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
Carfi lzomib (CFZ) treatment increases the survival of patients with relapsed/refractory MM, but it is associated with a higher incidence of cardiovascular adverse events not commonly observed... Show moreCarfi lzomib (CFZ) treatment increases the survival of patients with relapsed/refractory MM, but it is associated with a higher incidence of cardiovascular adverse events not commonly observed after bortezomib (BTZ). Both CFZ and BTZ inhibit the rate-limiting proteasome beta 5 subunit activity at lower concentrations. However, only CFZ co-inhibits the activity of proteasome beta 5 and beta 2 subunits at higher doses, in contrast to the beta 5 and beta 1 co-inhibition provided by high dose BTZ. We hypothesized that the unique beta 5 and beta 2 subunit inhibition pattern explains the CFZ-related acute cardiotoxicity. Show less
Background: Therapeutic vaccines based on synthetic long peptides (SLPs) have a great potential for immunotherapy of cancer patients as these SLPs include both human leukocyte antigen (HLA) class I... Show moreBackground: Therapeutic vaccines based on synthetic long peptides (SLPs) have a great potential for immunotherapy of cancer patients as these SLPs include both human leukocyte antigen (HLA) class I and II epitopes and no patient selection for HLA types is required. The antigen-induced immune response can be strengthened with immune stimulating additives. Amplivant (AV) is a synthetic Toll-like receptor 2 ligand which can be directly conjugated to tumor peptide antigens. In preclinical studies, AV-conjugation to antigens led to both enhanced antigen presentation by dendritic cells and T-cell priming and caused superior induction of effective anti-tumor responses. Moreover, AV-conjugated SLPs showed a 100 times higher immune response compared to unconjugated SLP. The current study is a first-in-human trial to investigate safety and immunogenicity of AV-conjugated human papillomavirus (HPV)16-SLPs. Methods: A dose escalation phase I trial was performed in 24 patients with HPV16 positive (pre-) malignant lesions. AV was conjugated to two SLPs derived from the most immunodominant regions of the HPV16 E6 oncoprotein. Four dose groups (1, 5, 20 or 50 μg of each peptide) in 6 patients each were studied. The vaccine was injected three times intradermally in DMSO / water with a three-week interval. Adverse events (AE) were collected according to CTCAE v4.0 up to 26 weeks. Peptide-specific T-cell immune responses were determined in blood samples taken before and after vaccination using complementary immunological assays (proliferation assay, IFNγ-ELISPOT and cytokine bead array). Results: Toxicity after three AV-conjugated HPV16-SLP vaccinations was limited to CTCAE grade 1 or 2, with predominantly inflammation at the vaccination site and sometimes flu-like symptoms, which generally resolved within one day. Dose increase resulted from no AE in the lowest dose group to mild/moderate AE in all vaccinated persons in the highest dose group. In the lowest dose group, minor vaccine-induced T-cell responses were observed in three of six vaccinated persons. In the highest dose group, all patients displayed a strong HPV16-specific T-cell response after vaccination. The induced T-cell response against HPV16 lasted until the end of the trial. Conclusions: This first-in-human study showed that AV conjugated to SLPs can safely be used as an intradermal therapeutic vaccine. AV-conjugated HPV16-SLP was able to induce robust HPV16-specific T-cell immunity in patients treated for HPV16 positive (pre-) malignancies without any other vaccine adjuvant or formulation. Increase in dose resulted in both a higher number of mild adverse events as well as stronger T-cell immunity. Clinical trial information: NCT02821494.Show less
Cyanobacterial blooms are a global ecological problem that directly threatens human health and crop safety. Cyanobacteria have toxic effects on aquatic microorganisms, which could drive the... Show moreCyanobacterial blooms are a global ecological problem that directly threatens human health and crop safety. Cyanobacteria have toxic effects on aquatic microorganisms, which could drive the selection for resistance genes. The effect of cyanobacterial blooms on the dispersal and abundance of antibiotic-resistance genes (ARGs) of concern to human health remains poorly known. We herein investigated the effect of cyanobacterial blooms on ARG composition in Lake Taihu, China. The numbers and relative abundances of total ARGs increased obviously during a Planktothrix bloom. More pathogenic microorganisms were present during this bloom than during a Planktothrix bloom or during the non-bloom period. Microcosmic experiments using additional aquatic ecosystems (an urban river and Lake West) found that a coculture of Microcystis aeruginosa and Planktothrix agardhii increased the richness of the bacterial community, because its phycosphere provided a richer microniche for bacterial colonization and growth. Antibiotic-resistance bacteria were naturally in a rich position, successfully increasing the momentum for the emergence and spread of ARGs. These results demonstrate that cyanobacterial blooms are a crucial driver of ARG diffusion and enrichment in freshwater, thus providing a reference for the ecology and evolution of ARGs and ARBs and for better assessing and managing water quality. Show less
Fu, Y.; Snelder, N.; Graaf, P.H. van der; Hasselt, J.G.C. van 2020
