Lessons Learned from a Full-Scale Dyke Failure Test

A full-scale failure test has been performed on an old river dyke in the Netherlands, to determine its actual strength against failure due to the uplift mechanism and to validate the Van model for the stability analysis of dykes prone to uplift induced failure. The test has been a success and clearly showed the relevance and significance of the uplift mechanism. In combination with earlier verifications, the Van model was found to be suitable, which has already lead to significant reductions on dyke reinforcement projects. The large gap between the actual strength and the calculated strength was confirmed. This gap appeared to be partly necessary because of the large variation in the results of dyke stability analyses by different geotechnical consultants. For the near future, the test may serve as an important benchmark for the development of a more rationally based safety philosophy

Changes in energy expenditure associated with ingestion of high protein, high fat versus high protein, low fat meals among underweight, normal weight, and overweight females

Background: Metabolic rate is known to rise above basal levels after eating, especially following protein consumption. Yet, this postprandial rise in metabolism appears to vary among individuals. This study examined changes in energy expenditure in response to ingestion of a high protein, high fat (HPHF) meal versus an isocaloric high protein, low fat (HPLF) meal in underweight, normal weight, or overweight females (n = 21) aged 19–28 years. Methods: Energy expenditure, measured using indirect calorimetry, was assessed before and every 30 minutes for 3.5 hours following consumption of the meals on two separate occasions. Height and weight were measured using standard techniques. Body composition was measured using bioelectrical impedance analysis. Results: Significant positive correlations were found between body mass index (BMI) and baseline metabolic rate (MR) (r = 0.539; p = 0.017), between body weight and baseline MR (r = 0.567; p = 0.011), between BMI and average total change in MR (r = 0.591; p = 0.008), and between body weight and average total change in MR (r = 0.464; p = 0.045). Metabolic rate (kcal/min) was significantly higher in the overweight group than the normal weight group, which was significantly higher than the underweight group across all times and treatments. However, when metabolic rate was expressed per kg fat free mass (ffm), no significant difference was found in postprandial energy expenditure between the overweight and normal groups. Changes in MR (kcal/min and kcal/min/kg ffm) from the baseline rate did not significantly differ in the underweight (n = 3) or in the overweight subjects (n = 5) following consumption of either meal at any time. Changes in MR (kcal/min and kcal/min/kg ffm) from baseline were significantly higher in normal weight subjects (n = 11) across all times following consumption of the HPHF meal versus the HPLF meal. Conclusion: There is no diet-induced thermogenic advantage between the HPHF and HPLF meals in overweight and underweight subjects. In contrast, in normal weight subjects, ingestion of a HPHF meal significantly increases MR (69.3 kcal/3.5 hr) versus consumption of a HPLF meal and provides a short-term metabolic advantage

Wingless Signalling Alters the Levels, Subcellular Distribution and Dynamics of Armadillo and E-Cadherin in Third Instar Larval Wing Imaginal Discs

Background: Armadillo, the Drosophila orthologue of vertebrate beta-catenin, plays a dual role as the key effector of Wingless/Wnt1 signalling, and as a bridge between E-Cadherin and the actin cytoskeleton. In the absence of ligand, Armadillo is phosphorylated and targeted to the proteasome. Upon binding of Wg to its receptors, the "degradation complex'' is inhibited; Armadillo is stabilised and enters the nucleus to transcribe targets. Methodology/Principal Findings: Although the relationship between signalling and adhesion has been extensively studied, few in vivo data exist concerning how the "transcriptional'' and "adhesive'' pools of Armadillo are regulated to orchestrate development. We have therefore addressed how the subcellular distribution of Armadillo and its association with E-Cadherin change in larval wing imaginal discs, under wild type conditions and upon signalling. Using confocal microscopy, we show that Armadillo and E-Cadherin are spatio-temporally regulated during development, and that a punctate species becomes concentrated in a subapical compartment in response to Wingless. In order to further dissect this phenomenon, we overexpressed Armadillo mutants exhibiting different levels of activity and stability, but retaining E-Cadherin binding. Arm(S10) displaces endogenous Armadillo from the AJ and the basolateral membrane, while leaving E-Cadherin relatively undisturbed. Surprisingly, Delta NArm(1-155) caused displacement of both Armadillo and E-Cadherin, results supported by our novel method of quantification. However, only membrane-targeted Myr-Delta NArm(1-155) produced comparable nuclear accumulation of Armadillo and signalling to Arm(S10). These experiments also highlighted a row of cells at the A/P boundary depleted of E-Cadherin at the AJ, but containing actin. Conclusions/Significance: Taken together, our results provide in vivo evidence for a complex non-linear relationship between Armadillo levels, subcellular distribution and Wingless signalling. Moreover, this study highlights the importance of Armadillo in regulating the subcellular distribution of E-CadherinPublisher PDFPeer reviewe

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Epidemiology and management of rhinosinusitis

Acute and chronic rhinosinusitis are different diseases with different aetiology and they require different treatment. In this thesis we evaluated the prevalence of acute and chronic rhinosinusitis in the general population and in primary care. We investigated which factors are related to rhinosinusitis and whether general practitioners (GPs) distinguish between acute and chronic rhinosinusitis. We evaluated their management of rhinosinusitis (especially with regard to antibiotics). Furthermore we discuss the complications that can occur as a result of acute rhinosinusitis and whether these complications could have been prevented by prescribing antibiotics. In the general population we found a prevalence of 18% for acute rhinosinusitis and 16% for chronic rhinosinusitis. Ninety-six percent of GPs say they differentiate between acute and chronic rhinosinusitis, but they use different definitions (54% of these definitions correspond to the European guideline, EPOS). For mild and moderate symptoms of acute rhinosinusitis, 21% and 34% of the GPs, respectively, consider prescribing antibiotics (while there is no indication according to the guideline). The prescription of antibiotics for acute rhinosinusitis does not prevent the occurrence of complications. We think it would help if, in addition to the current guideline on acute rhinosinusitis, a separate guideline on chronic rhinosinusitis for GPs is developed to help distinguishing acute and chronic rhinosinusitis. Until that time, we advise GPs to use the European guideline for the diagnosis and treatment of rhinosinusitis. In comparison to doctors abroad, Dutch GPs are reluctant to prescribe antibiotics, but this can be further reduced

Identification and in vivo role of the Armadillo-Legless interaction.

The Wnt signalling system controls many fundamental processes during animal development and its deregulation has been causally linked to colorectal cancer. Transduction of Wnt signals entails the association of beta-catenin with nuclear TCF DNA-binding factors and the subsequent activation of target genes. Using genetic assays in Drosophila, we have recently identified a presumptive adaptor protein, Legless (Lgs), that binds to beta-catenin and mediates signalling activity by recruiting the transcriptional activator Pygopus (Pygo). Here, we characterize the beta-catenin/Lgs interaction and show: (1) that it is critically dependent on two acidic amino acid residues in the first Armadillo repeat of beta-catenin; (2) that it is spatially and functionally separable from the binding sites for TCF factors, APC and E-cadherin; (3) that it is required in endogenous as well as constitutively active forms of beta-catenin for Wingless signalling output in Drosophila; and (4) that in its absence animals develop with the same phenotypic consequences as animals lacking Lgs altogether. Based on these findings, and because Lgs and Pygo have human homologues that can substitute for their Drosophila counterparts, we infer that the beta-catenin/Lgs binding site may thus serve as an attractive drug target for therapeutic intervention in beta-catenin-dependent cancer progression

The influence of upstram turbulence on local-scour holes

Excessive local scour can progressively undermine the foundation of a structure. Because complete protection against scour is too expensive generally, the maximum scour-depth and the upstream slope of the scour hole have to be predicted to minimize the risk of failure. In 1961 a systematical research 'tY'ith respect to scour holes started in the Netherlands at Delft Hydraulics within the scope of the Delta works. After the catastrophic flood disaster in 1953 the Delta plan was made to protect the RhineMeuse-Scheldt delta for future disasters. Dams with large scale sluices were planned in some estuaries. The severe scour expected necessitated a better understanding of the scour process. To find detailed information about the physical processes playing a role in scour many experiments were carried out, in which various parameters of the flow and the scoured material were varied. From the results of experiments in flumes with all difficulties of scale effects and limitations in instrumentation some empirical relations were obtained, which describe the erosion process as function of time and place (Breusers, 1966). In these empirical relations a not well defined turbulence coefficient was introduced. Up to now this coefficient was related to the geometry upstream of the scour hole, which relation was based on trial and error. Based on theoretical grounds an analytical relation for the depth-averaged turbulence intensity is derived in this paper. This relation, which implies a modification of the turbulence coefficient in the Breusers scour formula, is verified using approximately 300 experiments. The modified scour formula yields results that compare reasonably well to measured and computed developments of a scour hole in case of a uniform flow upstream of the scour hole corresponding with a large protected bed area. The computations were based on the two-dimensional Navier-Stokes and convection-diffusion equations (Hoffmans, 1992). The present paper aims at extension of the domain of application of the scour formula to non-uniform flow conditions upstream.Hydraulic EngineeringCivil Engineering and Geoscience