Evaluating the impact of river restoration on the local groundwater and ecological system: a case study in NE Flanders

River restoration changes the interaction between groundwater and surface water. Therefore, it is expected to have an impact on ecosystems at the interface between groundwater and surface water. Quantifying and generalizing the level of change of this interaction for different hydrogeological environments is scientifically and practically challenging. In this paper we investigated the impact of different restoration measures and the effect on the interaction of the temporal resolution of the groundwater modeling methodology. The interaction is analysed in the water bodies and wetlands in the valley of the Zwarte Beek, one of the most valuable nature reserves of Flanders. In the past, several changes have been made to the river and drainage system. These adaptations are now considered to be bottlenecks in maintaining a good ecological and hydrological status of its water dependent biotopes. Hence, in the context of the EU Water Framework Directive, it is necessary to (at least partly) restore the initial natural situation. The measures proposed include the reinstatement of old meanders and the removal of a weir. By removing the weir, fish migration is again possible. Reconnecting old meanders increases the habitat diversity. We used transient groundwater modeling to evaluate the impact on the groundwater system of the wetlands. Results indicate that a peat layer, present in most of the wetland, minimizes the effects of the restoration on the groundwater table. The largest changes are confined to the areas near the old meanders and the weir. Steady-state situations do not allow a calculation of average lowest and highest groundwater levels, which are essential for simulating ecological site conditions. Hence, transient simulations with 14 days time steps are required to detect a considerably greater range of groundwater fluctuation than indicated by the seasonal simulation. It is shown that the river restoration project thus resulted in an improvement of the structure of the watercourse rather than the rewetting of the valley. We concluded also that high resolution transient groundwater modeling is an essential step towards river restoration and ecohydrological predictions

Centimeter-scale secondary information on hydraulic conductivity using a hand-held air permeameter on borehole cores

Saturated hydraulic conductivity (Ks) is one of the most important parameters determining groundwater flow and contaminant transport in both unsaturated and saturated porous media. Determining the small-scale variability of this parameter is key to evaluate implications on effective parameters at the larger scale. Moreover, for stochastic simulations of groundwater flow and contaminant transport, accurate models on the spatial variability of Ks are very much needed. While several well-established laboratory methods exist for determining Ks, investigating the small-scale variability remains a challenge. If several tens to hundreds of metres of borehole core has to be hydraulically characterised at the centimetre to decimetre scale, several hundreds to thousands of Ks measurements are required, which makes it very costly and time-consuming should traditional methods be used. With reliable air permeameters becoming increasingly available from the late 80’s, a fast and effective indirect method exists to determine Ks. Therefore, the use of hand-held air permeameter measurements for determining very accurate small-scale heterogeneity about Ks is very appealing. Very little is known, however, on its applicability for borehole cores that typically carry a small sediment volume. Therefore, the method was tested on several borehole cores of different size, originating from the Campine basin, Northern Belgium. The studied sediments are of Miocene to Pleistocene age, with a marine to continental origin, and consist of sand to clayey sand with distinct clay lenses, resulting in a Ks range of 7 orders of magnitude. During previous studies, two samples were taken from borehole cores each two meters for performing constant head lab permeameter tests. This data is now used as a reference for the air permeameter measurements that are performed with a resolution of 5 centimetres. Preliminary results indicate a very good correlation between the previously gathered constant head Ks data and the air permeability measurements, but a systematic bias seems to exist. A geostatistical analysis with cross-validation is performed to assess the predictive uncertainty on Ks, using both types of data. We conclude that performing hand-held air permeameter measurements on undisturbed borehole cores provides a very cost-effective way to obtain very detailed information in the framework of stochastic simulation and conditioning of heterogeneous hydraulic conductivity fields

Real-World Effectiveness, Safety, and Health-Related Quality of Life in Patients Receiving Adjuvant Nivolumab for Melanoma in Belgium and Luxembourg: Results of PRESERV MEL

peer reviewedBackground: Nivolumab, an anti–programmed cell death 1 immuno-oncology therapy, is approved as an adjuvant treatment for patients with completely resected stage III or stage IV melanoma. PRESERV MEL (Prospective and REtrospective Study of nivolumab thERapy in adjuVant MELanoma) is a real-world observational study evaluating the effectiveness and safety of adjuvant nivolumab in patients with completely resected stage III or stage IV melanoma in clinical practice in Belgium and Luxembourg. Methods: Patients were enrolled prospectively and retrospectively during a 2-year period (January 2019–January 2021), and will be followed for 5 years. The results reported here are for the second interim analysis (cutoff date 31 December 2021). The index date was the date of first administration of adjuvant nivolumab. Patients received nivolumab for up to 12 months per label. Outcomes included relapse-free survival (RFS), adverse events (AEs)/treatment-related AEs (TRAEs), and health-related quality of life (HRQoL; assessed in prospectively enrolled patients using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), Functional Assessment of Cancer Therapy—Melanoma (FACT-M), and EQ-5D-3L instruments). HRQoL was evaluated at group level (mean change in scores from baseline based on minimally important differences) and individual patient level (percentage of patients with clinically important scores based on threshold of clinical importance). Outcomes were analyzed descriptively. Results: The study enrolled 152 patients (125 prospective, 27 retrospective) at 15 hospitals in Belgium and Luxembourg. Minimum potential follow-up at time of analysis was 11.4 months. Median age was 60 years (range 29–85), and 53% of patients were male. At 12 and 18 months, the RFS rates were 74.7% (95% confidence interval (CI): 66.9–80.9) and 68.4% (95% CI: 60.0–75.5), respectively. Median RFS was not reached. Grade 3 or 4 TRAEs were reported in 14% of patients. AEs led to treatment discontinuation in 23% of patients. Deaths occurred in 3% of patients and were not related to treatment. Questionnaire completion rates for HRQoL were high at baseline (90–94%) and at 24 months (78–81%). In the group-level analysis for HRQoL, mean changes in scores from baseline remained stable and did not exceed prespecified thresholds for minimally important differences during and after treatment, except for a clinically meaningful improvement in FACT-M surgery subscale scores. In the individual patient-level analysis for EORTC QLQ-C30 subscales, the percentages of patients who reported clinically relevant scores for fatigue and cognitive impairment increased during treatment (at 9 months) compared with baseline. After treatment cessation (at 18 months), the percentage of patients who reported clinically relevant scores for fatigue decreased. However, the percentages of patients who reported clinically relevant scores for emotional, cognitive, and social impairment increased at 18 months compared with during treatment. Most patients with emotional impairment at 9 and 18 months did not experience disease recurrence (91% and 89%, respectively). Conclusions: These results confirm the real-world effectiveness and safety of nivolumab as an adjuvant treatment for patients with completely resected stage III or stage IV melanoma. Cancer-specific, disease-specific, and generic HRQoL were maintained during and after treatment. The percentage of patients reporting emotional and cognitive impairment increased after treatment cessation, emphasizing the need for further investigation and tailored supportive care in these patients

Reactive oxygen species generation by bovine blood neutrophils with different CXCR1 (IL8RA) genotype following Interleukin-8 incubation

Background: Associations between polymorphisms in the bovine CXCR1 gene, encoding the chemokine (C-X-C motif) receptor 1 (IL8RA), and neutrophil traits and mastitis have been described. In the present study, blood neutrophils were isolated from 20 early lactating heifers with different CXCR1 genotype at position 735 or 980. The cells were incubated with different concentrations of recombinant bovine IL-8 (rbIL-8) for 2 or 6 h and stimulated with phorbol 12-myristate 13-acetate (PMA) or opsonized zymosan particles (OZP). Potential association between CXCR1 genotype and production of reactive oxygen species (ROS) was studied. Results: Although on single nucleotide polymorphisms (SNPs) may potentially affect CXCR1 function, SNPs c.735C > G and c.980A > G showed no association with ROS production with or without incubation of rbIL-8. Neutrophils incubated with rbIL-8 for 2 or 6 h showed higher PMA- and lower OZP-induced ROS production compared to control without rbIL-8. Conclusions: In the present study no association could be detected between superoxide production by isolated bovine neutrophils during early lactation and CXCR1 gene polymorphism. IL-8 showed to possess inhibitory effects on ROS generation in bovine neutrophils

Estimation of hydraulic conductivity and its uncertainty from grain-size data using GLUE and artificial neural networks

peer reviewedaudience: researcher, professionalVarious approaches exist to relate saturated hydraulic conductivity (Ks) to grain-size data. Most methods use a single grain-size parameter and hence omit the information encompassed by the entire grain-size distribution. This study compares two data-driven modelling methods, i.e.multiple linear regression and artificial neural networks, that use the entire grain-size distribution data as input for Ks prediction. Besides the predictive capacity of the methods, the uncertainty associated with the model predictions is also evaluated, since such information is important for stochastic groundwater flow and contaminant transport modelling. Artificial neural networks (ANNs) are combined with a generalized likelihood uncertainty estimation (GLUE) approach to predict Ks from grain-size data. The resulting GLUE-ANN hydraulic conductivity predictions and associated uncertainty estimates are compared with those obtained from the multiple linear regression models by a leave-one-out cross-validation. The GLUE-ANN ensemble prediction proved to be slightly better than multiple linear regression. The prediction uncertainty, however, was reduced by half an order of magnitude on average, and decreased at most by an order of magnitude. This demonstrates that the proposed method outperforms classical data-driven modelling techniques. Moreover, a comparison with methods from literature demonstrates the importance of site specific calibration. The dataset used for this purpose originates mainly from unconsolidated sandy sediments of the Neogene aquifer, northern Belgium. The proposed predictive models are developed for 173 grain-size -Ks pairs. Finally, an application with the optimized models is presented for a borehole lacking Ks data

Study protocol for a multicenter randomized controlled trial to compare the efficacy of end-ischemic dual hypothermic oxygenated machine perfusion with static cold storage in preventing non-anastomotic biliary strictures after transplantation of liver grafts donated after circulatory death: DHOPE-DCD trial

Background: The major concern in liver transplantation of grafts from donation after circulatory death (DCD) donors remains the high incidence of non-anastomotic biliary strictures (NAS). Machine perfusion has been proposed as an alternative strategy for organ preservation which reduces ischemia-reperfusion injury (IRI). Experimental studies have shown that dual hypothermic oxygenated machine perfusion (DHOPE) is associated with less IRI, improved hepatocellular function, and better preserved mitochondrial and endothelial function compared to conventional static cold storage (SCS). Moreover, DHOPE was safely applied with promising results in a recently performed phase-1 study. The aim of the current study is to determine the efficacy of DHOPE in reducing the incidence of NAS after DCD liver transplantation. Methods: This is an international multicenter randomized controlled trial. Adult patients (≥18 yrs. old) undergoing transplantation of a DCD donor liver (Maastricht category III) will be randomized between the intervention and control group. In the intervention group, livers will be subjected to two hours of end-ischemic DHOPE after SCS and before implantation. In the control group, livers will be subjected to care as usual with conventional SCS only. Primary outcome is the incidence of symptomatic NAS diagnosed by a blinded adjudication committee. In all patients, magnetic resonance cholangiography will be obtained at six months after transplantation. Discussion: DHOPE is associated with reduced IRI of the bile ducts. Whether reduced IRI of the bile ducts leads to lower incidence of NAS after DCD liver transplantation can only be examined in a randomized controlled trial. Trial registration: The trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283