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Breaking down barriers : creating a community of learning development at the University of St Andrews
Get PDFThis presentation outlined a collaboration that delivered an integrated in-sessional academic and learning development provision for students at the University of St Andrews. Staff from the student learning development team in the Centre for Educational Enhancement and Development, and the Academic English Service, situated in the International Education Institute, partnered to bring previously segregated provisions together for academic year 2023/24. Historically both units have provided separate in-sessional one-to-one tutorials dictated by students’ first language or stage of study, but with overlap in some skills areas such as writing development. Each service had different parameters in terms of who could access the tutorials and how often they could do so. Due to the restrictions of each provision, and the siloed nature of the services, we identified that students were often not accessing the most appropriate form of tutorial, and that some tutorials were not being used to best effect. The provision has been reimagined to proffer a new Academic Development Community with the aim of creating a more effective and inclusive resource. This presentation unpicks motivations for pursuing a unified service and reflects on the changes made. The session shared the results of qualitative and quantitative student feedback on the newly aligned provision, and the perceptions of focus group participants on the unified service and relationship with contributing units. Combining the feedback collected thus far with our own professional reflections we explored the outcomes of these changes, as well as the challenges encountered in our collaborative approach. We concluded by sharing the future directions of this collaboration
A loss-of-function mutation in human Oxidation Resistance 1 disrupts the spatial-temporal regulation of histone arginine methylation in neurodevelopment
Get PDFFunding was provided by the Research Council of Norway, South-East Norway Regional Health Authority and Central Region Norway Health Authority. The Proteomics and Metabolomics Core Facility PROMEC is funded by NTNU and the Central Norway Regional Health Authority and is a member of the National Network of Advanced Proteomics Infrastructure (NAPI), which is funded by the RCN INFRASTRUKTUR-program (295910).Background Oxidation Resistance 1 (OXR1) gene is a highly conserved gene of the TLDc domain-containing family. OXR1 is involved in fundamental biological and cellular processes, including DNA damage response, antioxidant pathways, cell cycle, neuronal protection, and arginine methylation. In 2019, five patients from three families carrying four biallelic loss-of-function variants in OXR1 were reported to be associated with cerebellar atrophy. However, the impact of OXR1 on cellular functions and molecular mechanisms in the human brain is largely unknown. Notably, no human disease models are available to explore the pathological impact of OXR1 deficiency. Results We report a novel loss-of-function mutation in the TLDc domain of the human OXR1 gene, resulting in early-onset epilepsy, developmental delay, cognitive disabilities, and cerebellar atrophy. Patient lymphoblasts show impaired cell survival, proliferation, and hypersensitivity to oxidative stress. These phenotypes are rescued by TLDc domain replacement. We generate patient-derived induced pluripotent stem cells (iPSCs) revealing impaired neural differentiation along with dysregulation of genes essential for neurodevelopment. We identify that OXR1 influences histone arginine methylation by activating protein arginine methyltransferases (PRMTs), suggesting OXR1-dependent mechanisms regulating gene expression during neurodevelopment. We model the function of OXR1 in early human brain development using patient-derived brain organoids revealing that OXR1 contributes to the spatial–temporal regulation of histone arginine methylation in specific brain regions. Conclusions This study provides new insights into pathological features and molecular underpinnings associated with OXR1 deficiency in patients.Peer reviewe
Astrophysical tests of conformal gravity
Get PDFConformal Gravity (CG) is an alternative gravity theory which aims to explain observations without requiring dark matter or a cosmological constant, as in General Relativity (GR). The theory features an action formed from the Weyl tensor and includes a conformal Yukawa cou- pling to the Higgs field, making the total action invariant under conformal transformations. This thesis aims to test CG using astrophysical observations, including cosmology, lensing and clusters. I use SNIa and quasars as standard candles to show that the SNIa provided strong evi- dence, and the full sample provide decisive evidence against the Mannheim CG cosmology, and in favour of ΛCDM. Following the work of Horne (2006), I compare estimates of the dynami- cal mass from X-ray observations in the cluster A2029 to the predictions from the Mannheim potential in CG. I find that CG can fit the cluster without dark matter, but with the Mannheim potential altered by setting γ∗ = 0 and with different values of the Mannheim parameters than in galaxies. Considering lensing, we present the derivation of the bend angle for a point mass in CG, as derived in Horne et al. (in prep). We find that γ makes no 1st-order contribution to the deflection angle, requiring κ 0. Using this deflection angle, I fit to the SLACS and SL2S samples of galaxy lenses and to the lensing cluster MS2137.3-2353 to determine κ. I find that for SLACS is κ = −7.2 × 10⁻⁴⁹ m⁻² and for SL2S is κ = −3.3 × 10⁻⁴⁹ m⁻²; The tangential and radial arcs MS2137.3-2353 imply κ = −9.6 × 10⁻⁵¹ m⁻² and κ = −8.4 × 10⁻⁵¹ m⁻², respectively. I find evidence that CG cannot fit both images in MS2137.3-2353 simultaneously with the point mass approximation. From these tests I conclude that CG cannot yet be considered a viable alternative theory of gravity to GR
Substance use, risk behaviours and well-being after admission to a quasi-residential abstinence-based rehabilitation programme : 4-year follow up
Get PDFBackground Tackling Scotland's drug-related deaths and improving outcomes from substance misuse treatments, including residential rehabilitation, is a national priority. Aims To analyse and report outcomes up to 4 years after attendance at a substance misuse residential rehabilitation programme (Lothians and Edinburgh Abstinence Programme). Method In total, 145 participants were recruited to this longitudinal quantitative cohort study of an abstinence-based residential rehabilitation programme based on the therapeutic community model; 87 of these participants were followed up at 4 years. Outcomes are reported for seven subsections of the Addiction Severity Index-X (ASI-X), together with frequency of alcohol use, heroin use, injecting drug use and rates of abstinence from substances of misuse. Results Significant improvement in most outcomes at 4 years compared with admission scores were found. Completing the programme was associated with greater rates of abstinence, reduced alcohol use and improvements in alcohol status score (Mann–Whitney U = 626, P = 0.013), work satisfaction score (U = 596, P = 0.016) and psychiatric status score (U = 562, P = 0.007) on the ASI-X, in comparison with non-completion. Abstinence rates improved from 12% at baseline to 48% at 4 years, with the rate for those completing the programme increasing from 14.5% to 60.7% (χ2(2, 87) = 9.738, P = 0.002). Remaining abstinent from substances at follow-up was associated with better outcomes in the medical (U = 540, P < 0.001), psychiatric (U = 273.5, P < 0.001) and alcohol (U = 322.5, P < 0.001) subsections of the ASI-X. Conclusions Attending this abstinence-based rehabilitation programme was associated with positive changes in psychological and social well-being and harm reduction from substance use at 4-year follow-up, with stability of change from years 1 to 4.Peer reviewe
Effect of α-substitution on the reactivity of C(sp3)−H bonds in Pd0-catalyzed C−H arylation
Get PDFFunding: This work was supported by the Swiss National Science Foundation (200021_184608) and the University of Basel.We report mechanistic studies on the reactivity of different α-substituted C(sp3)–H bonds, −CHnR (R = H, Me, CO2Me, CONMe2, OMe, and Ph, as well as the cyclopropyl and isopropyl derivatives −CH(CH2)2 and −CHMe2) in the context of Pd0-catalyzed C(sp3)–H arylation. Primary kinetic isotope effects, kH/kD, were determined experimentally for R = H (3.2) and Me (3.5), and these, along with the determination of reaction orders and computational studies, indicate rate-limiting C–H activation for all substituents except when R = CO2Me. This last result was confirmed experimentally (kH/kD ∼ 1). A reactivity scale for C(sp3)–H activation was then determined: CH2CO2Me > CH(CH2)2 ≥ CH2CONMe2 > CH3 ≫ CH2Ph > CH2Me > CH2OMe ≫ CHMe2. C–H activation involves AMLA/CMD transition states featuring intramolecular O → H–C H-bonding assisted by C–H → Pd agostic bonding. The “AMLA coefficient”, χ, is introduced to quantify the energies associated with these interactions via natural bond orbital 2nd order perturbation theory analysis. Higher barriers correlate with lower χ values, which in turn signal a greater agostic interaction in the transition state. We believe that this reactivity scale and the underlying factors that determine this will be of use for future studies in transition-metal-catalyzed C(sp3)–H activation proceeding via the AMLA/CMD mechanism.Peer reviewe
Carving up the network of powers
Get PDFDo powers have parts? Mereological thinking is typically guided by two different metaphors: building vs. carving. The building picture treats wholes as constructed from fundamental bits; the carving treats wholes as the result of carving some interconnected space. After considering some suggestions for how to view powers as built from other components, I'll opt for the carving picture, and suggest that a mereology of powers can be generated by carving and underlying space of an interconnected web of fundamental powers. The space of powers is a network of manifestation/triggering connections that can be modelled graph-theoretically along the lines of Bird (2007) and Tugby (2013). The identity of a fundamental power is importantly tied up with its position in the overall structure. I'll consider the idea that powers are completely identified by their position in the structure (as pandispositionalists have thought), which then places limits on the sorts of structures that powers theorists can help themselves too. I'll also consider another novel suggestion on the identity of powers borrowed from non-wellfounded set theory. I’ll show how to identify principles governing ‘carving’ the web into groups of closely connected powers, such that one group can naturally be called ‘part’ of another group, and explore the resulting mereology
Thermodynamic growth of sea ice : assessing the role of salinity using a quasi-static modelling framework
Get PDFSea ice is a mushy layer, a porous material whose properties depend on the relative proportions of solid and liquid. The growth of sea ice is governed by heat transfer through the ice together with appropriate boundary conditions at the interfaces with the atmosphere and ocean. The salinity of sea ice has a major effect on its thermal properties so might naïvely be expected to have a major effect on its growth rate. However, previous studies observed a low sensitivity throughout the winter growth season. The goal of this study is to identify the controlling physical mechanisms that explain this observation. We develop a simplified quasi-static framework by applying a similarity transformation to the underlying heat equation and neglecting the explicit time dependence. We find three key processes controlling the sensitivity of growth rate to salinity. First, the trade-off between thermal conductivity and (latent) heat capacity leads to low sensitivity to salinity even at moderately high salinity and brine volume fraction. Second, the feedback on the temperature profile reduces the sensitivity relative to models that assume a linear profile, such as zero-layer Semtner models. Third, thicker ice has the opposite sensitivity of growth rate to salinity compared with thinner ice, sensitivities that counteract each other as the ice grows. Beyond its use in diagnosing these sensitivities, we show that the quasi-static approach offers a valuable sea-ice model of intermediate complexity between zero-layer Semtner models and full partial-differential-equation-based models such as Maykut–Untersteiner/Bitz–Lipscomb and mushy-layer models.Peer reviewe
Health, education, and social care provision after diagnosis of childhood visual disability
Get PDFFunding: A Fight for Sight grant (1525/26) and the Ulverscroft Foundation for the Ulverscroft Vision Research Group. ALS received support from the National Institute for Health Research (NIHR) Moorfields Biomedical Research Centre, an NIHR Lectureship, and an NIHR Clinician Scientist award (CS-2018-18-ST2-005). JSR is supported in part by the NIHR Moorfield Biomedical Research Centre, and an NIHR Senior Investigator award. UCL Institute of Child Health/Great Ormond Street Hospital for children received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.Aim To investigate the health, education, and social care provision for children newly diagnosed with visual disability. Method This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vision. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision. Results BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2 p < 0.001), or had an EHCP (11% vs 7%, χ2 p < 0.01). Interpretation Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.Peer reviewe
Roundtable - Movie: A Journal of Film Criticism and the past, present, and future of film criticism
Get PDFNon peer reviewe
Determining the sources of (sub)permil-level inaccuracy during laser ablation-MC-ICPMS boron isotope measurements of carbonates
No full textFunding: FIERCE is financially supported by the Wilhelm and Else Heraeus Foundation and by the Deutsche Forschungsgemeinschaft (DFG : INST 161/921-1 FUGG, INST 161/923-1 FUGG and INST 161/1073-1 FUGG), which is gratefully acknowledged. This research was funded through the VeWA consortium by the LOEWE programme of the Hessen Ministry of Higher Education, Research and the Arts, Germany. James Rae, Hana Jurikova, and Matthew Dumont acknowledge funding from the Royal Society of Edinburgh (RSE Saltire International Collaboration, grant number 1964), and Hana Jurikova also thanks the Leverhulme Trust Early Career Fellowship for funding (ECF-2023-199).Recent developments in spatially-resolved boron isotopic analysis using laser ablation as a means of sample introduction to MC-ICPMS instruments (LA-MC-ICPMS) increasingly allow researchers to explore the spatial heterogeneity of the boron isotopic composition of a range of geochemical applications, for example in palaeoclimatology and mantle petrology. However, previous work has shown that a diffuse interference centred near 10B, when measuring samples with a calcium-rich matrix, can significantly bias especially the measurement on 10B, affecting the accuracy of boron isotope measurements. Although several correction approaches have yielded sufficiently accurate analyses of δ11B in calcium carbonate, the root cause of this interference is still not fully resolved. Here, we explore the various potential sources of inaccuracy in boron isotope measurements made using (LA-)MC-ICPMS by experimenting with dry and wet plasma conditions, in both solution and laser ablation mode (in the former case, our solution (Ca–Mg)/B ratios broadly mimic those found in natural samples). In solution mode, we find that irrespective of wet or dry plasma conditions, the introduction of a Ca-containing matrix yields a baseline up to ∼4 and ∼14 times higher around m/z ≈ 10 for wet and dry plasma conditions, respectively, compared to both a Mg-only matrix and lack of matrix. In order to explore this further, we performed mass scans around m/z ≈ 10 during laser ablation of different carbonates with varying matrix [Ca]. These show that the m/z ≈ 10 interference scales linearly with a mixture of the calcium content of the analyte matrix and 40Ar4+ ion beam intensity, as previously hypothesised. Moreover, by experimenting with different plasma loading scenarios during the ablation of CaCO3, i.e. varying laser spot sizes, we find that permil-level inaccuracies in δ11B may occur when the analyte ablated mass is significantly different than that of the standard used to calibrate instrumental mass bias. This is important given that we also show that different commonly-used reference materials ablate at very different rates, which illustrates the need for a careful standardisation approach irrespective of broader matrix effects when sub-permil level accuracy and precision are desirable when utilising LA-MC-ICPMS.Peer reviewe
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