Open Research Exeter - University of Exeter
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GLP-1RA precision medicine in people with type 2 diabetes: current insights and future prospects
No full textGlucagon-like peptide-1 receptor agonists (GLP-1RAs) have become an essential drug class for treating type 2 diabetes, offering proven benefits in glycemic control, weight reduction, and cardiovascular and renal protection. However, growing evidence of heterogeneity in GLP-1RA treatment effects highlights the potential for developing precision medicine approaches to more accurately allocate GLP-1RAs to maximize patient benefit. In this Review, we explore the evidence for treatment effect heterogeneity with GLP-1RAs, focusing on clinical and genetic factors that robustly influence established therapeutic outcomes. We also highlight the potential of recent predictive models that integrate routine clinical data with personalize treatment decisions, comparing GLP-1RA to other major type 2 diabetes drug classes. While such models have shown considerable promise in identifying optimal type 2 diabetes treatment based on glycemic response, their utility for informing treatment choice for other clinical outcomes remains largely unexplored.</p
Recovery from perturbation is highly individual and similar between different perturbation types and metrics: A dynamical systems perspective of flexibility in walking gait
No full textBackgroundFlexibility refers to how individuals can adopt alternative solutions to regain or maintain regular walking patterns when constraints are modified. Flexibility is an important yet still emerging characteristic of motor coordination.Research questionsIn walking gait, what are the characteristics of flexibility?MethodsTwenty male participants (age 21–30) walked on a split-belt treadmill. Sudden perturbations in the form of belt accelerations or decelerations (direction) during mid-stance phase were applied at pseudo-random intervals (20–30 stride cycles). Kinematic data of the lower body were collected using Vicon motion capture.To represent flexibility, Continuous Relative Phase (CRP) variability was calculated for ankle-knee and knee-hip and pelvis-trunk couplings. The relaxation time of CRP variability after perturbation was used to evaluate the main effects of participant, successive perturbations, CRP coupling and perturbation direction. The relaxation time was considered as a component of how flexibility was channelled after perturbation.Repeated measures ANOVA and a univariate analysis was conducted to determine main effects on relaxation time.ResultsSignificant main effects of participant and the effect of successive perturbations were observed, while CRP coupling and perturbation direction did not have an effect on relaxation time.Significance: During perturbed walking on a treadmill, the response to perturbation was individual specific, a practice effect to the perturbation was present, and relaxation time did not differ by coupling or perturbation direction. This study provides a foundation for future studies to examine aspects of flexibility during walking, which can be applied to different participant populations.</p
Palaeoceanographic conditions and palaeoproductivity changes from the sub-Antarctic island South Georgia since the late deglacial, using marine micropalaeontology and geochemistry
No full textThis thesis presents a high-resolution multiproxy reconstruction of palaeoceanographic conditions and palaeoproductivity on the South Georgia shelf spanning the late deglacial through the Holocene. South Georgia lies within the path of the Antarctic Circumpolar Current (ACC) and the Southern Hemisphere Westerly Winds (SWW), south of the current position of the Antarctic Polar Front and encircled by the Southern ACC Front (SACCF). South Georgia is one of the few locations in the sub-Antarctic where it is possible to compare both terrestrial and marine records. Two sediment cores (GC666 and GC673) from the north-eastern shelf were analysed to reconstruct changes in oceanography, productivity, and glacial activity. Core GC666, recovered from the mid-shelf off Royal Bay, spans ca. 15.3 cal. kyr BP to present, while core GC673, from Cumberland Bay fjord, covers ca. 9.5 cal. kyr BP to present. Multiproxy methods include benthic foraminiferal and diatom assemblage analysis, XRF elemental analysis, and alkenone-derived sea-surface temperatures (SST). The base of GC666 contains laminated sediments (ca. 15.2 to 14.7 cal. kyr BP) interpreted as seasonal alternations between Chaetoceros-dominated biogenic laminae formed during the spring/early summer melt, and terrigenous laminae deposited from late summer glacial outwash and ice-rafted debris. This depositional setting is consistent with a calving-bay re-entrant formed during rapid deglacial ice retreat, supporting the interpretation that South Georgia reached the shelf edge in places during the Last Glacial Maximum. Warming during the late Pleistocene caused ice sheet retreat, though this was briefly reversed during the Antarctic Cold Reversal, when sea-ice associated diatoms increased and tidewater glaciers expanded. The Holocene climate evolution seems to show three phases. Early Holocene SST cooling between 10 and 8.2 cal. kyr BP is attributed to Antarctic meltwater input and the poleward migration of the SWW. This was followed by warming during the remainder of the early Holocene and during the mid Holocene climatic optimum (ca. 6.5 to 4.2 cal. kyr BP) with warmer SSTs and lower productivity resulting from greatly reduced glacial outwash-derived iron. The late Holocene Neoglacial (from ca. 4.2 cal. kyr BP) is characterised by cooling, increased sedimentation, and renewed productivity, consistent with Neoglacial advances. Cooler temperatures caused a northward migration of the SWW towards South Georgia, increasing precipitation rates and replenishing glaciers.</p
Organic-walled microphytoplankton from the West Midlands, England, following the end-Triassic mass extinction: palynological evidence from the Prees 2 borehole, Cheshire Basin
No full textThe end-Triassic mass extinction (ETME) was one of the most severe biotic crises of the Phanerozoic, driven by environmental changes linked to Central Atlantic Magmatic Province volcanism. While the ETME is a well-studied event, its expression in organic-walled phytoplankton, particularly acritarchs, remains relatively unexplored. Palynological analysis of the Prees 2 borehole, NW England (West Midlands), spanning from the upper Rhaetian to the lower Sinemurian, reveals exceptionally diverse aquatic palynomorph assemblages. The aquatic palynological assemblages, in the context of ammonite, miospore and lithostratigraphic data, show how phytoplankton communities responded to stress and subsequent stabilization. In the upper Rhaetian, the dominance of xerophytic coniferous pollen reflects warm, semi-arid palaeoenvironmental conditions, while euryhaline palynomorphs are in a nearshore environment. Subsequent phases show increased terrestrial humidity as evidenced by the palynoflora, coinciding with reduced aquatic diversity in an assemblage adapted to low-oxygen conditions. The base of the Hettangian is marked by sustained Cheirolepidiaceae dominance and a transition from short-spined Micrhystridid occurrences (reflecting low-oxygen conditions) progressing to an increased aquatic morphological diversity phase. This latter phase includes alterations in acritarch assemblages and the proliferation of dinoflagellate cysts, indicating a shift from a proximal shallow-water to a shelf palaeoenvironmental setting. Our findings demonstrate that acritarchs are valuable indicators of palaeoenvironmental change, capturing transient ‘bloom’ phases linked to post-extinction instability and offering new insights into Early Jurassic palaeoecology and recovery following the ETME.</p
Enabling the Development of Sustainable Aquaculture in Qatar
No full textAchieving food security is a major global challenge for the growing human population.Aquaculture offers a promising solution, and it is expanding rapidly; however, aquaticproduction systems are highly susceptible to a number of challenges including diseaseemergence. In Qatar, aquaculture is still developing and presents specific challengesgiven that it is set in an arid region with limited water resources and an extremeenvironment with high temperature and salinity. The main aims of this thesis were: (i) toestablish the first histological atlas for two important teleost species for aquaculture inQatar, the hamour (Epinephelus coioides) and the safi (Siganus canaliculatus), (ii) toinvestigate the presence of pathogens in wild and farmed aquatic species of relevance toArabian Gulf aquaculture, and (iii) to document the gill bacterial communities in the wildand aquaculture setting for the hamour using a microbiome approach. For both atlases,the histological analysis was conducted for nine organs including the skin and muscle,gill, liver, intestine, male and female gonads, heart, kidney, and spleen, (excluding skinfor hamour). These atlas presents, for the first time, the histological characterization ofthe heart, kidney and spleen in the safi, and the heart in the hamour, addressing a criticalknowledge gap in the literature. The findings confirm that the histological features oforgans previously studied for both species (skin and muscle, gills, liver, intestine, andgonads), are largely consistent with existing literature. All organs in both speciesdisplayed well-preserved histoarchitecture consistent with healthy teleost anatomy, withsome tissue-specific characteristics likely reflecting adaptation to the high-salinityenvironment. The safi gills showed epithelial lifting, while the hamour kidney exhibitedmulti-glomerular arrangements. Pathogen screening revealed no pathogens in farmedfish; however, non-infectious lesions were observed in several individuals. These includeda hepatic lesion, consistent with cholangiofibrosis observed in the liver of an individualhamour and nephrocalcinosis diagnosed in the kidneys of five safi individuals inaquaculture settings. In wild individuals, histopathological analysis identifiedgranulomatous lesions in 26 % of the safi individuals studied and nematodes in the liverof one hamour. Microbiome analysis showed that microbial diversity (Shannon entropy)2was consistently higher in swab samples compared to gill tissue biopsies in both wild andaquaculture groups. Microbial richness was generally higher in wild fish compared toaquaculture, with the swab samples being more representative of the gill surface.Taxonomic analysis identified a core set of genera shared across sample types, withVibrio present in all groups. Vibrio abundance was higher in wild samples, whileAlgibacter was prominent in aquaculture fish. Based on these data, it is recommendedthat swabs, a non-invasive technique, can be useful for routine health monitoring, earlypathogen detection, and environmental microbiome assessments, however, they mayunderrepresent tightly associated microbes or internal microbiota. These findings areparticularly relevant for aquaculture in Qatar, where baseline microbial data are limitedand were incorporating microbial monitoring as part of fish health surveillance couldimprove early disease detection. As aquaculture continues to grow in Qatar and acrossthe Arabian Gulf, understanding the responses of hamour and safi to captive rearingconditions is essential for promoting physiological resilience, welfare and productivity andcontribute to the sustainability of food production systems.</p
Measuring associations among social Identification, group norms, and alcohol consumption: Testing a Social Identity Model of Behavioural Associations (SIMBA)
No full textDrawing upon both social identity and balanced identity theories, the social identity model of behavioral associations (SIMBA) presents a novel way of conceptualizing and measuring the relationships among the constructs of social identity, group norms, and individual-level behavior—that is, as cognitive-behavioral associations that mutually interact in a triadic constellation and can be measured both implicitly and explicitly. While the social identity approach suggests that the interaction between social identity and group norms shapes individual behavior, the SIMBA—through adopting the methodological underpinnings of balanced identity theory—advances this theorizing to highlight that interactions among the three constructs are reciprocal and extend to the prediction of both social identity and group norms. Across four studies (total N = 540), we tested the SIMBA in the context of drinking behavior in relation to student (Studies 1, 2, and 3) and British national (Study 4) identities. On implicit measures, there was good support for the prediction that the strength of any one association in the SIMBA could be predicted by the interactive strength of the remaining two. Evidence for this prediction was largely absent on explicit Likert-type measures; we argue that this difference may be dependent on the explicit measures possessing theoretically meaningful zero points.Public Significance StatementThe research supports the utility of a new theoretical and methodological framework, the social identity model of behavioral associations, which conceptualizes and measures interactive relations among social identity, group norms, and behavior—some of the most central constructs in social psychology. While providing a framework for predicting engagement in behavior that is both group-based and identity-infused, the model also demonstrates how our behavioral associations might influence the extent to which we identify with a particular group and what is seen to be normative. Theoretically, the social identity model of behavioral associations shifts the focus away from typically thinking of identity and norms as predictor variables within the social identity approach to thinking of the relationships among all constructs as mutual, thereby offering greater explanatory potential.</p
Extending the Fuzzy-Trace Theory Informed Model of Guilty Plea Decision Making: Accounting for Factual Guilt and Innocence
No full textObjective: Understanding how sentence differentials influence plea decision making is vital to identifying when plea offers might lead to convictions that conflict with normative goals (e.g., avoiding wrongful conviction). We clarify previous findings by introducing and testing predictions of a Fuzzy-Trace Theory informed model relating plea discount to plea acceptance in mock guilty defendants and extend the work to mock innocent defendants. Hypotheses: We expected plea rates in guilty defendants to increase with increases in plea discount but to change more steeply when a change in plea discount created a categorically distinct change in sentence (vs. a less meaningful reduction). Innocent defendants were expected to be unresponsive to changes in plea discount until a breaking point at which the discount created a sufficient categorical difference between plea and trial sentences to compete with innocence and the values associated with it. Method: We conducted a vignette-based experiment with 3,646 participants. We manipulated potential trial sentence (9 years, 18 years), factual guilt (guilty, innocent), and discount (nine levels; 10%–90%) in a between-subject design and asked participants to accept or reject an offer. Results: As predicted, mock guilty participants were generally responsive to changes in plea discount but showed increased sensitivity at meaningfully distinct points along the range of discounts. Mock innocent participants showed a more extreme pattern. As expected, plea rates in mock innocent participants were generally unaffected by incremental changes in plea discounts but showed jumps at “break points,” particularly when perceived conviction probability was high. Conclusions: Results support our conceptual model of gist-based plea decision making and demonstrate important differences in cognition underlying decisions in those asked to assume guilt versus innocence.Public Significance StatementThis study shows that sentence discounts awarded to defendants who plead guilty may impact guilty and innocent defendants differently. These results have important implications for policy reform because they suggest that by offering discounts that create a moderate (but not large) categorical distinction between trial and plea sentences, we might maximize the number of guilty defendants pleading guilty while retaining low plea rates among factually innocent defendants.</p
A girls’-eye view: Exploring television representations of Italian girlhood through the lens of Italian female Adolescence
No full textIncreasingly, Italian TV addresses crucial issues with respect to girlhood: the representation of female adolescence within media culture; the multiple possibilities of appropriation open to young people as their personalities evolve; and girl friendship as a postfeminist idea of sisterhood (Winch, Girlfriends and postfeminist sisterhood. Basingstoke: Palgrave, 2013). It puts sex and sexualisation in the spotlight, leads us to reflect on the aesthetic pleasures of teen viewing (Colling, The aesthetic pleasures of girl teen film. New York: London: Bloomsbury. 2017), and speaks to the way teen television expresses “affective dissonances” with regard to ideals of postfeminist girlhood (Dobson and Kanai, From “Can-Do” girls to insecure and angry: affective dissonances in young women’s post-recessional media. Feminist Media Studies 19 (6):771–786, 2018). Drawing on over 80 interviews with girls aged between 14 and 19 from across Italy, this chapter addresses how Italian TV products sit on a continuum of transnational teen media consumption and representations of femininity. The results demonstrate that TV shows such as Baby (2018–2020), SKAM Italia (2018–), and Mare fuori/The Sea Beyond (2020–) provide female adolescents with many different points of temporary attachment within media discourses: they can select and combine different female role models, creating a bricolage of personalities, an identity under construction.</p
Dynamic Sub-Sequence Warping: A representation-based similarity measure for long time series
No full textDynamic time warping (DTW), a typical elastic similarity measure that compares one-to-many points, has been proven effective for various time-series data mining tasks. However, it requires a quadratic time complexity O(n2) proportional to the length of time-series data, which undermines its applications involving long time series. In this paper, a represen?tation-based similarity measure called Dynamic Sub-Sequence Warping (DSSW) is proposed. Instead of working on the raw data directly, we perform data representation to extract the distributional features of time series. Then, the similarity between two time series is measured by aligning the corresponding sub-sequences composed of the extracted features. We evaluate the proposed method through a supervised learning task on extensive real-world datasets. The results show that DSSW outperforms the prevalent DTW-based methods in terms of precision, and achieves one order of magnitude faster execution time on average compared with DTW.</p