From short-term store to multicomponent working memory: The role of the modal model

The term “modal model” reflects the importance of Atkinson and Shiffrin’s paper in capturing the major developments in the cognitive psychology of memory that were achieved over the previous decade, providing an integrated framework that has formed the basis for many future developments. The fact that it is still the most cited model from that period some 50 years later has, we suggest, implications for the model itself and for theorising in psychology more generally. We review the essential foundations of the model before going on to discuss briefly the way in which one of its components, the short-term store, had influenced our own concept of a multicomponent working memory. This is followed by a discussion of recent claims that the concept of a short-term store be replaced by an interpretation in terms of activated long-term memory. We present several reasons to question these proposals. We conclude with a brief discussion of the implications of the longevity of the modal model for styles of theorising in cognitive psychology

Sense of agency in the human brain

In adult life, people normally know what they are doing. This experience of controlling one's own actions and, through them, the course of events in the outside world is called 'sense of agency'. It forms a central feature of human experience; however, the brain mechanisms that produce the sense of agency have only recently begun to be investigated systematically. This recent progress has been driven by the development of better measures of the experience of agency, improved design of cognitive and behavioural experiments, and a growing understanding of the brain circuits that generate this distinctive but elusive experience. The sense of agency is a mental and neural state of cardinal importance in human civilization, because it is frequently altered in psychopathology and because it underpins the concept of responsibility in human societies

Safety and efficacy of bempedoic Acid to reduce LDL cholesterol

BACKGROUND Short-term studies have shown that bempedoic acid, an inhibitor of ATP citrate lyase, reduces levels of low-density lipoprotein (LDL) cholesterol. Data are limited regarding the safety and efficacy of bempedoic acid treatment in long-term studies involving patients with hypercholesterolemia who are receiving guideline-recommended statin therapy. METHODS We conducted a randomized, controlled trial involving patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both. Patients had to have an LDL cholesterol level of at least 70 mg per deciliter while they were receiving maximally tolerated statin therapy with or without additional lipid-lowering therapy. (Maximally tolerated statin therapy was defined as the highest intensity statin regimen that a patient was able to maintain, as determined by the investigator.) Patients were randomly assigned in a 2:1 ratio to receive bempedoic acid or placebo. The primary end point was safety, and the principal secondary end point (principal efficacy end point) was the percentage change in the LDL cholesterol level at week 12 of 52 weeks. RESULTS The trial involved 2230 patients, of whom 1488 were assigned to receive bempedoic acid and 742 to receive placebo. The mean (±SD) LDL cholesterol level at baseline was 103.2±29.4 mg per deciliter. The incidence of adverse events (1167 of 1487 patients [78.5%] in the bempedoic acid group and 584 of 742 [78.7%] in the placebo group) and serious adverse events (216 patients [14.5%] and 104 [14.0%], respectively) did not differ substantially between the two groups during the intervention period, but the incidence of adverse events leading to discontinuation of the regimen was higher in the bempedoic acid group than in the placebo group (162 patients [10.9%] vs. 53 [7.1%]), as was the incidence of gout (18 patients [1.2%] vs. 2 [0.3%]). At week 12, bempedoic acid reduced the mean LDL cholesterol level by 19.2 mg per deciliter, representing a change of −16.5% from baseline (difference vs. placebo in change from baseline, –18.1 percentage points; 95% confidence interval, –20.0 to –16.1; P<0.001). Safety and efficacy findings were consistent, regardless of the intensity of background statin therapy. CONCLUSIONS In this 52-week trial, bempedoic acid added to maximally tolerated statin therapy did not lead to a higher incidence of overall adverse events than placebo and led to significantly lower LDL cholesterol levels. (Funded by Esperion Therapeutics and the NIHR Imperial Biomedical Research Centre; CLEAR Harmony ClinicalTrials.gov number, NCT02666664.