Even though it has been established that a hyetograph's shape affects the results of hydrological simulations, common engineering practice does not always account for this fact. Instead, a single design storm is often considered sufficient for designing a urban drainage system. This study examines the impact that this design paradigm, combined with the uncertainty introduced by subjective choices made during the design process, has on the robustness of a designed system.
View Article and Find Full Text PDFIn this study, we show that pollutants of emerging concern are, by nature, prone to the emergence of epistemic uncertainty. We also show that the current uncertainty quantification methods used for pollutant modelling rely almost exclusively on parameter uncertainty, which is not adequate to tackle epistemic uncertainty affecting the model structure. We, therefore, suggest a paradigm shift in the current pollutant modelling approaches by adding a term explicitly accounting for epistemic uncertainties.
View Article and Find Full Text PDFEighty-four autumn (ACS, = 45)- and spring (SCS, = 39)-calved multiparous early lactation Holstein cows were assigned to groups of either: (a) grazing + mixed ration (MR) during partial confinement in outdoor soil-bedded pens with shade (OD-GRZ); (b) grazing + MR during partial confinement in a compost-bedded pack barn with cooling (CB-GRZ); or (c) total confinement fed a totally mixed ration (CB-TMR) in a compost-bedded pack barn. Data were analyzed using the SAS MIXED procedure with significance at ≤ 0.05.
View Article and Find Full Text PDFIronically, healthcare systems are key agents in respiratory-related diseases and estimated deaths because of the high impact of their greenhouse gas emissions, along with industry, transportation, and housing. Based on safety requirements, hospitals and related services use an extensive number of consumables, most of which end up incinerated at the end of their life cycle. A thorough assessment of the carbon footprint of such devices typically requires knowing precise information about the manufacturing process, which is rarely available in detail because of the many materials, pieces, and steps involved during the fabrication.
View Article and Find Full Text PDFThe aim of this study was to determine if intranasal administration of oxytocin modifies sexual behaviour and the stress response in young rams during sexual tests with ewes in oestrus. Ten rams were used in a cross-over design. At Day 0, the control group (CG, n = 5) received isotonic saline spray intranasally, and the treated group (OTG, n = 5) received oxytocin (24 IU) intranasally, 40 min before the sexual test.
View Article and Find Full Text PDFUsing APP/PS1 mice that overproduce amyloid-β (Aβ) peptides, we investigated whether intranasal infection with a neurovirulent clinical strain of herpes simplex virus 1 (HSV-1) before Aβ deposition could accelerate or increase Alzheimer's disease-like pathology. After HSV-1 infection, APP/PS1 mice presented a similar disease as wild type animals based on body weight changes, clinical symptoms, and survival rates. The number and volume of Aβ plaques, the number of microglia, and the percentages of circulating monocyte subsets were similar in APP/PS1 mice infected or not with HSV-1.
View Article and Find Full Text PDFPlant-pollinator interactions evolved early in the angiosperm radiation. Ongoing environmental changes are however leading to pollinator declines that may cause pollen limitation to plants and change the evolutionary pressures shaping plant mating systems. We used resurrection ecology methodology to contrast ancestors and contemporary descendants in four natural populations of the field pansy (Viola arvensis) in the Paris region (France), a depauperate pollinator environment.
View Article and Find Full Text PDFDue to climate change and rapid urbanisation, many Norwegian cities and urban areas suffer from pluvial flooding caused by intense rainfall exceeding the capacity of the stormwater management system. This results in increased runoff rates, volumes and peak flows in the drainage network. In response to these challenges, the authors explore the potential of utilising the urban surface's ability to transport floodwater as an integral component of the stormwater infrastructure.
View Article and Find Full Text PDFWe study the impact of public health messages on intentions to vaccinate and vaccination uptakes, especially among hesitant groups. We performed an experiment comparing the effects of egoistic and altruistic messages on COVID-19 vaccine intentions and behaviour. We administered different messages at random in a survey of 6379 adults in December 2020, following up with participants in the nationally representative survey Citizens' Attitudes Under COVID-19 Project covering nine high-income countries (Australia, Austria, France, Germany, Italy, New Zealand, Sweden, the UK and the USA).
View Article and Find Full Text PDFThrombotic thrombocytopenic purpura (TTP) is a low prevalence disease characterized by severe deficiency of the enzyme ADAMTS13, leading to the development of thrombotic microangiopathy (TMA) and often resulting in severe organ disfunction. TTP is an extremely serious condition and, therefore, timely and appropriate treatment is critical to prevent life-threatening complications.Over the past 25 years, significant advances in the understanding of the pathophysiology of immune TTP have led to the development of readily available techniques for measuring ADAMTS13 levels, as well as new drugs that are particularly effective in the acute phase and in preventing relapses.
View Article and Find Full Text PDFBackground: Stenosis is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses.
View Article and Find Full Text PDFBackground: Purinergic P2Y and P2Y receptors (P2Y-R and P2Y-R) are G protein-coupled receptors (GPCR) activated by adenosine diphosphate (ADP) to mediate platelet activation, thereby playing a pivotal role in hemostasis and thrombosis. While P2Y-R is the major target of antiplatelet drugs, no P2Y-R antagonist has yet been developed for clinical use. However, accumulating data suggest that P2Y-R inhibition would ensure efficient platelet inhibition with minimal effects on bleeding.
View Article and Find Full Text PDFConflicting results on melatonin synthesis in multiple sclerosis (MS) have been reported due to variabilities in patient lifestyles, which are not considered when supplementing melatonin. Since melatonin acts through its receptors, we identified melatonin receptors in oligodendrocytes (OLs) in the corpus callosum, where demyelination occurs; the subventricular zone, where neural stem/progenitor cells (NSPCs) are located; and the choroid plexus, which functions as a blood-cerebrospinal fluid barrier. Moreover, using chimeric mice, resident macrophages were found to express melatonin receptors, whereas bone marrow-derived macrophages lost this expression in the demyelinated brain.
View Article and Find Full Text PDFSelatogrel is a potent inhibitor of adenosine diphosphate (ADP) binding to the P2Y12 receptor, preventing platelet activation. We have previously shown that the P2Y12 receptor constitutively activates Gi- and Go-protein-mediated signaling in human platelets. Here, we report that selatogrel acts as an inverse agonist of the P2Y12 receptor.
View Article and Find Full Text PDFBackground: Recently, real-world data confirmed the effectiveness of caplacizumab in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP); however, limitations as different treatment protocols from multicenter experiences and the front-line use of rituximab could overshadow the real impact of the addition of caplacizumab.
Study Design And Methods: We report the clinical characteristics and response to treatment of 30 consecutive cases of aTTP treated under a homogeneous therapeutic protocol with the only exception of the addition of caplacizumab in the last 10 cases (caplacizumab group), whose primary outcome we compare with the previous 20 cases (control group).
Results: Caplacizumab was started at a median of 2.
Unlabelled: Alzheimer's disease (AD) is the most common form of dementia in the world. The prevalence is steadily increasing due to an aging population and the lack of effective treatments. However, modulation of innate immune cells is a new therapeutic avenue, which is quite effective at delaying disease onset and improving cognitive decline.
View Article and Find Full Text PDFHistorically, green infrastructure for stormwater management has been event-based designed. This study aims to realign the green infrastructure design strategies with principles for robust decision making, through the example of green roofs design with the variational method and exemplified using the Norwegian context of the 3-step approach (3SA) for stormwater management. The 3SA consists of planning solutions to handle day-to-day rain at site scale through infiltration (step 1) and detention (step 2), and extreme events with safe floodways (step 3).
View Article and Find Full Text PDFG protein-coupled receptors (GPCRs) form the largest family of cell surface receptors. Despite considerable insights into their pharmacology, the GPCR architecture at the cell surface still remains largely unexplored. Herein, we present the specific unfolding of different GPCRs at the surface of living mammalian cells by atomic force microscopy-based single molecule force spectroscopy (AFM-SMFS).
View Article and Find Full Text PDFAlzheimer's disease (AD) constitutes a major cause of dementia, affecting more women than men. It is characterized by amyloid-β (Aβ) deposition and neurofibrillary tangles (NFTs) formation, associated with a progressive cognitive decline. Evidence indicates that AD onset increases the prevalence of cerebral microinfarcts caused by vascular pathologies, which occur in approximately in half of AD patients.
View Article and Find Full Text PDFBackground: Endoscopic balloon dilation (EBD) is the established endoscopic treatment for short strictures in Crohn's disease. Fully covered self-expandable metal stents (FCSEMS) have been used for endoscopic treatment of patients for whom EBD was unsuccessful. We aimed to determine the efficacy and safety of the two endoscopic treatments in patients with Crohn's disease with stenosis and compare the mean cost of both treatments.
View Article and Find Full Text PDFPharmacol Rev
January 2022
Alzheimer disease (AD) is the first progressive neurodegenerative disease worldwide, and the disease is characterized by an accumulation of amyloid in the brain and neurovasculature that triggers cognitive decline and neuroinflammation. The innate immune system has a preponderant role in AD. The last decade, scientists focused their efforts on therapies aiming to modulate innate immunity.
View Article and Find Full Text PDFThe ecological niche defines the favourable range of a species in a multidimensional space of ecological factors that determine the presence and function of individuals. This fundamental concept in ecology is widely used to understand plant species coexistence and segregation. In this study, we test for ecological differentiation among six annual Lythrum species that are characteristic of temporary pools in the South of France, where they either coexist or occur separately.
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