Buurttuin! leren van de Jardins Partagés in Frankrijk

Buurtuinen, zijn er in Nederland nog nauwelijks. De publicatie laat zien wat is een buurttuin is en hoe maak je zo'n tuin in de praktijk maakt

De groene metropool; werkbezoek van minister Veerman en bestuurders van de G30 aan Parijs en omgeving, 7, 8 en 9 april 2004

Alterra heeft de minister van LNV samen met een groep bestuurders van de 30 grootste gemeenten in Nederland rondgeleid tijdens een werkbezoek aan opmerkelijke parken en groenstructuren in Parijs en omgeving. Dit rapport is de neerslag van de discussies die naar aanleiding van de geboden inzichten gevoerd zijn over het thema Groen In en Om de stad, van de conclusies die zijn getrokken en van de vervolgafspraken die zijn gemaakt. Het staat vast dat de durf te investeren in groene parels voor de toekomst absoluut zijn vruchten afwerpt

Energy Efficiency and GHG Emissions: Prospective Scenarios for the Aluminium Industry

This study examines the possibilities for energy efficiency and GHG emission improvements in the European aluminium industry. The first part of the study presents the status quo of the industry in the EU28 and Iceland by compiling a database of existing plants with their production characteristics and the best available and innovative technologies (BATs/ITs). A model EU is then developed to simulate the trend in each plant towards 2050. The use of the model in different scenarios allows the analysis of the cost-effectiveness of investments in BATs/ITs. The results show that in absolute terms, for the whole industry the energy consumption and direct GHG emissions can decrease from 2010 to 2050 by 21% and 66%, respectively. And, in almost all scenarios, for the primary aluminium production there is a convergence in the reduction of specific energy consumption and direct GHG emissions of 23% and 72%, respectively. Since most of the savings come from technologies that are in early stages of research, there is a clear need of a decided push and of creating the right conditions to make these potential savings happen.JRC.F.6-Energy Technology Policy Outloo

Polygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease

BACKGROUND: Anti-tumour necrosis factor alpha (TNFα) therapy is widely used in the management of Crohn’s disease (CD) and ulcerative colitis (UC). However, up to a third of patients do not respond to induction therapy and another third of patients lose response over time. To aid patient stratification, polygenetic risk scores have been identified as predictors of response to anti-TNFα therapy. We aimed to replicate the association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients, to establish its clinical validity. MATERIALS AND METHODS: Primary non-response, primary response, durable response and loss of response to anti-TNFα therapy was retrospectively assessed for each patient using stringent definitions. Genome wide genotyping was performed and previously described polygenetic risk scores for primary non-response and durable response were calculated. We compared polygenetic risk scores between patients with primary response and primary non-response, and between patients with durable response and loss of response, using separate analyses for CD and UC. RESULTS: Out of 334 patients with CD, 15 (4%) patients met criteria for primary non-response, 221 (66%) for primary response, 115 (34%) for durable response and 35 (10%) for loss of response. Out of 112 patients with UC, 12 (11%) met criteria for primary non-response, 68 (61%) for primary response, 19 (17%) for durable response and 20 (18%) for loss of response. No significant differences in polygenetic risk scores were found between primary non-responders and primary responders, and between durable responders and loss of responders. CONCLUSIONS: We could not replicate the previously reported association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients with CD or UC. Currently, there is insufficient evidence to use polygenetic risk scores to predict response to anti-TNFα therapy in patients with IBD

Proteomic analyses do not reveal subclinical inflammation in fatigued patients with quiescent Inflammatory Bowel Disease

BackgroundFatigue is a common and clinically challenging symptom in patients with inflammatory bowel diseases (IBD). While fatigue occurs most often in patients with active disease, up to 50% of patients with quiescent disease still report significant fatigue of unknown aetiology. Here, we aimed to investigate whether fatigue in patients with quiescent IBD is reflected by circulating inflammatory proteins, that in turn might reflect ongoing subclinical inflammation.MethodsNinety-two (92) different inflammation-related proteins were measured in plasma of 350 patients with quiescent IBD (188 Crohn’s disease [CD]; 162 ulcerative colitis [UC]). Quiescent IBD was defined as clinical (Harvey-Bradshaw Index [HBI] <5 or Simple Clinical Colitis Activity Index [SCCAI] <2.5) and biochemical remission (C-reactive protein [CRP] <5 mg/L) at time of sampling. Fatigue severity was assessed on a visual analogue scale (VAS).ResultsNone of the analysed plasma proteins were differentially abundant between mildly (1st quartile, Q1) or severely (4th quartile, Q4) fatigued patients under a false discovery rate of 10%. Considering nominal significance (P<0.05), however, leukemia inhibitory factor receptor (LIF-R) concentrations were inversely associated with severe fatigue, also after adjustment for confounding factors (P <0.05) (Figure 1). Although solely LIF-R showed weak ability to discriminate between mild (Q1) and severe (Q4) fatigue (area under the curve [AUC]=0.61, 95% CI: 0.53–0.69, P<0.05), a combined set of the top seven (7) fatigue-associated proteins (LIF-R, vascular endothelial growth factor-A [VEGF-A], glial-derived neurotrophic factor [GDNF], interleukin-20 receptor subunit alpha [IL-20RA], Delta and Notch-like epidermal growth factor-related receptor [DNER], T-cell surface glycoprotein CD5 [CD5], and extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE], also known as protein S100-A12, all P<0.10) was observed to have reasonable discriminative performance (AUC=0.82 [95% CI: 0.74–0.91], P<0.01).ConclusionFatigue in patients with IBD is not clearly reflected by distinct circulating inflammatory protein signatures, which suggests that subclinical immune activation as defined by the studied panel of inflammatory proteins could not be detected. Reduced shedding of the LIF-R protein could be related to fatigue in IBD through modification of the oncostatin-M (OSM) signaling pathway, or through induction of pro-inflammatory phenotypes of T-cells, macrophages, or neural cells. Future studies are warranted to investigate other proteomic or metabolic markers that may accurately reflect fatigue in quiescent IBD, which might represent alternative pathophysiological pathways

Latent cytomegalovirus infection does not influence long-term disease outcomes in inflammatory bowel disease, but is associated with later onset of disease

Objectives: Cytomegalovirus (CMV) infection is common in the general population. CMV infection negatively affects disease course in transplant recipients and HIV patients. Whereas primary CMV infections may occur sporadically in seronegative patients, all seropositive patients with inflammatory bowel syndrome (IBD) are at risk for CMV reactivation due to the inflammatory mucosal and use of immunosuppressive medication. It is unclear whether latent CMV infection, and risk of reactivations, influences long-term disease outcomes. In this study, we aim to explore whether CMV infection affects disease outcomes in IBD patients. Methods: We performed a cross-sectional cohort study with 1404 patients with IBD from a single center. Clinical characteristics and disease outcomes were prospectively collected. We scrutinized CMV serology test results and performed additional CMV serology testing if serum was available. Results: Out of 699 IBD patients with CMV serology, 303 (43.3%) were seropositive, comparable to the general Dutch population. CMV seropositivity was associated with older age, longer IBD disease duration, non-Western origin, birth outside the Netherlands and a lower educational level (p-values ≤.004). CMV seropositivity was not associated with more complicated long-term disease outcomes of IBD (p-values >.05). Seropositive patients presented with symptoms and were diagnosed at an older age compared to seronegative patients (p-values <.01). Conclusions: CMV seropositivity does not influence disease outcomes of IBD patients and seems to be associated with a delay in IBD onset. Guidelines regarding CMV screening in patients with IBD are currently based on a low level of evidence. These data support the recommendation that routine CMV serology measurement is not necessary in the clinical care of IBD

Mucosal microbiota modulate host intestinal immune signatures in Inflammatory Bowel Disease

BackgroundHost intestinal immune gene signatures and microbial dysregulations expose potential mechanisms in the pathogenesis of inflammatory bowel diseases (IBD). Profiling of mucosa-attached microbiota allows the understanding of locally present microbial communities and their immediate impact on the host. This study evaluated interactions between host mucosal gene expression and intestinal mucosa-attached microbiota in IBD.MethodsIntestinal mucosal bulk RNA-sequencing data was combined with mucosal 16S rRNA gene sequencing data from 696 intestinal biopsies derived from 337 patients with IBD (181 with Crohn’s disease [CD] and 156 with ulcerative colitis [UC]) and 16 non-IBD controls. Hierarchical all-against-all associations testing (HAllA) was used to assess factors affecting host gene expressions and microbiota. Mucosal cell enrichments were predicted by deconvolution. Linear mixed interaction models were used to investigate host-microbiota interactions, adjusting for age, sex, BMI and batch effects. Variation explanation analysis was performed by Lasso regression.ResultsIn total, 15,934 intestinal genes and 113 microbial taxa were identified and included in subsequent analyses. Host intestinal gene expressions were characterized by tissue- and inflammation-specificity, whereas intraindividual variability of the mucosal microbiota dominated over disease location and inflammation effects. We observed forty associations between the mucosal expression of genes and the abundance of specific microbes independent of dysbiosis (FDR&lt;0.05). Examples include a positive association between aryl hydrocarbon receptor (AHR) and Bifidobacterium, and a negative association between interleukin 18 receptor 1 (IL18R1) and Lachnoclostridium. Furthermore, 112 gene-microbiota interactions changed in patients with microbial dysbiosis compared to non-dysbiosis (FDR&lt;0.05). These interactions were enriched in immune-related and extracellular matrix organization pathways. For example, the IL1R1 gene was positively associated with Collinsella abundance in non-dysbiotic patients, whereas an inverse association was observed in high dysbiosis. Finally, the presence of mucosal microbial taxa explained up to 10% of the variation in cell type enrichment, affecting epithelial cells, macrophages and regulatory T-cells.ConclusionInteractions between host intestinal gene expressions and mucosa-attached microbiota are disrupted in patients with IBD. Furthermore, mucosal microbiota are highly personalized and potentially contribute to intestinal cell type alterations. Our study unravels key immune-mediated molecular pathways and relevant bacteria in intestinal tissue, which may guide drug development and precision medicine in IBD

Environmental factors associated with biological use and surgery in inflammatory bowel disease

Background and Aim: While major efforts were made studying the complex etiology of inflammatory bowel disease (IBD) including environmental factors, less is known about underlying causes leading to the heterogeneous and highly variable course of disease. As cigarette smoking cessation is the best-known environmental factor with beneficial effect in Crohn's disease (CD), more exposome factors are likely involved. Further insights into the role of the exposome in heterogeneity of disease might not only further knowledge of underlying pathways, but also allow for better risk stratification. Methods: Seven hundred twenty-eight IBD patients completed the validated Groningen IBD Environmental Questionnaire, collecting exposome data for 93 exposome factors. Associations with disease course, that is, for need for surgery or biological therapy, were evaluated using univariate and multivariate-adjusted logistic regression modeling. Results: No significant associations were seen after Bonferroni correction. However, 11 novel exposome factors were identified with P < 0.05. Two factors were associated with course of CD and ulcerative colitis (UC): beer (CD OR0.3/UC OR0.3) and cannabis (0.5/2.2). While in CD, carpet flooring (0.5) was associated with biological use, and four factors were associated with surgery: working shifts (1.8), appendectomy (2.4), frequent tooth brushing (2.8), and large household size (0.1). For UC, migrants more often required biologicals (10.2). Childhood underweight (3.4), amphetamine use (6.2), and cocaine use (4.8) were associated with surgery. Five factors were replicated. Conclusions: We identified 16 environmental factors nominally associated with biological use and surgery in established IBD. These new insights form an important stepping stone to guide research on biological pathways involved, risk stratification, tailor-made interventions, and preventive strategies in IBD

Serological Biomarkers of Extracellular Matrix Turnover and Neutrophil Activity Are Associated with Long-Term Use of Vedolizumab in Patients with Crohn’s Disease

Crohn’s disease (CD) is a relapsing-remitting inflammatory disease of the gastrointestinal (GI) tract characterized by increased extracellular matrix (ECM) remodeling. The introduction of the α4β7-integrin inhibitor vedolizumab (VEDO) has improved disease management, although there is a high rate of primary non-response in patients with CD. We studied whether ECM biomarkers of neutrophil activity and mucosal damage could predict long-term response to VEDO in patients with CD. Serum levels of human neutrophil elastase (HNE)-derived fragments of calprotectin (CPa9-HNE), and matrix metalloproteinase (MMP)-derived fragments of type I (C1M), III (C3M), IV (C4M), and VI (C6Ma3) collagen, type III collagen formation (PRO-C3), basement membrane turnover (PRO-C4) and T-cell activity (C4G), were measured using protein fingerprint assays in patients with CD (n = 32) before VEDO therapy. Long-term response was defined as VEDO treatment of at least 12 months. CPa9-HNE was significantly increased at baseline in non-responders compared with responders (p < 0.05). C1M, C3M, C4M, C6Ma3, and PRO-C4 were also significantly increased at baseline in non-responders compared with responders (all p < 0.05). All biomarkers were associated with response to VEDO (all p < 0.05). To conclude, baseline levels of serum biomarkers for neutrophil activity and mucosal damage are linked to the pathology of CD, and are associated with long-term use of VEDO in patients with CD. Therefore, these biomarkers warrant further validation and could aid in therapeutic decision-making concerning vedolizumab therapy