Mobility as a Service (MaaS) and new mobility concepts mutually inspire each other, provide alternatives for the private car-oriented transport system as we know it, and will offer more mobility... Show moreMobility as a Service (MaaS) and new mobility concepts mutually inspire each other, provide alternatives for the private car-oriented transport system as we know it, and will offer more mobility choices in a single journey than ever. This multitude of mobility choices however poses challenges in modeling the travelers’ mode choices in travel demand prediction models. To address these challenges, this paper develops a multimodal tour-based mode choice model as part of an activity-based demand model. By explicitly modeling access and egress modes, this choice model creates multimodal mode chain sets on a tour level based on restrictions with respect to personal vehicle ownership, MaaS subscription ownership and vehicle states, and subsequently makes mode choices for every traveler. For the creation of these mode chain sets, we introduce the concept of mode categorization. Seven mode categories are proposed, which include both private and shared mobility concepts. This categorization makes sure that modes are mutually sufficiently different in nature, so that reasonably unbiased mode chain choices can be made. Furthermore, the reduction to seven categories enables the study of large scenarios, while the introduced categories still represent new and already existing modes well. The potential of the model is illustrated by simulating travel demand in the Metropolitan region Rotterdam-The Hague. The results show that our model is capable of making plausible mode choices in the presence of MaaS and new mobility concepts, and can be used to assess the impact of mobility hubs where access and egress mode choice is important. Show less
Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest... Show moreEating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors. Show less
Vascular inflammation is present in many cardiovascular diseases, and exogenous glucocorticoids have traditionally been used as a therapy to suppress inflammation. However, recent data have shown... Show moreVascular inflammation is present in many cardiovascular diseases, and exogenous glucocorticoids have traditionally been used as a therapy to suppress inflammation. However, recent data have shown that endogenous glucocorticoids, acting through the endothelial glucocorticoid receptor, act as negative regulators of inflammation. Here, we performed ChIP for the glucocorticoid receptor, followed by next-generation sequencing in mouse endothelial cells to investigate how the endothelial glucocorticoid receptor regulates vascular inflammation. We identified a role of the Wnt signaling pathway in this setting and show that loss of the endothelial glucocorticoid receptor results in upregulation of Wnt signaling both in vitro and in vivo using our validated mouse model. Furthermore, we demonstrate glucocorticoid receptor regulation of a key gene in the Wnt pathway, Frzb, via a glucocorticoid response element gleaned from our genomic data. These results suggest a role for endothelial Wnt signaling modulation in states of vascular inflammation. Show less
