Wetropolis extreme rainfall and flood demonstrator: from mathematical design to outreach

Government and consulting experts on flood mitigation generally face difficulties when trying to explain the science of extreme flooding to the general public, in particular the concept of a return period. Too often, for example, people perceive they are safe for the next 100 years after a 1:100-year return-period flood has hit their town. UK flood practitioners therefore gave us the challenge to design an outreach tool that conceptualises the science of flooding in a way that is accessible to and directly engages the public, and in particular demonstrates what a return period is. Furthermore, we were tasked with designing a live 3-D physical model rather than a graphical or animated 2-D game on a screen. We show here how we tackled that challenge by designing, constructing, and showcasing the Wetropolis Flood Demonstrator. Wetropolis is a transportable and conceptual physical model with random rainfall, river flow, a flood plain, an upland reservoir, a porous moor, representing the upper catchment and visualising groundwater flow, and a city which can flood following extreme and random rainfall. A key novelty is the supply of rainfall every Wetropolis day. Several aspects of Wetropolis are considered. i. We present the modular mathematical and numerical design on which Wetropolis is based. It guided the choice of parameter values of Wetropolis, which was loosely inspired by the Leeds Boxing Day floods of the River Aire in 2015. The design model further serves as the building block and inspiration for adaptations suited to particular local demands. Moreover, the model is purposely lean and therefore quick to compute, serving flexibility in the outreach-tool design, but is less suitable for any detailed scientific validation. ii. The constructed Wetropolis is described here in broad terms, but we include a link to a GitHub site with details to inspire other bespoke designs. The goal, again, is to facilitate new adaptations of Wetropolis for particular catchments different to the Leeds River Aire case. iii. Our experience in showcasing Wetropolis is summarised and discussed, with the purpose of giving an overview as well as inspiring improved and bespoke adaptations. While Wetropolis should be experienced live, with videos found on the GitHub site, here we provide a photographic overview. To date, Wetropolis has been showcased to 500 to 1000 people at public workshops and exhibitions on recent UK floods, as well as to flood practitioners and scientists at various research and stakeholder workshops. iv. We conclude with some ongoing design changes, including how people can experience natural flood management in a revised Wetropolis design. Finally, we also discuss how Wetropolis, although originally focussed solely on outreach, led to a new cost-effectiveness analysis and protocol for assessing flood-mitigation plans and inspired other physical models for use in education and water management

High Stakes of the Small EU Partnership Instrument on the Eve of the 2017 Mid-Term Review

The European Union (EU)’s so-called Partnership Instrument (PI) captures the changing psychology of EU relations with rising powers, and has been designed to give more room for manoeuvre for EU external action. Two years of practice leading up to the 2017 Mid-Term Review have shown that the PI is instrument-driven rather than objective-driven, and that its strategic potential is undermined by lengthy committee-based procedures and sector-based programming. In an arena of vested interests, the PI’s significance is tied up with what EU stakeholders want to make of the European External Action Service (EEAS). National foreign ministries struggle to connect national objectives with EU interests, apart from the wider debate not addressed here as to where European interests come from when they are not based on national objectives. This article argues that national foreign ministries should consider the potentially positive effect on EU external action of this relatively small initiative, notably as the instrument to connect one European entity to other global powerhouses. EU Member States have so far been unable to link fully with the PI, and – like the EEAS and the European Parliament – they have too little clout to exert influence on the European Commission. The EU Global Strategy offers a window of opportunity for making the PI more political, expedient and flexible. FGGA – Publicaties zonder aanstelling Universiteit Leide

Revisiting Hele-Shaw dynamics to better understand beach evolution

Wave action, particularly during storms, drives the evo lution of beaches. Beach evolution by non-linear break ing waves is poorly understood due to its three-dimensional character, the range of scales involved, and our limited understanding of particle-wave interactions. We show how a novel, three-phase extension to the classic “Hele-Shaw” laboratory experiment can be designed that creates beach morphologies with breaking waves in a quasi-two-dimensional setting. Our thin Hele-Shaw cell simplifies the inherent complexity of three-phase dynamics: all dynamics become clearly visible and measurable. We show that beaches can be created in tens of minutes by several types of breaking waves, with about one-second periods. Quasi-steady beach morphologies emerge as function of initial water depth, at-rest bed level and wave-maker frequency. These are classified mathematically and lead to beaches, berms and sand bars

Definition of the σW regulon of Bacillus subtilis in the absence of stress

Bacteria employ extracytoplasmic function (ECF) sigma factors for their responses to environmental stresses. Despite intensive research, the molecular dissection of ECF sigma factor regulons has remained a major challenge due to overlaps in the ECF sigma factor-regulated genes and the stimuli that activate the different ECF sigma factors. Here we have employed tiling arrays to single out the ECF σW regulon of the Gram-positive bacterium Bacillus subtilis from the overlapping ECF σX, σY, and σM regulons. For this purpose, we profiled the transcriptome of a B. subtilis sigW mutant under non-stress conditions to select candidate genes that are strictly σW-regulated. Under these conditions, σW exhibits a basal level of activity. Subsequently, we verified the σW-dependency of candidate genes by comparing their transcript profiles to transcriptome data obtained with the parental B. subtilis strain 168 grown under 104 different conditions, including relevant stress conditions, such as salt shock. In addition, we investigated the transcriptomes of rasP or prsW mutant strains that lack the proteases involved in the degradation of the σW anti-sigma factor RsiW and subsequent activation of the σW-regulon. Taken together, our studies identify 89 genes as being strictly σW-regulated, including several genes for non-coding RNAs. The effects of rasP or prsW mutations on the expression of σW-dependent genes were relatively mild, which implies that σW-dependent transcription under non-stress conditions is not strictly related to RasP and PrsW. Lastly, we show that the pleiotropic phenotype of rasP mutant cells, which have defects in competence development, protein secretion and membrane protein production, is not mirrored in the transcript profile of these cells. This implies that RasP is not only important for transcriptional regulation via σW, but that this membrane protease also exerts other important post-transcriptional regulatory functions

Prolonged fibroblast growth factor 19 response in patients with primary sclerosing cholangitis after an oral chenodeoxycholic acid challenge

Bile salts likely contribute to liver injury in patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Fibroblast growth factor 19 (FGF19) is a bile salt-induced enterokine with hepatoprotective potential as it suppresses de novo bile salt synthesis. Here, we evaluated the bile salt receptor FXR/FGF19 gut-liver axis in PSC and PBC patients. Fasted patients with PSC (n = 12) and PBC (n = 10), and healthy controls (HC; n = 10) were orally challenged with the natural FXR agonist chenodeoxycholic acid (CDCA 15 mg/kg). Blood was sampled hourly until 8 h afterwards. Serum FGF19 and bile salt excursions were determined. Serum levels of 7 alpha-hydroxy-4-cholesten-3-one (C4), reflecting bile salt synthesis, were measured as a biomarker of FGF19 response. Baseline serum FGF19 levels were comparable between groups, while fasted bile salt levels in PSC patients were elevated. Upon CDCA challenge, HC and PBC patients showed a serum FGF19 peak after 4 h followed by a decline. PSC patients showed a prolonged and elevated serum FGF19 response up to 8 h, combined with a sustained serum elevation of CDCA and other bile salts. In general, C4 levels declined following FGF19 elevation. In PSC patients with less favorable prognosis, baseline C4 levels were drastically suppressed and did not further decline. Following an oral CDCA challenge, PSC patients showed an impaired clearance of CDCA and a prolonged serum FGF19 response. FXR agonist therapy in PSC could cause prolonged exposure to elevated levels of FGF19, and we propose careful monitoring for detrimental side effects in patient studies

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Flexibility along the Neck of the Neogene Terror Bird Andalgalornis steulleti (Aves Phorusrhacidae)

BACKGROUND: Andalgalornis steulleti from the upper Miocene-lower Pliocene (≈6 million years ago) of Argentina is a medium-sized patagornithine phorusrhacid. It was a member of the predominantly South American radiation of 'terror birds' (Phorusrhacidae) that were apex predators throughout much of the Cenozoic. A previous biomechanical study suggests that the skull would be prepared to make sudden movements in the sagittal plane to subdue prey. METHODOLOGY/PRINCIPAL FINDINGS: We analyze the flexion patterns of the neck of Andalgalornis based on the neck vertebrae morphology and biometrics. The transitional cervical vertebrae 5th and 9th clearly separate regions 1-2 and 2-3 respectively. Bifurcate neural spines are developed in the cervical vertebrae 7th to 12th suggesting the presence of a very intricate ligamentary system and of a very well developed epaxial musculature. The presence of the lig. elasticum interespinale is inferred. High neural spines of R3 suggest that this region concentrates the major stresses during downstrokes. CONCLUSIONS/SIGNIFICANCE: The musculoskeletal system of Andalgalornis seems to be prepared (1) to support a particularly big head during normal stance, and (2) to help the neck (and the head) rising after the maximum ventroflexion during a strike. The study herein is the first interpretation of the potential performance of the neck of Andalgalornis in its entirety and we considered this an important starting point to understand and reconstruct the flexion pattern of other phorusrhacids from which the neck is unknown

Prevalence of neoplasia at colonoscopy among testicular cancer survivors treated with platinum-based chemotherapy

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have an increased risk of colorectal cancer (CRC). We determined the yield of colonoscopy in TCS to assess its potential in reducing CRC incidence and mortality. We conducted a colonoscopy screening study among TCS in four Dutch hospitals to assess the yield of colorectal neoplasia. Neoplasia was defined as adenomas, serrated polyps (SPs), advanced adenomas (AAs: ≥10 mm diameter, high-grade dysplasia or ≥25% villous component), advanced serrated polyps (ASPs: ≥10 mm diameter or dysplasia) or CRC. Advanced neoplasia (AN) was defined as AA, ASP or CRC. Colonoscopy yield was compared to average-risk American males who underwent screening colonoscopy (n = 24,193) using a propensity score matched analysis, adjusted for age, smoking status, alcohol consumption and body mass index. A total of 137 TCS underwent colonoscopy. Median age was 50 years among TCS (IQR 43–57) vs 55 years (IQR 51–62) among American controls. A total of 126 TCS were matched to 602 controls. The prevalence of AN was higher in TCS than in controls (8.7% vs 1.7%; P =.0002). Nonadvanced adenomas and SPs were detected in 45.2% of TCS vs 5.5% of controls (P &lt;.0001). No lesions were detected in 46.0% of TCS vs 92.9% of controls (P &lt;.0001). TCS treated with platinum-based chemotherapy have a higher prevalence of neoplasia and AN than matched controls. These results support our hypothesis that platinum-based chemotherapy increases the risk of colorectal neoplasia in TCS. Cost-effectiveness studies are warranted to ascertain the threshold of AN prevalence that justifies the recommendation of colonoscopy for TCS.</p