Social welfare aims to support financially vulnerable households by protecting them from financial shocks and providing them with a basic standard of living. Many eligible households, however, do... Show moreSocial welfare aims to support financially vulnerable households by protecting them from financial shocks and providing them with a basic standard of living. Many eligible households, however, do not take up social welfare. We present the results of in-depth interviews with 31 members of financially vulnerable households in two large Dutch cities about their experiences with welfare. We examined the role of money in their lives, what inhibited them from taking up social welfare, and how they sought support. For many interviewed households, money was a source of stress. The fear of reclaims and mistrust of government institutions were the main inhibitors to participating in welfare programs. Whereas the experience of shame and stigma were substantial inhibitors for claiming local welfare benefits, they were not for participating in national welfare programs. Formal and informal help promoted welfare participation, but many participants lacked access to both. We discuss policies that could decrease the perceived uncertainty of benefits receipt and give directions for future research. Show less
This chapter provides the volume's general conceptual framework. It begins by addressing why new approaches to accountability are needed, arguing that accountability literature has reached a... Show moreThis chapter provides the volume's general conceptual framework. It begins by addressing why new approaches to accountability are needed, arguing that accountability literature has reached a stalemate as a result of an impasse between deductive and inductive approaches to accountability in the EU. It then argues that overcoming the stalemate requires developing a generalised framework of what accountability is for, deriving four accountability goods to be used in subsequent chapters. The chapter argues that each of the goods can be delivered in procedural or substantive ways, focusing either on the process by which decisions are made or the substantive worth of decisions themselves. The chapter concludes by discussing the strengths and weaknesses of both varieties of accountability before mapping out how the concepts will be applied across policy fields and institutions in subsequent chapters. Show less
Tajioui, I.; Neerven, T. van; Tol, M.J. van; Bas, J. M.; Veltman, D.; Wee, N.J.A. van der; Leeuw, M. de 2023
Over the past decade innovative technologies such as Virtual Reality (VR) and smartphone applications (apps) have demonstrated their potential for increasing well-being in various fields, such as ... Show moreOver the past decade innovative technologies such as Virtual Reality (VR) and smartphone applications (apps) have demonstrated their potential for increasing well-being in various fields, such as (mental) health care and education. Although still in its infancy, the application of such technologies for treatment purposes in the forensic context and criminal justice practice is nascent. This chapter reviews the literature and describes the state of the art of VR and apps in the forensic domain to explore the shared and unique possibilities for risk assessment, offender rehabilitation, and reintegration. In total, 18 VR applications and 18 smartphone apps were located in scientific databases and through web search. Aside from a review, we present a prospective vision of the unique treatment potential of VR and apps, as well as their complementary use. We conclude with limitations and ethical considerations. Show less
Hagenbeek, F.; Hubers, N.; Dongen, J. van; Pool, R.; Roetman, P.; Harms, A.C.; ... ; Boomsma, D. 2022
Risk assessment of chemical substances is always a challenging process. It can be supported by using the potential of the in silico methods such as the read-across approach. Several frameworks and... Show moreRisk assessment of chemical substances is always a challenging process. It can be supported by using the potential of the in silico methods such as the read-across approach. Several frameworks and methodologies can be found, e.g. the Read-across Assessment Framework (RAAF) developed by ECHA, which describes how the analysis is carried out using the read-across approach. However, they are focused on classical chemical substances, not nanomaterials. Thus, our goal was to evaluate publicly available read-across frameworks in the context of ENM. Especially, in view of the recent update of the REACH regulations (Annex VI), which introduced the concept of “nanoform” of the substance. We examined the possibilities as well as the challenges for nanomaterials when applying available frameworks by carrying out readacross case studies for selected nanoforms of nano-SiO2. Structural properties of five ENMs and data related to their ecotoxicity were extracted from the JRC Repository characterization dossier on nanoSiO2 amorphous materials and the corresponding NanoReg2 H2020 project deliverable. From all endpoints available, toxicity results towards the Carp leucocyte cell line were considered as the most appropriate. For the purposes of the case study, we decided to treat one of the nano-SiO2 as a target (NM200) and the four others (NM 201- 204) as source analogues. The analysis consisted of several steps: i) identification and characterization of all nanoforms; ii) development of grouping hypothesis; iii) assignment to groups; iv) data gathering; v) applicability assessment; vi) filling data gaps. After passing through all the stages we were able to estimate the toxicity of target ENM. The formulated hypothesis of the read-across approach for the assessment of ecotoxicity was as follows: SiO2 nanoforms can be separated into two distinct groups based on how the following properties influenced cytotoxicity in fish cells: i) surface area, ii) coating mass, iii) size distribution in stock and media solutions, iv) polydispersity in stock and media solutions. This leads to the follow-up hypothesis of novel SiO2 ENMs with similar physicochemical/structural parameters inducing similar toxicological activities in fish cells. Subsequently, we employed similarity analysis in the space of the mentioned properties. Based on the calculated Euclidean distances, the target nanoform (NM200), has been placed within the group of toxic source analogues (NM201 and 204). Therefore, according to the worst-case approach, one can assume that the target nanoform will be highly toxic to fish cells. The results and lessons learned from this exercise will be discussed further in the context of the work carried out in the PATROLS project. Show less
Aging is associated with changes in the composition and function of the immune system, such as decreased B cell numbers and reduced antibody responses (1). In addition, aging is related to an... Show moreAging is associated with changes in the composition and function of the immune system, such as decreased B cell numbers and reduced antibody responses (1). In addition, aging is related to an increased incidence of inflammatory diseases, such as the lipid-driven chronic inflammatory disease atherosclerosis, the main underlying cause of cardiovascular disease (2). B cells play a major role in atherosclerosis progression by antibody secretion, antigen presentation and T cell regulation. Different B cell subsets, with either proatherogenic or antiatherogenic properties, have been identified in atherosclerosis, but the impact of aging on B cells during atherosclerosis remains to be elucidated. In contrast to young atherosclerotic mice where few B cells are found within the plaque, single cell RNA sequencing and flow cytometry data from our group revealed that B cells are one of the most dominant leukocytes present in atherosclerotic aortas from naturally aged LDLr-/- mice. In this study, we aimed to gain further insights into the role of these aged B cells on T cell immunity in atherosclerosis by depleting B cells in aged atherosclerotic mice. Aged (85-95 weeks) atherosclerotic male LDLr-/- mice were kept on a chow diet for six weeks, during which the mice received 250 μg B cell-depleting anti-CD20 antibody (Genentech) (n=12) or 250 μg rat IgG2a isotype control (n=12) once a week intraperitoneally. Mice that received the anti-CD20 antibody showed effective B cell depletion in the blood and lymphoid organs, such as the spleen and lymph nodes, but also locally in the atherosclerotic plaque. In addition, B cell depleted mice showed a significant increase in the percentage of T-bet expressing CD4+ T cells in aortic plaques compared to control mice (αCD20: 25.05±2.88% vs. ctrl: 15.94±2.14%, p<0.05). Furthermore, the percentage of RORyt+ and IL-17+ CD4+ T cells in the spleen and heart draining lymph nodes was increased after B cell depletion, indicating a shift towards Th17 differentiation.Collectively, we show that CD20+ B cell depletion in aged LDLr-/- mice skews CD4+ T cells towards a Th1 phenotype in the atherosclerotic plaque and towards a Th17 phenotype in lymphoid organs, suggesting a protective role for aged B cells in atherosclerosis. However, B cells are a heterogeneous population and further research should elucidate whether aged B cells exert a pro- or anti-atherogenic role. In conclusion, our results indicate that aged B cells have an important function in CD4+ T cell differentiation and could be attractive targets to combat age-related cardiovascular disease. Show less
Acute cardiovascular diseases, such as myocardial infarction or stroke, are still a major cause of death in Western Society. The main underlying pathology of cardiovascular diseases is... Show moreAcute cardiovascular diseases, such as myocardial infarction or stroke, are still a major cause of death in Western Society. The main underlying pathology of cardiovascular diseases is atherosclerosis, which is caused by the accumulation of lipids and inflammatory cells in the vessel wall, in so-called atherosclerotic plaques. Mast cells accumulate within these atherosclerotic plaques and activation of mast cells leads to the progression and destabilization of advanced plaques via the secretion of pro-inflammatory mediators and cytokines. Mast cells can be activated by various stimuli, of which crosslinking of the Fce receptor I (FceRI) with IgE-antigen complexes is best known. Bruton’s tyrosine kinase (BTK), a cytoplasmic nonreceptor tyrosine kinase, is involved in the downstream signaling of FceRI-mediated mast cell activation and degranulation. Therefore, BTK might be an attractive target to interfere in the FceRI-mediated mast cell activation pathway. In this study, we thus aimed to assess the effects of the BTK inhibitor ACP-196 on FceRI-mediated mast cell activation, plaque progression and destabilization in an atherosclerotic mouse model.Male LDLr knockout mice, 7-11 weeks old, were treated with ACP-196 (25 mg/kg p.o., n=15) or control solvent (n=14) three times per week for eight weeks. During treatment, mice were fed a Western-type diet (WTD) to induce atherosclerotic plaque formation. During the experiment, plasma total cholesterol levels and body weight did not differ between the control and treatment group. After eight weeks, mice were sacrificed and hearts were isolated to determine atherosclerotic plaque size and stability in the aortic root by histology. Other immunological relevant tissues, such as aorta, spleen and mediastinal lymph nodes were harvested to examine mast cell activation status and other immune cells by flow cytometry. After eight weeks of ACP-196 treatment in LDLr knockout mice, a significant 59% reduction in the frequency of CD117+ FceRI+ mast cells was observed in aortic plaques of ACP-196 treated mice (0.24±0.06%) compared to control mice (0.57 ±0.08%, p<0.05), while relative mast cell activation status was not affected. Additionally, ACP-196 treatment inhibited B cell maturation in the circulation, spleen, mediastinal lymph nodes and peritoneal cavity of LDLr knockout mice compared to control mice. However, these effects on immune cells did not translate into effects on atherosclerosis, as ACP-196 treatment (size:12.3±2%; collagen:14.5±1.9%) did not significantly affect atherosclerotic plaque size and collagen content when compared to control mice (size:11.5±1.4%; collagen: 13.6±1.5%).Conclusively, these findings suggest that ACP-196 treatment leads to reduced migration of mast cells to the atherosclerotic plaques of LDLr knockout mice, but does not directly affect mast cell activation and initial atherosclerotic lesion development. Show less
Cytotoxic CD4+ T cells have previously been found in peripheral blood of patients with coronary artery disease (1), however their occurrence in atherosclerotic plaques and their association with... Show moreCytotoxic CD4+ T cells have previously been found in peripheral blood of patients with coronary artery disease (1), however their occurrence in atherosclerotic plaques and their association with the pathophysiology of atherosclerosis has not been established. Single-cell RNA sequencing was performed on human carotid atherosclerotic plaques of 18 patients to identify specific T cell populations (2). Next, human femoral and carotid atherosclerotic plaques (n=95) and matched blood samples (n=49) were analyzed by flow cytometry for the presence of CD4+GZMB+ T cells. Plaque morphology was assessed by Movat’s Pentachrome staining. A distinct cytotoxic GZMB+ PRF1+ CD28- CD4+ T cell cluster was identified using single-cell RNA sequencing. Furthermore, flow cytometry analysis showed that the percentage of GZMB+CD4+ T cells was significantly elevated in plaque compared to blood (Blood: 12.17±2.0 vs. Plaque: 17.40±1.0; P=0.0002). Moreover, a significant positive correlation was observed between the percentage of GZMB+CD4+ T cells in blood versus plaque (P=0.031). In line with the proinflammatory character of these cells, we found a positive association of GZMB+CD4+ T cells (P=0.036) with necrotic core size, whereas no correlation was found with this subtype in the circulation. In this study we have shown an enrichment of cytotoxic CD4+ T cells in atherosclerotic lesions, which positively correlate with necrotic core size. Future studies are aimed at elucidating the role of these cells in advanced atherosclerosis. Show less
Schaik, J. van; Kormelink, E.; Schouten-van Meeteren, N.; Vos-Kerkhof, E. de; Bakker, B.; Fiocco, M.; ... ; Santen, H. van 2022
