The theory of the mad genius, a popular cultural fixture for centuries, has received widespread attention in the behavioral sciences. Focusing on a longstanding debate over whether creativity and mental health are positively or negatively correlated, this study first summarized recent relevant studies and meta-analyses and then provided an updated evaluation of this correlation by describing a new and useful perspective for considering the relationship between creativity and mental health. Here, a modified version of the dual-pathway model of creativity was developed to explain the seemingly paradoxical relationship between creativity and mental health. This model can greatly enrich the scientific understanding of the so-called mad genius controversy and further promote the scientific exploration of the link between creativity and mental health or psychopathology.
Aim: Inhibition of thrombin-mediated signaling processes using a vascular dose of rivaroxaban in adjunct to antiplatelet therapy, known as dual-pathway inhibition (DPI), reduces atherothrombotic events in patients with stable atherosclerotic disease. However, there are limited data on the pharmacodynamic (PD) effects of this strategy.
Methods and Results: This investigation was conducted in selected cohorts of patients (n=40) with stable atherosclerotic disease enrolled within a larger prospective PD study who were treated with either aspirin plus clopidogrel (DAPT), aspirin plus rivaroxaban 2.5 mg/bid (DPI) or DAPT plus rivaroxaban 2.5 mg/bid. Multiple PD assays assessing of markers of thrombosis were used. PD endpoints included platelet-mediated global thrombogenicity measured by light transmittance aggregometry (LTA) following stimuli with CATF [collagen‐related peptide +adenosine diphosphate (ADP) +tissue factor (TF)], markers of P2Y12 reactivity, markers of platelet aggregation using LTA following several stimuli (arachidonic acid, ADP, collagen, TF, and TRAP), thrombin generation and thrombus formation. There was no difference in platelet-mediated global thrombogenicity between groups. Rivaroxaban significantly reduced thrombin generation and was associated with a trend towards reduced TF-induced platelet aggregation. Clopidogrel-based treatments reduced markers of P2Y12 signaling and TRAP‐induced platelet aggregation. There were no differences between groups on markers of cyclooxygenase‐1 mediated activity.
Conclusions: Compared with DAPT, DPI does not result in any differences in platelet-mediated global thrombogenicity, but reduces thrombin generation. These PD observations support that modulating thrombin generation by means of factor Xa inhibition in adjunct to antiplatelet therapy provides effective antithrombotic effects, supporting the efficacy and safety findings of DPI observed in clinical
We expand upon prior work (Gibbons et al., 2012) relating childhood stressor effects, particularly harsh childhood environments, to risky behavior and ultimately physical health by adding longer-term outcomes – deoxyribonucleic acid (DNA) methylation-based measures of accelerated aging (DNAm-aging). Further, following work on the effects of early exposure to danger (McLaughlin et al., 2014), we also identify an additional pathway from harsh childhood environments to DNAm-aging that we label the danger/FKBP5 pathway, which includes early exposure to dangerous community conditions that are thought to impact glucocorticoid regulation and pro-inflammatory mechanisms. Because different DNAm-aging indices provide different windows on accelerated aging, we contrast effects on early indices of DNAm-aging based on chronological age with later indices that focused on predicting biological outcomes. We utilize data from Family and Community Health Study participants (N = 449) from age 10 to 29. We find that harshness influences parenting, which, in turn, influences accelerated DNAm-aging through the risky cognitions and substance use (i.e., behavioral) pathway outlined by Gibbons et al. (2012). Harshness is also associated with increased exposure to threat/danger, which, in turn, leads to accelerated DNAm-aging through effects on FKBP5 activity and enhanced pro-inflammatory tendencies (i.e., the danger/FKBP5 pathway).
Arterial thrombotic events in younger patients without a readily apparent etiology present significant diagnostic and management challenges. We present a structured approach to diagnosis with consideration of common causes, including atherosclerosis and embolism, as well as uncommon causes, including medications and substances, vascular and anatomic abnormalities, systemic disorders, and thrombophilias. We highlight areas of management that have evolved within the past 5 years, including the use of dual-pathway inhibition in atherosclerotic disease, antithrombotic therapy selection in embolic stroke of undetermined source and left ventricular thrombus, the role of closure of patent foramen ovale for secondary stroke prevention, and the thrombotic potential of coronavirus disease 2019 infection and vaccination. We conclude with a representative case to illustrate the application of the diagnostic framework and discuss the importance of consideration of bleeding risk and patient preference in determining the appropriate management plan.
Inhibition of thrombin-mediated signalling processes using a vascular dose of rivaroxaban in adjunct to single antiplatelet therapy, known as dual-pathway inhibition (DPI), reduces atherothrombotic events in patients with stable atherosclerotic disease. However, there is limited data on the pharmacodynamic (PD) effects of this strategy.
This investigation was conducted in selected cohorts of patients (n = 40) with stable atherosclerotic disease enrolled from a larger prospective, open-label, parallel-group PD study who were treated with either aspirin, aspirin plus rivaroxaban 2.5 mg/bid or clopidogrel plus rivaroxaban 2.5 mg/bid. Multiple PD assays providing a comprehensive assessment of markers of thrombosis were used. The primary endpoint was the comparison between groups of platelet-mediated global thrombogenicity by light transmittance aggregometry (LTA) following stimuli with collagen-related peptide + adenosine diphosphate + tissue factor (CATF).
There were no differences in the primary endpoint between aspirin vs. aspirin plus rivaroxaban 2.5 mg/bid (P = 0.110), aspirin vs. clopidogrel plus rivaroxaban 2.5 mg/bid (P = 0.611) or aspirin plus rivaroxaban 2.5 mg/bid vs. clopidogrel plus rivaroxaban 2.5 mg/bid (P = 0.315). Rivaroxaban-based treatments significantly reduced markers of thrombin generation (peak thrombin and thrombin velocity index). Clopidogrel-based treatments reduced markers of P2Y12 signalling (LTA ADP 20 max and VerifyNow). Aspirin-based treatments reduced markers of markers of cyclooxygenase-1 activity (LTA collagen).
Compared with aspirin alone, DPI with either aspirin or clopidogrel might provide superior ischaemic protection by targeting pathways alternative to those affected by antiplatelet agents with only a moderate trade-off in bleeding as supported by similar platelet-mediated global thrombogenicity between treatments.
Background and objectives
Peripheral artery disease (PAD) affects more than 200 million people worldwide and it is associated with an increased risk for cardiovascular morbidity and mortality. Current recommendations regarding the management of PAD have been controversial. Our meta-analysis investigated the efficacy of direct Xa inhibitor plus antiplatelet, also known as dual-pathway inhibition (DPI), on the individual components of major adverse cardiovascular events (stroke, myocardial infarction, and cardiovascular death) and major adverse limb events (amputation, restenosis, revascularization, and acute limb ischemia), the composite of MACE and MALE and its safety, in terms of bleeding, compared to antiplatelet therapy among patients with PAD.
We performed a random-effects meta-analysis among patients with PAD comparing DPI to antiplatelet therapy. PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov were searched from their dates of inception to August 2020 for Randomized Controlled Trials. Three studies met the inclusion criteria for final analysis. The selected studies were assessed for risk of bias using the Cochrane RoB2 tool and the overall quality of evidence was assessed using the GRADE approach.
Among patients with PAD, DPI significantly reduces the risk of adverse limb events excluding amputation (RR 0.69, 95% CI 0.57–0.83) and composite MACE and MALE (RR 0.80, 95% CI 0.69–0.93) but significantly increases risk of major bleeding (RR 1.43, 95% CI 1.06–1.93) compared to antiplatelet therapy alone. Overall, DPI did not reduce myocardial infarction, stroke, cardiovascular death, or amputation, or increase the risk of fatal bleeding.
Among patients with PAD, DPI is more effective than antiplatelet therapy alone in preventing adverse limb events excluding amputation with an increased risk of major bleeding. We recommend the use of DPI among patients with PAD who are at a low risk of bleeding.
Type of funding sources: None.
Narcissists successfully emerge as leaders. However, the processes by which this occurs are mostly unknown. Following a dual-pathway approach and differentiating between agentic (narcissistic admiration) and antagonistic (narcissistic rivalry) narcissism, we investigated the behavioral processes underlying narcissists’ leadership emergence in social groups. We applied data from a multimethodological laboratory study ( N = 311) comprising three groups of variables: personality traits, expressed interaction behaviors, and interpersonal perceptions. Prior to the laboratory sessions, participants provided self-reported answers to various narcissism measures. Interpersonal perceptions were obtained from round-robin ratings after participants completed the Lost on the Moon task in small groups. Participants’ behaviors during the group discussion were videotaped and coded by trained raters. Results supported the notion of a pathway from agentic narcissism to leadership (measured as target effects of being seen as a leader) determined by narcissistic admiration, dominant-expressive behavior, and being seen as assertive. To clarify narcissism’s relationship to leadership emergence, the effects were (a) contrasted with narcissism’s effects on popularity and (b) set in relation to process pathways leading from intelligence and physical attractiveness to leadership. The findings underscore the benefits of a behavioral pathway approach for unravelling the impact of narcissism on leadership emergence.