324139 research outputs found
Sort by
A state-dependent memory for sodium chloride in Drosophila melanogaster and comparative neural transcriptomic analyses of Drosophila and Apis mellifera
No full textAssociative learning and memory, combined with internal state signals, optimise the behaviours of foraging animals. The Mushroom Bodies (MBs) of insects coordinate associative learning and are comprised of intrinsic neurones called Kenyon Cells (KCs). KCs represent sensory information in a parallel stream. Valence information, like rewarding nutrient signals, is provided to the MB by dopaminergic neurones (DANs). DANs direct learning-relevant plasticity of connections between KCs and downstream MB output neurones. This thesis investigates a state-dependent NaCl-memory in Drosophila melanogaster and explores midbrain transcriptomic changes in response to NaCl-feeding. In addition, transcriptomic profiles of Apis mellifera KCs and DANs were characterised and compared to those of Drosophila to understand conserved transcriptomic cell profiles between the two species.Using an olfactory associative learning paradigm, with a naively appetitive (low) or naively aversive (high) concentration of NaCl as the unconditioned stimulus, we tested the existence of a state-dependent NaCl memory in Drosophila. Nutrient-deprived Drosophila form an immediate, but short-lived, low NaCl memory. A long-lasting memory was found for high NaCl; the valence of this memory depended on nutrient status. Nutrient-deprived Drosophila approached the conditioned odour, NaCl-fed Drosophila showed no detectable preference for either the conditioned nor alternative odour and satiated Drosophila avoided the conditioned odour. This aversive behaviour was more pronounced in females. To understand the transcriptional changes that occur in the brain in response to NaCl feeding, we analysed single-cell RNA sequencing (scRNA-seq) data of nutrient-deprived or NaCl-fed Drosophila midbrains. However, the quality of this data was impacted by a high level of adapter sequence contamination in sequenced reads, but preliminary analysis identified potential nutrient-deficit signals.ScRNA-seq analysis of twelve pollen-foraging Apis dorsal protocerebra identified nine KC clusters. Transcriptomic comparison of Drosophila and Apis KC clusters found little similarity; however, marker genes for Drosophila reward and punishment-encoding DANs annotated two discrete Apis DAN clusters
The 9th International RASopathies Symposium
No full textThe RASopathies are a group of congenital disorders with overlapping clinical manifestations that are caused by pathogenic germline or early somatic variants that result in the hyperactivation of the RAS/mitogen‐activated protein kinase (MAPK) signaling pathway. Given the heterogeneous clinical presentations of these disorders that involve abnormalities across multiple organ systems, multidisciplinary clinical management and progress in scientific research are essential for optimal patient diagnosis and care. The 9th International RASopathies Symposium, a biennial meeting, was organized by the patient advocacy group RASopathies Network and showcased recent discoveries, case studies, and advances in preclinical research. Participants, who included scientists, clinicians, industry representatives, patients, and family advocates, explored knowledge gaps, innovative clinical approaches, and lived experiences of individuals with a RASopathy. Sessions centered around organ systems were introduced with a patient perspective to highlight the burden of disease, continued with presentations from established and early‐career investigators. Overall, the RASopathies Symposia serve as a catalyst for sustained community collaboration focused on enhancing patient health and accelerating the translation of discoveries into effective treatments
A psychometric evaluation of the NICHD Parent-Infant Interaction Scales to inform clinical practice
No full textBackground: There is no recommended measure of parent-infant interaction that is psychometrically robust, feasible (i.e., brief and simple to use) and validated for use from birth to 12 months for routine use in Perinatal Mental Health Services (PMHS). This study tested the cross-sectional construct validity of the global sensitivity scale and a sensitivity composite from the NICHD Parent-Infant Interaction scales in a clinical sample of parents and babies, and the inter-rater reliability of all the NICHD scales in a sub-sample of dyads with infants under 3 months of age. Methods: Secondary analysis using parent-infant interaction videos from a Randomized Controlled Trial in specialist PMHS in England were used. Participants were 275 dyads who completed baseline self-reports (parental mental health symptoms, parent-reported bonding) and parent-infant observation tasks where sensitivity was measured (free play, book sharing, clothing change). Parents with infants over 2 months of age (N = 180), also completed measures of child development. Non-parametric correlations and linear regression were conducted to assess construct validity and intra-class correlations were conducted to evaluate inter-rater reliability. Results: Amongst dyads with infants 0–3 months, inter-rater reliability was good for the global and composite sensitivity scale, but poor-to-moderate for the scales of parental intrusiveness, dyadic mutuality and the infant scales. In the full sample of dyads, there was a small but significant negative association between the global and composite sensitivity scales and parental mental health symptom severity, but this association was not statistically significant when sensitivity was observed in the free play alone. In terms of child development, greater sensitivity was only associated with fewer socio-emotional problems when it was observed during the clothing change task. There was a statistically significant negative association between observed sensitivity and bonding difficulties, and the strength of this association was greater for younger infants than older infants. Conclusion: These findings contribute to the evidence base of the NICHD scales in a PMHS setting and suggest ways that the clinical utility of the NICHD scales could be improved for routine practice
The efficacy of interactive communication interventions for motivating blood donation: a systematic review
No full textBackground and Objectives The global blood product shortage is a persistent problem that urgently needs addressing. Research has investigated the effects of incentives, different interventions, and different modes of communication on promoting blood donation, yet there has been no systematic review comparing interactive communication-based interventions. Identifying effective methods to recruit and retain blood donors could inform future intervention design and improve resource allocation, thereby reducing strain on blood-product supply. Materials and Methods This review brings together relevant literature found on Medline, CENTRAL, Embase and PsychINFO, to address the questions: "What are the most effective interaction interventions for promoting blood donation?" and "Are these different between encouraging first time and returning blood donors?". A total of 35 studies were included in this review. Results Overall, the quality of research into communication-based interventions was poor, with several studies lacking sufficient detail to make clear conclusions. Evidence for three common interventions (phone calls, educational sessions, and motivational interviews) was conflicting. Additionally, there was limited research into web-based interventions and recruitment of first-time donors. Conclusion Reporting of communication interventions for blood donation could be improved, and our review suggests a more heterogeneous approach to donor recruitment may be advantageous
Art, paradox, and the sacred in Heidegger
No full textIn this project I argue that that there exists paradox in Heidegger which illuminates the nexus between art, the sacred, and world-disclosure. Heidegger has worked out a reasonably good picture of these three domains individually and emphasized their essential connectedness in his writings after Being and Time, but provided frustratingly little to explain or motivate the nature of this connection. Perhaps consequently, this area has also been largely under-served in the existing secondary scholarly literature. I aim to contribute a novel and constructive reading to both, and one which makes explicit what I take to be another significant (and equally underdeveloped) implicit theme in Heidegger’s later work – paradox. I derive a starting definition of paradox independently from Heidegger’s account of the sacred, that is, his general engagement with religious phenomena, and then from his account of the work of art, yielding the following result: in both domains, there is a necessary paradoxical quality, an actionable contradiction in which the terms are co-instantiated and immediate. This analytic definition is expanded with reference to Kierkegaard to accommodate the ways we may relate to it as a horizon that requires personal risk, and then tested as an explanatory mechanism against points of intersection between art and the sacred. In the end, having derived a sense of paradox from the text and used it constructively back towards the text, a secondary theme gently emerges; one in which the world takes on a sacramental quality, and sacrifice appears as a means of responsiveness to Being
Teaching and assessing writing in the age of AI: reflections from the Oxford University Press Signature Event
No full textThe rapid integration of generative artificial intelligence (GenAI) into educational practice presents profound opportunities for English language teaching, learning and assessment. Drawing on our panel discussion at the 2025 IATEFL Oxford University Press Signature Event, here we explore emerging tensions and possibilities for the teaching of writing and assessment in the age of AI. We argue for a reframing of risk that foregrounds equity, inclusion and human agency, examining both technological advancements and pedagogical implications. Through critical perspectives, practitioner insight and applied case studies, we outline a research-informed path for integrating AI tools in ways that support accessible and effective learning environments
Exploring primary teachers’ notions of big ideas in statistics: insights from Maharashtra, India
No full textThis study examines primary mathematics teachers’ understanding of the big ideas in statistics through a sequential explanatory mixed methods design in the state of Maharashtra, India. Adopting a pragmatic perspective, the study integrates quantitative and qualitative methods to gain a comprehensive view of teachers’ statistical knowledge and pedagogy. In the quantitative phase, a survey questionnaire was administered to 251 primary teachers across the state. The instrument assessed statistical content knowledge through five big ideas in statistics, framed within the statistical inquiry cycle. The mean score was 4.87 (SD = 2.08) out of 12, indicating overall low performance. No significant differences were found based on teaching experience, school type, or language of instruction. However, teachers with postgraduate qualifications scored slightly higher than those with only undergraduate degrees (p < 0.01). Teachers' confidence, measured on a Likert scale, did not correspond with their actual performance, suggesting limited awareness of knowledge gaps.The qualitative phase involved semi-structured cognitive interviews focusing on teachers’ current classroom practices, their reasoning behind survey responses, and their pedagogical content knowledge (PCK) in statistics. Analysis showed that correct answers on the survey did not necessarily reflect deep conceptual understanding. Teachers’ knowledge was often context-bound; they performed better with familiar, context-specific tasks but struggled to transfer understanding to unfamiliar situations. In several cases, teachers’ reasoning resembled that of early learners of statistics, indicating a persistent gap in statistical knowledge. While interviews also revealed that teachers’ PCK was constrained by their limited statistical content knowledge, teachers appeared more confident when discussing the PCK task that was grounded in the classroom context. This suggests that professional development could productively begin with contextually relevant activities before expanding to broader statistical concepts.The study highlights critical gaps in teachers’ statistical understanding and awareness, providing an evidence base for targeted professional development initiatives. It underscores the need for approaches that strengthen both content knowledge and pedagogical strategies, enabling teachers to better support students’ statistical reasoning
Exploring mitigation and aggravation: a socio-legal analysis of sentencing in Cyprus
No full textThis thesis examines how judges in Cyprus apply mitigating and aggravating factors at sentencing. Although sentencing has been widely studied, these factors have received less sustained attention than other aspects of the process. They form a recognised element of judicial discretion in common law jurisdictions, though their application remains unsettled. There is no shared understanding of what renders a factor mitigating or aggravating, and judicial assessments often diverge, revealing conceptual uncertainty, limited appellate direction, and reliance on assumptions. In Cyprus, judges retain broad discretion to determine which factors are relevant and the weight each should carry. In the absence of a sentencing council, outcomes may differ and judicial reasoning may be harder to examine. While discretion enables individualised justice, it may also weaken consistency and reviewability within the Cypriot context. The present study constitutes the first hybrid (doctrinal and empirical) analysis of sentencing factors in Cyprus, combining a taxonomy with appellate analysis, qualitative interviews, and examination of judicial reasoning, sentencing method, and penal theory. It addresses how factors are identified, explained, and weighed, and how premises influence those assessments. Although centred on Cyprus, the analysis contributes to wider discussions on transparency, justification, and structure in sentencing. It shows how clearer reasoning on mitigating and aggravating factors may support fairness, legitimacy, and the responsible exercise of judicial discretion
Skeletal muscle adaptation to muscle activity and hypoxia: Differential structural and metabolic remodelling
No full textDelivery and utilisation of oxygen are critical determinants of skeletal muscle function, and therefore aerobic performance. Angiogenesis, the process of microvascular bed expansion, may be initiated by several tissue‐level stimuli (e.g. of haemodynamic, myogenic or metabolic origin), which are typically present during dynamic exercise. Understanding the relative contribution of these distinct physiological stimuli to skeletal muscle remodelling is needed to develop effective therapeutic strategies to alleviate impaired tissue oxygen supply. In the present study, we uncoupled the predominantly mechanotransductive (i.e. elevated vascular shear stress and cyclical muscle activation) and predominantly chemotransductive (i.e. local tissue hypoxia) stimuli present during exercise by exposing C57b6 mice to either indirect muscle stimulation (10 Hz; ST) or systemic hypoxia (10% oxygen; H), for 7 days, respectively. Furthermore, we combined these stimuli (H+ST) to determine whether the effects were additive. After 7 days of intervention, the tibialis anterior muscle was sampled for histological quantification of microvascular supply and metabolomics analysis. We showed that ST promoted a significant angiogenic response within the muscle whereas H did not. Interestingly, the combined H+ST group had a blunted angiogenic response. Branch‐chain amino acid levels were significantly decreased following ST, H and H+ST, consistent with an increased metabolic requirement for ATP, which represents an energy deficit. Proximate metabolites of the glycolytic pathway were significantly reduced following hypoxia, but not stimulation. Together, these observations are commensurate with mechanotransduction triggering structural remodelling of muscle that preserves the metabolome of muscle tissue, whereas chemotransduction inhibits the angiogenic response induced by ST, possibly as a consequence of altered glycolytic metabolism. image Key points: Angiogenesis, the process of microvascular bed expansion, may be initiated by several tissue‐level stimuli (e.g. haemodynamic, myogenic or metabolic in origin), which are typically present during dynamic exercise. There has been controversy about the structural (capillary) response of skeletal muscle to altered O2 status, involving decreased supply (hypoxia) or increased demand (activity). Here, we demonstrate that 7 days of activation of skeletal muscle by indirect electrical stimulation led to significant expansion of the capillary bed. However, a similar adaptive structural response was not observed following hypoxia. When combining indirect stimulation and hypoxia, hypoxia appears to blunt structural remodelling. Proximate metabolites of the glycolytic pathway were significantly reduced following hypoxia, but not stimulation. Together, these observations suggest that mechanotransduction (via indirect stimulation) triggers structural remodelling of muscle that preserves the metabolome of muscle tissue, whereas chemotransduction (via hypoxia) inhibits the angiogenic response induced by stimulation, possibly because of altered glycolytic metabolism
