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

How do included and excluded students with SEBD function socially and academically after 1,5 year of special education services?

The present study tested three conflicting hypotheses as to how students with social/emotional/behavioural difficulties (SEBD), who showed similar social-emotional, behavioural and academic functioning prior to placement, function socially and academically after they have received additional support either in inclusive regular education or in exclusive special education. Thirty-six included and 15 excluded students with SEBD participated. We collected data from students and teachers with classroom surveys, individual testing sessions with students with SEBD, and from application files. Using Bayesian statistics, our results suggest that excluded students are better socially embedded in exclusive special education and that they perform better academically than comparable included students with SEBD. Special education services in exclusive settings may thus afford certain benefits to some students with SEBD, not typically found in regular education, which can be considered a first indication that there may be valid counterarguments against the ‘inclusion for all’ perspective on educational needs

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

Perspectives and Concerns on Late Effects Regarding Sexuality among Adolescents and Young Adults Treated for Testicular Germ Cell Tumor: The PRICELESS-Study-A Qualitative Study

This study aimed to explore perspectives and concerns regarding sexuality among adolescents and young adults (AYAs) possibly experiencing late effects after testicular germ cell tumor (TGCT) treatment. A qualitative study was performed in which semi-structured interviews were held with thirteen AYAs from a center of expertise for TGCT in the Netherlands. Data were analyzed using Braun and Clark's thematic analysis method. Seven interacting and interconnected themes were found: desire to have children, rediscovering sexuality, insecurity about sexual performance, acceptance of physical change, loss of masculinity, burden on relationship, and openness in discussing sexuality. Concerns about the desire to have children seem to play a significant role. In conclusion, TGCT patients face multiple changes (physical, emotional, relational, and sexual), followed by a difficult period of acceptance, after which a new phase of rediscovering sexuality appeared. These findings can help to make healthcare professionals aware of the underlying mechanisms and concerns about sexuality. Furthermore, insights can help to develop sexuality-themed items for a broader monitoring tool to structurally assess the late effects to support discussing sexuality

Analysis of obstetric complications and uterine connective tissue in tenascin-X-deficient humans and mice

Tenascin-X (TNX) is a large, multi-domain, extracellular matrix glycoprotein. Complete deficiency of TNX in humans leads to a recessive form of Ehlers-Danlos syndrome (EDS), and TNX haploinsufficiency is a cause of hypermobility type EDS. EDS patients appear to have a higher risk of several complications during pregnancy, such as pelvic instability, premature rupture of membranes, and postpartum hemorrhage. Here, we present a study of genitourinary and obstetric complications in TNX-deficient women of reproductive age. We have found complications, such as uterus prolapses, that are in agreement with previous findings in other EDS types. In TNX knockout (KO) mice, we have observed mild pregnancy-related abnormalities. Morphological and immunohistological analysis of uterine tissues has not revealed obvious quantitative or spatial differences between TNX KO and wildtype mice with respect to collagen types I, III, V, and XII or elastic fibers. We conclude that TNX-deficient women are at risk of obstetric complications, but that TNX KO mice show only a mild phenotype. Furthermore, we show that TNX is involved in the stability of elastic fibers rather than in their initial deposition

Medications and addictive substances potentially inducing or attenuating sleep bruxism and/or awake bruxism

Bruxism is a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. It can occur during sleep, indicated as sleep bruxism, or during wakefulness, indicated as awake bruxism. Exogenous risk indicators of sleep bruxism and/or awake bruxism are, among others, medications and addictive substances, whereas also several medications seem to have the potential to attenuate sleep bruxism and/or awake bruxism. The objective of this study was to present a narrative literature on medications and addictive substances potentially inducing or aggravating sleep bruxism and/or awake bruxism and on medications potentially attenuating sleep bruxism and/or awake bruxism. Literature reviews reporting evidence or indications for sleep bruxism and/or awake bruxism as an adverse effect of several (classes of) medications as well as some addictive substances and literature reviews on medications potentially attenuating sleep bruxism and/or awake bruxism were used as starting point and guidelines to describe the topics mentioned. Additionally, two literature searches were established on PubMed. Three types of bruxism were distinguished: sleep bruxism, awake bruxism and non-specified bruxism. Generally, there are insufficient evidence-based data to draw definite conclusions concerning medications and addictive substances inducing or aggravating sleep bruxism and/or awake bruxism as well as concerning medications attenuating sleep bruxism and/or awake bruxism. There are insufficient evidence-based data to draw definite conclusions concerning medications and addictive substances inducing or aggravating sleep bruxism and/or awake bruxism as well as concerning medications attenuating sleep bruxism and/or awake bruxism.Peer reviewe

Oral ribose supplementation in dystroglycanopathy:A single case study

Three forms of muscular dystrophy-dystroglycanopathies are linked to the ribitol pathway. These include mutations in the isoprenoid synthase domain-containing protein (ISPD), fukutin-related protein (FKRP), and fukutin (FKTN) genes. The aforementioned enzymes are required for generation of the ribitol phosphate linkage in the O-glycan of alpha-dystroglycan. Mild cases of dystroglycanopathy present with slowly progressive muscle weakness, while in severe cases the eyes and brain are also involved. Previous research showed that ribose increased the intracellular concentrations of cytidine diphosphate-ribitol (CDP-ribitol) and had a therapeutic effect. Here, we report the safety and effects of oral ribose supplementation during 6 months in a patient with limb girdle muscular dystrophy type 2I (LGMD2I) due to a homozygous FKRP mutation. Ribose was well tolerated in doses of 9 g or 18 g/day. Supplementation with 18 g of ribose resulted in a decrease of creatine kinase levels of 70%. Moreover, metabolomics showed a significant increase in CDP-ribitol levels with 18 g of ribose supplementation (p &lt; 0.001). Although objective improvement in clinical and patient-reported outcome measures was not observed, the patient reported subjective improvement of muscle strength, fatigue, and pain. This case study indicates that ribose supplementation in patients with dystroglycanopathy is safe and highlights the importance for future studies regarding its potential effects.</p

Oral ribose supplementation in dystroglycanopathy:A single case study

Three forms of muscular dystrophy-dystroglycanopathies are linked to the ribitol pathway. These include mutations in the isoprenoid synthase domain-containing protein (ISPD), fukutin-related protein (FKRP), and fukutin (FKTN) genes. The aforementioned enzymes are required for generation of the ribitol phosphate linkage in the O-glycan of alpha-dystroglycan. Mild cases of dystroglycanopathy present with slowly progressive muscle weakness, while in severe cases the eyes and brain are also involved. Previous research showed that ribose increased the intracellular concentrations of cytidine diphosphate-ribitol (CDP-ribitol) and had a therapeutic effect. Here, we report the safety and effects of oral ribose supplementation during 6 months in a patient with limb girdle muscular dystrophy type 2I (LGMD2I) due to a homozygous FKRP mutation. Ribose was well tolerated in doses of 9 g or 18 g/day. Supplementation with 18 g of ribose resulted in a decrease of creatine kinase levels of 70%. Moreover, metabolomics showed a significant increase in CDP-ribitol levels with 18 g of ribose supplementation (p &lt; 0.001). Although objective improvement in clinical and patient-reported outcome measures was not observed, the patient reported subjective improvement of muscle strength, fatigue, and pain. This case study indicates that ribose supplementation in patients with dystroglycanopathy is safe and highlights the importance for future studies regarding its potential effects.</p

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