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Background Findings from clinical trials of proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors have led to concern that these drugs or the low levels of low-density lipoprotein (LDL) cholesterol that result from their use are associated with cognitive deficits. Methods In a subgroup of patients from a randomized, placebo-controlled trial of evolocumab added to statin therapy, we prospectively assessed cognitive function using the Cambridge Neuropsychological Test Automated Battery. The primary end point was the score on the spatial working memory strategy index of executive function (scores range from 4 to 28, with lower scores indicating a more efficient use of strategy and planning). Secondary end points were the scores for working memory (scores range from 0 to 279, with lower scores indicating fewer errors), episodic memory (scores range from 0 to 70, with lower scores indicating fewer errors), and psychomotor speed (scores range from 100 to 5100 msec, with faster times representing better performance). Assessments of cognitive function were performed at baseline, week 24, yearly, and at the end of the trial. The primary analysis was a noninferiority comparison of the mean change from baseline in the score on the spatial working memory strategy index of executive function between the patients who received evolocumab and those who received placebo; the noninferiority margin was set at 20% of the standard deviation of the score in the placebo group. Results A total of 1204 patients were followed for a median of 19 months; the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was −0.21±2.62 in the evolocumab group and −0.29±2.81 in the placebo group (P

Atrial fibrillation/ flutter (AF) is a common comorbidity in patients with heart failure (HF). We examined the influence of AF on the response to the selective cardiac myosin activator, omecamtiv mecarbil (OM), in patients with HFrEF. COSMIC-HF (NCT 01786512) was a Phase 2 multicenter, randomized

Ordered 11-mercaptoundecanoic acid (MUA) structures formed from self-assembly on evaporated gold electrodes were probed with potassium ferricyanide through electrochemical titration. The ferricyanide response was limited at these highly blocking films at low salt concentrations necessitating addition of 1 M KCl electrolyte. Voltammetry results strongly support the penetration of ferricyanide probe molecules into the SAM films for electron transfer. Recent models for electrochemical titration of SAMs, and interactions in weak polyelectrolytes are evoked for data analysis. The pKa determined using the electrochemical titration model was 5.6 ± 0.2 for 50% MUA/50% 6-mercaptohexanol monolayers and 5.8 ± 0.2 for the 100% MUA films. Utilizing a statistical mechanical model for weak polyelectrolytes at the water–solid interface (1 − pK) and a pK of 5.7, an intermolecular interaction component ( β E ¯ ) of 2 was obtained for the 100% COOH films and β E ¯ of 1 for the 50% COOH films, which suggests a more deprotonated 50% MUA film with less intermolecular interactions compared to pure MUA films.

Programmers are often faced with the necessity to visualize source code and grasp its structure. In a survey we studied how developers deal with this task. Based on our findings, we present the software visualization tool Code Gestalt, which assists programmers in quickly creating class diagrams. We evaluated and refined our concept using two prototypes. As a result, Code Gestalt introduces the tag overlay and thematic relations. These augmentations to class diagrams display similarities in the vocabulary used in the underlying source code. This simple, yet effective toolset empowers the user to explore and visualize software systems. The preliminary results of a user study investigating Code Gestalt indicate good usability.