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A stable NTN1 fluorescent reporter chicken reveals cell specific molecular signatures during optic fissure closure
No full textNTN1 is expressed in a wide range of developmental tissues and is essential for normal development. Here we describe the generation of a Netrin-1 reporter chicken line (NTN1-T2A-eGFP) by targeting green fluorescent protein into the NTN1 locus using CRISPR/Cas9 methodology. Our strategy gave 100% transmission of heterozygous (NTN1T2A-eGFP/+) embryos in which GFP localisation faithfully replicated endogenous NTN1 expression in the optic fissure and neural tube floorplate. Furthermore, all NTN1T2A-eGFP/+ embryos and hatched birds appeared phenotypically normal. We applied this resource to a pertinent developmental context - coloboma is a structural eye malformation characterised by failure of epithelial fusion during optic fissure closure (OFC) and NTN1 is specifically expressed in fusion pioneer cells at the edges of the optic fissure. We therefore optimised the isolation of GFP expressing cells from embryonic NTN1T2A-eGFP/+ eyes using spectral fluorescence cell-sorting and applied transcriptomic profiling of pioneer cells, which revealed multiple new OFC markers and novel pathways for developmental tissue fusion and coloboma. This work provides a novel fluorescent NTN1 chicken reporter line with broad experimental utility and is the first to directly molecularly characterise pioneer cells during OF
Outcomes for patients with alcohol-related liver disease admitted to Scottish intensive care units 2010-2018
No full textINTRODUCTION: Alcohol-related liver disease is recognised as a major cause of liver-related morbidity and mortality. Our aim was to report the prevalence of, and outcomes from, alcohol-related liver disease after admission to ICUs in Scotland.METHODS: We performed a secondary data analysis using linked Scottish national databases of all adult general ICUs in Scotland. We compared emergency non-surgical patients admitted to ICU with and without alcohol-related liver disease. The primary outcome was ICU mortality, and secondary outcomes were ICU admission rate ratio; 60-day mortality; 2-year mortality; duration of ICU and hospital stay; and need for hospital readmission.RESULTS: Of the 49,420/103,103 (47.9%) patients admitted to ICU with emergency non-surgical diagnoses between 2010 and 2018, we identified 2629/49,420 (5.3%) patients with alcohol-related liver disease. Patients with alcohol-related liver disease were more likely to receive three-organ support (14.0% vs. 10.0%, p < 0.001). Mortality in the ICU was higher in patients with alcohol-related liver disease (964/2629 (36.7%) vs. 10,517/46,791 (22.5%), respectively; aOR 2.03 (95%CI 1.85-2.24)). Patients with alcohol-related liver disease who specifically presented to ICU with a gastrointestinal bleed had a lower ICU mortality (95/487 (19.5%)). Sixty-day mortality of patients with alcohol-related liver disease increased with higher levels of organ support (186/516 (36.0%) mortality with zero organs supported vs. 162/196 (82.7%) mortality with three organs supported).DISCUSSION: Early mortality was high in patients with alcohol-related liver disease who were admitted to ICU, especially if multi-organ support was required. However, nearly one-fifth of patients on multi-organ support survived to hospital discharge. Early mortality for patients with alcohol-related liver disease admitted with a gastrointestinal bleed was considerably lower and should be taken into consideration when considering management in ICU. In discussion with the patient and hepatologists, a trial of organ support with continuous re-evaluation may be appropriate.</p
Is there a right to revelatory autonomy?
No full textWe address the question of when it is permissible to interfere in the “transformative choices” of others—choices whether or not to undergo experiences that provide us with knowledge we can only get by undergoing them, and which as a result transform our core values and preferences. In doing so, we criticise Farbod Akhlaghi’s recent (2023) claim to have discovered a new moral right, such that interference in the transformative choices of others is permissible when and only when the chooser’s “right to revelatory autonomy” (RRA) is outweighed. In building our case for a more plausible answer to the question, we challenge all aspects of Akhlaghi’s account. We first argue that it fares no better epistemically than other accounts he rejects, and that it fails to provide a more plausible explanation of permissible interference. We then examine RRA itself closely, showing that on its most plausible reading it is both over-inclusive (since it cannot hold in relation to a wide range of transformative choices) and under-inclusive (since it would hold for many choices unlikely to be transformative in the relevant sense). While Akhlaghi’s core insight—that our practices of interference (including by attempts to rationally persuade) in the transformative choices of others are much less likely to be justified than we standardly take them to be—is both true and important, the deontic innovation with which he tries to illuminate this point serves only to obscure it
Ecologization, part 1:Towards assets-actifs and care practices
No full textThis paper analyses the emergence of a new mode of economization: Ecologization. Drawing on Caliskan and Callon’s programmatic articles on economization and marketization, it prototypes an approach to make visible and analyse ecologization in its emergent phase. We define ecologization as the management of human and non-human collectives oriented towards the provision of services that take care of all the active assets, i.e. assets-actifs they mobilize or engage. We propose that these nascent care practices assemble and mobilize a series of new engagements that attend to both humans and non-humans, as well as taking care of the value of their existence and the maintenance they require. This process moves beyond passive forms of assetization and entails designing, managing and maintaining dynamic assets-actifs. The current instalment (Part 1) analyses the emergence of ecologization and its difference from ecological economics and other green economic frameworks, followed by the second instalment (Part 2) that discusses the activities involved in ecologization processes and the ways in which human actors from a variety of practices, including social scientists, contribute to their design, revision and management.</p
Translinguistic apposition:Structure and function of a language choice practice in Kinyarwanda news articles
No full textIntroduction: This paper investigates the structure and function of translinguistic apposition in Kinyarwanda news articles. In the structure, a Kinyarwanda noun phrase and a French / English noun phrase are juxtaposed as if the second clarified the first. Two major issues are identified, namely the possibility of translinguistic apposition as practical action and its implicativeness relative to preceding and subsequent choices. These issues are identified against the background of two important discourse organisational principles, namely the principle of progressivity and that of the preference for same language discourse. Methods: Data were collected in two media blogs in Rwanda, namely Igihe.com and Umuseke.com using the method of theoretical sampling. They were analysed, in the tradition of the Ethnomethodology of Written Discourse, using a conversation-analysis-inspired qualitative analysis. Results: Translinguistic apposition is found to be possible as practical action because, organised as a parenthetical, it is shielded off from the reach of the preference for same medium discourse. It is also found to serve as a discourse-based language management strategy. Its implicativeness derives from this function. Discussion: Implications for the study of bilingual language use and for the practice of lexical development at the macro level are discussed
School staff members’ professional agency in Finland, Scotland and Sweden – A comparative study
No full textProfessional agency has been comprehensively investigated in educational contexts, but there have been few quantitative or comparative studies. This quantitative study explored school staff members’ professional agency in Finland, Scotland, and Sweden, addressing three dimensions of agency: influencing at work, participation at work, and negotiating professional identity. The questionnaire data indicated fairly strong agency among lower secondary school staff members across the dimensions and countries. Professional agency was perceived to be stronger in Sweden than in Finland or Scotland. There were some differences between the countries in terms of the background variables (e.g. working experience) affecting professional agency in schools
Evaluating archaeological field survey with tephrochronology - a case study from southern Iceland
No full textParental social class and school examinations:A longitudinal investigation using linked administrative and survey data
No full textThis study investigates the relationship between parental social class and young people’s school examinations in England. This study uses a specialist data resource from the UK Household Longitudinal Study (Understanding Society) and linked administrative data from the National Pupil Database. The main aims are to better understand the effects of parental social class on Key Stage 2 results in primary school (at age 11) and General Certificate of Secondary Education (GCSE) results in secondary school (at age 16) (i.e. two critical stages in a pupil’s educational life course). There is a strong positive association between pupils’ Key Stage 2 scores and GCSE scores. There are significant parental social class inequalities in GCSE outcomes, and these divisions have clearly opened up by the end of primary school. This result is consequential for the development of policies that are designed to tackle social inequalities
Association between maternal mental health, the COVID-19 pandemic, and children's developmental outcomes in Scotland
No full textBackground: The number of reported maternal mental health (MH) difficulties during the COVID-19 pandemic was higher than during the pre-pandemic period. Findings on the link between the COVID-19 pandemic and children's developmental outcomes suggest lower scores on the Ages and Stages Questionnaire (ASQ-3) among children born during the COVID-19 pandemic compared to pre-pandemic cohorts. The present study explored the interaction between maternal MH and being born during the COVID-19 pandemic on children's developmental outcomes. Furthermore, it examined the combined effect of maternal MH and birth during the pandemic on children's developmental outcomes.Study designThis study used a linked administrative dataset from Scotland. Children born between 1st March 2020 and 30th June 2021, inclusive (n=32,683), and a comparative historical cohort that included those born between 1st April 2017 and 31st October 2018 in Scotland (n=50,257) were included. Regression models were used to adjust for covariates, with outcomes such as ASQ-3 scores and developmental concerns and predictors such as maternal MH and birth during the COVID-19 pandemic. Results A history of MH hospital admission was associated with increased odds of developmental concerns: OR= 1.038, 95% CI [1.012, 1.064], p=0.004** and reduced ASQ-3 scores (effect size=0.130, 95% CI [-0.204, -0.056], p<0.001***). There were mixed findings on the association between being born during the COVID-19 pandemic (developmental concerns: OR= 1.024, 95% CI [1.019, 1.029], p<0.001***) and ASQ-3 scores (ES= 0.012, 95% CI [-0.002, 0.025], p=0.08) but no interaction between a history of MH hospital admission and birth during the COVID-19 pandemic. However, there was an interaction effect on mental health assessed by psychiatric outpatient attendance records association and birth during the COVID-19 pandemic on the ASQ-3 scores SD; -0.07 (ES =-0.066, 95% CI [-0.106, -0.027], p<0.001***). ConclusionsOur findings suggest that being born during the COVID-19 pandemic and maternal MH influenced child development with relatively small effects, with mixed findings on their combined presence. Our study only examined developmental outcomes up to age 13 – 15 months. Future studies should explore the potential long-term effects of being born during the pandemic and MH.<br/
Tractable generative modelling of cosmological numerical simulations
No full textCosmological simulations aim to understand the matter distribution in the universe by employing either semi-analytic methods or hydrodynamical models of matter distribution. These simulations describe the evolution of baryonic structures within dark matter potential wells, where dark matter is modeled as a self-gravitating, collisionless system. Despite advances in reducing computational costs, these simulations still require millions of CPU hours to achieve stable solutions. This raises the question: can generative models predict galaxy properties from a partial history of their dynamical evolution? Tractable probabilistic models, such as sum-product networks, enable efficient computation of conditional probabilities, allowing conditional marginals to be computed in time linear to the model size. In this work, we investigate the application of sum-product networks to compactly represent and learn distributions for predictions in concordance cosmology. Using the Eagle suite of cosmological hydrodynamical simulations, we demonstrate that these graphical models can effectively reproduce mock galaxy catalogs, capturing the relationship between baryonic and dark matter with promising accuracy
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