Explore the vast range of titles available.

Heart failure (HF) is one of the most complex chronic disorders with high prevalence, mainly due to the ageing population and better treatment of underlying diseases. Prevalence will continue to rise and is estimated to reach 3% of the population in Western countries by 2025. It is the most important cause of hospitalisation in subjects aged 65 years or more, resulting in high costs and major social impact. The current “one-size-fits-all” approach in the treatment of HF does not result in best outcome for all patients. These facts are an imminent threat to good quality management of patients with HF. An unorthodox approach from a new vision on care is required. We propose a novel predictive, preventive and personalised medicine approach where patients are truly leading their management, supported by an easily accessible online application that takes advantage of artificial intelligence. This strategy paper describes the needs in HF care, the needed paradigm shift and the elements that are required to achieve this shift. Through the inspiring collaboration of clinical and high-tech partners from North-West Europe combining state of the art HF care, artificial intelligence, serious gaming and patient coaching, a virtual doctor is being created. The results are expected to advance and personalise self-care, where standard care tasks are performed by the patients themselves, in principle without involvement of healthcare professionals, the latter being able to focus on complex conditions. This new vision on care will significantly reduce costs per patient while improving outcomes to enable long-term sustainability of top-level HF care.

Chronic diseases are the leading causes of morbidity and mortality in Europe, accounting for more than 2/3 of all death causes and 75 % of the healthcare costs. Heart failure is one of the most prominent, prevalent and complex chronic conditions and is accompanied with multiple other chronic diseases. The current approach to care has important shortcomings with respect to diagnosis, treatment and care processes. A critical aspect of this situation is that interaction between stakeholders is limited and chronic diseases are usually addressed in isolation. Health care in Western countries requires an innovative approach to address chronic diseases to provide sustainability of care and to limit the excessive costs that may threaten the current systems. The increasing prevalence of chronic diseases combined with their enormous economic impact and the increasing shortage of healthcare providers are among the most critical threats. Attempts to solve these problems have failed, and future limitations in financial resources will result in much lower quality of care. Thus, changing the approach to care for chronic diseases is of utmost social importance.

1. A high expression of angiotensin II receptors and of angiotensin-converting enzyme (ACE) activity was detected in confluent NIH 3T3 fibroblasts.2. Characterization with selective ligands, dithiothreitol, and GTPγS, indicated that only the AT2 subtype was expressed.3. AT2 receptors and ACE expression were strictly dependent on the cell density and growth phase of the cells, with AT2 receptors being expressed earlier than ACE. In contrast, high expression of AT2 receptors irrespective of their growth state was observed in NIH 3T3 cells lacking contact inhibition upon neoplastic transformation with ras.4. Our results imply a possible relation of AT2 receptors to cell growth and cell–cell contact.

This paper discusses the impact of a gradual, pre-announced significant increase of the minimum wage during 2013?16 in Romania. The main finding is that the positive effects prevail when the starting level of increase in the minimum wage is very low and the economy is in a negative output gap. Evidence shows that employment has increased, mainly at the minimum wage level, therefore making a shift toward a more balanced wage distribution. This measure might have contributed to a decrease of the shadow economy and a decrease in the share of people at risk of poverty. The impact on inflation was very limited, and the impact on the public budget was positive. Moreover, firms'profits were not affected, as the negative impact of the measure on unit labor costs and exports was limited.

Multinational corporations use highly complex structures of parents and subsidiaries to organize their operations and ownership. Offshore Financial Centers (OFCs) facilitate these structures through low taxation and lenient regulation, but are increasingly under scrutiny, for instance for enabling tax avoidance. Therefore, the identification of OFC jurisdictions has become a politicized and contested issue. We introduce a novel data-driven approach for identifying OFCs based on the global corporate ownership network, in which over 98 million firms (nodes) are connected through 71 million ownership relations. This granular firm-level network data uniquely allows identifying both sink-OFCs and conduit-OFCs. Sink-OFCs attract and retain foreign capital while conduit-OFCs are attractive intermediate destinations in the routing of international investments and enable the transfer of capital without taxation. We identify 24 sink-OFCs. In addition, a small set of five countries – the Netherlands, the United Kingdom, Ireland, Singapore and Switzerland – canalize the majority of corporate offshore investment as conduit-OFCs. Each conduit jurisdiction is specialized in a geographical area and there is significant specialization based on industrial sectors. Against the idea of OFCs as exotic small islands that cannot be regulated, we show that many sink and conduit-OFCs are highly developed countries.

Large-scale human social network structure is typically inferred from digital trace samples of online social media platforms or mobile communication data. Instead, here we investigate the social network structure of a complete population, where people are connected by high-quality links sourced from administrative registers of family, household, work, school, and next-door neighbors. We examine this multilayer social opportunity structure through three common concepts in network analysis: degree, closure, and distance. Findings present how particular network layers contribute to presumably universal scale-free and small-world properties of networks. Furthermore, we suggest a novel measure of excess closure and apply this in a life-course perspective to show how the social opportunity structure of individuals varies along age, socio-economic status, and education level.

Extracellular vesicles (EVs) are mediators of cell communication during health and disease, and abundantly released by platelets upon activation or during ageing. Platelet EVs exert modulatory effects on immune and vascular cells. Platelet EVs may modulate the function of vascular smooth muscle cells (SMC). Platelet EVs were isolated from platelet-rich plasma and incubated with SMC in order to assess binding, proliferation, migration and pro-inflammatory phenotype of the cells. Platelet EVs firmly bound to resting SMC through the platelet integrin α IIb β 3 , while binding also occurred in a CX3CL1-CX3CR1-dependent manner after cytokine stimulation. Platelet EVs increased SMC migration comparable to platelet derived growth factor or platelet factor 4 and induced SMC proliferation, which relied on CD40- and P-selectin interactions. Flow-resistant monocyte adhesion to platelet EV-treated SMC was increased compared with resting SMC. Again, this adhesion depended on integrin α IIb β 3 and P-selectin, and to a lesser extent on CD40 and CX3CR1. Treatment of SMC with platelet EVs induced interleukin 6 secretion. Finally, platelet EVs induced a synthetic SMC morphology and decreased calponin expression. Collectively, these data indicate that platelet EVs exert a strong immunomodulatory activity on SMC. In particular, platelet EVs induce a switch towards a pro-inflammatory phenotype, stimulating vascular remodelling.

The CC chemokine ligand 18 (CCL18) is a chemokine highly expressed in chronic inflammation in humans. Recent observations of elevated CCL18 plasma levels in patients with acute cardiovascular syndromes prompted an investigation into the role of CCL18 in the pathogenesis of human and mouse atherosclerosis. CCL18 was profoundly upregulated in ruptured human atherosclerotic plaque, particularly within macrophages. Repeated administration of CCL18 in Western-type diet-fed mice or PCSK9 -overexpressing wild type (WT) mice led to increased plaque burden, enriched in CD3 T cells. In subsequent experimental and molecular modeling studies, we identified CCR6 as a functional receptor mediating CCL18 chemotaxis, intracellular Ca flux, and downstream signaling in human Jurkat and mouse T cells. CCL18 failed to induce these effects in murine spleen T cells with CCR6 deficiency. The ability of CCR6 to act as CCL18 receptor was confirmed in an inflammation model, where subcutaneous CCL18 injection induced profound focal skin inflammation in WT but not in mice. This inflammation featured edema and marked infiltration of various leukocyte subsets, including T cells with a Th17 signature, supporting CCR6's role as a Th17 chemotactic receptor. Notably, focal overexpression of CCL18 in plaques was associated with an increased presence of CCR6 (T) cells. Our studies are the first to identify the CCL18/CCR6 axis as a regulator of immune responses in advanced murine and human atherosclerosis.

The dominance of online social media data as a source for large-scale social network studies has recently been challenged by networks constructed from state-curated register data. In this paper focused on the cross-comparison of the network structures, we investigate the similarities and differences of the Dutch online social network (OSN) Hyves and a register-based social network (RSN) of the Netherlands. First and foremost, we find that node metrics and the connectivity of the two population-scale networks are similar, with more long-distance ties captured by the OSN, and with the OSN ties proving to be predictive of RSN ties. These results hold when correcting for population size and geographical distance, notwithstanding that these two factors appear to be the main drivers of connectivity. Second, we show using multiple algorithms that the community structure of the two networks is similar and that neither follows strict administrative geographical delineations (e.g., provinces). Instead, communities appear to either center around large metropolitan areas or, outside of the country’s most urbanized area, comprise large blocks of interdependent municipalities. Beyond population and distance-related patterns, communities also highlight the persistence of deeply rooted sociocultural communities such as the Dutch Bible belt. The findings presented in this work aid in interpreting results from future studies in which register-based social networks are used to obtain insights into the social network structure of an entire population.