Performance measures for upper gastrointestinal endoscopy:A European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative

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Bridging the legitimacy gap—translating theory into practical signposts for legitimate flood risk governance

Legitimacy is widely regarded as a founding principle of ‘good’ and effective governance, yet despite intense academic debate and policy discourse, the concept remains conceptually confusing and poorly articulated in practice. To bridge this gap, this research performed an interpretive thematic analysis of academic scholarship across public administration, public policy, law, political science and geography. Three core themes were identified in relation to representative deliberation, procedural and distributive equity and justice, and socio-political acceptability, with numerous sub-themes therein. In an attempt to clarify conceptual confusion, this paper grounds these theoretical debates in the context of flood risk governance where numerous legitimacy dilemmas exist. A number of questions are presented as conceptual ‘sign posts’ to encourage reflexive governance in the future. Thus, more broadly, we assert the importance of bringing legitimacy to the forefront of contemporary flood risk governance discourse and practice, moving beyond the realm of academic reflection

Increased aortic stiffness and blood pressure in non-classic Pompe disease

Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study. Intima media thickness and the distensibility of the right common carotid artery were measured using a Duplex scanner. Aortic augmentation index, central pulse pressure, aortic reflexion time and cfPWV were assessed using the SphygmoCor® system. CfPWV was higher in patients than in volunteers (8.8 versus 7.4 m/s, p < 0.001). This difference was still present after adjustment for age, gender, mean arterial blood pressure (MAP), heart rate and diabetes mellitus (p = 0.001), and was shown by subgroup analysis to apply to the 40-59 years age group (p = 0.004) and 60+ years age group (p = 0.01), but not to younger age groups (p = 0.99). Except for a shorter aortic reflexion time (p = 0.02), indirect indicators of arterial stiffness did not differ between patients and volunteers. Relative to volunteers (20 %), more Pompe patients had a history of hypertension (36 %, p = 0.005), and the MAP was higher than in volunteers (100 versus 92 mmHg, p < 0.001). This study shows that patients with non-classic Pompe disease have increased aortic stiffness and blood pressure. Whether this is due to glycogen accumulation requires further investigation. To reduce the potential risk of cardiovascular diseases, we recommend that blood pressure and other common cardiovascular risk factors are monitored regularly

Fatigue in neuromuscular disorders: focus on Guillain–Barré syndrome and Pompe disease

Fatigue accounts for an important part of the burden experienced by patients with neuromuscular disorders. Substantial high prevalence rates of fatigue are reported in a wide range of neuromuscular disorders, such as Guillain–Barré syndrome and Pompe disease. Fatigue can be subdivided into experienced fatigue and physiological fatigue. Physiological fatigue in turn can be of central or peripheral origin. Peripheral fatigue is an important contributor to fatigue in neuromuscular disorders, but in reaction to neuromuscular disease fatigue of central origin can be an important protective mechanism to restrict further damage. In most cases, severity of fatigue seems to be related with disease severity, possibly with the exception of fatigue occurring in a monophasic disorder like Guillain–Barré syndrome. Treatment of fatigue in neuromuscular disease starts with symptomatic treatment of the underlying disease. When symptoms of fatigue persist, non-pharmacological interventions, such as exercise and cognitive behavioral therapy, can be initiated

Extreme behavioural shifts by baboons exploiting risky, resource-rich, human-modified environments

Abstract A range of species exploit anthropogenic food resources in behaviour known as ‘raiding’. Such behavioural flexibility is considered a central component of a species’ ability to cope with human-induced environmental changes. Here, we study the behavioural processes by which raiding male chacma baboons (Papio ursinus) exploit the opportunities and mitigate the risks presented by raiding in the suburbs of Cape Town, South Africa. Ecological sampling and interviews conducted with ‘rangers’ (employed to manage the baboons’ space use) revealed that baboons are at risk of being herded out of urban spaces that contain high-energy anthropogenic food sources. Baboon-attached motion/GPS tracking collars showed that raiding male baboons spent almost all of their time at the urban edge, engaging in short, high-activity forays into the urban space. Moreover, activity levels were increased where the likelihood of deterrence by rangers was greater. Overall, these raiding baboons display a time-activity balance that is drastically altered in comparison to individuals living in more remote regions. We suggest our methods can be used to obtain precise estimates of management impact for this and other species in conflict with people

Phosphorylation of the Leukemic Oncoprotein EVI1 on Serine 196 Modulates DNA Binding, Transcriptional Repression and Transforming Ability

The EVI1 (ecotropic viral integration site 1) gene at 3q26 codes for a transcriptional regulator with an essential role in haematopoiesis. Overexpression of EVI1 in acute myeloid leukaemia (AML) is frequently associated with 3q26 rearrangements and confers extremely poor prognosis. EVI1 mediates transcriptional regulation, signalling, and epigenetic modifications by interacting with DNA, proteins and protein complexes. To explore to what extent protein phosphorylation impacts on EVI1 functions, we analysed endogenous EVI1 protein from a high EVI1 expressing Fanconi anaemia (FA) derived AML cell line. Mass spectrometric analysis of immunoprecipitated EVI1 revealed phosphorylation at serine 196 (S196) in the sixth zinc finger of the N-terminal zinc finger domain. Mutated EVI1 with an aspartate substitution at serine 196 (S196D), which mimics serine phosphorylation of this site, exhibited reduced DNA-binding and transcriptional repression from a gene promotor selectively targeted by the N-terminal zinc finger domain. Forced expression of the S196D mutant significantly reduced EVI1 mediated transformation of Rat1 fibroblasts. While EVI1-mediated serial replating of murine haematopoietic progenitors was maintained by EVI1-S196D, this was associated with significantly higher Evi1-trancript levels compared with WT-EVI1 or EVI1-S196A, mimicking S196 non-phosphorylated EVI1. These data suggest that EVI1 function is modulated by phosphorylation of the first zinc finger domain

Fear of predation drives stable and differentiated social relationships in guppies

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.Social relationships can have important consequences for fitness in animals. Whilst numerous studies have shown that individuals often join larger groups in response to perceived predation risk (i.e. fear of predation), the importance of predation risk in driving the formation and stability of social relationships within groups has been relatively ignored. We experimentally tested how predation threat influenced fine-scale social network structure using Trinidadian guppies (Poecilia reticulata). When perceived predation risk was high, individuals developed stable and more differentiated social ties compared to when perceived risk was low. Intriguingly, social differentiation coincided with shoals being somewhat smaller under high-perceived risk, suggesting a possible conflict between forming stable social relationships and larger social groups. Individuals most at risk of predation (large and bold individuals) showed the most exaggerated responses in several social measures. Taken together, we provide the first experimental evidence that proximate risk of predation can increase the intensity of social relationships and fine-scale social structure in animal populations.DPC acknowledges funding from the National Environmental Research Council (NE/E001181/1) and Leverhulme Trust (RPG-175) and SKD and DPC acknowledge funding from The Danish Council for Independent Research (DFF – 1323-00105)

Increased Anion Channel Activity Is an Unavoidable Event in Ozone-Induced Programmed Cell Death

Ozone is a major secondary air pollutant often reaching high concentrations in urban areas under strong daylight, high temperature and stagnant high-pressure systems. Ozone in the troposphere is a pollutant that is harmful to the plant. generation by salicylic and abscisic acids. Anion channel activation was also shown to promote the accumulation of transcripts encoding vacuolar processing enzymes, a family of proteases previously reported to contribute to the disruption of vacuole integrity observed during programmed cell death.-induced programmed cell death. Because ion channels and more specifically anion channels assume a crucial position in cells, an understanding about the underlying role(s) for ion channels in the signalling pathway leading to programmed cell death is a subject that warrants future investigation

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials