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Background Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings. Methods We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110. Findings 41 344 children were vaccinated in April–May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, pInterpretation Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses. Funding The study was funded by the Bill & Melinda Gates Foundation.

Background A significant proportion of children and young people with juvenile idiopathic arthritis (JIA) do not achieve inactive disease during the first two years following diagnosis. Refinements to clinical care pathways have the potential to improve clinical outcomes but a lack of consistent and contemporaneous clinical data presently precludes standard setting and implementation of meaningful quality improvement programmes. This study was the first to pilot clinical data collection and analysis using the CAPTURE-JIA dataset, and to explore patient and clinician-reported feasibility and acceptability data. Methods A multiphase mixed-methods approach enabled prospective collection of quantitative data to examine the feasibility and efficacy of dataset collection and of qualitative data informing the context and processes of implementation. An initial paper pilot informed the design of a bespoke electronic data collection system (the Agileware system), with a subsequent electronic pilot informing the final CAPTURE-JIA data collection tool. Results Paper collection of patient data was feasible but time-consuming in the clinical setting. Phase 1 paper pilot data (121 patients) identified three themes: problematic data items (14/62 data items received >40% missing data), formatting of data collection forms and a clinician-highlighted need for digital data collection, informing Phase 2 electronic data collection tool development. Patients and families were universally supportive of the collection and analysis of anonymised patient data to inform clinical care. No apparent preference for paper / electronic data collection was reported by families. Phase 3 electronic pilot data (38 patients) appeared complete and the system reported to be easy to use. Analysis of the study dataset and a dummy longitudinal dataset confirmed that all eleven JIA national audit questions can be answered using the electronic system. Conclusions Multicentre CAPTURE-JIA data collection is feasible and acceptable, with a bespoke data collection system highlighted as the most satisfactory solution. The study is informing ongoing work towards a streamlined and flexible national paediatric data collection system to drive quality improvement in clinical care.

Background Paediatric rheumatic diseases are a leading cause of acquired disability in Southeast Asia and Asia-Pacific Countries (SE ASIA/ASIAPAC). The aims of this study were to identify and describe the challenges to the delivery of patient care and identify solutions to raise awareness about paediatric rheumatic diseases. Methods The anonymised online survey included 27 items about paediatric rheumatology (PR) clinical care and training programmes. The survey was piloted and then distributed via Survey-Monkey™ between March and July 2019. It was sent to existing group lists of physicians and allied health professionals (AHPs), who were involved in the care pathways and management of children with rheumatic diseases in SE ASIA/ASIAPAC. Results Of 340 participants from 14 countries, 261 participants had been involved in PR care. The majority of the participants were general paediatricians. The main reported barriers to providing specialised multidisciplinary service were the absence or inadequacy of the provision of specialists and AHPs in addition to financial issues. Access to medicines was variable and financial constraints cited as the major obstacle to accessing biological drugs within clinical settings. The lack of a critical mass of specialist paediatric rheumatologists was the main perceived barrier to PR training. Conclusions There are multiple challenges to PR services in SE ASIA/ASIAPAC countries. There is need for more specialist multidisciplinary services and greater access to medicines and biological therapies. The lack of specialist paediatric rheumatologists is the main barrier for greater access to PR training.

As lecturers involved in teacher training and childhood studies, we are interested in the impact that children can have on their school lives and believe that it is often underestimated. Approximat...

Background Typhoid fever is a major public health problem in low-resource settings. Vaccination can help curb the disease and might reduce transmission. We have previously reported an interim analysis of the efficacy of typhoid conjugate vaccine (TCV) in Nepali children. Here we report the final results after 2 years of follow-up. Methods We did a participant-masked and observer-masked individually randomised trial in Lalitpur, Nepal, in which 20 019 children aged 9 months to younger than 16 years were randomly assigned in a 1:1 ratio to receive a single dose of TCV (Typbar TCV, Bharat Biotech International, India) or capsular group A meningococcal conjugate vaccine (MenA). Participants were followed up until April 9, 2020. The primary outcome was blood culture-confirmed typhoid fever. Cases were captured via passive surveillance and active telephone surveillance followed by medical record review. The trial is registered at ISRCTN registry, ISRCTN43385161 and is ongoing. Findings From Nov 20, 2017, to April 9, 2018, of 20 119 children screened, 20 019 participants were randomly assigned to receive TCV or MenA vaccine. There were 75 cases of blood culture-confirmed typhoid fever included in the analysis (13 in the TCV group and 62 in the MenA group) over the 2-year period. The protective efficacy of TCV against blood culture-confirmed typhoid fever at 2 years was 79·0% (95% CI 61·9–88·5; p Interpretation The final results of this randomised, controlled trial are in keeping with the results of our published interim analysis. There is no evidence of waning protection over a 2-year period. These findings add further support for the WHO recommendations on control of enteric fever. Funding Bill & Melinda Gates Foundation.

BACKGROUNDParkinson’s disease is the second most common neurodegenerative condition and associated with increasing cognitive dysfunction as the disease progresses. However, subtle cognitive deficits can be detected at diagnosis in 42% of individuals, suggesting that damage may already be present. Our aim was to determine clinical and structural differences in those recently diagnosed with PD who later develop cognitive impairment, and whether these changes predict future cognitive decline.METHODSClinical and imaging data was acquired from the Parkinson’s Progression Markers Initiative for 318 individuals with a diagnosis of Parkinson’s disease and baseline 3T T1-weighted MRI. The cohort was divided according to cognitive status over follow-up, with 9 individuals developing Parkinson’s disease dementia, 102 developing mild cognitive impairment and 207 remaining cognitively unaffected.FINDINGSAt baseline, those who went on to develop cognitive impairment (mild cognitive impairment or dementia) wereolder with more severe motor and non-motor symptoms (anosmia, rapid eye movement sleep behaviour disorder, depression). Grey matter loss was present in those destined for Parkinson’s disease dementia in theprecuneus, hippocampi, primary olfactory cortex, lingual gyrus, temporal cortex and cerebellum. Those who later developed mild cognitive impairment had an attenuated but similar pattern ofgrey matter loss in the temporal lobe, lingual gyrus and cerebellum. Using support vector machines with a feature selection step, future cognitive impairment could be predicted using 11 clinical variables (AUC = 0.81), structural imaging (AUC = 0.72) or a combination of these two modalities (AUC = 0.85). These models more accurately predicted those who developed dementia (subgroup sensitivity 100%).INTERPRETATIONSignificant abnormalities in cortical structure is present at least three years before dementia manifests in Parkinson’s disease, with associated differences in clinical profiles. Combining this data provides a technique to accurately identify future cognitive impairment, providing a non-invasive way to stratify individuals early on.

Background The PMM Portfolio is comprised of the Paediatric Musculoskeletal Matters (PMM) website, the paediatric Gait, Arms, Legs and Spine (pGALS) app and e-learning modules (ELM). The target audiences are non-specialists in paediatric musculoskeletal medicine. Our study aimed to evaluate impact on learning and clinical practice. Methods Mixed methods (analytics, online survey, interviews) were used with PMM and ELM registered users and purposive sampling of users using international contacts within paediatrics and paediatric rheumatology. Data was analysed using descriptive statistics and qualitative techniques. A Paired T-Test compared self-rated confidence before and after use of the PMM Portfolio. Results There has been wide reach for all the e-resources; PMM website (662,827 hits, 262,476 users, 214 countries, data 31st July 2020); pGALS app (12,670 downloads, 70 countries, data 31st July 2020); ELM (150 users, 30 countries, data 30th May 2019). There were 164 responses (students, trainees and health care professionals) to the survey from 25 countries. Most responders deemed the PMM Portfolio useful / very useful for their learning with significantly increased self-rated confidence in their clinical examination and reasoning skills following access to the PMM website, p = p = p = Conclusions The PMM Portfolio was developed to aid learning for clinicians who are not specialists in paediatric MSK medicine. Our evaluation demonstrates wide international reach and positive feedback on learning. The PMM Portfolio is a highly useful e-resource for paediatric rheumatologists in their teaching of others to raise awareness, facilitate early diagnosis and referral of children with suspected disease. The wide user engagement informed future PMM Portfolio development and the mixed method of evaluation is transferable to other e-resources.

The success of immunosuppressive therapies to preserve pancreatic islets and treat Type 1 Diabetes (T1D) has, so far, been limited either due to safety concerns or lack of persistent efficacy. Restricting T cell suppression to the pancreas, thereby avoiding systemic immunosuppression, may overcome these issues and is thus an attractive option for T1D. One possible approach to inhibit the destruction of pancreatic β-cells in T1D is to activate the PD-1 receptor on autoreactive T cells only when they enter in the pancreas. The PD-1 pathway is a key immune checkpoint that limits T cell responses and helps to maintain peripheral tolerance. Blocking this pathway in cancer patients has been shown to cause diabetes-like symptoms. Therefore, stimulating PD-1 to inhibit autoreactive T cells and treat this disease is an appealing concept. To create β-cell-restricted inhibitors of autoreactive T cells, we designed targeted PD-1 agonist bispecific molecules that contain a high affinity TCR specific for a pHLA complex expressed on the surface of pancreatic β-cells. We show that these bispecific molecules bind specifically to immortalized β-cell lines and primary β-cells from disaggregated pancreatic islets. Once bound to target pHLA, these bispecifics engage PD-1 on attacking T cells and inhibit TCR signaling resulting in potent inhibition of T cell effector functions. At picomolar concentrations, these bispecifics suppress secretion of inflammatory cytokines from cytotoxic T cells and inhibit β-cell killing by autoreactive CD8+ T cells. Importantly, these PD-1 agonists are unable to inhibit T cells when free in solution and not bound to target cells. Hence, these immune modulating bispecifics have the potential to limit autoimmunity in pancreatic islets while avoiding systemic immunosuppression. These features make them an attractive and novel platform to treat T1D. Disclosure G. Bossi: Employee; Self; Immunocore Limited. V. Gonzalez: None. C. M. Lucato: None. K. Page: None. N. Smith: Employee; Self; Immunocore Limited. L. Whaley: Employee; Self; Immunocore Limited. H. Ghadbane: Employee; Self; Immunocore Ltd. D. Knight: Employee; Self; Immunocore Limited. E. Henderson: Employee; Self; Immunocore Ltd. S. Hearty: Employee; Self; Immunocore Limited. T. Mahon: None. A. P. Curnock: Employee; Self; Immunocore Ltd. P. Weber: Employee; Self; Immunocore Ltd., Stock/Shareholder; Self; Vertex Pharmaceuticals Incorporated. P. Weber: Employee; Self; Immunocore Ltd., Stock/Shareholder; Self; Vertex Pharmaceuticals Incorporated. J. Kumaran: None. L. J. Bawden: Employee; Self; Immunocore Ltd. R. Figueiredo: None. K. E. Wiseman: None. R. O’dwyer: Employee; Self; Immunocore ltd. D. Overton: None.

Hypertrophic cardiomyopathy (HCM) is common, inherited and characterised by unexplained thickening of the myocardium. The British Society of Echocardiography (BSE) has recently published a minimum dataset for transthoracic echocardiography detailing the core views needed for a standard echocardiogram. For patients with confirmed or suspected HCM, additional views and measurements are necessary. This guideline, therefore, supplements the minimum dataset and describes a tailored, stepwise approach to the echocardiographic examination, and echocardiography's position in the diagnostic pathway, before advising on the imaging of disease complications and invasive treatments.

Objectives Data collected during routine clinic visits are key to driving successful quality improvement in clinical services and enabling integration of research into routine care. The purpose of this study was to develop a standardized core dataset for juvenile idiopathic arthritis (JIA) (termed CAPTURE-JIA), enabling routine clinical collection of research-quality patient data useful to all relevant stakeholder groups (clinicians, service-providers, researchers, health service planners and patients/families) and including outcomes of relevance to patients/families. Methods Collaborative consensus-based approaches (including Delphi and World Café methodologies) were employed. The study was divided into discrete phases, including collaborative working with other groups developing relevant core datasets and a two-stage Delphi process, with the aim of rationalizing the initially long data item list to a clinically feasible size. Results The initial stage of the process identified collection of 297 discrete data items by one or more of fifteen NHS paediatric rheumatology centres. Following the two-stage Delphi process, culminating in a consensus workshop (May 2015), the final approved CAPTURE-JIA dataset consists of 62 discrete and defined clinical data items including novel JIA-specific patient-reported outcome and experience measures. Conclusions CAPTURE-JIA is the first ‘JIA core dataset’ to include data items considered essential by key stakeholder groups engaged with leading and improving the clinical care of children and young people with JIA. Collecting essential patient information in a standard way is a major step towards improving the quality and consistency of clinical services, facilitating collaborative and effective working, benchmarking clinical services against quality indicators and aligning treatment strategies and clinical research opportunities.

Typhoid fever is estimated to affect over 20 million people per year worldwide, with infants, children, and adolescents in south-central and southeast Asia experiencing the greatest burden of disease. The Typhoid Vaccine Acceleration Consortium (TyVAC) aims to support the introduction of typhoid conjugate vaccines into Gavi-eligible countries in an effort to reduce morbidity and mortality from typhoid. TyVAC-Nepal is a large-scale, participant- and observer-blind, individually randomized, controlled trial evaluating the efficacy of a newly developed typhoid conjugate vaccine in an urban setting in Nepal. In order to effectively deliver the trial, a number of key elements required meticulous planning. Public engagement strategies were considered early, and involved the implementation of a tiered approach. Approximately 300 staff were employed and trained in order to achieve the mass vaccination of 20 000 children aged 9 months to ≤16 years old over a 4-month period. There were 19 vaccination clinics established across the Lalitpur metropolitan city in the Kathmandu valley. Participants will be followed for 2 years post-vaccination to measure the rate reduction of blood culture–confirmed typhoid fever in the vaccination arm as compared to the control arm. The experience of conducting this large-scale vaccine trial suggests that comprehensive planning, continuous monitoring, and an ability to adapt plans in response to feedback are key.

Background Enteric fever is estimated to affect 11–20 million people worldwide each year. Morbidity and mortality from enteric fever primarily occur in lower-income countries, with children under 5 years of age experiencing a significant portion of the burden. Over the last few decades, the control of enteric fever has focused primarily on improved water and sanitation, with the available vaccines unsuitable for children and primarily used by travelers. A new typhoid conjugate vaccine (Vi-TCV), prequalified by the World Health Organization (WHO) and highly immunogenic in children under 5, has the potential to reduce the typhoid burden in endemic countries. Methods This study is a double-blinded, randomized, controlled trial with a 2-year follow-up to assess the protective impact of the Vi-TCV vaccine, compared with a control vaccine, in children from 9 months to 16 years of age. The primary outcome of interest is the reduction in the number of culture-confirmed typhoid cases attributable to Vi-TCV. Approximately 20 000 children living in the Lalitpur district, within the Kathmandu valley, will be enrolled in the study and followed to measure both safety and efficacy data, which will include adverse events, hospitalizations, antibiotic use, and fever frequency. Results Both the intervention and control vaccines are WHO prequalified vaccines, which provide a health benefit to all participants. Children have been chosen to participate because they bear a substantial burden of both typhoid morbidity and mortality in this population. The results of this study will be disseminated through a series of published articles. The findings will also be made available to the participants and the broader community, as well as local stakeholders, within Nepal. Conclusions This is the first large-scale, individually randomized, controlled trial of Vi-TCV in children in an endemic setting, and will provide new data on Vi-TCV field efficacy. With Vi-TCV introduction being considered in high-burden countries, this study will support important policy decisions. Clinical Trials Registration The trial is registered on the ISRCTN registry (for details, see https://doi.org/10.1186/ISRCTN43385161; registry number: ISRCTN 43385161).

Background Many children and young people with juvenile idiopathic arthritis (JIA) experience delay in diagnosis and access to right care. The reasons for delay are multi-factorial and influenced by patient and family, clinician and organisational factors. Our aim was to explore the experiences of care, from initial symptoms to initial referral to paediatric rheumatology. Methods We analysed one-to-one and joint qualitative interviews with families of children with JIA (n = 36) presenting to a regional paediatric rheumatology service in the UK. We interviewed 51 family members (including mothers, fathers, patients, grandmothers and an aunt) and 10 health professionals (including orthopaedic surgeons, paediatricians, paediatric immunologist, General Practitioner and nurse) and a teacher involved in the care pathway of these JIA patients. Interviews were audio-recorded and analysed according to the standard procedures of rigorous qualitative analysis - coding, constant comparison, memoing and deviant case analysis. Results The median age of the children was 6 years old (range 1–17), with a spread of JIA subtypes. The median reported time to first PRh MDT visit from symptom onset was 22 weeks (range 4-364 weeks). Three key factors emerged in the pathways to appropriate care: (i) the persistence of symptoms (e.g. ‘change’ such as limp or avoidance of previously enjoyed activities); (ii) the persistence of parents help-seeking actions (e.g. repeat visits to primary and hospital care with concern that their child is not ‘normal’; iii) the experience and skills of health professionals resulting in different trajectories (e.g. no-real-concern-at-this-point or further-investigation-is-required). JIA was more likely to be considered amongst health practitioner if they had prior experiences of a child with JIA (moreso with a ‘protracted pathway’) or exposure to paediatric rheumatology in their training. Conversely JIA was more likely to be overlooked if the child had comorbidity such as learning disability or a chronic illness. Conclusions Care pathways are often ‘turbulent’ prior to a diagnosis of JIA with physical and emotional distress for families. There is need for greater awareness about JIA amongst health care professionals and observations of change (from family and non-health care professionals such as teachers) are key to trigger referral for paediatric rheumatology opinion.

Purpose This collaborative paper (working together) describes collaborative practice development and research by and with people from the learning disabilities community. This paper aims to show some of the activities which supported the collaborative practice development and research to show and encourage others to do more collaboration. The paper format is based on a previous collaborative paper published in the Tizard Learning Disability Review (Chapman et al., 2013). Design/methodology/approach The collaborative practice development and feasibility study [1] focuses on an intervention called Keep Safe. This is an intervention for young people with learning disabilities who are 12 years and older and have shown “out-of-control” or harmful sexual behaviour. Findings The paper gives examples of activities of the Keep Safe Advisory Group in planning, doing and thinking about Keep Safe development and feasibility. The authors list some good things and some difficulties in collaborating. They look at which parts of Frankena et al.’s (2019a) Consensus Statement on how to do inclusive research were done, which ones were not, and why. Social implications The paper ends with some thoughts about collaborating with people from the learning disabilities community: for people with learning disabilities, practitioners and researchers. Originality/value The paper is original in its illustration of collaborative practice development and research and measuring the activities against the inclusive research consensus statement.

Objectives Musculoskeletal (MSK) presentations are common (reported prevalence of one in eight children) and a frequent cause of consultations (6% of 7-year-olds in a cohort study from the UK). Many causes are self-limiting or raised as concerns about normal development (so-called normal variants). We aimed to describe a new model of care to identify children who might be managed in the community by paediatric physiotherapists and/or podiatrists rather than referral to hospital specialist services. Methods Using mixed methods, we tested the feasibility, acceptability and transferability of the model in two UK sites. Evaluation included patient flow, referral times, diagnosis and feedback (using questionnaires, focus groups and interviews). Results All general practitioner referrals for MSK presentations (in individuals Conclusion The triage model is acceptable, feasible and transferable to enable appropriate care in the community for a proportion of children with MSK complaints. This is a multi-professional model of better working together between primary community and specialist providers.

Background Musculoskeletal (MSK) problems in children and young people (CYP) are common. The majority present to healthcare professionals in the community, but it can be challenging to identify those with serious disease. pGALS (paediatric Gait, Arms, Legs and Spine) was developed as a simple MSK clinical assessment to discern abnormal joints, initially within paediatric rheumatology and general paediatrics; pGALS can detect joint and functional problems in CYP with other serious conditions but alone is unlikely to be specific enough to diagnose definitive conditions or signpost referrals to orthopaedics, rheumatology, neurology or general paediatrics. Our aim was to scope the literature about MSK assessments applicable to CYP used in practice, focusing on evidence of validity in the context of diagnosis and assessment of Juvenile Idiopathic Arthritis (JIA), Mucopolysaccharidoses (MPS), Muscular Dystrophy (MD) and Developmental Coordination Disorder (DCD) as exemplar MSK conditions. Methods Scoping review using a Library search tool (including several databases), Google Scholar, and consulting NICE guidance/pathways. Search terms included dyspraxia, paediatric MSK assessment, screening tools, balance, rheumatology, assessment tools for MD, MPS, JIA. Studies cited within relevant articles were also checked. Results 32 articles were deemed appropriate, describing specific assessment or screening tools in the context of diagnosis. Within DCD, motor co-ordination batteries aid diagnosis as part of specialist assessment, but are regarded as too lengthy for the purpose of screening; a questionnaire may be a useful first-step diagnostic tool, along with assessment of static balance (found to be significantly worse in children with DCD). In paediatric rheumatology, pGALS is the only validated screening tool to discern normal from abnormal. For neuromuscular conditions the North Star Ambulatory Assessment is valid, reliable and practical as a functional assessment, and includes activities necessary to remain functionally ambulant. With regards to MPS, searches did not reveal specific MSK tests, but evidence suggests that skeletal malformations and joint problems are the most frequently presenting signs. pGALS performs well to identify abnormal joints with restriction within an MPS group. Conclusion This review supports the development of a ‘pGALSplus’ toolkit to facilitate identification of CYP with potentially serious disease. pGALSplus will be targeted at community-based clinicians and will likely include physical examination, questionnaire(s) and appropriate adjuncts.

What is the relationship between capitalism and sexuality, and why are they so often assumed to be antithetical? The book interrogates these questions by bringing together insights from two fields that have often overlooked each other, international political economy and queer theory. It develops a queer political economy lens to understand how the history of capitalism has been intimately entangled with the history of sexuality. Yet central to this story has been the construction of sexuality as something that needs to be protected from capitalism’s adulterating influence at all costs. As the author examines, this is no accident since capitalism profits greatly from the illusion that economic and sexual relations exist in distinct realms that can and must be kept apart. Focusing on the specific site of sex work in Britain, the volume draws on wide-ranging archival research to chart a genealogy of capitalist development from the Middle Ages to the present day. It shows that capitalism has long been organized around the extraction of unpaid sexual labor that, in turn, has been made possible by the creation and maintenance of a dualism between sex and work. By exposing the historical mechanisms through which the economy/sexuality dichotomy has been constituted, the book opens up new space for critical inquiry into the intersections between sex, work, and economic and sexual injustice.

Gut microbiota influences many aspects of host health including immune, metabolic, and gut health. We examined the effect of a fermented whey concentrate (FWC) drink rich in L-(+)-Lactic acid, consumed daily, in 18 healthy men (n = 5) and women (n = 13) in free-living conditions.Objective: The aims of this 6-weeks pilot trial were to (i) identify changes in the gut microbiota composition and fecal short chain fatty acid (SCFA) profile, and (ii) to monitor changes in glucose homeostasis.Results: Total fecal SCFA (mM) concentration remained constant throughout the intervention. Proportionally, there was a significant change in the composition of different SCFAs compared to baseline. Acetate levels were significantly reduced (−6.5%; p < 0.01), coupled to a significant increase in the relative amounts of propionate (+2.2%; p < 0.01) and butyrate (+4.2%; p < 0.01), respectively. No changes in the relative abundance of any specific bacteria were detected. No significant changes were observed in glucose homeostasis in response to an oral glucose tolerance test.Conclusion: Daily consumption of a fermented whey product led to significant changes in fecal SCFA metabolite profile, indicating some potential prebiotic activity. These changes did not result in any detectable differences in microbiota composition. Post-hoc analysis indicated that baseline microbiota composition might be indicative of participants likely to see changes in SCFA levels. However, due to the lack of a control group these findings would need to be verified in a rigorously controlled trial. Future work is also required to identify the biological mechanisms underlying the observed changes in microbiota activity and to explore if these processes can be harnessed to favorably impact host health.Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT03615339; retrospectively registered on 03/08/2018.

Background Measuring the outcomes that matter to children and young people (CYP) with juvenile idiopathic arthritis (JIA), is a necessary precursor to patient-centred improvements in quality of clinical care. We present a two-centre validation of novel JIA patient-reported outcome and experience measures (PROM and PREM) developed as part of the CAPTURE-JIA project. Methods CYP with JIA were recruited from paediatric rheumatology clinics, completing the CAPTURE-JIA PROM and PREM, CHAQ and CHU 9D. A subset participated in face-to-face interviews and completed the PROM/PREM 1 week later. The OMERACT filter was applied and the three domains of validation assessed. Truth assessments included cognitive interviewing, sensitivity analysis and Spearman’s correlations. Discrimination assessments included specificity and reliability testing. Feasibility was assessed using time to form completion and proportion of missing data. Results Eighty-two CYP and their families were recruited; ten cognitive interviews and fifteen PROM/PREM test/retests were conducted. Truth: CYP and parents understood the PROM/PREM and felt important areas were covered. PROM criteria had high sensitivities (> 70%) against similar items on the CHU 9D, with the exception of fatigue (58%). Correlations between similar PROM and CHU 9D criteria were moderate to very strong (coefficients 0.40–0.82.) Discrimination: high specificities (> 70%) on corresponding PROM and CHU 9D domains. Feasibility: median completion times for PROM 60 s (IQR 38–75) and PREM 49 s (IQR 30–60) respectively. Conclusion The CAPTURE-JIA PROM and PREM are valid and feasible in UK paediatric rheumatology clinics. Embedding routine collection into clinical care would be a major step towards improving quality of care.

A 2 year old, female entire African pygmy hedgehog was presented for diagnostic investigation of a 2-month reduction in appetite, with weight loss, and recent vomiting. Clinical examination revealed a large, firm mass originating from the left cranial abdomen. Ultrasound guided fine needle aspirates of the mass, the liver and the mesenteric lymph nodes revealed a population of pleomorphic round cells, some of which contained variable numbers of round, clear vacuoles, consistent with a diagnosis of lymphoma with Mott cell differentiation. At post-mortem examination, there was marked diffuse splenic enlargement, with infiltration by a soft tissue mass. There were multiple coalescing masses in the liver, pallor of the kidneys, and enlargement of the mesenteric lymph nodes. On histological examination, the spleen, lymph nodes, and masses in the liver were extensively infiltrated by proliferating lymphoid cells with plasmacytoid and Mott cell differentiation. Cells with Mott cell morphology had accumulation of periodic acid-Schiff positive material in cytoplasmic inclusions, and were positive for cytoplasmic nucleic acids when stained with methyl green pyronin. In the population of neoplastic lymphoid cells, a majority of cells expressed the transcription factor Pax5, which drives B cell differentiation, and a minority expressed transcription factor IRF4/MUM-1, which drives plasma cell differentiation, consistent with a B cell lymphoma with plasmacytoid differentiation.

Background Juvenile idiopathic arthritis (JIA), the most common chronic rheumatic disease of childhood, is characterised by synovitis. Clinical assessments of synovitis are imperfect, relying on composite and indirect measures of disease activity including clinician-reported measures, patient-reported measures and blood markers. Contrast-enhanced MRI is a more sensitive synovitis assessment technique but clinical utility is currently limited by availability and inter-observer variation. Improved quantitative MRI techniques may enable future development of more stringent MRI-defined remission criteria. The objective of this study was to determine the utility and feasibility of quantitative MRI measurement of synovial volume and vascularity in JIA before and twelve weeks after intra-articular glucocorticoid injection (IAGI) of the knee and to assess the acceptability of MRI to participating families. Methods Children and young people with JIA and a new episode of knee synovitis requiring IAGI were recruited from the Great North Children’s Hospital in Newcastle upon Tyne. Quantitative contrast-enhanced MRI was performed prior to and twelve weeks after IAGI, in addition to standard clinical assessment tools, including the three-variable clinical juvenile arthritis disease activity score (cJADAS) and active joint count. Results Eleven young people (5 male, median age 13 years, range 7–16) with JIA knee flare were recruited and 10 completed follow-up assessment. Following IAGI, the median (interquartile range) cJADAS improved from 8.5 (2.7) to 1.6 (3.9), whilst the median synovial volume improved from 38.5cm3 (82.1cm3) to 0.0cm3 (0.2cm3). Six patients presented with frank synovitis outside normal limits on routine MRI reporting. A further three had baseline MRI reports within normal limits but the quantitative measurements identified measurable synovial uptake. Post-IAGI quantitative measurements highlighted significant improvements in 9 patients. Conclusions IAGI led to a marked reduction in synovial volume, with quantitative MRI identifying more patients with an improved synovial volume than routine qualitative clinical reporting. Improvements in cJADAS scores were more variable with the patient/parent global assessment component contributing most to the scores. Further work is indicated, exploring the utility of quantitative MRI in the assessment of less accessible joints and comparing the impact of different treatment modalities.

Purpose Understanding and predicting the behaviours of households within a community is a key concern for fire services as they plan to deliver effective and efficient public services. In this paper, an agent-based modelling approach is used to deepen understandings of changing patterns of behaviour within a community. The paper aims to discuss this issue. Design/methodology/approach This “Premonition” model draws on historical data of fire incidents and community interventions (e.g. home safety checks, fire safety campaigns, etc.) collated by South Yorkshire Fire and Rescue, UK, to unpack patterns of changing household behaviours within the region. Findings Findings from simulations carried out using the Premonition model, show that by targeting close-knit groups of connected households, the effectiveness of preventative interventions and utilisation of associated resources is enhanced. Furthermore, by repeating these interventions with the same households over time, risk factors within the wider area are further reduced. Originality/value The study thus shows that annual repeat visits to fewer and more targeted high-risk postcodes increase the overall reduction in risk within an area, when compared with a scattered coverage approach using one-off (i.e. not repeat) household visits within a postcode.