comprehensive reasoned judgements on the merits, costs, and expediency of dietary DHA and ARA interventions

APOE genotype modifies the plasma oxylipin response to omega-3 polyunsaturated fatty acid supplementation in healthy individuals

The omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mediate inflammation in large part by affecting pro-inflammatory and anti-inflammatory/pro-resolving oxylipin concentrations. Common gene variants are thought to underlie the large inter-individual variation in oxylipin levels in response to n-3 PUFA supplementation, which in turn is likely to contribute to the overall heterogeneity in response to n-3 PUFA intervention. Given its known role in inflammation and as a modulator of the physiological response to EPA and DHA, here we explore, for the first time, the differential response of plasma hydroxy-, epoxy- and dihydroxy-arachidonic acid, EPA and DHA oxylipins according to apolipoprotein E (APOE) genotype using samples from a dose-response parallel design RCT. Healthy participants were given doses of EPA+DHA equivalent to intakes of 1, 2, and 4 portions of oily fish per week for 12 months. There was no difference in the plasma levels of EPA, DHA or ARA between the wildtype APOE3/E3 and APOE4 carrier groups after 3 or 12 months of n-3 PUFA supplementation. At 12 months, hydroxy EPAs (HEPEs) and hydroxy-DHAs (HDHAs) were higher in APOE4 carriers, with the difference most evident at the highest EPA+DHA intake. A significant APOE *n-3 PUFA dose effect was observed for the CYP-ω hydroxylase products 19-HEPE (p = 0.027) and 20-HEPE (p = 0.011). 8-HEPE, which, along with several other plasma oxylipins, is an activator of peroxisome proliferator activated receptors (PPARs), showed the highest fold change in APOE4 carriers (14-fold) compared to APOE3/E3 (4-fold) (p = 0.014). Low basal plasma EPA levels (EPA 1.22% of total fatty acids). In conclusion, APOE genotype modulated the plasma oxylipin response to increased EPA+DHA intake, with APOE4 carriers presenting with the greatest increases following high dose n-3 PUFA supplementation for 12 months

Disgust Enhances the Recollection of Negative Emotional Images

Memory is typically better for emotional relative to neutral images, an effect generally considered to be mediated by arousal. However, this explanation cannot explain the full pattern of findings in the literature. Two experiments are reported that investigate the differential effects of categorical affective states upon emotional memory and the contributions of stimulus dimensions other than pleasantness and arousal to any memory advantage. In Experiment 1, disgusting images were better remembered than equally unpleasant frightening ones, despite the disgusting images being less arousing. In Experiment 2, regression analyses identified affective impact – a factor shown previously to influence the allocation of visual attention and amygdala response to negative emotional images – as the strongest predictor of remembering. These findings raise significant issues that the arousal account of emotional memory cannot readily address. The term impact refers to an undifferentiated emotional response to a stimulus, without requiring detailed consideration of specific dimensions of image content. We argue that ratings of impact relate to how the self is affected. The present data call for further consideration of the theoretical specifications of the mechanisms that lead to enhanced memory for emotional stimuli and their neural substrates