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Dilemmas and Decision Making in Cancer Care:A Practice-Based Approach
No full textThis book presents realistic cancer-related clinical dilemmas and provides guidance on how to assess options and make ethical decisions. The provided case studies explore how decisions are made in ethically and sometimes morally challenging situations in practice. Approaches to care delivery focus on the perspective of the individual in terms of their practical, social, psychological, and emotional needs. Considerations are integrated with a range of solutions-focused perspectives to allow readers to discuss clinical dilemmas in a safe space while applying and expanding their professional knowledge. This book provides an invaluable resource for any healthcare student, clinical supervisor, academic educator, and anybody working within the cancer setting
Towards a comprehensive river barrier mapping solution to support environmental management
No full textThe environmental effects of large dams on river connectivity are well recognized and mapped globally. However, datasets describing the distribution and attributes of smaller barriers (such as weirs and culverts) are lacking or incomplete for many regions. This has hindered accurate impact assessments for water resource planning, biased understanding of restoration potential and limited research aiming to understand and mitigate river fragmentation effects. Developing an efficient method to accurately record river barriers, including small ones, has become a priority. We critically examine barrier mapping approaches, from field survey to automated detection, showcasing recent approaches to recording, counting and classifying river barriers. We demonstrate how incomplete barrier databases, particularly those lacking many small barriers, provide a flawed basis for water management and ecological restoration planning. We discuss the efficiency and accuracy of alternative barrier mapping approaches, highlight future priorities and emphasize harmonizing barrier assessment methods to generate reliable, freely available information for effective basin-level management
Evolution of breathers with spectrally skewed forcing and damping
Get PDFSlowly modulated nonlinear waves are accurately described in the framework of the conservative nonlinear Schrödinger equation (NLS). However, in many physical systems, the wave evolution is affected by energy gains and losses, therefore requiring introduction of forcing or damping in the NLS framework. Here, we analyze the idealized case in which the forcing term varies linearly with frequency such as the growth rate of positive components matches the decay rate of the negative ones. We reveal that the system is linearly unstable and prone to overall energy growth. The evolution of classical breather solutions is showcased in this framework. The most notable effects are the distortion of the breathers, which speed-up, and in the case of the Kuznetsov-Ma breather results in faster recurrence. Concurrently, spectral asymmetry between low and high frequency components develops
Public opinions of a net outcome policy: The case of biodiversity net gain in England
Get PDFIncreasingly, there is social pressure for organisations and governments to recognize and address their biodiversity impact or risk reputational (and potentially financial) damage. Biodiversity Net Gain (BNG) is being introduced globally as a means of addressing biodiversity loss and has recently been mandated in England. Understanding public opinions of BNG is crucial for assessing the likelihood of BNG-related project rejection, which has significant implications for operational risk. Using a questionnaire with a nationally representative by age and gender (for England) sample of 500 people, we found that most respondents had limited knowledge of BNG, with 21% reporting experience with a project aiming to achieve BNG, but generally accepted its core assumptions: that habitat creation, restoration, or enhancement can achieve net biodiversity gains after development losses (58.2%), and that biodiversity can be measured using a standardised metric (42.8%). While distrust was high among most actors involved in BNG, particularly developers (48.2% somewhat or strongly distrust), wildlife charities and ecological consultants were trusted by most respondents (75.6% and 66.0% somewhat or strongly trust respectively). Over half (55.6%) of the respondents felt that a project's environmental impact is acceptable if it achieves BNG. As a result, BNG may act to reassure the majority of the public about a project’s biodiversity impacts thereby reducing operational risk. Our findings suggest four strategies to further boost BNG's acceptability: providing understandable information for stakeholders, involving trusted actors like wildlife charities, avoiding the use of pre-existing biodiversity credits; and ensuring developers are seen as responsible for compensatory sites
Delayed diagnosis of axial spondyloarthritis: The crucial role of primary care — how you can make a difference
No full textInvestigating the evolution and function of LWY effectors in Phytophthora pathogens
Get PDFSuccessful colonization on hosts depends on pathogen secreted virulence proteins, termed effectors. For the devastating Phytophthora pathogens, many effectors are composed of tandem repeats of the (L)WY motif. Each (L)WY unit forms a conserved 3 or 5 α-helical bundle. Multiple units can be concatenated through a conserved linkage to form the WY1-(LWY)n architecture. Despite the structural conservation, the (L)WY units are sequence-wise variable, leading to the hypothesis that they may mediate diverse interactions with host molecules. Shuffling of these (L)WY units further promotes functional diversification. In this thesis, I examined the role of (L)WY tandem repeats in promoting effector evolution in Phytophthora.
I identified (L)WY-encoding sequences across five Phytophthora species, revealing 73-173 LWY effector genes per genome. 15%-63% of these LWY genes encode proteins lacking the N-terminal secretion Signal Peptide (SP), with a subset also missing the host-targeting RxLR motif. This suggests these variants may serve as a genetic reservoir for unit recombination or be secreted through non-canonical mechanisms. The LWY genes form multi-gene clusters, potentially facilitating recombination. I identified a recombination event in which two (L)WY effectors recombined to form a hybrid effector. Analysis of host targets revealed both shared and unique host interactors with the “parent” and hybrid effectors, demonstrating recombination as a mechanism that drives the evolution of novel virulence activity in (L)WY effectors.
I classified the (L)WY units based on their surface residues and identified specific (L)WY-LWY combinations as potential functional modules using a co-occurrence analysis. Selected LWY effectors that carry these modules were further characterized for host interactors in Nicotiana benthamiana using immunoprecipitation and mass-spectrometry. In addition to the known PP2A-interacting module, this analysis revealed additional modules that may recruit E2 ligases in the host.
This thesis provides important insights into the modularity-driven evolution of pathogen effectors and reveals novel virulence mechanisms in Phytophthora
Claudin-3, lipopolysaccharide binding protein, and jaundice clearance in infants with biliary atresia
Get PDFObjective: To explore the relationship among bacterial translocation, intestinal barrier integrity, and systemic inflammation in early biliary atresia (BA). Study design: Newly diagnosed infants with BA were assessed longitudinally before as well as 6, 12, and 24 weeks after undergoing Kasai portoenterostomy. Plasma immune marker measurement included interleukin (IL)-2, interferon-gamma (IFNγ), IL-4, IL-10, tumor necrosis factor alpha, IL-6, IL-8, IL-1β, IL-17, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Bacterial translocation (lipopolysaccharide binding protein [LBP]; D-lactate), intestinal barrier (claudin-3; intestinal fatty acid binding protein [IFABP], fecal calprotectin) biomarkers, and fecal microbiota genus abundance were analyzed. Results: Fifty-five infants were included, of whom 60% cleared their jaundice. Early post-Kasai, upregulation of plasma adhesion molecules and pro-inflammatory cytokines were associated with poorer jaundice clearance and liver fibrosis and correlated with jaundice severity. Elevated claudin-3 early post-Kasai was associated with poor jaundice clearance [OR 1.02 (1.00, 1.04); P = .02] and jaundice severity [P < .01]. On multivariable analysis, early ICAM-1 elevation (OR 1.008 [1.002, 1.014]; P = .01) and claudin-3 (OR 1.038 [1.009, 1.068]; P = .02), represented independent prognostic markers for persistent jaundice. Increased longitudinal trends of LBP (OR 0.79 [0.71, 0.89]; P < .01) and IFABP (OR <0.01 [2.4E-43, 0.24]; P = .04) were associated with poor jaundice clearance. LBP positively correlated with pro-inflammatory-cytokines (IL-6, P < .01: TNFα, P < .01) and ICAM-1 (P < .01) early post-Kasai. Fecal calprotectin positively correlated with jaundice severity (P < .01) by 24 weeks post-Kasai. No correlation between fecal microbiota abundance and bacterial translocation/intestinal integrity markers was demonstrated. Conclusions: Bacterial translocation may be linked to post-Kasai BA-immune pathways. Claudin-3 could represent a novel biomarker of early intestinal permeability in BA; links to the gut microbiota need further exploration
Comprehensive analysis of Enterococcus spp. from two European healthy infant cohorts shows stable genomic traits including antimicrobial resistance (AMR)
Get PDFEnterococcus spp. some of which are pathogenic, are common gut microbiota members, including also infants. Infants may be more susceptible to Enterococcus due to their developing gut ecosystems. It is unclear whether antibiotic resistance genes (ARGs) and certain genomic traits in enterococci are restricted to the human subpopulation or more widespread. Furthermore, the correlation between these traits and geographic variation is poorly understood. Therefore, we sequenced 100 strains isolated from full-term healthy infants’ fecal samples from two geographically distant European cohorts (MAMI in Spain and LucKi from the Netherlands) to explore the diversity of Enterococcus spp. within the infant’s gut microbiome and assess cohort-specific traits such as ARGs. Most isolates were E. faecalis and E. gallinarum, with a total of 11 species identified. We found a rich reservoir of ARGs, plasmids, prophages and virulence factors in the infant strains, with minimal cohort-specific differences in resistome profiles. In addition, Epx, a pore-forming toxin associated with pathogenicity, was found in E.hirae strains. While metabolic profiles were similar across cohorts, E. faecalis strains harbored more virulence genes and prophages compared to other species. An analysis of public Enterococcus genomes revealed that multi-drug resistant (MDR) strains exist without any significant geographic or temporal pattern. Phenotypic resistance analysis indicated that 28% of MAMI strains were gentamicin resistant, compared to 5% of the strains from the LucKi cohort, though LucKi isolates were also resistant to other antibiotics. We also selected ten E. faecalis isolates with varying virulence gene repertoires for phenotypic virulence testing in Caenorhabditis elegans and found them killing at various rates, however no clear pattern emerged in correlation with any specific genetic determinant. Overall, our results suggest that Enterococcus spp. including ARGs, are highly mobile across Europe and beyond. Their adaptability likely facilitates long-distance dissemination, with strains being acquired early in life from community environments
Deliverable 1.2 – Leveraging bio-geo-physical data outputs to enhance social value for climate adaptation. Interim Report
Get PDFEngaging with Knowledge Co-Production:Critical Reflections from Global Doctoral Researchers
Get PDFThere has been a recent shift across social science disciplines to engaging with co- production as a practical strategy for urban equality and as a guiding principle in research design (Osuteye et al. 2019), and many doctoral researchers are keen to engage with co-production in their research projects. Conventionally, doctoral programmes are designed to be time-bound, pre-defined, rigidly structured and independent, and to result in an individual piece of work. Therefore, critical aspects of co-production do not easily align with traditional doctoral programmes and there is a gap in the current literature and methodological precedents regarding the feasibility of co-production within a doctoral environment. In this chapter, we – a group of ten doctoral students – reflect on our experiences of engaging with co-production as a research practice within UK doctoral programmes. In January 2021, we participated in the first Knowledge in Action Towards Urban Equality (KNOW) Doctoral Training Course (also known as KNOW DTC), entitled ‘Co-producing Doctoral Urban Research in the Global South’, and have continued to work together to critically examine and document our experiences, which form the basis of this chapter