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We examined the impact of APOE genotype on plasma lipids and glucose in a secondary analysis of data from a five-arm, randomised controlled, parallel dietary intervention trial (‘RISCK’ study), to investigate the impact of replacing saturated fatty acids (SFA) with either monounsaturated fat (MUFA) or carbohydrate of high or low glycaemic index (GI) on CVD risk factors and insulin sensitivity. We tested the impact of APOE genotype (carriage of E2 and E4 alleles versus E3/E3), determined retrospectively, on plasma lipids, lipoproteins and glucose homeostasis at baseline (n = 469), and on the change in these variables after 24 weeks of dietary intervention (n = 389). At baseline, carriers of E2 (n = 70), E4 (n = 125) and E3/E3 (n = 274) expressed marked differences in total plasma cholesterol (TC, p = 0.001), low density lipoprotein cholesterol (LDL-C, p < 0.0001), apolipoprotein B (apo B, p < 0.0001) and total to high density lipoprotein cholesterol ratio (TC:HDL-C, p = 0.002), with plasma concentrations decreasing in the order E4 > E3/E3 > E2. Following intervention, there was evidence of a significant diet x genotype interaction with significantly greater decreases in TC (p = 0.02) and apo B (p = 0.006) among carriers of E4 when SFA was replaced with low GI carbohydrate on a lower fat diet (TC −0.28 mmol/L p = 0.03; apo B −0.1 g/L p = 0.02), and a relative increase in TC (in comparison to E3/E3) when SFA was replaced with MUFA and high GI carbohydrates (TC 0.3 mmol/L, p = 0.03). Among carriers of E2 (compared with E3/E3) there was an increase in triacylglycerol (TAG) when SFA was replaced with MUFA and low GI carbohydrates 0.46 mmol/L p = 0.001). There were no significant interactions between APOE genotype and diet for changes in indices of glucose homeostasis. In conclusion, variations in APOE genotype led to differential effects on the lipid response to the replacement of SFA with MUFA and low GI carbohydrates.

Background The physiotherapy profession has undergone a paradigmatic shift in recent years, where a ‘biopsychosocial’ model of care has acquired popularity in response to mounting research evidence indicating better patient outcomes when used alongside traditional physiotherapy. However, research has not examined how this new dimension to traditional physical therapy is implemented within the therapeutic consultation. Methods The study aimed to investigate physiotherapists’ reported approaches to back pain care in the context of increasing pressure to address patients’ psychosocial concerns. A secondary analysis of semi-structured qualitative interviews with 12 UK physiotherapists was conducted. Respondents were sampled from a national survey, to include a broad mix of physiotherapists. Data were analysed thematically, adopting the constant comparative methodology. Results The combination of traditional physical therapy with a broader biopsychosocial approach presented significant challenges. Physiotherapists responded by attempting to navigate patients’ biopsychosocial problems through use of various strategies, such as setting boundaries around their clinical role and addressing lay health beliefs of patients through the provision of reassurance and lifestyle advice. Conclusions As psychosocial issues, alongside biomechanical factors, command a prominent place within the back pain consultation, physiotherapists may benefit from further specific training and mentoring support in identifying specific strategies for combining the best of traditional physiotherapy approaches with greater focus on patients’ beliefs, fears and social context.

We show that if A ⊂ {1,...,N} contains no nontrivial three-term arithmetic progressions then ∥A∥ = O(N/log 1−o(1) N).

Background Informal caregivers are often expected to support patients transitioning from hospital to home and yet are routinely overlooked in discharge planning. This gap can leave caregivers unprepared and unsupported, contributing to avoidable complications and distress. In response, we co‐designed a personalised discharge planning toolkit to support meaningful conversations between hospital staff and informal caregivers. Methods Using a participatory action research approach, we conducted four co‐design workshops with 22 stakeholders, including informal caregivers, healthcare professionals and voluntary sector representatives. Workshops and analysis were guided by Normalisation Process Theory, the Implementation STakeholder Engagement Model (I‐STEM) and Meleis' Transitions Theory. Data were analysed using reflexive thematic analysis and collaborative synthesis. Findings Stakeholders identified a shared need for a simple, conversation‐based tool that would help caregivers articulate their needs, receive timely information and build confidence in their role. The resulting toolkit comprises five co‐produced tools underpinned by a set of key principles, ranging from early admission resources to post‐discharge supports, all designed to support personalised, caregiver‐inclusive discharge planning. Participants emphasised the importance of respectful dialogue, a named point of contact, and clarity about post‐discharge support. Yet, variation in local infrastructure and workforce capacity remain barriers to implementation. Conclusion A personalised discharge toolkit co‐designed with caregivers and professionals can strengthen transitional care and promote caregiver preparedness. Embedding this prototype into routine hospital practice will require organisational support, digital readiness and sustained attention to equity and inclusion. Patient or Public Contribution This study was co‐produced through a participatory action research (PAR) approach involving individuals with lived experience of caregiving, alongside health and social care professionals and voluntary sector representatives. Informal caregivers actively shaped the design, delivery and iterative development of the personalised discharge planning toolkit across four co‐design workshops. Their insights informed key themes including recognition of caregiver identity, communication challenges and post‐discharge support needs. Caregivers contributed to analysis and interpretation of findings through discussion, feedback and validation during and after workshops, ensuring the toolkit was grounded in real‐world experiences and addressed the complexities of caregiving transitions.

IntroductionPersistent physical symptoms (which cannot be adequately attributed to physical disease) affect around 1 million people (2% of adults) in the UK. They affect patients’ quality of life and account for at least one third of referrals from General Practitioners (GPs) to specialists. These referrals give patients little benefit but have a real cost to health services time and diagnostic resources. The symptoms clinic has been designed to help people make sense of persistent physical symptoms (especially if medical tests have been negative) and to reduce the impact of symptoms on daily life.Methods and analysisThis pragmatic, multicentre, randomised controlled trial will assess the clinical and cost-effectiveness of the symptoms clinic intervention plus usual care compared with usual care alone. Patients were identified through GP searches and mail-outs and recruited by the central research team. 354 participants were recruited and individually randomised (1:1). The primary outcome is the self-reported Physical Health Questionnaire-15 at 52 weeks postrandomisation. Secondary outcome measures include the EuroQol 5 dimension 5 level and healthcare resource use. Outcome measures will also be collected at 13 and 26 weeks postrandomisation. A process evaluation will be conducted including consultation content analysis and interviews with participants and key stakeholders.Ethics and disseminationEthics approval has been obtained via Greater Manchester Central Research Ethics Committee (Reference 18/NW/0422). The results of the trial will be submitted for publication in peer-reviewed journals, presented at relevant conferences and disseminated to trial participants and patient interest groups.Trial registration numberISRCTN57050216.

Follow up from universal vision screening at four to five years has been shown to be low in England, potentially increasing the risk of vision disorders not being treated. This study explores vision specialists' views on the perceived barriers and facilitators encountered when engaging with parents and young children, and the strategies adopted to improve child/parent centred care. Fifteen semi-structured qualitative interviews were conducted with eye care professionals to explore perspectives on the challenges of treating children. Thematic analysis was performed to identify key barriers and the strategies eye care professionals adopt to enhance person-centred eye care when working with young children and their families. Two overarching themes were identified related to the professional-patient relationship. The first reflects the challenges which vision specialists experience when treating children, considering lack of eye health education and negative attitudes to diagnosis and treatment as major barriers. The second discusses the strategies adopted to tackle those barriers. Three strategies are proposed to enhance child-centred eye care: more eye health education, more personalised communication to enhance referral uptake and the development of better coordinated pathways of care between schools, communities and hospital services. Keywords: Child Health, Health Professionals, Screening, eye health care, treatment uptake

Background Changing clinicians' behaviour is recognised as a major challenge. It is clear that behaviour change not only depends on demonstrating the proven effectiveness of clinical interventions; contextual and occupational factors, such as 'change readiness', may be central to their implementation. This paper highlights the context of behaviour change in relation to a healthcare innovation introduced within primary care, highlighting the importance of organisational and interpersonal factors that may help explain the dynamics of implementation. Methods Qualitative interviews were conducted with general practitioners (GPs) before (n = 32) and after (n = 9) the introduction of a subgrouping for targeted treatment system. GPs were offered an electronic six-item subgrouping tool, to identify patients according to their risk of poor outcome ('high', 'low') in order to help inform their decision making about treatment approaches. Recruitment was based on a 'maximum diversification sample', to obtain a wide representation of views across all five practices. A coding scheme was developed based on the emergent findings, and the data were analysed using 'constant comparison', drawing upon insights and developing connections between themes. We adopted the normalisation process theory (NPT) to explain the uptake of the new system and to examine the relevance of coherence for the implementation of innovations in organisations. Results GPs perceived back pain as a low clinical priority, and highlighted the importance of 'practical' and 'relational' coherence in decisions to adopt and engage with the new subgrouping for targeted treatment system. Health professionals often engage in 'sense making' about new innovations to 'road test' their applicability or relevance to daily clinical routines. Low back pain was generally perceived as an 'uninteresting' and clinically unchallenging health problem by GPs, which may partly explain their lack of engagement with the new subgrouping for targeted treatment system. The adoption of this new way of working by GPs was determined by the meaning that they ascribed to it in the context of their daily clinical routines. Conclusions We conclude that the key obstacle to implementation of the new subgrouping for targeted treatment system for low back pain in primary care was an initial failure to achieve 'coherence' of the desired practice change with GPs. Despite this, GPs used the tool to different degrees, though this signified a general commitment to participating in the study rather than a deeper attitude change towards the new system.

Suppose that A is a k × d matrix of integers and write $\\Re _A:{\\mathbb N}\\to {\\mathbb N}\\cup \\{ \\infty \\} $ for the function taking r to the largest N such that there is an r-colouring $\\mathcal {C}$ of [N] with $\\bigcup _{C \\in \\mathcal {C}}{C^d}\\cap \\ker A =\\emptyset $. We show that if ℜA(r) < ∞ for all $r\\in {\\mathbb N}$ then $\\mathfrak {R}_A(r) \\leqslant \\exp (\\exp (r^{O_{A}(1)}))$ for all r ⩾ 2. When the kernel of A consists only of Brauer configurations – that is, vectors of the form (y, x, x + y, …, x + (d − 2)y) – the above statement has been proved by Chapman and Prendiville with good bounds on the OA(1) term.

We show that there is an absolute $c>0$ such that if $A$ is a finite set of integers, then there is a set $S\\subset A$ of size at least $\\log ^{1+c}|A|$ such that the restricted sumset $\\{s+s^{\\prime }:s,s^{\\prime }\\in S\\text{ and }s\\neq s^{\\prime }\\}$ is disjoint from $A$. (The logarithm here is to base $3$.)

A conventional understanding of perception assigns sensory organs the role of capturing the environment. Better sensors result in more accurate encoding of stimuli, allowing for cognitive processing downstream. Here we show that plasticity in sensory neurons mediates a behavioral switch in C. elegans between attraction to NaCl in naïve animals and avoidance of NaCl in preconditioned animals, called gustatory plasticity. Ca2+ imaging in ASE and ASH NaCl sensing neurons reveals multiple cell-autonomous and distributed circuit adaptation mechanisms. A computational model quantitatively accounts for observed behaviors and reveals roles for sensory neurons in the control and modulation of motor behaviors, decision making and navigational strategy. Sensory adaptation dynamically alters the encoding of the environment. Rather than encoding the stimulus directly, therefore, we propose that these C. elegans sensors dynamically encode a context-dependent value of the stimulus. Our results demonstrate how adaptive sensory computation can directly control an animal’s behavioral state.Martijn Dekkers and Felix Salfelder et al. combine experimental approaches and mathematical modeling to determine the contribution of the two main NaCl sensory neurons (termed ASEL and ASER) and the nociceptive neurons (termed ASH) in C. elegans to the context-dependent switching between NaCl attraction and avoidance. Their results show that regulated sensitivity of these sensory neurons to NaCl allows the animal to dynamically modulate its behavioral response and suggest a role for sensory modulation in balancing exploration and exploitation during foraging.