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Does remission of type 2 diabetes matter? A qualitative study of healthcare professionals’ perspectives and views about supporting remission in primary care
Get PDFBackground: Trials conducted in highly-selected populations have shown that type 2 diabetes (T2D) remission is possible, but the feasibility and acceptability of supporting remission in routine clinical practice remains uncertain. Aim: We explored primary care professionals’ perceptions and understandings of T2D remission and their views about supporting remission within routine clinical care.Methods: Semi-structured interviews were conducted with 14 GPs and nine nurses working in Scottish general practices. Data were analysed thematically.Results: Most participants considered remission to be a motivational tool, but were unsure that it actually altered clinical management, due to patients still requiring follow-up, and their expectations that remission is often temporary because of the constant effort required to sustain remission in an obesogenic environment. These perceptions together with participants’ concerns about loss to follow-up of patients who were likely to relapse and/or were still at high cardiovascular risk appeared to underpin a reluctance to code remission in medical records. Most participants did not consider remission support to be a clinical priority. Moreover, they described being sensitive to the pitfalls of only encouraging some patients to pursue remission, because if resources were directed towards apparently more motivated, affluent individuals there was a risk that this could widen health inequalities. Conclusion: For integration of remission support into mainstream T2D care to be successful, primary care professionals may need to be persuaded that remission matters more than encouraging well-managed T2D. They would also benefit from clear guidance on follow-up and optimal support for people in remission. <br/
GABA/Glutamate Neuron Differentiation Imbalance and Increased AKT/mTOR Signaling in CNTNAP2-/- Cerebral Organoids
Get PDFBACKGROUND: The polygenic nature of autism spectrum disorder (ASD) requires the identification of converging genetic pathways during early development to elucidate its complexity and varied manifestations.METHODS: We developed a human cerebral organoid model from induced pluripotent stem cells with targeted genome editing to abolish protein expression of the CNTNAP2 ASD risk gene.RESULTS: CNTNAP2-/- cerebral organoids displayed accelerated cell cycle, ventricular zone disorganization, and increased cortical folding. Proteomic analysis revealed disruptions in glutamatergic/GABAergic (gamma-aminobutyric acidergic) synaptic pathways and neurodevelopment, and transcriptomic analysis revealed differentially expressed genes belonging to inhibitory neuron-related gene networks. Interestingly, there was a weak correlation between the 2 datasets, suggesting nuanced translational control mechanisms. Along these lines, we found upregulated AKT/mTOR (mechanistic target of rapamycin) signaling in CNTNAP2-/- organoids. Spatial transcriptomic analysis of CNTNAP2-/- ventricular-like zones demonstrated pervasive changes in gene expression, implicating upregulation of cell cycle regulation, synaptic, and glutamatergic/GABAergic pathways. We noted significant overlap of all day-30 organoid omics datasets differentially expressed genes from idiopathic ASD (macrocephaly) induced pluripotent stem cell-derived telencephalic organoids, where FOXG1 was upregulated. Moreover, we detected increased GAD1-expressing and decreased TBR1-expressing cells, suggesting altered GABAergic/glutamatergic neuron development.CONCLUSIONS: These findings potentially highlight a shared mechanism in the early cortical development of various forms of ASD, further elucidate the role of CNTNAP2 in ASD pathophysiology and cortical development, and pave the way for targeted therapies that use cerebral organoids as preclinical models.</p
Young adults’ perspectives on sex education at school in Scotland
Get PDFThere is a wealth of evidence on the benefits to young people’s health and academic achievement from timely, good-quality sex education. Conversely, sex education that is poor or too late poses risks to mental and physical health. This small-scale qualitative study set in Scotland used semi-structured questionnaires to ask 48 young adults to reflect on the sex education that they received at school and to consider its usefulness to their lives. Findings reveal that what was taught often came too late to be useful and was covered in insufficient depth by teachers who often seemed awkward or to lack confidence. The narrow heteronormative focus often made LGBT young people feel excluded or stigmatised. There are clear implications for teacher educators, school leaders and policy makers: the need to review how teachers are prepared for their role in sex education and reconsider how the subject is situated within the curriculum and the school timetable. Although often seen as a discrete part of curriculum, sex education is influenced by and builds on what is happening across all learning, and reciprocally, if done well, sex education can enhance the positive relationships necessary for a safe, inclusive learning culture across the whole school
Licensing and Niche Competition in Spermatogenesis: Mathematical Models Suggest Complementary Regulation of Tissue Maintenance
Get PDFTo maintain and regenerate adult tissues after injury, division and differentiation of tissue-resident stem cells must be precisely regulated. It remains elusive which regulatory strategies prevent exhaustion or overgrowth of the stem cell pool, whether there is coordination between multiple mechanisms, and how to detect them from snapshots. In Drosophila testes, somatic stem cells transition to a state that licenses them to differentiate, but remain capable of returning to the niche and resuming cell division. Here, we build stochastic mathematical models for the somatic stem cell population to investigate how licensing contributes to homeostasis. We find that licensing, in combination with differentiation occurring in pairs, is sufficient to maintain homeostasis and prevent stem cell extinction from stochastic fluctuations. Experimental data have shown that stem cells are competing for niche access, and our mathematical models demonstrate that this contributes to the reduction in the variability of stem cell numbers but does not prevent extinction. Hence, a combination of both regulation strategies, licensing with pairwise differentiation and competition for niche access, may be needed to reduce variability and prevent extinction simultaneously.</p
Graveyard Walk
Get PDFEdinburgh's graveyards are rich with social and natural history. The grave robbers may be long gone but the watch towers erected to safeguard bodies from the body snatchers who supplied the medical schools with anatomical material are now watching as other dramas play out between the tombstones. Meanwhile they themselves are crumbling and returning to the earth. Many of Edinburgh's graveyards lie at the hear of the Edinburgh World Heritage Site. They are suffering not only at the hands of weathering and erosion but also from limited resources, anti-social behaviour and a lack of awareness of their value as local green open spaces. Nature however is very much aware of the value of these wonderful oases and this evening walk will hopefully provide participants with a rich and lively graveyard experience. Expect darkness, storytelling and perhaps even an encounter with a fox or owl. Please bring appropriate clothing, sensible walking shoes and a phone torch
Mosquitoes Reared in Nearby Insectaries at the Same Institution Have Significantly Divergent Microbiomes
Get PDFThe microbiome influences critical aspects of mosquito biology and variations in microbial composition can impact the outcomes of laboratory studies. To investigate how biotic and abiotic conditions in an insectary affect the composition of the mosquito microbiome, a single cohort of Aedes aegypti eggs was divided into three batches and transferred to three different climate-controlled insectaries within the Liverpool School of Tropical Medicine. The bacterial microbiome composition was compared as mosquitoes developed, the microbiome of the mosquitoes' food sources was characterised, environmental conditions over time in each insectary were measured, and mosquito development and survival were recorded. While developmental success was similar across all three insectaries, differences in microbiome composition were observed between mosquitoes from each insectary. Environmental conditions and bacterial input via food sources varied between insectaries, potentially contributing to the observed differences in microbiome composition. At both adult and larval stages, specific members of the mosquito microbiome were associated with particular insectaries; the insectary with less stable and cooler conditions resulted in a slower pupation rate and higher diversity of the larval microbiome. These findings underscore that even minor inconsistencies in rearing conditions can affect the composition of the mosquito microbiome, which may influence experimental outcomes.</p
Non-invasive detection method for Bonamia ostreae infected Ostrea edulis
Get PDFPopulations of the native European flat oyster (Ostrea edulis) have been in decline for the past two centuries through a combination of exploitation, disease and climatic events. Ongoing efforts to restore these animals to suitable habitats throughout Europe are increasing in number and magnitude but have been hindered by pathogens such as the protist parasite Bonamia ostreae. Detecting such pathogens in animals before relocation to disease-free restoration or farm sites remains a major issue. Current detection methods rely on sacrificially dissecting a subset of the animals to perform qPCR and histology. While very sensitive, this method is destructive and the animals which are moved are themselves untested. Here, we present a non-invasive scalable method to detect Bonamia ostrea in O. edulis. Following overnight quarantine in aerated seawater, faeces and pseudofaeces produced by the oysters is collected. The DNA is extracted from this material and analysed by qPCR for presence of the pathogen. This approach proves more sensitive for pathogen detection than eDNA sampling from the water alone. Furthermore, when tested alongside conventional histology and tissue-extracted DNA qPCR results, our method demonstrated comparable sensitivity levels. Future studies aim to adapt this method to detecting other aquatic diseases or invasive species but it should be noted that this may be a pathogen-specific characteristic
Quantile regression of tobacco tax pass-through in the UK 2017- 2021: How have manufacturers passed through tax changes for different tobacco products in small retailers? Analysis at the national level and by neighbourhood of deprivation.
Get PDFBackground The effectiveness of tax increases in reducing tobacco consumption relies on the tobacco retailers and producers passing on increases to consumers (tax pass-through). Previous UK research on supermarkets found heterogeneous levels of tax pass-through across the market segments and price distribution of tobacco products. This study uses data from small retailers across the UK to assess whether recent tax changes have been passed on to consumers and if this varies across the price distribution, between countries of the UK and by neighbourhood deprivation.Methods We use panel data quantile regression analysis of tobacco sales in small retailers in the UK from March 2017 to December 2021 combined with UK tax rates and store-level index of multiple deprivation (IMD). We calculated the rate of tax pass-through for factory-made cigarettes (FM) and roll-your-own tobacco (RYO).Results Following increases in the duty payable on tobacco, we find evidence of overshifting across the entire price distribution for FM and RYO. For England, Scotland and Wales, the rate of the overshift in tax increased with product price. For Scotland, we find that stores in the least deprived IMD pass-through taxes at a higher rate.Conclusions Our evidence shows heterogeneous levels of tax pass-through by price, region and level of deprivation. The findings emphasise the importance of understanding the pricing strategies of the tobacco industry (TI) and how these vary across the UK to develop robust approaches to mitigate the pricing strategies of the TI
Predicting the flexural modulus of variable-pitch-angle, porous-Bouligand-structured 3D-printed polymer
Get PDFOur study considered porous Bouligand structured polymer, comprising polymer fibres with porous spaces between them. These are more complicated structures than the non-porous Bouligand, since the addition of porosity into the material creates a secondary variable besides fibre pitch. There is currently no analytical model available to predict the modulus of such materials. Our paper explores the correlation between porosity, polymer fibre pitch angle, and flexural modulus in porous Bouligand structured polymers. Our structures were digitally manufactured using stereolithography (SLA) additive manufacturing methods, after which they were subjected to three-point bending tests. Our aim was to simply and parametrically develop an analytical model that would capture the influences of both porosity and polymer fibre pitch angle on the flexural modulus of the material. Our model is expressed as =(3+2++), and we derive this by applying non-linear regression to our experimental data. This model predicts the flexural modulus, , of porous Bouligand structured polymer as a function of both porosity and pitch angle. Here, is defined as the solid material modulus, , multiplied by porosity, and is a linear reduction in the modulus as a function of increasing porosity, while signifies the polymer fibre pitch angle. This relationship is relatively accurate within the range of 10° ≤ θf ≤ 50°, and for porosity values ranging from 0.277≤0.356, as supported by our evidence to date
Leveraging ancestral recombination graphs for quantitative genetic analysis of rice yield in indica and japonica subspecies
No full textRice (Oryza sativa L.) has two main subspecies, indica and japonica, which coexist in many regions but are often treated separately during breeding. Combining both subspecies in quantitative genetic analyses could enhance genetic improvement, however, this requires appropriately modelling their genetic history. The ancestral recombination graph (ARG) is an effective population genetics tool that comprehensively and succinctly represents a species’ genetic history. This study evaluated the use of an ARG, encoded as a tree sequence, to improve quantitative genetic analyses of indica and japonica rice. Using data from Uruguay’s National Rice Breeding Program, we inferred ancestral alleles, constructed and dated an ARG, and examined its application in genomic prediction and genome-wide association studies. We compared the predictive ability of a branch-based relationship matrix (BRM) built from an ARG against conventional relationship matrices from pedigree and single nucleotide polymorphism (SNP) site data. We then estimated BRM’s SNP site effects to identify potential sites of interest and better understand how these map onto the tree sequence branches. The results showed that the ARG captured key biological signals, encoded genomic data more efficiently than conventional formats, and resulted in the highest predictive ability when combining both subspecies. Although the ARG-based approach did not substantially outperform conventional approaches for between-species prediction, this approach holds promise for plant breeding with larger datasets and could enhance genome-wide association studies by elucidating haplotype ancestry and the evolution of their value. Overall, our results demonstrated the potential of ARGs for the quantitative genetic analysis of diverse populations
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