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You’re not speaking my language: policy discontinuity and coordination gaps between the UK’s national economic strategies and its place-based policies
Full text linkLack of consistency and coordination has long been noted as a failing of UK government policies but it has previously been difficult to assess the extent of the policy discontinuity. We present evidence from text analysis of a startling lack of coordination in Government policy with a special focus on the Levelling Up White Paper, the Conservative Government’s flagship policy statement to address spatial inequalities, and its other recent national economic policy documents. We confirm this linguistic discontinuity by analysing the context of statements about innovation policies from the Plan for Growth and Innovation Strategy with those in the Levelling Up White Paper. ‘Joined-up government’ is as far away as ever in the UK, in the context of the systemic challenges of spatial economic inequality
The orphan receptor GPR88 controls impulsivity and is a risk factor for Attention-Deficit/Hyperactivity Disorder.
Full text linkThe neural orphan G protein coupled receptor GPR88 is predominant in the striatum and cortex of both rodents and humans, and considered a potential target for brain disorders. Previous studies have shown multiple behavioral phenotypes in Gpr88 knockout mice, and human genetic studies have reported association with psychosis. Here we tested the possibility that GPR88 contributes to Attention Deficit Hyperactivity Disorder (ADHD). In the mouse, we tested Gpr88 knockout mice in three behavioral paradigms, best translatable between rodents and humans, and found higher motor impulsivity and reduced attention together with the reported hyperactivity. Atomoxetine, a typical ADHD drug, reduced impulsivity in mutant mice. Conditional Gpr88 knockout mice in either D1R-type or D2R-type medium spiny neurons revealed distinct implications of the two receptor populations in waiting and stopping impulsivity. Thus, animal data demonstrate that deficient GPR88 activity causally promotes ADHD-like behaviors, and identify circuit mechanisms underlying GPR88-regulated impulsivity. In humans, we performed a family-based genetic study including 567 nuclear families with DSM-IV diagnosis of ADHD. There was a minor association for SNP rs2036212 with diagnosis, treatment response and cognition. A stronger association was found for SNP rs2809817 upon patient stratification, suggesting that the T allele is a risk factor when prenatal stress is involved. Human data therefore identify GPR88 variants associated with the disease, and highlight a potential role of life trajectories to modulate GPR88 function. Overall, animal and human data concur to suggest that GPR88 signaling should be considered a key factor for diagnostic and treatment of ADHD
Apoyando las socio-bioeconomías de bosques en pie y ríos que fluyen saludables en la Amazonía
Full text linkPrinciples of practice for a whole school approach to self-harm: a qualitative study.
Full text linkBACKGROUND: Self-harm is common among adolescents and recognised as a significant public health issue. This study aimed to explore the perspectives of young people and school staff about how schools should respond to self-harm and subsequently develop principles of practice. METHODS: Seven focus groups were carried out with school staff and young people. Qualitative data were thematically analysed using the Framework Method to generate themes [1, 2]. The findings were translated into actionable items by applying the Implementation in Schools Framework [3]. RESULTS: Staff and students had overlapping views about how schools should address self-harm. These were captured in three themes (1) Understanding the nature and scope of self-harm in schools, (2) Building whole school capacity to respond to self-harm, (3) Creating a supportive school environment. Principles of practice were generated to guide schools in their approach to self-harm. CONCLUSION: For many young people, schools are a key setting for early intervention in self-harm; however, staff often feel ill-equipped to respond and clear guidance is lacking. This study has developed evidence-informed principles of practice for UK schools, drawing on the perspectives of staff and young people to inform a whole school approach. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-025-25538-3
Propagation and topology in turbulent premixed flames
Full text linkIn this work, the phenomenon of self-interaction in turbulent premixed flames is investigated. This refers to the self-intersection of a highly curved flame iso-surface, which leads to local annihilation at the point of intersection as the enveloped mixture is depleted. With a rise in turbulence intensity, the frequency of self-interaction greatly increases, while at the same time, the increase in turbulent flame speed becomes non-linear and is inhibited (known as self-inhibition). Accordingly, these interactions provide a plausible mechanism for the rapid destruction of flame surface area, especially at high turbulence intensities. By analysing their dynamics, self-interactions are investigated as a potential cause for self-inhibition of turbulent flame speed.
First, a direct numerical simulation dataset is produced with methane-air as the reactant mixture burning in the thin reaction zone regime. Here, preliminary break-up (through self-interaction) of the reaction zone is seen with increasing turbulence intensity, as the flame speed is simultaneously inhibited. Critical points in the reaction progress field - where the scalar gradient becomes zero as a result of annihilation - are then used to establish self-interactions, while the local Hessian informs the topology of self-interaction. In total, four geometric types of interactions are identified, namely, reactant pocket, reactant tunnel, product tunnel, and product pocket - such that the former two locally enclose reactants, while the latter two envelop products. Each topology may further be formed through normal interaction (displacement along the normal), or conversely, counter-normal interaction (displacement against the normal), thus resulting in eight total types.
Following, the dynamics of self-interaction in a turbulent premixed flame is examined. Out of the eight total types, six interactions are found to occur more frequently. In general, both types of pockets tend to propagate towards the centre, whereas the two tunnels can interact in either normal or counter-normal fashion. Local stretch rate profiles - that closely follow curvature in the vicinity of self-interaction - show that the process of pocket formation is locally destructive to flame surface area. In particular, the appearance of reactant pockets is only associated with local area destruction unlike any other configuration. The mechanisms that govern this area change for each topology are also highlighted.
Finally, the change in structure and morphology of the global flame surface is addressed in light of local topologies. For a given intensity, a relative increase in the number of both reactant-enclosing topologies coincides with a globally destructive area balance. Here too, the uniquely inhibitive nature of reactant pocket formation is evident. Lastly, by examining reaction zone interactions, which increasingly favour destruction at higher intensities, the correlation between self-inhibition and self-interaction is established. Further implications of these findings for complex hydrogen-enriched flames are also discussed briefly as ongoing work. In this manner, novel insights into the propagation characteristics of turbulent premixed flames subject to self-interaction are provided in this thesis
Strategies for automatic generation of information processing pathway maps.
Full text linkInformation Processing Pathway Maps (IPPMs) are a concise way to represent the evidence for the transformation of information as it travels around the brain. However, their construction currently relies on hand-drawn maps from electrophysical recordings such as magnetoencephalography (MEG) and electroencephalography (EEG). This is both inefficient and contains an element of subjectivity. A better approach would be to automatically generate IPPMs from the data and objectively evaluate their accuracy. In this work, we propose a range of possible strategies and compare them to select the best. To this end, we (a) provide a test dataset against which automatic IPPM creation procedures can be evaluated; (b) suggest two novel evaluation metrics-causality violation and transform recall-from which these proposed procedures can be evaluated; (c) conduct a simulation study to evaluate how well ground-truth IPPMs can be recovered using the automatic procedure; and (d) propose and evaluate a selection of different IPPM creation procedures. Our results suggest that the max pooling approach gives the best results on these metrics. We conclude with a discussion of the limitations of this framework, and possible future directions
The influence of age and the presence of prostate cancer on prostate volume, PSA and PSA density.
No full textOBJECTIVE: To assess prostate volume (PV) changes with age in symptomatic and asymptomatic men with and without clinically significant prostate cancer (csPCa). In symptomatic patients, we additionally analysed the effect of age and csPCa on PSA and PSA-density (PSA-D) and compared these to current National Institute for Health and Care Excellence (NICE) recommended PSA age-range thresholds. Patients and Methods This single-centre retrospective cross-sectional study included 2512 men: 760 asymptomatic, disease-free men and 1752 patients referred on a PCa diagnostic pathway. Magnetic resonance imaging-derived whole-gland PV was recorded for all patients. A machine-learning pipeline with k-fold cross validation modelled relationships between PV and age. RESULTS: In asymptomatic men (median PV 25.4 mL), the mean PV per age-group increased non-linearly with age, from 18.7 mL at an increase of 0.10 mL/year aged 18 years, to 41.3 mL at 0.68 mL/year aged 89 years, with increased rate of change from the age of 48.9 years. Significant positive relationships were shown between PSA and age in patients with and without csPCa (r2 = 0.09 vs 0.13, respectively), with PSA increasing by mean 0.17 ng/mL/year across groups. Patients with csPCa had consistently higher PSA levels. PSA-D showed significant age-related linear increases in patients with csPCa but remained consistently lower in those without csPCa at all ages (0.10-0.11 ng/mL2), allowing differentiation at a threshold of >0.15 ng/mL2. CONCLUSION: In asymptomatic men, PV changed non-linearly with age. Age-related PSA thresholds are supported; however, a static PSA-D threshold of 0.15 ng/mL2 can be applied across all age ranges
PPIE in clinical trials at scale: analysis of the first 3,250 responses on the POrtal for Patient and Public Engagement in Dementia (POPPED)
No full textINTRODUCTION: Patient and public involvement and engagement (PPIE) improves research quality but is often limited in scale. This study explored the potential for large-scale PPIE using a web-based approach.
METHODS: We created an online portal to gather public views on dementia research and a UK-based adaptive platform trial testing repurposed Alzheimer’s disease drugs. Participants ranked four anonymized drugs and completed discrete choice experiments on treatment trade-offs. Analyses were stratified by sex, age, and dementia experience.
RESULTS: Among 3,250 people across 27 countries (87.4% UK-based), 79.6% expressed positive attitudes toward the trial. Metformin was the most preferred drug, followed by Atomoxetine, Isosorbide Mononitrate, and Levetiracetam. Probability of severe side effects was the most influential treatment attribute, followed by probability of mild side effects and type of evidence. Subgroup analyses supported the main findings.
DISCUSSION: Web-based PPIE can effectively inform dementia research at scale and provides a reusable resource for other studies
The socioeconomic patterning of Great Britain's fast-food outlets and supermarkets: A repeated cross-sectional study of area-level deprivation and food outlet density from 2011 to 2024.
No full textAlthough previous research has demonstrated socioeconomic differences in the distribution of food outlets, no study to date has examined these patterns across the entire territory of Great Britain (GB) over time. This study provides an up-to-date repeated cross-sectional analysis into distributional changes in GB's fast-food outlets and supermarkets from 2011 to 2024 and its socioeconomic distribution. In this study, coordinates of all fast-food outlets and supermarkets in GB from the Ordnance Survey Points-of-Interest data were used to calculate outlet densities within small areas, adjusted by yearly population estimates and linked to Index of Multiple Deprivation measures. Counts of the different food outlets were combined in the modified Retail Food Environment Index (mRFEI). Multi-level linear regression and beta-regression models were used to assess associations between deprivation and fast-food outlet density, supermarket density and mRFEI). Results show that in GB, fast-food outlet density increased by 36 %, supermarket density increased by 17 % and mRFEI decreased by 5 % from 2011 to 2024. More deprived areas were associated with greater fast-food outlet density and lower mRFEI in all years compared to less deprived areas; the gap in fast-food outlet density between the most and least deprived areas widened by 28 % from 2011 to 2024. There were no statistically significant trends in supermarket density by area-level deprivation. Our findings indicate that higher densities of fast-food outlets in more deprived areas are not compensated for by a similar higher density of supermarkets. This imbalance may be limiting healthier dietary choices for residents in these areas. Given the links between food outlet exposure and dietary behaviours in GB, policies aiming to improve dietary outcomes should prioritise more deprived areas, thereby contributing to the reduction of socioeconomic inequalities in the retail food environment, diet, and health outcomes
Measurement of the top-quark Yukawa coupling from production in the lepton+jets final state using pp collisions at TeV with the ATLAS detector
No full text
A
bstract
The top-quark Yukawa coupling is extracted from the distribution of the top-quark pair (
t
t
¯
) invariant mass in proton-proton collisions using 140 fb
−
1
of data at
s
=
13
TeV collected in 2015–2018 by the ATLAS experiment at the Large Hadron Collider. In the region near the production threshold, the
t
t
¯
invariant mass spectrum is sensitive to electroweak virtual corrections, including contributions from Higgs boson exchange, thereby providing sensitivity to the top-quark Yukawa coupling. This is the first measurement in ATLAS that aims to obtain this coupling exploiting this approach. The
t
t
¯
system is reconstructed in the single-lepton final state, requiring exactly one isolated electron or muon and at least four jets with at least two identified as originating from
b
-quarks. The measured Yukawa coupling is found to be in good agreement with the Standard Model prediction. An upper limit on the top-quark Yukawa coupling strength of
Y
t
<
2
.
1 relative to the Standard Model prediction is observed at 95% confidence level, consistent with the expected sensitivity.
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