Onderzoeksrapportage impact Dutch Grand Prix Zandvoort 2023

Gemeente Zandvoort en de organisatie van de Dutch Grand Prix (DGP) hebben Breda University of Applied Sciences (BUas) gevraagd om de economische, sociale en maatschappelijke impact van het evenement Dutch Grand Prix 2023 en haar side events (onder de noemer Zandvoort Racefestival) te onderzoeken.Het onderzoek is uitgevoerd middels online en/of face-to-face afgenomen gestructureerde vragenlijsten onder 726 bezoekers van het circuit, 286 bezoekers aan het dorp Zandvoort, 108 ondernemers van Zandvoort en 3418 bewoners van Zandvoort (736), Bloemendaal (37), Haarlem (2322), Haarlemmermeer (162), Heemstede (59) en Noordwijk (102). Daarnaast is aanvullende informatie opgevraagd bij de organisatie van de Dutch Grand Prix, Stichting Zandvoort Beyond, Zandvoort Marketing en Gemeente Zandvoort.Voor het berekenen van de economische impact is gebruik gemaakt van de richtlijnen zoals deze opgesteld zijn door de Werkgroep Evaluatie Sportevenementen (WESP). Er is inzicht verkregen in de additionele bestedingen van DGP-bezoekers en de DGP-organisatie.In de berekening van economische impact is niet gecorrigeerd voor verdringingseffecten. Sponsoractivaties (zoals afhuur van gelegenheden in Zandvoort, inhuur personeel, verzorgen eten en drinken voor genodigden) zijn niet in kaart gebracht. Bestedingen van bezoekers die niet het circuit maar wel het dorp hebben bezocht tijdens het raceweekend zijn eveneens niet meegenomen in de berekening van de economische impact. Het winstcijfer van de DGP-organisatie wordt niet gedeeld en is ook niet meegenomen in de berekening van de economische impact

Onderzoeksrapportage impact Dutch Grand Prix Zandvoort 2023

Gemeente Zandvoort en de organisatie van de Dutch Grand Prix (DGP) hebben Breda University of Applied Sciences (BUas) gevraagd om de economische, sociale en maatschappelijke impact van het evenement Dutch Grand Prix 2023 en haar side events (onder de noemer Zandvoort Racefestival) te onderzoeken.Het onderzoek is uitgevoerd middels online en/of face-to-face afgenomen gestructureerde vragenlijsten onder 726 bezoekers van het circuit, 286 bezoekers aan het dorp Zandvoort, 108 ondernemers van Zandvoort en 3418 bewoners van Zandvoort (736), Bloemendaal (37), Haarlem (2322), Haarlemmermeer (162), Heemstede (59) en Noordwijk (102). Daarnaast is aanvullende informatie opgevraagd bij de organisatie van de Dutch Grand Prix, Stichting Zandvoort Beyond, Zandvoort Marketing en Gemeente Zandvoort.Voor het berekenen van de economische impact is gebruik gemaakt van de richtlijnen zoals deze opgesteld zijn door de Werkgroep Evaluatie Sportevenementen (WESP). Er is inzicht verkregen in de additionele bestedingen van DGP-bezoekers en de DGP-organisatie.In de berekening van economische impact is niet gecorrigeerd voor verdringingseffecten. Sponsoractivaties (zoals afhuur van gelegenheden in Zandvoort, inhuur personeel, verzorgen eten en drinken voor genodigden) zijn niet in kaart gebracht. Bestedingen van bezoekers die niet het circuit maar wel het dorp hebben bezocht tijdens het raceweekend zijn eveneens niet meegenomen in de berekening van de economische impact. Het winstcijfer van de DGP-organisatie wordt niet gedeeld en is ook niet meegenomen in de berekening van de economische impact

‘Christians, out here?’ Encountering Street-Pastors in the post-secular spaces of the UK’s night-time economy

This paper explores the concept of the post-secular city by examining the growing presence of Street-Pastors in the night-time economy of British cities. Street-Pastors are Christian volunteers who work to ensure the safety of people on a ‘night out’. We contribute to work that has called for greater attention to be placed on the ways in which religious faith and ethics are performed to create liminal spaces of understanding in urban areas. Drawing upon in-depth ethnographic research conducted in a range of UK towns and cities, we consider this distinct form of faith-based patrolling in relation to the spatial processes and practices of urban-nightscapes. By exploring the geographies of Street-Pastors, we not only contribute to more nuanced accounts of ‘drinking spaces’ but provide an empirical engagement with the growing body of work on urban rhythms and encounters

Functional Impairment of Human Myeloid Dendritic Cells during Schistosoma haematobium Infection

Chronic Schistosoma infection is often characterized by a state of T cell hyporesponsiveness of the host. Suppression of dendritic cell (DC) function could be one of the mechanisms underlying this phenomenon, since Schistosoma antigens are potent modulators of dendritic cell function in vitro. Yet, it remains to be established whether DC function is modulated during chronic human Schistosoma infection in vivo. To address this question, the effect of Schistosoma haematobium infection on the function of human blood DC was evaluated. We found that plasmacytoid (pDC) and myeloid DC (mDC) from infected subjects were present at lower frequencies in peripheral blood and that mDC displayed lower expression levels of HLA-DR compared to those from uninfected individuals. Furthermore, mDC from infected subjects, but not pDC, were found to have a reduced capacity to respond to TLR ligands, as determined by MAPK signaling, cytokine production and expression of maturation markers. Moreover, the T cell activating capacity of TLR-matured mDC from infected subjects was lower, likely as a result of reduced HLA-DR expression. Collectively these data show that S. haematobium infection is associated with functional impairment of human DC function in vivo and provide new insights into the underlying mechanisms of T cell hyporesponsiveness during chronic schistosomiasis

Enhanced Pro-Inflammatory Cytokine Responses following Toll-Like-Receptor Ligation in Schistosoma haematobium-Infected Schoolchildren from Rural Gabon

BACKGROUND: Schistosoma infection is thought to lead to down-regulation of the host's immune response. This has been shown for adaptive immune responses, but the effect on innate immunity, that initiates and shapes the adaptive response, has not been extensively studied. In a first study to characterize these responses, we investigated the effect of Schistosoma haematobium infection on cytokine responses of Gabonese schoolchildren to a number of Toll-like receptor (TLR) ligands. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) were collected from S. haematobium-infected and uninfected schoolchildren from the rural area of Zile in Gabon. PBMCs were incubated for 24 h and 72 h with various TLR ligands, as well as schistosomal egg antigen (SEA) and adult worm antigen (AWA). Pro-inflammatory TNF-alpha and anti-inflammatory/regulatory IL-10 cytokine concentrations were determined in culture supernatants. PRINCIPAL FINDINGS: Infected children produced higher adaptive IL-10 responses than uninfected children against schistosomal antigens (72 h incubation). On the other hand, infected children had higher TNF-alpha responses than uninfected children and significantly higher TNF-alpha to IL-10 ratios in response to FSL-1 and Pam3, ligands of TLR2/6 and TLR2/1 respectively. A similar trend was observed for the TLR4 ligand LPS while Poly(I:C) (Mda5/TLR3 ligand) did not induce substantial cytokine responses (24 h incubation). CONCLUSIONS: This pilot study shows that Schistosoma-infected children develop a more pro-inflammatory TLR2-mediated response in the face of a more anti-inflammatory adaptive immune response. This suggests that S. haematobium infection does not suppress the host's innate immune system in the context of single TLR ligation

Simian virus 40 inhibits differentiation and maturation of rhesus macaque DC-SIGN+-dendritic cells

Dendritic cells (DC) are the initiators and modulators of the immune responses. Some species of pathogenic microorganisms have developed immune evasion strategies by controlling antigen presentation function of DC. Simian virus 40 (SV40) is a DNA tumor virus of rhesus monkey origin. It can induce cell transformation and tumorigenesis in many vertebrate species, but often causes no visible effects and persists as a latent infection in rhesus monkeys under natural conditions. To investigate the interaction between SV40 and rhesus monkey DC, rhesus monkey peripheral blood monocyte-derived DC were induced using recombinant human Interleukin-4 (rhIL-4) and infective SV40, the phenotype and function of DC-specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN)+ DC were analyzed by flow cytometry (FCM) and mixed lymphocyte reaction (MLR). Results showed that SV40 can down-regulate the expression of CD83 and CD86 on DC and impair DC-induced activation of T cell proliferation. These findings suggest that SV40 might also cause immune suppression by influencing differentiation and maturation of DC

Multivariable regression analysis in Schistosoma mansoni-infected individuals in the Sudan reveals unique immunoepidemiological profiles in uninfected, egg+ and non-egg+ infected individuals

Background: In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in schoolaged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity. Methodology: This retrospective study evaluated immunoepidemiological aspects in 234 individuals(range 4–85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles(cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis. Principal Findings: Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis. Conclusions/Significance: Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways/mechanisms of IL-2 and IL-1β as potential diagnostic markers in order to distinguish patent from non-patent individuals

Chronic Helminth Infections Protect Against Allergic Diseases by Active Regulatory Processes

Developed countries are suffering from an epidemic rise in immunologic disorders, such as allergy-related diseases and certain autoimmunities. Several studies have demonstrated a negative association between helminth infections and inflammatory diseases (eg, allergy), providing a strong case for the involvement of helminth infections in this respect. However, some studies point in the opposite direction. The discrepancy may be explained by differences in frequency, dose, time, and type of helminth. In this review, new studies are discussed that may support the concept that chronic helminth infections in particular—but not acute infections—are associated with the expression of regulatory networks necessary for downmodulating allergic immune responses to harmless antigens. Furthermore, different components of regulatory networks are highlighted, such as the role of regulatory T and B cells, modulation of dendritic cells, early innate signals from structural cells (eg, epithelial cells), and their individual contributions to protection against allergic diseases. It is of great interest to define and characterize specific helminth molecules that have profound immunomodulatory capacities as targets for therapeutic application in the treatment or prophylaxis of allergic manifestations

DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance

Tissue effector cells of the monocyte lineage can differentiate into different cell types with specific cell function depending on their environment. The phenotype, developmental requirements, and functional mechanisms of immune protective macrophages that mediate the induction of transplantation tolerance remain elusive. Here, we demonstrate that costimulatory blockade favored accumulation of DC-SIGN-expressing macrophages that inhibited CD8(+) T cell immunity and promoted CD4(+)Foxp3(+) Treg cell expansion in numbers. Mechanistically, that simultaneous DC-SIGN engagement by fucosylated ligands and TLR4 signaling was required for production of immunoregulatory IL-10 associated with prolonged allograft survival. Deletion of DC-SIGN-expressing macrophages in vivo, interfering with their CSF1-dependent development, or preventing the DC-SIGN signaling pathway abrogated tolerance. Together, the results provide new insights into the tolerogenic effects of costimulatory blockade and identify DC-SIGN(+) suppressive macrophages as crucial mediators of immunological tolerance with the concomitant therapeutic implications in the clinic.This work was supported by the COST Action BM1305: Action to Focus and Accelerate Cell Tolerogenic Therapies (A FACTT), the Mount Sinai Recanati/Miller Transplantation Institute developmental funds, AST/Pfizer Basic Science Faculty Development Grant, Ministerio de Educacióny Ciencia SAF2010-15062, SAF2013-48834-R, and Fundación Mutua Madrileñ a grants to J.O. A portion of this work appears as part of the doctoral thesis of P.C.S