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Background and aims Predicting the treatment outcomes of biological therapies is an unmet need in Crohn's Disease. In this study, we explored the potential of serum neutrophil‐related biomarkers to predict infliximab therapeutic results and disease progression in Crohn's Disease patients, over a 2‐year period, in a real‐world setting. Methods The study included 100 asymptomatic Crohn's Disease patients in the IFX maintenance phase from the prospective, observational, multicenter DIRECT study. Patients were categorized according to a composite outcome reflecting progression that included surgery, hospitalizations, new fistulae, abscess or stricture, and drug treatment escalation. Serum neutrophil elastase, lipocalin‐2, lactoferrin, and resistin (non‐neutrophil control) were analyzed via multiplex magnetic bead assays at multiple touchpoints. Fecal calprotectin was assessed by ELISA. Results Over up to 2 years of follow‐up, serum biomarkers did not differentiate between the composite outcome groups, whereas fecal calprotectin was significantly higher in patients with worse outcomes. During the infliximab maintenance phase, there was a significant, sustained reduction of neutrophil elastase (p < 0.001), lipocalin‐2 (p < 0.001), and lactoferrin (p < 0.001), but not of resistin, despite stable neutrophil levels. Correlations between NE and NGAL levels were strong (Pearson correlations 0.75–0.85); all other correlations were of small magnitude. Conclusion Our real‐world data do not support using serum neutrophil elastase, lipocalin‐2, or lactoferrin concentrations as predictors of treatment outcomes or disease evolution in infliximab ‐treated Crohn's Disease patients. On the other hand, the sustained decrease in biomarkers over time suggests that neutrophil stabilization might be an additional infliximab mechanism of action.

Background: The loss of response to adalimumab (ADL) has been related to low serum concentrations at trough. Currently, most methods commercially available for the quantification of ADL are enzyme-linked immunosorbent assay (ELISA) based, with a turnaround time of approximately 8 h, delaying the target dosage adjustment to the subsequent infusion. In this study, we aimed to evaluate the performance of the newly available rapid-test ADL quantification assay by comparing it with three established ELISA methods, using spiked samples and a set of clinical samples. Methods: Spiked samples from control donors and 120 serum samples from inflammatory bowel disease (IBD) patients undergoing ADL therapy were quantified using lateral flow Quantum Blue® Adalimumab and, the ELISA formats from Immundiagnostik, R-Biopharm and an in-house assay. Results: The rapid-test assay had intraclass correlation coefficients of 0.590, 0.864 and 0.761 when comparing with the Immundiagnostik, R-Biopharm and in-house assays, respectively. For the five therapeutic windows, the accuracy was high: ADL rapid test compared with the Immundiagnostik (58–88%); R-Biopharm, 68–89%; and in house, 60–88%; and kappa statistics revealed 0.492–0.602, 0.531–0.659 and 0.545–0.682, respectively. Conclusions: The Quantum Blue® Adalimumab assay can replace the commonly used ELISA-based ADL quantification kits and it is a reliable alternative to these methods. This rapid-test assay enables the quantitative determination of ADL serum trough level in only 15 min. The developed assay allows measurement of ADL over a wide range. Hence, it represents a valuable tool for the clinician to assess the ADL trough level.

Modelling can be a useful management tool because models allow the understanding of water body response to different pollution pressure scenarios which may help on the decision-making process and in prosecuting the Water Framework Directive objectives. This study aims to evaluate the usage of simple water quality models (Qual2Kw) applied to small river basins in order to better understand the response of a river to different loads of nitrogen and phosphorus. Qual2Kw model was applied to Cértima River (Portugal), a small river that ends in a shallow lake called Pateira Fermentelos and represents a very important ecosystem to the local community. Along its pathway, Cértima River has a significant enrichment in nutrients due to agriculture, livestock, domestic sewage and industrial effluents discharged into the river. In case of nitrogen, the highest loads are from domestic (44%) and diffuse (35%) sources. The main sources of phosphorous are domestic (46%), livestock (24%) and diffuse sources (20%). Cértima River is strongly enriched with nutrients, and neither nitrogen nor phosphorous is limiting the algal growth. According to the criterion of Dodds et al. (Water Res, 32(5):1455-1462, 1998), the river is classified as eutrophic. By comparing in stream measurements with Qual2Kw simulations, it can be concluded that it would be necessary to decrease the actual pollutants loads of nitrogen and phosphorous 5 and 10 times, respectively, in order to change Cértima River classification from eutrophic to mesotrophic.

A sampling programme was devised to assess in terms of 5-day biochemical oxygen demand (BOD5), chemical oxygen demand (COD) and suspended solids (SS) removal the performance of one anaerobic, one facultative and two maturation ponds in series, for treating the wastewaters resulting from a slaughterhouse killing approximately 625 pigs/week. The results show that, in spite of poor maintenance,which has been causing bank erosion and macrophyte infestation, the system has coped with large variations in flow and organic load, reducing to a minimum the impact of the effluent discharge on the receiving creek.

Future observations of cosmic microwave background (CMB) polarisation have the potential to answer some of the most fundamental questions of modern physics and cosmology. In this paper, we list the requirements for a future CMB polarisation survey addressing these scientific objectives, and discuss the design drivers of the CORE space mission proposed to ESA in answer to the \"M5\" call for a medium-sized mission. The rationale and options, and the methodologies used to assess the mission's performance, are of interest to other future CMB mission design studies. CORE is designed as a near-ultimate CMB polarisation mission which, for optimal complementarity with ground-based observations, will perform the observations that are known to be essential to CMB polarisation scienceand cannot be obtained by any other means than a dedicated space mission.