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Childhood obesity levels continue to rise, with significant impact on individuals and the NHS. The ‘Complications of Excess Weight’ (CEW) clinics provide support to young people with complications of their weight. Our objective was to co-develop, with young people, a new intervention; AIM2Change, to enable young people to develop their intrinsic motivation to manage weight, using Acceptance and Commitment Therapy (ACT), with a person-centred approach. Young people from the Care of Childhood Obesity (CoCO) clinic in Bristol, UK, were recruited to co-develop this intervention. The study was registered on ISRCTN (ISRCTN16607863). The seven-session, ACT-based intervention was delivered one-to-one, securely online. Qualitative interviews were conducted after each intervention session was delivered. Qualitative data were coded and reviewed regularly to make iterative changes to individual sessions and the overall programme. Fourteen co-developers were recruited, of whom nine completed the co-development process (female = 4; median age (IQR)=15(1.5); 4 with a parent; Indices of Multiple Deprivation (IMD) median = 3.5, range = 1–10). Iterative changes made during co-development included introducing an earlier focus on eating behaviour and body image, with more practical activities to increase engagement. Thematic analysis of co-developer feedback identified four themes: theoretical understanding; delivery and receipt of therapy; view of strategies and engagement; real world benefits of co-development process. Framework analysis was conducted to map data pertaining to these themes into matrices according to each participant and session. Insights from the co-development process have shaped AIM2Change to optimise the intervention’s value, relevance and acceptability. Findings suggest that AIM2Change meets an unmet need in delivery of current childhood weight management services.

Background This paper details the development of the Adolescent Intrinsic Motivation ‘AIM2Change’ intervention to support weight-management in young people previously unable to make changes whilst attending a tier 3 weight management service for children and young people. AIM2Change is an acceptance and commitment therapy based intervention that will be delivered one-to-one online over a seven-week period. Methods To develop this intervention, we have triangulated results from a qualitative research study, patient and public involvement groups (PPI) and a COM-B (capability, opportunity, motivation, behaviour) analysis, in a method informed by the person-based approach. Results The integrated development approach yielded a broad range of perspectives and facilitated the creation of a tailored intervention to meet the needs of the patient group whist remaining pragmatic and deliverable. Conclusions The next steps for this intervention will be in-depth co-development of the therapy sessions with service users, before implementing a proof of concept trial.

The eating habits of children and adults have been impacted by the COVID-19 pandemic, with evidence of increases in snacking and emotional eating, including eating to relieve boredom. We explored the experiences of families with children aged 4-8 years who had recently participated in a healthy eating pilot trial when the first national lockdown began in England. Eleven mothers were interviewed in April and May 2020. Interview questions were developed based on the COM-B model of behaviour. Four main themes were constructed using inductive thematic analysis. The first theme related to an initial panic phase, in which having enough food was the primary concern. The second related to ongoing challenges during the lockdown, with sub-themes including difficulties accessing food, managing children's food requests and balancing home and work responsibilities. The perception that energy-dense foods met families' needs during this time led to increased purchasing of (and thus exposure to) energy-dense foods. In the third theme, families described a turning point, with a desire to eat a healthier diet than they had in the early stages of the lockdown. Finally, in the fourth theme, families reported a number of strategies for adapting and encouraging a balanced diet with their children. Our results suggest that even if parents have the capability (e.g. knowledge) and motivation to provide a healthy diet for their family, opportunity challenges (e.g. time, access to resources, environmental stressors) mean this is not always practical. Healthy eating interventions should not assume parents lack motivation and should be sensitive to the context within which parents make feeding decisions.

A multidisciplinary approach to weight management is offered at tier 3 pediatric weight management services in the United Kingdom. Encouraging dietary change is a major aim, with patients meeting with dieticians, endocrinologists, psychologists, nurse specialists, and social workers on average every other month. This research sought to trial an inhibitory control training smartphone app-FoodT-with the clinic population of a pediatric weight management service. FoodT has shown positive impacts on food choice in adult users, with resulting weight loss. It was hoped that when delivered as an adjunctive treatment alongside the extensive social, medical, psychological, and dietetic interventions already offered at the clinic, the introduction of inhibitory control training may offer patients another tool that supports eating choice. In this feasibility trial, recruitment, retention, and app use were the primary outcomes. An extensive battery of measures was included to test the feasibility and acceptability of these measures for future powered trials. FoodT was offered to pediatric patients and their parents during a routine clinic appointment, and patients were asked to use the app at home every day for the first week and once per week for the rest of the month. Feasibility and acceptability were measured in terms of recruitment, engagement with the app, and retention to the trial. A battery of psychometric tests was given before and after app use to assess the acceptability of collecting data on changes to food choices and experiences that would inform future trial work. A total of 12 children and 10 parents consented (22/62, 35% of those approached). Further, 1 child and no parents achieved the recommended training schedule. No participants completed the posttrial measures. The reasons for not wanting to be recruited to the trial included participants not considering their weight to be connected to eating choices and not feeling that the app suited their needs. No reasons are known for noncompletion. It is unclear whether the intervention itself or the research processes, including the battery of measures, prevented completion. It is therefore difficult to make any decisions as to the value that the app has within this setting. Important lessons have been learned from this research that have potential broad relevance, including the importance of co-designing interventions with service users and avoiding deterring people from early-stage participation in extensive data collection.

This preliminary review was conducted to inform the design of a new service to support families with children with Prader-Willi syndrome (PWS). Families were invited to attend a pilot clinic at a hospital outpatient department, comprising appointments with a multi-disciplinary team (MDT). Following the clinic, families (n=6) were invited to take part in semi-structured qualitative interviews that were audio-recorded, transcribed and analysed using thematic analysis. Families reported that the clinic offered enhanced support in the following categories: integrated care; professional input; signposting to social support (respite and financial); connection with the wider PWS community; and behavioural support. This is the first paper that documents the parental perspective of an MDT clinic for children with PWS. The families felt an MDT clinic was superior to current care, offering more convenient access to an enhanced service, which would provide integrated and consistent care for their children’s diverse, challenging and changing needs.

ObjectiveThis study seeks to understand family’s perceptions of their care at a paediatric weight management service, with a view to informing service improvement.DesignA qualitative service review conducted via semistructured interviews with parents (n=11) and children (n=3) who attended the clinic. The recruitment was open to all, but those who were not succeeding in their weight-loss goals self-selected to participate. Self-Determination Theory was used as a framework to explore families’ experiences of the clinic.SettingRecruitment occurred during clinical appointments and interviews were conducted over the phone in the days following the appointments.PatientsThe service sees paediatric patients with a body mass index >99th percentile, with comorbidities or safeguarding concerns.InterventionsThe clinic’s service includes appointments typically every 2 months, with a multidisciplinary team including consultant endocrinologists, a dietician, a clinical psychologist, a social worker and a clinical nurse specialist.Main outcome measuresFamilies’ feedback on the multi-disciplinary team (MDT) clinic, and their perceptions of how improvements could be made.ResultsFamilies perceive a lack of autonomy, competency and feel a lack of connectivity both in their lives broadly and within their experience at the clinic.ConclusionsInterventions in families struggling with weight improvements should see the clinical team placing more emphasis on working alongside parents to develop young people’s sense of self-determination. Expectations must be set that success originates from changes outside of clinical appointments and that the clinical team is in place to support the family’s development of sustainable, self-determined lifestyle habits.

Childhood obesity levels continue to rise, with significant impact on individuals and the NHS. The 'Complications of Excess Weight' (CEW) clinics provide support to young people with complications of their weight. Our objective was to co-develop, with young people, a new intervention; AIM2Change, to enable young people to develop their intrinsic motivation to manage weight, using Acceptance and Commitment Therapy (ACT), with a person-centred approach. Young people from the Care of Childhood Obesity (CoCO) clinic in Bristol, UK, were recruited to co-develop this intervention. The study was registered on ISRCTN (ISRCTN16607863). The seven-session, ACT-based intervention was delivered one-to-one, securely online. Qualitative interviews were conducted after each intervention session was delivered. Qualitative data were coded and reviewed regularly to make iterative changes to individual sessions and the overall programme. Fourteen co-developers were recruited, of whom nine completed the co-development process (female = 4; median age (IQR)=15(1.5); 4 with a parent; Indices of Multiple Deprivation (IMD) median = 3.5, range = 1-10). Iterative changes made during co-development included introducing an earlier focus on eating behaviour and body image, with more practical activities to increase engagement. Thematic analysis of co-developer feedback identified four themes: theoretical understanding; delivery and receipt of therapy; view of strategies and engagement; real world benefits of co-development process. Framework analysis was conducted to map data pertaining to these themes into matrices according to each participant and session. Insights from the co-development process have shaped AIM2Change to optimise the intervention's value, relevance and acceptability. Findings suggest that AIM2Change meets an unmet need in delivery of current childhood weight management services.

Autosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end stage renal disease characterized by progressive expansion of kidney cysts. To better understand the cell types and states driving ADPKD progression, we analyze eight ADPKD and five healthy human kidney samples, generating single cell multiomic atlas consisting of ~100,000 single nucleus transcriptomes and ~50,000 single nucleus epigenomes. Activation of proinflammatory, profibrotic signaling pathways are driven by proximal tubular cells with a failed repair transcriptomic signature, proinflammatory fibroblasts and collecting duct cells. We identify GPRC5A as a marker for cyst-lining collecting duct cells that exhibits increased transcription factor binding motif availability for NF-κB, TEAD, CREB and retinoic acid receptors. We identify and validate a distal enhancer regulating GPRC5A expression containing these motifs. This single cell multiomic analysis of human ADPKD reveals previously unrecognized cellular heterogeneity and provides a foundation to develop better diagnostic and therapeutic approaches. Autosomal dominant polycystic kidney disease (ADPKD) is a complicated disease that involves numerous cell types. Here the authors used a multiomics approach consisting of single nucleus transcriptomes and epigenomes to redefine cell states in ADPKD and to dissect the cellular interactions and molecular mechanisms of ADPKD.

The need for improved prediction of clinical response is driving the development of cancer models with enhanced physiological relevance. A new concept of ‘precision biomaterials’ is emerging, encompassing patient-mimetic biomaterial models that seek to accurately detect, treat and model cancer by faithfully recapitulating key microenvironmental characteristics. Despite recent advances allowing tissue-mimetic stiffness and molecular composition to be replicated in vitro, approaches for reproducing the 3D fibre architectures found in tumour extracellular matrix (ECM) remain relatively unexplored. Although the precise influences of patient-specific fibre architecture are unclear, we summarize the known roles of tumour fibre architecture, underlining their implications in cell–matrix interactions and ultimately clinical outcome. We then explore the challenges in reproducing tissue-specific 3D fibre architecture(s) in vitro, highlighting relevant biomaterial fabrication techniques and their benefits and limitations. Finally, we discuss imaging and image analysis techniques (focussing on collagen I-optimized approaches) that could hold the key to mapping tumour-specific ECM into high-fidelity biomaterial models. We anticipate that an interdisciplinary approach, combining materials science, cancer research and image analysis, will elucidate the role of 3D fibre architecture in tumour development, leading to the next generation of patient-mimetic models for mechanistic studies and drug discovery. Although there has been increasing interest in developing models that mimic the tumour microenvironment (TME), these models often fail to replicate the complex 3D fibre architectures observed in tumours. Here, Ashworth and Cox address this, discuss the current design and fabrication challenges, and outline state-of-the-art biomaterial technologies useful for recreating tissue-specific 3D architectures in vitro.

Proteolytic processing is an irreversible posttranslational modification affecting a large portion of the proteome. Protease-cleaved mediators frequently exhibit altered activity, and biological pathways are often regulated by proteolytic processing. Many of these mechanisms have not been appreciated as being protease-dependent, and the potential in unraveling a complex new dimension of biological control is increasingly recognized. Proteases are currently believed to act individually or in isolated cascades. However, conclusive but scattered biochemical evidence indicates broader regulation of proteases by protease and inhibitor interactions. Therefore, to systematically study such interactions, we assembled curated protease cleavage and inhibition data into a global, computational representation, termed the protease web. This revealed that proteases pervasively influence the activity of other proteases directly or by cleaving intermediate proteases or protease inhibitors. The protease web spans four classes of proteases and inhibitors and so links both recently and classically described protease groups and cascades, which can no longer be viewed as operating in isolation in vivo. We demonstrated that this observation, termed reachability, is robust to alterations in the data and will only increase in the future as additional data are added. We further show how subnetworks of the web are operational in 23 different tissues reflecting different phenotypes. We applied our network to develop novel insights into biologically relevant protease interactions using cell-specific proteases of the polymorphonuclear leukocyte as a system. Predictions from the protease web on the activity of matrix metalloproteinase 8 (MMP8) and neutrophil elastase being linked by an inactivating cleavage of serpinA1 by MMP8 were validated and explain perplexing Mmp8-/- versus wild-type polymorphonuclear chemokine cleavages in vivo. Our findings supply systematically derived and validated evidence for the existence of the protease web, a network that affects the activity of most proteases and thereby influences the functional state of the proteome and cell activity.