Experiments and large-scale epidemiological studies indicate the importance of green space for mental health. However, little research has been conducted to elucidate whether these mental health benefits are more dependent upon the quantity or quality of the green space.there are good parks, playgrounds and play spaces in this neighbourhood.” Multilevel negative binomial growth curve regression models were used to examine the patterning of symptoms of psychological distress across the postpartum period in relation to green space quantity and quality, adjusting for person-level and geographical markers of confounding. The same variables were also fitted in multilevel logistic regressions to examine the odds of reporting serious mental illness (as defined by K6 scores ≥ 13 out of 24).Symptoms of psychological distress were measured in 3897 women who did not change neighbourhood up to 15 years postpartum using the Kessler 6 psychological distress scale from 2004 onwards. The percentage land-use of the neighbourhood was used to ascertain a measure of green space quantity. A Likert scale was used to measure green space quality in response to the statement “Symptoms of psychological distress were fewer among women who agreed (rate ratio (RR) 0.95, 95%CI 0.91 to 0.98) and strongly agreed  local parks were good quality. The odds of reporting serious mental illness were also lower among women who agreed (odds ratio (OR) 0.88, 95%CI 0.77 to 1.00) and strongly agreed  local parks were good quality. No association was found between green space quantity and symptoms of psychological distress or the odds of reporting serious mental illness.This study suggests it may be how mothers perceive green space nearby and what those spaces enable them to do, rather than simply how much there is overall, that is important for promoting mental health in the postpartum period. In conclusion, community consultation is likely to be a crucial part of strategies that maximise the health benefits of urban greening for everyone. Urban greening and restoration of green space is widely believed to promote mental health through a range of pathways. This is supported by evidence from experiments and large-scale observational studies –4 which Reviewing many of the epidemiological studies conducted so far on adults in Australia , 18, 19,‘Fit for purpose’ is a concept that pushes beyond quantity to notions of quality, which given its policy relevance is a surprisingly far less researched issue in epidemiological studies of green space and health. In fact, only three studies have examined the potential mental health benefit of quality green space in adult samples. One study in Perth  found lower odds of psychological distress among participants living near moderate to high quality green spaces, but no association with green space quantity . A studyAccordingly, our aim was to answer the question ‘is green space quantity or quality more important for mental health?’ using a longitudinal study. We focussed upon adult women who were followed-up biennially from 0-1y up to 15y postpartum. The purpose of focussing upon women postpartum was to recognise an under-researched yet very large population subgroup within which depression is common and a significant cause of morbidity and mortality , 35. ForData on mothers in the postpartum period was obtained from Australia’s definitive birth cohort, the Longitudinal Study of Australian Children (LSAC). Permission to obtain and analyse the LSAC was granted through a formal application to The Department of Social Services of the Australian Government (the data custodian). The LSAC began in 2004 and involved biennial follow-up of approximately 10,000 children and at least one parent each. The majority of the parents who participated were mothers . Samplinn = 3526); 2006 (n = 3429); 2008 (n = 3191); 2010 (n = 3469); 2012 (n = 3425); and (2014 (n = 3367).This study used an accelerated cohort design  that mad“During the last 30 days, how often did: (1) you feel nervous?; (2) you feel hopeless?; (3) you feel restless or fidgety?; (4) you feel so depressed that nothing could cheer you up?; (5) you feel that everything was an effort?; and (6) you feel worthless?” Responses were rated as 0 = “none of the time”, 1 = “a little of the time”, 2 = “some of the time”, 3 = “most of the time” and 4 = “all of the time”. In the current study, the sum of all six responses was used as the outcome variable, in order to examine incremental changes that may occur across the postpartum period. The score was scaled with a base value of 0, ranging up to 24. Assessment of the odds of serious mental illness was defined using scores of 13 or greater out of 24 [Symptoms of psychological distress were measured using the Kessler 6 Psychological Distress Scale (K6) in each wave , 42. Theut of 24 .“there are good parks, playgrounds and play spaces in this neighbourhood” into ‘did not agree’, ‘agreed’ and ‘strongly agreed’. In specifying whether a mother felt good parks and similar spaces were available nearby, this focussed on quality and avoided simply detecting whether any green space was proximal. This is an important caveat as some previous work with a different dataset in Australia has reported lower odds of psychological distress among people living nearby higher quality green space, but no association between psychological distress and the quantity of green space per se [Different sources of data were used to measure green space quantity and quality. The quantity of green space was measured according to the percentage of the land-use of the ‘Statistical Area 2’ of residence covered in ‘parkland’ according to the Australian Bureau of Statistics (ABS). This land-use category did not include agricultural land. Data on green space was extracted from the ABS’s 2006 meshblock classification and aggregated to the Statistical Area 2 unit, which was designed by the ABS with populations of 10,000 on average  and to represent local communities and functional areas that contain commercial and transport hubs in areas outside of cities . Mother’e per se .Socioeconomic and geographical factors play an important role in determining mental health  and alsoThe percentage of the sample at high risk of psychological distress were described across the postpartum period and in relation to other sample characteristics. Multivariate analysis was then conducted using multilevel negative binomial regression models in MLwIN V3.00 . Each moThe overall sample of 3897 included 20,407 observations nested within 859 areas and a prevalence of serious mental illness K6 ≥ 13) at 12.4%. Table 3 at 12.4In adjusted multilevel negative binomial regressions there was no convincing evidence of an average effect of green space quantity on symptoms of psychological distress, nor of an interaction between green space quantity and the number of years since childbirth Table , Model 3The key finding from this longitudinal study is that green space quality, but not quantity, is associated with fewer symptoms of psychological distress and lower odds of serious mental illness among women up to 15 years postpartum. The second key finding was that the potential effect of green space quality and non-effect of green space quantity on mental health appeared to be relatively consistent across this period of time in the women’s lives. To our knowledge, this is only the fourth study to have examined associations between mental health and measures of green space quantity and quality. It is the first to do so longitudinally. It is also the first study to investigate for evidence of mental health benefits of green space among women in postpartum, a period that can pose significant psychological challenges. Most of the research on green space and health in or around this important lifecourse stage focusses upon birth outcomes such as birthweight . Just tw. The results of both Australian studies contrast with evidence from the Netherlands where both measures of quantity and quality seemed to matter [The findings from this study align relatively closely with another set in a different area of Australia on a general population sample, which also found evidence of a mental health benefit from proximity to quality green space, but not the availability of green space per se . The reso matter . A samplThe results of this study with respect to green space quantity were unexpected, given the multiple pathways by which green space quantity may influence mental health. Green space quality has been found to be more important than green space quantity in another study of mental health with different data in Australia . HoweverIt is important to acknowledge potential circularity in the association between symptoms of psychological distress and self-reported green space quality. It is also plausible that in some contexts there may be good quality playgrounds and play spaces that are not set within some form of green space. Other features of the local environment not examined in this study may also play a confounding or modifying role, such as differences in walkability and places other than green spaces that mothers of young children may walk to, and potentially come into contact with green space as part of their journeys. Lastly, potentially mediating pathways linking green space quality and mental health in the postpartum period warrant dedicated investigation using longitudinal data and causal mediation models .If the results are interpreted as reflecting potentially causal relationships, this longitudinal study has provided evidence that green space quality matters for protecting mental health among women in the postpartum period. By contrast, the amount of green space nearby was not associated with fewer symptoms of psychological distress. Although this study is not without limitations, it seems reasonably clear from the findings of this study and just a few others before it to have examined mental health in relation to measures of green space quality, that efforts to redesign and restore green spaces need to involve community consultation in order to optimise the health benefits. Further research on green space quality and mental health generally and among women in the postpartum period is warranted to better understand what aspects of green space quality matter when, where and for whom.


Ciliary and flagellar motility is caused by the ensemble action of inner and outer dynein arm motors acting on axonemal doublet microtubules. The switch point or switching hypothesis, for which much experimental and computational evidence exists, requires that dyneins on only one side of the axoneme are actively working during bending, and that this active motor region propagate along the axonemal length. Generation of a reverse bend results from switching active sliding to the opposite side of the axoneme. However, the mechanochemical states of individual dynein arms within both straight and curved regions and how these change during beating has until now eluded experimental observation. Recently, Lin and Nicastro used high‐resolution cryo‐electron tomography to determine the power stroke state of dyneins along flagella of sea urchin sperm that were rapidly frozen while actively beating. The results reveal that axonemal dyneins are generally in a pre‐power stroke conformation that is thought to yield a force‐balanced state in straight regions; inhibition of this conformational state and microtubule release on specific doublets may then lead to a force imbalance across the axoneme allowing for microtubule sliding and consequently the initiation and formation of a ciliary bend. Propagation of this inhibitory signal from base‐to‐tip and switching the microtubule doublet subsets that are inhibited is proposed to result in oscillatory motion. For micNow in a recent report, Lin and Nicastro  use cryo2Dyneins are highly complex multimeric motors built around one to three ~540 kDa heavy chain (HC) motor units King, ; understChlamydomonas, RS3 is present in a truncated form lacking the spoke head and most of the shaft). Each monomeric dynein within the repeat is distinct and indeed they have different motor and ATPase properties , while the other  has the Ca2+‐binding calmodulin homologue centrin , rather than dynein arms, connects doublet microtubules 5 and 6  state tightly bound to the B‐tubule. Not only was this the case in straight regions, but also in segments of the axonemes or inhibited sperm tails that were passively bent, presumably by fluid forces imparted during sample preparation. Similar results were obtained for the inner arm dyneins in both EHNA‐inhibited sperm and ATP‐depleted axonemes, indicating that in situ all motors undergo nucleotide release and can achieve the post‐power stroke conformation in both straight and curved axonemal regions.−21 Nm2) compared to either demembranated (14 × 10−21 Nm2) or live, actively beating, sperm  that, at least in the equivalent Chlamydomonas γ HC, is located at the tip of the microtubule‐binding stalk, interacts with tubulin and might alter or modify mechanochemical coupling  of the outer arm were also detected. In IM1, both HCs are in a post‐power stroke‐like state, whereas in IM2 and IM3 either the α (IM3) or β (IM2) HC is in a transitional conformation, while the other HC remains in the post‐power stroke‐like state. The microtubule binding stalks of these intermediate structures were not clearly defined in the tomograms due to positional variation from one dynein to the next and information loss during imaging averaging. However, they are thought to represent either microtubule‐detached or weakly bound states; clearly explicitly testing this prediction will be a key next step.Chlamydomonas mutant (oda4‐s7) lacking only the motor domain of the β HC has a motility phenotype similar to that observed in strains completely lacking the outer arm ; that is, they are forced‐balanced and immotile presumably because they cannot initiate the inhibitory signal that would allow bending.Together, these observations provide direct support for two key tenets of the switch‐point hypothesis—namely, that dyneins on opposite sides of a curved region are in different functional states, and that this functional dichotomy switches with bend direction. Furthermore, they support an interpretation of dynein activity whereby axonemal motors are inherently in the active conformation, and that bend initiation and propagation is a result of a subset transitioning to a microtubule‐detached or inhibited state which disrupts the force balance allowing for active sliding driven by dyneins on the uninhibited side of the axoneme. This is consistent with the observations of Shingyoji et al.  who demoAnalysis of the inner arm system revealed a more complex response. In both inhibited sperm and ATP‐depleted axonemes, these dyneins were in states similar to outer arms. Furthermore, in actively beating sperm they mostly adopted a pre‐power stroke state, although with a higher degree of variability than observed for outer arms. However, two distinct responses were observed in curved regions. The two‐HC I1/f dynein and three of the monomeric HC dyneins  were found in intermediate or inhibited states on doublets that correspond to those observed for outer arms. This suggests that both outer arms and these specific inner arms, the I1/f dynein and monomeric dyneins associated with RS1 (dynein a) and RS3 (dyneins g and d), may respond to the same, currently unknown, inhibitory signal. However, coupling between this inhibitory signal and the inner arm system is more nuanced as some small groups of inner arms on only one or two doublets in “transition” regions immediately adjacent to curves were also in the microtubule‐detached inhibited state. As rapidly frozen sperm flagella in essence provide a temporal snapshot of dynein activity during wave propagation, the presumption is that these are motors in the process of initiating the ciliary bend or recovering from it. One possible confounding issue here is that during preparation of the actively swimming sperm samples, most liquid must be removed from the electron microscopy grid immediately prior to plunge freezing, which might impart high hydrodynamic forces for a sufficient period that it could alter dynein activity. Using a mutant lacking the motor domain of the I1/f dynein β HC, Lin and Nicastro  also obsChlamydomonas mutants lacking dynein c have approximately normal swimming behavior under standard solution conditions but a greatly reduced ability to generate propulsive force when the medium viscosity is increased  and both surrounding RS2 (dyneins c and e)—did not exhibit inhibited states that corresponded to bend direction. These dyneins therefore may not be essential for initiating or propagating a waveform but rather provide either regulatory inputs or allow responses to altered hydrodynamic or other external conditions. For example, dynein c is a very fast microtubule motor in vitro (~16 μm/s) and dynein c‐mediated microtubule translocation velocity is significantly enhanced by the presence of the inherently slow (~1 μm/s) dynein e motor , in which two motor heads stack together forming an interface that buries the linkers that cross the AAA ring and in which the microtubule‐binding stalks are crossed, thus structurally inhibiting the main mechanical elements (Torisawa et al., Finally, although oscillatory bending with either planar or three‐dimensional waveforms are the most common forms of ciliary motion, other modalities occur. For example, cilia at the embryonic node beat with a vortical motion sweeping out a cone‐shaped volume through rotational movement apparently driven by motors near the axonemal base (Nonaka et al., In conclusion, the cryo‐ET studies of Lin and Nicastro  have pro


Neural coupling between the central nervous system and the periphery is essential for the neural control of movement. Corticomuscular coherence is a popular linear technique to assess synchronised oscillatory activity in the sensorimotor system. This oscillatory coupling originates from ascending somatosensory feedback and descending motor commands. However, corticomuscular coherence cannot separate this bidirectionality. Furthermore, the sensorimotor system is nonlinear, resulting in cross‐frequency coupling. Cross‐frequency oscillations cannot be assessed nor exploited by linear measures. Here, we emphasise the need of novel coupling measures, which provide directionality and acknowledge nonlinearity, to unveil neural coupling in the sensorimotor system. We highlight recent advances in the field and argue that assessing directionality and nonlinearity of neural coupling will break new ground in the study of the control of movement in healthy and neurologically impaired individuals. Previous reviews mainly focused on the functional meaning of CMC as well as its clinical applications  and beta (~20 Hz) band  modelling of stochastic processes which allows disentangling of the ‘cause‐and‐effect’ relation within a closed loop. However, the phase of the directional coherence presents the relative timing between neural signals within the closed loop and affected by an unknown external noise source . In contrast to cross‐correlation reflecting et al., et al., et al., Recently, we proposed a frequency domain approach namely cross‐spectral coherence (CSC) to investigate the nonlinear corticomuscular interaction  method  to distinguish motor and somatosensory communications in the sensorimotor system; and (ii) to exploit the nonlinear nature of neural coupling between the central nervous system and the periphery. Applying these new approaches may eventually provide a more detailed mechanistic understanding of neural communications during movement control and lead to useful tools for studying motor disorder‐related diseases such as stroke and Parkinson's disease.Authors declare that they do not have any conflict of interests.YY and AS drafted and wrote the manuscript. JD and FH commented and revised the manuscript. Click here for additional data file.


To investigate potential risk factors for acquisition in seven countries of the meningitis belt.Households were followed up every 2 weeks for 2 months, then monthly for a further 4 months. Pharyngeal swabs were collected from all available household members at each visit and questionnaires completed. Risks of acquisition over the whole study period and for each visit were analysed by a series of logistic regressions.OR 3.6, 95% CI 1.4–9.9); (ii) smokers ; and (iii) those exposed to wood smoke at home (OR 2.6 95% CI 1.3–5.6). The risk of acquisition from one visit to the next was higher in those reporting a sore throat during the dry season  and lower in those reporting antibiotic use .Over the course of the study, acquisition was higher in: (i) 5‐to 14‐year olds, as compared with those 30 years or older (Acquisition of meningococcal carriage peaked in school age children. Recent symptoms of sore throat during the dry season, but not during the rainy season, were associated with a higher risk of acquisition. Upper respiratory tract infections may be an important driver of epidemics in the meningitis belt. Epidemics of meningococcal meningitis occur periodically in the African Meningitis Belt, an area of sub‐Saharan Africa stretching from Senegal in the west to Ethiopia in the east N. meningitidis were recruited for longitudinal studies Studies of carriage prevalence and acquisition will, therefore, lead to a better understanding of the epidemiology of meningococcal meningitis in the African meningitis belt. The African Meningococcal Carriage Consortium (MenAfriCar) undertook 20 cross‐sectional carriage surveys in seven African meningitis belt countries from July 2010 to July 2012, involving the collection of over 48 000 pharyngeal swabs. These studies found a higher frequency of carriage in children aged 5 to 14 years, in the dry season and in rural populations N. meningitidis across the African meningitis belt.Previous longitudinal studies in the meningitis belt have been undertaken mainly at the population level Households included in this study were recruited during the course of cross‐sectional surveys conducted in seven countries in the African meningitis belt  in 2010, 2011 and 2012. Details of the survey methods employed have been published previously Within 4 weeks of the identification of a carrier, all members of the putative carrier's household were invited to take part in further studies (Visit 1). The head of the household was asked about characteristics of the household, including numbers of rooms and bedrooms, sleeping arrangements, location of kitchen and cooking fuel, house construction, drinking water, sanitation and household assets such as vehicle ownership, livestock and electrical goods.A pharyngeal swab sample was obtained from all members of a household who gave consent and a questionnaire completed which included questions on: smoking; social activities; symptoms of recent respiratory tract infection; socio‐economic status and educational level; school attendance; travel history; recent medication including antibiotics; meningitis vaccination; and ethnic group. Carrier households were followed up 2‐weekly for 2 months (Visits 2–5) and monthly for a further four months (Visits 5–9). At each follow‐up visit, each household member was asked for a pharyngeal swab sample and to answer a short follow‐up questionnaire on factors that might have changed since the previous visit, such as symptoms of a respiratory tract infection.Neisseria species. Confirmed N. meningitidis were further characterised by genogroup (including capsule‐null) and porA genosubtype.Pharyngeal swab samples, taken from the posterior pharynx and tonsillar fossa via the mouth, were plated directly onto Modified Thayer Martin agar plates in the field, taken to the laboratory within 6 h of collection and processed as previously described https://pubmlst.org/neisseria). Data from the longitudinal questionnaires were merged using a common person ID or census number, person matching was checked, any duplicate entries were removed and aberrant values excluded.Data were managed using the Teleform system version 10.4.1  with a separate database module linking the main study database with genetic laboratory results from the Oxford PubMLST.org/neisseria database  were dropped.The genogroup‐specific acquisition rates and 95% confidence intervals were calculated as Poisson rates, counting the number of acquisitions occurring in non‐index carriers and the time at risk as the days between the first carriage‐negative swab and the first positive swab. A series of fixed‐effects logistic regressions were used to identify significant risk factors for acquisition. In the first round of regressions, individual risk factors were included in a multi‐variable logistic regression with the Acquisition was assessed over the full study period (study‐long) and visit‐by‐visit. Individuals were defined as positive for study‐long acquisition if they had a negative swab (no meningococci isolated) at visits 0 or 1 and a positive swab (any meningococci isolated) at any following visit. Individuals were defined as negative for study‐long acquisition if they had a negative swab at visits 0 or 1 and no positive swab at any subsequent visit. Individuals with three or more missed visits in total were excluded, as the possibility of acquisition during this missed period could not be ruled out and individuals carrying at visits 0 or 1 were also excluded.Individuals were defined as positive for visit‐by‐visit acquisition on a given visit if the individual had a positive swab at the current visit and a negative swab at the previous visit or carried a different strain at the previous visit and the strain was not previously carried during the study. Strains were assessed by genogroup and porA variable regions 1 and 2. Individuals were defined as negative for visit‐by‐visit acquisition on a given visit if the individual had a negative swab at the previous visit and a negative swab at the current visit. Individuals carrying an identical strain to that obtained at the previous visit and individuals who cleared carriage were excluded from the analysis. Tables We defined the dry season as January to May and the rainy season as June to December. Because we found a significant association between sore throat and season and also previous studies have demonstrated an interaction between meningococcal carriage, upper respiratory tract infection and season, we also tested for interaction between sore throat and season in our final model and found that the model with an interaction term fitted better than the model with no interaction Table .The study was approved by the ethics committee of the London School of Hygiene and Tropical Medicine and by the relevant ethical authorities in each African centre Overall, 169/861 (20%) of the non‐index carriers became pharyngeal carriers of a meningococcus at least once over the course of the study. A higher proportion of 5‐ to 14‐year‐olds acquired carriage than other age groups and a higher proportion of participants acquired carriage in Senegal, Niger, Ghana and Ethiopia relative to Chad and Mali  to have acquired carriage in that time period than those who did not have a sore throat in the rainy season Table . Those wThis longitudinal study found a higher risk of acquisition amongst individuals who reported a sore throat since the previous visit, but only during the dry season. An association between an upper respiratory tract infection and meningococcal carriage has been reported previously The 5 to 14‐year‐old age group had the highest acquisition rate. The highest prevalence of carriage in cross‐sectional MenAfriCar studies and in Burkina Faso in 2009 was similarly highest in 5 to 14‐year olds Additional factors linked to acquisition of meningococci over the course of this study were smoking tobacco and exposure to wood smoke. Smoking, passive exposure to smoke and to smokers has been shown to convey a high risk of carriage and invasive disease in high‐income countries Strengths of this study are the multi‐centre design across seven countries of the meningitis belt conducted at the same time, including a mix of urban and rural populations with a broad age range, the use of standardised field and laboratory protocols and a large sample size. Measuring acquisition rather than carriage ensures that the risk factors identified in this study are not biased by factors associated with longer carriage duration. A comprehensive range of risk factors was included, so that important confounding factors are unlikely to have been missed; however, the sampling of carriers and non‐carriers was not random and we would expect some misclassification of carriage status from the known low sensitivity of pharyngeal swabbing.Both the acquisition of meningococci found in this longitudinal study and prevalence of carriage in the MenAfriCar cross‐sectional studies varied considerably by country. Although laboratory methods were standardised across centres, differences in laboratory techniques could still have contributed to some of the differences observed. As most meningococcal acquisitions were either genogroup W or capsule‐null and outside epidemics, it cannot be assumed that risk factors for acquisition of other genogroups or during epidemics would be the same as those found in this study It was surprising that some risk factors such as household crowding that have long been known to raise the risk of carriage and disease Reported vaccination was clustered in particular time periods and countries corresponding to the introduction of group A conjugate vaccine. Vaccination was not found to be protective against carriage acquisition. However, we would not expect a group A conjugate vaccine to have a significant impact on carriage in this study as very few group A carriers were detected.We were not able to draw any conclusions regarding the relationship between carriage acquisition and disease incidence because none of the study sites reported an outbreak of meningitis during the follow‐up period.This study involved multiple countries and examined an exhaustive set of household and individual risk factors for meningococcal acquisition. The importance of identifying these risk factors is that acquisition is a necessary prerequisite for invasive disease. Acquisition studies also play a potential role in vaccine evaluation. Of particular interest for countries of the African meningitis belt is the finding that symptoms of upper respiratory tract infection are linked to risk of acquisition, but only in the dry season. The evidence is mounting that such infections are an important factor behind the risk of epidemics in the meningitis belt.Table S1. Case definition for study‐long acquisition.Table S2. Case definition for visit‐by‐visit acquisition.Table S3. Odds of sore throat adjusting for age, country, sex and season.Table S4. Likelihood ratio test comparing visit‐by‐visit model with and without term of interaction between season and sore throat.Click here for additional data file.


Juvenile idiopathic inflammatory myopathies have been recently reclassified into clinico‐serological subgroups. Myopathological correlates of the subgroups are incompletely understood.We studied muscle biopsies from 101 children with clinically and serologically defined juvenile idiopathic inflammatory myopathies from the UK JDM Cohort and Biomarker Study by applying the international JDM score tool, myopathological review and C5b‐9 complement analysis.Autoantibody data were available for 90/101 cases with 18/90 cases positive for anti‐TIF1γ, 15/90 anti‐NXP2, 11/90 anti‐MDA5, 5/90 anti‐Mi2 and 6/90 anti‐PmScl. JDM biopsy severity scores were consistently low in the anti‐MDA5 group, high in the anti‐Mi2 group, and widely distributed in the other groups. Biopsies were classified histologically as perifascicular atrophy (22/101), macrophage‐rich necrosis (6/101), scattered necrosis (2/101), clustered necrosis (2/101), inflammatory fibre invasion (2/101), chronic myopathic change (1/101), diffuse endomysial macrophage infiltrates (40/101) and minimal change (24/101). MDA5 cases segregated with the minimal change group and showed no capillary C5b‐9‐deposition. The Mi2 group displayed high severity scores and a tendency towards sarcolemmal complement deposition. NXP2 and TIF1γ groups showed a variety of pathologies with a high proportion of diffuse endomysial macrophage infiltrates and a high proportion of capillary C5b‐9 deposition.We have shown that juvenile idiopathic inflammatory myopathies have a spectrum of histopathological phenotypes and show distinct complement attack complex deposition patterns. Both correlate in some cases with the serological subtypes. Most cases do not show typical histological features associated with dermatomyositis (e.g. perifascicular atrophy). In contrast, more than half show relatively mild histopathological changes. Juvenile idiopathic inflammatory myopathies (IIM) are a group of diseases comprising immunologically mediated inflammatory muscle diseases in children. This group of diseases is being re‐appraised and reclassified based on an improved understanding of the autoantibody landscape and clinical phenotypes. In the traditional clinico‐pathological classification, juvenile IIMs include juvenile dermatomyositis, polymyositis and cases that ‘overlap’ with other connective tissue diseases. A parallel serological classification based on myositis‐specific antibodies (MSA) and myositis‐associated antibodies (MAA) has emerged over the past decade. Initial correlation between the clinical findings and autoantibody groups revealed subphenotypes allowing a refined clinical description of these diseases Early classification of IIMs on histopathological grounds into dermatomyositis, polymyositis, and inclusion body myositis was based on histochemical and morphological criteria. In 2003, an enlarged morphological ENMC classification also comprising nonspecific myositis and immune mediated necrotizing myopathies was published based on an international workshop consensus Several rare and less well‐correlated myopathological manifestations of inflammatory muscle disease have been described in addition to the more frequent patterns, including inflammatory myopathy with abundant macrophages (IMAM) Our study describes systematically the biopsy pathology of a large cohort of clinically and serologically diagnosed juvenile IIM patients, and to test the hypothesis that specific features may be associated with autoantibody groups. This cohort allows an unbiased view of the pathological changes in these diseases, since patient selection was not based on histological criteria. We adopted a two‐stage approach. In the first stage, we analysed the biopsies in a standardized manner using our validated international JDM biopsy score tool Paediatric patients with clinically diagnosed idiopathic inflammatory myopathy with or without skin changes were recruited to the UK JDCBS Frozen sections were stained with Haematoxylin & Eosin, modified Gömöri trichrome (GT), NADH tetrazolium reductase and Acid Phosphatase. Immunohistochemical studies were performed as described previously Scoring of biopsy samples was conducted using the validated JDM biopsy score tool as described previously In parallel with the use of the score tool, histological review of all 101 biopsies was carried out by a senior neuropathologist (PWS) independently of, and blinded to, scoring results, autoantibody status and clinical data. Stains and immunohistochemical studies were available as stated above. The aim of the histological review was a descriptive assessment of the dominant pathological features in each muscle biopsy. Groups were largely based on findings described in the context of typical myopathological diagnoses, such as perifascicular atrophy (PFA) in classic dermatomyositis, macrophage rich necrosis in IMAM Serum or plasma were screened for autoantibodies using immunoprecipitation as described previously Principal component analysis (PCA) was performed on the entire cohort to reduce the number of dimensions in the severity score data and enable visualization of potential underlying clusters. PCA analysis was performed using the R package FactoMineR n < 2) were excluded from statistical analysis. Post‐hoc comparisons were performed using Dunn's Multiple Comparison Test. Differences in autoantibody frequency across histological groups were analysed by the chi square test. For all analyses, P‐values of <0.05 were considered statistically significant. PCA of score tool data and subsequent analysis of domain specific data is based on all 101 cases, including cases treated with steroids at the time of biopsy, since steroid treated did not show a significant effect on total severity scores, as shown by Mann–Whitney test on total severity scores, P = 0.52. All cases were individually reviewed and assigned to histological groups. Analysis of the correlation of histological groups with serological and clinical data was restricted to cases without treatment at the time of biopsy.The distributions of domain score totals, CMAS score and dominant fibre pathology categories across autoantibody groups were analysed by Kruskal–Wallis test . For categorical variables, groups with small sample size . No other myositis specific autoantibody subgroups separated into clusters when projected onto the first two principal components, indicating that the score tool data could not explain the underlying variability in these groups. To better understand the source of this variability of the total scores, we next investigated the domain specific score data.As we have previously shown, muscle biopsy scores for patients with MDA5‐associated myopathies cluster in the mild range, Mi2‐associated cases cluster in the severe range, and TIF1γ‐ and NXP2‐associated cases vary across a wide range, Figure b,c). No significant differences between groups were seen in the vascular and connective tissue domains (data not shown). Severity scores correlated weakly with muscle strength at time of biopsy as we have shown previously d).In the PCA, inflammatory and muscle fibre domain scores accounted for a large proportion of the variance between these two groups. Domain specific analysis of the score tool data confirmed that the severity of inflammatory infiltrates and of fibre pathology differ between Mi2 and MDA5 antibody subgroups, whereas other myositis specific autoantibody groups, in particular TIF1γ and NXP2, had a wide range of scores for severity in these domains. . In particular, there were high levels of inflammation and a range of fibre pathology including PFA, necrosis and severe chronic myopathic changes. In contrast, the majority of patients with autoantibodies to MDA5 had very mild, almost normal, muscle biopsies, with little or no inflammation and minimal myofibre abnormalities, such as increased fibre size variability . However, eight of nine cases showed increased MHC Class I expression.Preliminary histological examination showed that all patients with autoantibodies to Mi‐2 had significant pathological change in their biopsies Figure e. In pay Figure e. Howeve, with intense inflammatory infiltrates and muscle fibre damage in the Mi2 group and minimal changes (MC) in the MDA5 group.Representative biopsy pathology for a patient with Mi2 and MDA5 autoantibodies are shown in Figure b). This patient also had a long time interval between disease onset and muscle biopsy of approximately 5 years, which could be related to the increased severity of pathology seen in this biopsy.The MDA5 group contained one outlier case both on PCA and domain‐specific analysis that did not cluster with other cases in the MDA5 group. This case scored higher for muscle fibre pathology, which showed PFA and SN Figure b. This Overall, score tool data analysis demonstrated that severity of muscle pathology is not randomly distributed across autoantibody groups in juvenile IIM.The score tool gives an overall measure of severity but does not indicate the underlying type of pathology. We hypothesized that there may be variation in the patterns of pathology that might explain the variability in the biopsies. Therefore, in our second analysis, biopsy histology was reviewed by an experienced pathologist who was blinded to score tool data, as well as the clinical and serological features. The primary aim was to determine if a pattern of pathology could be recognized in each biopsy and if so whether these findings correlated with serological or clinical data.a–e). Next, we identified a group that was distinguished by diffusely increased endomysial CD68‐positive cells in combination with increased sarcolemmal MHC class I expression, which we called the ‘diffuse endomysial macrophage infiltration’ pattern . This group was formally defined by the presence of an endomysial macrophage infiltrate score of 2, combined with MHC class I overexpression, but no or only rare atrophic or necrotic muscle fibres. Biopsies with DEMI infiltrates occasionally displayed rare regenerating fibres or rare lymphocytic infiltrates, but by definition, these were not prominent features. Another large group was characterized by PFA . PFA affected more than one layer of atrophic fibres on the edge of at least one fascicle. Small numbers of necrotic fibres were sometimes observed, but these were not a dominant feature. Biopsies with PFA often had increased perimysial lymphocytic infiltrates, and endomysial and perimysial fibrosis. A small group of biopsies was characterized by extensive and diffuse fibre necrosis, numerous macrophages and moderate, often endomysial, lymphocytic infiltrates, which we designated as the ‘macrophage‐rich necrosis’ pattern . Necrotic fibres in various stages of myophagocytosis were found in both peri‐ and intrafascicular location, scattered or confluent. PFA was sometimes present as a minor component.Descriptive categories and their frequency in this cohort are summarized in Table a–e). Two cases had scattered necrotic fibres  with very little inflammation, as is typically described in immune‐mediated necrotizing myopathy. Two cases showed invasion of normal appearing muscle fibres by lymphocytes, grouped as inflammatory FI . A single biopsy exclusively showed features of a severe chronic myopathy  with marked fibre size variation, internal nucleation and frequent whorled fibres. Finally, two biopsies could not be assigned to any of the above groups and were classified in an ‘other’ category. One of these showed features of neurogenic change and the other of diffuse fibre necrosis at a similar stage of phagocytosis consistent with rhabdomyolysis .Rare cases showed other distinctive pathologies. Two cases demonstrated clusters of necrotic fibres resembling a small infarct, termed ‘CN’, but no significant inflammatory infiltrates : MC cases account for almost all of the MDA5 group whereas DEMI cases were mostly NXP2 or TIF1γ, or NIA cases. None of the MC or DEMI cases had Mi2 antibodies. These results suggest that the distinction between MC and DEMI may be biologically significant. Differences between these two groups were apparent upon analysis of associated inflammatory infiltrates with generally higher lymphocyte scores in DEMI compared to MC . Histological groups correlated well with distinct ranges of JDM severity scores .To test the significance of the histopathological differences between MC and DEMI (DEMI) cases, we compared the autoantibody profile of both groups restricting biopsies to patients without steroid treatment at the time of biopsy. Analysis of the major myositis‐specific autoantibody groups demonstrated a clearly distinct distribution Figure a: MC caC Figure b,c. Hiss Figure d.e). In the NXP2 and TIF1γ serological groups, a combination of biopsies with DEMI infiltrates and PFA was present, explaining partly the variability of the severity scores observed in the first stage of this study. Interestingly, there were also other pathological patterns present, illustrated by a case with CN and one case with macrophage rich necrosis in the NXP2 . The Mi‐2 group appeared more homogeneous on score tool analysis with generally high severity scores, but upon histological review also showed heterogeneous histological patterns with two cases of PFA, one case of macrophage rich necrosis and one case with chronic myopathic change . However, Fisher's exact test did not demonstrate differences between the NXP2 and Mi2 groups. Given the small numbers, however, a difference cannot be excluded. Labelling patterns analysed according to histological subgroup are in keeping with the serological profile of each group, considering that the main serological groups in DEMI and PFA are NXP2, TIF1γ and NIA . A summary of the correlation of serological groups with histological groups, complement deposition pattern and JDM severity scores in absolute numbers is presented in Table C5b‐9 immunohistochemical studies were available for 96/101 biopsies and for 76/89 biopsies from untreated patients. Figure A Figure a. A sumSeveral observations are warranted for the smaller autoantibody groups and for MAA. PmScl patients did not show PFA on biopsy, but a mixture of MRN, inflammatory FI and endomysial macrophage infiltrates. Conversely, all cases with inflammatory FI fell into the PmScl group in keeping with a traditionally assumed association of PmScl with polymyositis a). Although the MC group shows an aggregate of high CMAS scores, and this is consistent with previous observations in MDA5 +ve JDM, there were also several patients with a low CMAS score in this group, possibly related to the serological heterogeneity of this group as presented in Figure Juvenile dermatomyositis . Only cases without prior steroid treatment were taken into consideration. Upon Kruskal–Wallis testing, there were significant differences between the major histological groups . The MC histological group showed low CK levels  with exception of a single case with a level of 4005 IU/l. The latter case was in the TIF1γ serological group and showed capillary complement deposition, in contrast with the MDA5 cases in the MC group. The wide range of CK levels in the histological group with DEMI infiltrates is remarkable and may suggest that these pathological features on biopsy can indeed be associated with considerable muscle abnormality and, as indicated by the CMAS score, with muscle weakness. There was no statistically significant difference between the PFA and DEMI group .CK levels were available for 73/101 cases Figure b. Only s Figure b. The MThis study examines muscle biopsies from a cohort of 101 patients with juvenile immune mediated myopathies to probe potential associations of myopathological features with autoantibody groups. Inclusion in the cohort was based on a clinical diagnosis of juvenile IIM. 90/101 cases underwent serological analysis by immunoprecipitation for myositis‐specific and myositis associated autoantibodies. Seventy percent of cases tested had identifiable autoantibodies. Since biopsy pathology was thus studied in an unbiased cohort with selection criteria which were independent of biopsy results, this study provided an opportunity for a comprehensive analysis of muscle biopsy pathology in this disease group.Mi2 patients demonstrated consistently high JDM severity scores, displayed a variety of histological patterns including PFA, macrophage rich necrosis and chronic myopathic change, and a tendency towards sarcolemmal rather than capillary complement deposition. The NXP2, TIF1γ and no identifiable autoantibody groups were characterized by a considerable variability in severity scores, a significant proportion of biopsies with DEMI infiltrates and MHC upregulation, several biopsies with PFA, and overall a large proportion of cases with capillary complement deposition. No myopathological differences between these three latter groups were apparent on the present analysis. The increased propensity for sarcolemmal complement deposition in the Mi2‐associated myopathies compared to NXP2 or TIF1γ has been previously reported in adult patients and our data suggest a similar relationship in juvenile IIMs Capillary deposition of C5b‐9 was present in a variable proportion in several autoantibody groups in our paediatric cohort. Results from adult TIF1γ‐positive patients indicate that in this age group, C5b‐9 deposition is significantly associated with paraneoplastic myositis MDA5‐associated myopathies generally had mild pathology according to the JDM score‐tool, did not show DEMI infiltrates or other inflammatory infiltrates, and lacked capillary C5b‐9 deposition. These cases cluster in the histological ‘MC’ group. The absence of major morphological changes in biopsies from juvenile MDA5 patients is in keeping with previous reports of minimal fibre pathology in both juvenile and adult cohorts of anti‐MDA5 associated dermatomyositis Our data suggest a pathomechanistic role for diffuse macrophage infiltrates, which are characteristic of the DEMI group. DEMI histology was found in a large proportion of patients from several serological groups and clinically often typical dermatomyositis. It has a serological profile distinct from the MC group, a different distribution of CK values, and different complement deposition patterns. Endomysial macrophages secrete the highly pro‐inflammatory protein MRP8/14 in juvenile dermatomyositis The rare myopathological manifestations of MSA‐associated inflammatory myopathies are an interesting group in our cohort. Previous publications on these are available mostly as small series of adult patients with pathologies such as macrophage rich inflammation and clusters of necrotic fibres MAA‐associated biopsies show a spectrum of pathologies often similar to those that have been reported in adult cases. Invasion of healthy appearing fibres by inflammatory cells is a feature associated with traditional myopathological descriptions of polymyositis and has been reported in association with PmScl antibodies in adult patients The international JDM score tool has been systematically standardized and its application across this large cohort produced robust evidence of a correlation between low scores in the MDA5 and high scores in the Mi2 serological groups, while the NXP2 and TIF1γ positive groups of patients showed a wide range of scores. Scoring also produced an array of data from different histopathological domains, which is amenable to advanced cluster analysis. This type of analysis appears well‐suited to muscle biopsies given that histopathological assessments normally integrates numerous morphological findings. PCA revealed clusters defined by inflammatory and fibre pathology parameters, indicating a high discriminatory value of these domains. Interestingly, assessment of these domains shows the highest interobserver agreement on validation studies The descriptive histological categories used in this study correlate poorly to not at all with clinical diagnosis and CMAS score. There are likely multiple factors causing this variability. The pathophysiology of muscle weakness in inflammatory myopathies is poorly understood and by implication their correlation with morphological change is not obvious. CK levels correlate somewhat better with histological groups than CMAS values probably for similar reasons given that the former reflects muscle fibre degeneration and loss of membrane integrity.A challenge for any study of pathological subgroups of IIM is to analyse the great variety of myopathological findings that can be seen in order to allow correlation with clinical or serological classifications. The JDM score tool delivers a standardized assignment of a severity score but was not designed to convey all aspects of individual myopathological change. To complement the score tool data, we reviewed all biopsies and chose to group them in descriptive categories based on the dominant pathological features seen in each biopsy. The histological categories used are modelled on major pathologies previously described in the myopathological literature on inflammatory myopathies. In some cases, precise definitions are difficult since the visual interpretation of ‘significant atrophy’, for instance, may vary from one pathologist to another. Yet, these categories are meant to uncover basic patterns and not to serve as discriminators for diagnostic entities. The fact that no apparent differences were disclosed between the NXP2, TIF1γ group and the group without identifiable autoantibodies does not exclude possible differences between these groups in regard to other markers of pathology. Importantly, this study did not aim to define diagnostic criteria using histological features. The strength of our study resides in an unbiased overview of a large cohort with a diverse autoantibody spectrum.In conclusion, we have mapped myopathological manifestations in a large cohort of patients with clinically and serologically defined juvenile IIM using a dual approach with evaluation based on the validated JDM score tool in a first stage and histological review and grouping in a second. Our results show certain biopsy characteristics of the MDA5 and Mi2 serological groups, but no obvious differences between NXP2, TIF1γ and the group with NIA. Endomysial macrophage infiltrates were a prominent feature in many biopsies with the notable exception of the MDA5 group, supporting a pathomechanistic role for tissue macrophages. Biopsies from myositis‐specific autoantibody groups demonstrated histological variability and variable proportions of capillary C5b‐9 deposition. The clinical and pathomechanistic significance of this variability deserves further study.Funding for the UK JDM Cohort and Biomarker study has been provided by generous grants from the Wellcome Trust UK (085860), Action Medical Research UK (SP4252), The Myositis Support Group UK, Arthritis Research UK , The Henry Smith Charity and Great Ormond Street Children's Charity (V1268), and the National Institute for Health Research (NIHR) Translational Research Collaboration (TRC) Rare Diseases. This research was supported by the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and GOS Institute of Child Health University College London (UCL). The JDM Cohort study is adopted onto the NIHR Comprehensive Research Network. The Arthritis Research UK Centre for Adolescent Rheumatology at UCL, UCL Hospital and GOSH is supported by grants from Arthritis Research UK [20164] and Great Ormond Street Children's Charity. This is a summary of independent research funded by the NIHR's Rare Diseases Translational Research Collaboration and NIHR Biomedical Research Centre at Great Ormond Street Hospital; LW and CD were supported by the NIHR Biomedical Research Centre at Great Ormond Street Hospital. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.SAY: JDM score tool analysis, interpretation of data, drafting and revision of manuscript; PWS: Histological analysis, interpretation of data, drafting and revision of manuscript; CTP: Statistical analysis and interpretation, PCA; ES: Score tool evaluation; HV: Immunohistochemical procedures and biobanking; SS: Database administration and analysis; SLT and NJM: Autoantibody analyses and interpretation; JLH: Study design, interpretation of data and revision of manuscript; TSJ: Study design, interpretation of data and revision of manuscript; LRW: Study design, interpretation of data, funding, manuscript revision.Neuropathology and Applied Neurobiology are committed to peer‐review integrity and upholding the highest standards of review. As such, this article was peer‐reviewed by independent, anonymous expert referees and the authors (TJ and JH) had no role in either the editorial decision or the handling of the paper.The authors declare no conflict of interest. The Editors of


School summer holiday clubs in deprived areas of Wales were evaluated to examine opportunities for healthy eating and physical activity and explore delivery processes.Ten Food and Fun clubs participated in 2016. Quantitative data  assessed the opportunity to provide children with breakfast and lunch. A sub‐sample of children wore an accelerometer (N = 41) to evaluate the opportunity for achieving 1‐hour of moderate to vigorous activity (MVPA) at club. Features of successful club delivery were identified through; focus groups  and interviews .Opportunities for healthy eating were delivered with high fidelity: 86% of children reported breakfast consumption and 75% eating a healthy lunch. On club days, children reported consuming fewer sugary snacks (66%), fewer sugary drinks (81%), and more fruits and vegetables (67%). About 71% of children achieved the recommended MVPA at club, with children engaging in more MVPA  on average compared to non‐club days. Successful delivery processes were: use of school facilities and staff; flexible partnership‐working; and whole family involvement.Schools appear to provide a suitable setting for the delivery of healthy eating and physical activity opportunities during school summer holidays. A large number of children are currently receiving inadequate food for a healthy diet, due to the growing problem of food insecurity.The school environment has been shown to play an important role in promoting healthier diets among children.Sedentary behavior during the school holidays is also a worldwide concern, with only 15% of 11‐ to 15‐year olds currently managing an hour of daily activityConcerns about child health and well‐being during the school holidays have led to the development and implementation of new summer holiday initiatives aiming to increase access to food and physical activity provision, especially in low‐income communities.As of yet, no formal evaluation of a UK‐based summer holiday club has been carried out. One such initiative based in the United Kingdom, is Food and Fun clubs, implemented within schools in areas of high deprivation across Wales. Developed and piloted in 2015 within one local authority, Food and Fun is a multi‐agency project providing healthy meals (adhering to school nutrition standards), nutrition skills and physical activities during the summer holiday period. The aims of this study were to (1) investigate the healthy eating and physical activity opportunities provided at Food and Fun holiday clubs and (2) explore the barriers and facilitators to delivering these clubs.During the school summer holiday period of 2016, 10 schools (6 primary school and 4 secondary school sites) from 5 local authorities in Wales delivered a Food and Fun club and agreed to participate within the evaluation study. Five of the 6 primary school sites invited pupils attending their own school while the remaining primary school site invited Year 5 and 6 children (age 9‐11) from various local primary schools as well as their own pupils. Of the secondary school sites, 2 schools provided open access clubs for all local children; one school invited its own Year 8 and 9 students (age 12‐14); and one school provided a “transition” program for its incoming Year 7 students (age 10‐11). Recruitment strategies varied by school, with a mixture of targeted  and inclusive approaches  being used.For each child invited to attend a Food and Fun club, parents and guardians were provided with study information and the opportunity to part or fully opt their child out of the study. Parents were also offered the opportunity to participate in the study through completing a survey and/or taking part in a focus group. Separate opt‐in consent was obtained for collecting objective physical activity data from children. Child assent was also collected prior to each component of data collection.Across the 10 schools, club registers revealed that 323 children attended at least 1 day, with the majority (78%) of children aged 7‐11 years (range 3‐14 years). Attendance records showed that 53% of children attended at least 6 of the 12 days provided, with 13.6% attending all 12 days. There were 300 occurrences in which a parent attended a family day at club to eat lunch with their child. The proportion of children eligible for free school meals across the school sites ranged from 22% to 57% (mean 34.9%).Children were provided with a 22‐point survey to explore their views and experiences of club attendance, daily activities and eating habits during non‐club days, and home environment. Parents or a guardian were provided with a similarly designed 41‐point survey, which included extra sections covering demographics, financial circumstances and food availability and diet at home. Dietary questions were used to assess intervention fidelity of clubs providing 2 nutritious meals a day.To assess the proportion of children achieving 60 minutes of moderate to vigorous activity (MVPA) on club days, a sub‐sample of children were asked to wear an ActiGraph GT3x+  accelerometer for 7 consecutive days. The monitor was attached to a belt and placed around the right hip of each child, with instructions to remove the device only during hours of bathing or sleeping.Children actively participated in focus groups to voice their opinions of the Food and Fun club. With use of playful and artistic methods , children discussed a typical lunch both within the home and club environment, and their routine activities when the club is closed. Parent focus groups explored the challenges to providing food and fun activities during the summer holidays, beneficial impacts of the club and their recommendations for the future.With use of an interview topic guide, a variety of staff members and volunteers at each club were asked to reflect on their job role, feedback comments from children and parents, the potential benefits of the project and their experiences of working at a club.A researcher attended the last club day of each week (maximum of 4 visits), coinciding with a family club day (parents and siblings were invited to club to enjoy a free lunch). During the first week, a sub‐sample of children were fitted with initialized accelerometers and later provided with a £10 gift voucher upon return of the device. During the second week, children and parents completed surveys during club time and focus groups and interviews were conducted during the third or fourth week. A £10 gift voucher was provided for each parent taking part in a focus group.am and 11 pm. A cut‐point of ≥2296 counts per minutet tests were used to determine if children who provided 3 days of valid data differed to those that did not provide valid data on the following characteristics; sex, year group, and material deprivation. Significance levels were set at p ≤ .05. Paired sample t tests were used to examine differences between accelerometer data on club days and non‐club days. To test for equality of proportions meeting the recommended daily activity levels across the 3 days a Cochran's Q testDescriptive statistics of survey data were calculated to describe the sample and examine opportunities for healthy eating and physical activity. Raw accelerometer data were processed with the ActiLife software . Periods of ≥60 minutes of zero values were defined as accelerometer “non‐wear” time and discarded. Participants were included in the analysis if they provided ≥3 days of data  with at least 500 minutes of data between 6 Focus groups and interviews were conducted in person, audio‐recorded and transcribed verbatim, with NVivo 11 software  used for all analyzes. Two members of the research team reviewed the transcripts, after which the following method was adopted: line by line open coding (descriptive labeling), axial coding , and selective coding (exploring key codes and variables).A total of 196 children and 84 parents/guardians completed a survey  of children surveyed reported eating breakfast and 75% (N = 147) a healthy lunch on a club day. Of those not eating breakfast at club, 12% (N = 24) reported eating breakfast at home before going to club. When asked to respond “yes (including ‘sometimes’)” or “no” to statements regarding food intake at club compared to food intake at home, 67% (N = 131), 66% (N = 129), and 81% (N = 159) reported “yes” to consuming; more fruit and vegetables, fewer sugary snacks and fewer sugary and fizzy drinks, respectively, at club. One in 5 children (N = 39) reported that they do not get enough to eat at home because they run out of food and 28% (N = 55) reported feeling hungry at home a lot.Among parental survey responses, 36% (N = 27) and 11% (N = 7) reported that their child ate unhealthy foods or not enough food, respectively, when the club was not open. One‐fifth of parents (N = 17) reported meal skipping so that their child would have food to eat. With the running of the club, 53% (N = 44) stated that food lasted longer at home and 36% (N = 16) reported fewer meal skipping than they usually would during holiday months.Valid accelerometer data were available for 24% (N = 48) of surveyed children, with an equal split of both sexes. No differences  were observed between the sub‐sample of children provided with an accelerometer and the wider study population. Of the 78 accelerometers given out, 3 were unreturned, 10 had faulty data and 17 did not meet the inclusion criteria. We found that sex and material deprivation were predictive of data validity, with boys and those reporting greater material deprivation scores more likely to provide insufficient data (p ≤ .05 on both accounts). The goal of the intervention was for children to achieve the recommended 60 minutes of MVPA at club. Accelerometer data (Table Themes within 3 domains emerged from the interviews and focus group data: 1) use of existing school facilities and staff, (2) the power of partnerships and a flexible model, and (3) involving the whole family. Table  use of eA common theme across all staff interviews was the benefit of using the school facilities and the recruitment of existing staff members. Positive themes related to the use of high‐quality, trained staff, staff familiarity with children and families attending, and the opportunity for continual learning in future term times . Echoing staff, parents highlighted the reassurance felt of using a safe and secure environment with trusted staff running the club.Exploiting the use of existing school facilities, in particular kitchen facilities and sports equipment was also highlighted, with catering staff emphasizing the ease of maintaining usual practice throughout the summer holidays, when facilities usually remained unused. Some staff perceived that hosting a Food and Fun club within the school setting was conducive to geographical targeting rather than other approaches which may lead to the labeling or stigmatizing of those families invited.A number of staff perceived the ability to create an environment enabling child autonomy and agency as an important aspect for catering to children's needs. Specific examples provided by staff included the style of authority adopted, for example, a play‐worker verses teacher approach, and adopting fun activities. Additionally, staff explicitly stated the need to avoid standard classroom activities, with some staff reporting a similarity between nutrition sessions and standard school lessons. The dislike of such instances was also expressed by children during focus groups.The ability to tailor the Food and Fun model at a local community level was found to be important. While all staff reported the provision of the standard Food and Fun daily components, 2 positive themes related directly to the running of the club: partnership working and flexibility of the model.Staff discussed the value of drawing on local assets and engaging with external organizations, relaying how this process revealed alternative ways of using existing school resources and enhanced the professional development of staff. Children and parents remarked on the variety and novelty of the activities delivered by both staff and volunteers at the club, with children stating that they had never had these opportunities before. While expressing their enjoyment of having a full‐timetable of activities, children also highlighted the enjoyment of undertaking free play where it was available. Alongside positive reports of wide community engagement, some parents noted the number of competing free schemes within the community. This was highlighted as a barrier for child attendance alongside inadequate advertising and a lack of transport to club.The importance of the model's flexibility was prominent in both staff and parental interviews. Staff perceived flexibility as instrumental to the recruitment and retention of quality staff and to the general running of the day, reporting ownership over daily content and delivery in achieving the club's aims and objectives. Parents positively viewed club opening times, stating that flexibility supported attendance. For example, running over a series of weeks allowed a trial period if their child was anxious or unsettled, a concern noted by parents, or attending for only some days if they had prior commitments.Children, parents and other family members expressed their enjoyment of sharing mealtimes together, with opportunities to share experiences and also socialize with other parents and community members. Staff and volunteers emphasized the value of a whole family approach, in order to achieve the club's aims and ethos and to engage hard to reach families. At clubs where this was particularly evident, staff and local agencies welcomed the opportunity to build new relationships with families and exchange information. On the other hand, some parents deemed the specific targeting of families as stigmatizing and did not feel this was appropriate for a summer holiday initiative.Parents liked having direct, open access to school staff and the school environment. Many parents said this gave them fresh insights, new perspectives and a deeper understanding of how their children behaved and interacted with others in school. In instances where existing school staff and volunteers were employed to deliver the club, familiarity was noted as a way of appeasing family concerns of attending club and building rapport, highlighted during parent focus groups.This study is the first to evaluate opportunities for summer holiday provision within the school‐setting in the United Kingdom. Findings from the 10 school sites highlighted that opportunities for children to eat 2 healthy meals a day and meet physical activity guidelines can be provided during the summer holiday period.In our sample, a lack of food availability during usual school holiday practices was evident. Nearly one‐third of children reported insufficient food and feeling hungry a lot at home and one‐fifth of parents reported meal skipping in order to provide food for their child. In the context of food provision, positive findings emerged from attending a Food and Fun club, with over half of parents reporting that the club enabled them to make food last longer and over one‐third having to skip fewer meals than they usually would during holiday months. The club aimed to provide children with 2 healthy meals a day, of which the majority of children reported consuming breakfast and three‐fourths a healthy lunch.a must for interventions aiming to address social inequalities.We found reports of healthier dietary intake among children at club, with fewer sugary snacks, fewer sugary drinks, and a greater intake of fruits and vegetables compared to diets at home. Findings from the current study suggest the potential for a dual mechanism, whereby food provision at club is not only addressing the lack of food availability during the school holidays but also replacing unhealthy food items with healthier alternatives. The importance of such mechanism has been stressed previously,Our results are consistent with prior findings from the United States that children are more likely to consume healthier diets during the school holidays if they are involved in a structured environment .To date a limited number of studies have directly examined levels of child activity during school holidays with existing reports largely concerning child fitness levels.The Food and Fun initiative consists of a 1‐hour daily physical activity session delivered by a member of staff or external sporting agency. Our findings indicated that the dose of physical activity was inconsistent, with over a quarter of children not achieving the recommended 1‐hour of MVPA on club days. Even though children were more likely to be active while attending club and the majority reported breathlessness and sweating during activities, our findings question the intensity and structure of sessions as not all children achieved the recommended levels on club days. Further research with a larger sample and use of observations would help identify the content, delivery, and involvement of children within these sessions.The results provide new evidence regarding the use of the school setting for providing holiday provision within the UK‐setting. We identified 3 main elements underpinning the delivery of a Food and Fun club: use of existing facilities, whole family approach and the power of partnerships and a flexible model. As such, the Food and Fun initiative demonstrates a working example of current policy recommendations,As a small‐scale evaluation with a cross‐sectional design, our findings are subject to several limitations including small sample size, selection and reporting bias, and limited generalizability. Measures of healthy eating opportunities were obtained from self‐reports and not direct observations, however, it is important to acknowledge that Food and Fun clubs benefit from school regulations with all meals adhering to Healthy School nutritional standards. The use of accelerometry increased the quality of activity data collected yet problems encountered such as unreturned devices and lack of wear time significantly reduced the anticipated data pool, often common reporting of accelerometry use within studies.This study represents an important early step in our understanding of how the school environment can aid the delivery of initiatives, such as Food and Fun clubs, during the school summer holidays. The school environment appeared to play a pivotal role in facilitating child and family attendance, with factors such as familiarity, safety, and resources influencing outcomes. Findings regarding the dose and fidelity of the intervention highlight areas that require further attention if any future full‐scale evaluation is to be carried out.Previous research suggests that food insecurity is a growing issue for school‐aged children and is linked to various adverse health and educational outcomes.Our findings offer some insight into delivery approaches to such initiatives that may be particularly acceptable and feasible to students and their parents, as well as to the staff that deliver them. For example, engaging existing school staff in such initiatives can be important for ensuring high‐quality delivery and for capitalizing on existing relationships and familiarity between staff, students, and parents. Employing external staff to run such initiatives may not be as well received. While our data suggest that initiatives should be coordinated and overseen by existing school staff, engaging external community organizations to support delivery of specific activities can help enhance the initiative; providing children with opportunities to try new experiences as well as creating links with community‐based opportunities for future engagement. In addition, regarding the content and focus of activities provided during such initiatives, our findings suggest that activities should be substantially different from typical classroom lessons, with an emphasis on fun and enjoyment.In terms of the practical implications on a day‐to‐day basis, schools should aim to maximize attendance through ensuring the initiative is accessible with transportation options. Schools should also seek to engage students' families on a weekly basis. This would allow further opportunities to maximize child attendance and provide time to impact positively on relationships between schools and families, and between families themselves.The School of Social Sciences Research Ethics Committee at Cardiff University (SREC/1882) approved this study.


South Asia is home to the largest number of stunted children worldwide: 65 million or 37% of all South Asian children under 5 were stunted in 2014. The costs to society as a result of stunting during childhood are high and include increased mortality, increased morbidity (in childhood and later as adults), decreased cognitive ability, poor educational outcomes, lost earnings and losses to national economic productivity. Conversely, investing in nutrition provides many benefits for poverty reduction and economic growth. This article draws from analyses conducted in four sub‐Saharan countries to demonstrate that investments in nutrition can also be very cost‐effective in South Asian countries. Specifically, the analyses demonstrate that scaling up a set of 10 critical nutrition‐specific interventions is highly cost‐effective when considered as a package. Most of the interventions are also very cost‐effective when considered individually. By modelling cost‐effectiveness of different scale‐up scenarios, the analysis offers insights into ways in which the impact of investing in nutrition interventions can be maximized under budget constraints. Rigorous estimations of the costs and benefits of nutrition investments, similar to those reported here for sub‐Saharan countries, are an important next step for all South Asian countries in order to drive political commitment and action and to enhance allocative efficiency of nutrition resources. The first 2 years of life – the first 1000 days between conception and age 2 – are the critical period for growth and development, while growth at older ages does not have the same effect on adult height and brain development  averted.2This work is ongoing by the World Bank with the support of the Bill and Melinda Gates Foundation. Scale‐up costs were estimated for 10 interventions in four African countries: Democratic Republic of the Congo (DRC), Mali, Nigeria and Togo.The preliminary results presented next are part of a larger effort to assess the cost and cost‐effectiveness of investing in nutrition in sub‐Saharan Africa.Lancet series on Maternal and Child Undernutrition  protocols or guidelines for large‐scale programming. In other cases, the capacity for scaling up the interventions is limited. Only those nutrition‐specific interventions that have strong evidence of effectiveness have a WHO protocol, and a feasible delivery mechanism for scale‐up is included.The 10 nutrition‐specific interventions considered are a modified package of the interventions included in the 2008 and 2013 Unit costs for each intervention were obtained from published sources or from in‐country stakeholders including governmental agencies, development partners and non‐governmental organizations implementing activities related to nutrition during in‐person interviews and remote follow‐up. Costing methodology followed the programme experience approach where the unit cost (cost per beneficiary) was calculated based on the budget/expenditure estimates of agencies implementing the interventions in each country. This approach generates unit cost data that capture all aspects of service delivery, including the costs of commodities, transportation and storage, personnel, training, supervision, monitoring and evaluation, relevant overhead and wastage for each intervention from actual programmes that are already in operation. Although the programme experience approach tends to yield cost estimates higher than those of the ingredient‐based approach, these estimates more accurately reflect real programmatic experience, including inefficiencies in service delivery. It should, however, be noted that the calculated costs are reported in financial or budgetary terms. They do not capture the full social resource requirements, which account for the opportunity costs of the time committed by beneficiaries accessing the services.Programme coverage data were obtained from the most recent Demographic and Health Survey (DHS), Multiple Indicator Cluster Survey or Standardized Monitoring and Assessment of Relief and Transitions survey in each country. Nutrition status, health and other demographic data were obtained from the most recent DHS or Multiple Indicator Cluster Survey. Population data were obtained from the most recent available national census and supplemented, if needed, by the DHS data .Y = (x1 + x2) − x3 where Y is the annual public investment required to scale‐up to full coverage; x1 is the additional total cost to scale‐up to full coverage; x2 is the additional cost for capacity development, monitoring and evaluation, and technical assistance; and x3 is the cost covered by households living above poverty line for selected interventions.The cost for the scale‐up of each intervention was calculated as follows: We have assumed a linear relationship between the cost and coverage with no economies or diseconomies of scale at the country level. ‘Full coverage’ is defined as 100% of the target population for all interventions except for community‐based treatment of severe acute malnutrition, for which full coverage is assumed to be 80%.3http://www.livessavedtool.org/.For details on the tool, see  Based on the lives saved and cases of stunting averted estimated using LiST, DALYs are estimated following the established convention of counting one life saved as 33.3 discounted DALYs averted and one case of stunting as 0.23 discounted DALY averted  DALYs averted, (2) number of lives saved and (3) cases of childhood stunting averted. The projected number of lives saved and the cases of childhood stunting averted are calculated using the Lives Saved Tool (LiST), which models reductions in mortality and prevalence of under‐5 stunting resulting from changes in intervention coverage.Estimates of benefits were combined with information on costs to produce the cost‐effectiveness measures for each intervention as well as for the overall package of interventions. The measures for cost‐effectiveness of nutrition‐specific interventions are calculated in terms of cost per DALY averted, cost per life saved and cost per case of stunting averted. The evaluation of cost‐effectiveness ratio in terms of DALYs averted is based on societal willingness to pay thresholds based on GDP per capita, using the categorization developed by WHO‐CHOICE WHO . An inteIn each country, we estimated the cost and impact of scaling up the high‐impact intervention at the national level . Given resource constraints, few countries are able to effectively scale‐up all 10 nutrition‐specific interventions to full national coverage immediately. We therefore model potential partial scale‐up scenarios with lower overall costs, based on considerations of burden of stunting, potential for impact, costs and capacity for implementation in the specific country. Three approaches are considered: (1) scaling up only in the regions with the highest burden of malnutrition; (2) scaling up only a subset of interventions nationwide; and (3) scaling up a subset of interventions only in the regions with the highest burden of malnutrition.6et al. More detailed results are presented in Shekar  The costs to scale‐up vary substantially across countries, ranging from US$13m in Togo to US$837m in Nigeria. The differences in the scale‐up costs are a result of variation in the number of beneficiaries, baseline coverage of the interventions and in unit costs. Based on the modelling results, the investments would save 115 000 DALYs in Togo, 509 000 DALYs in Mali, 2.6 million DALYs in the DRC and 6.3 million DALYs in Nigeria. For each country, the scale‐up would also save between 3000 and 180 000 lives and prevent between 60 000 and 3 million cases of stunting annually. Based on the WHO‐CHOICE criteria of cost‐effectiveness, investing in the scale‐up of the full intervention package is estimated to be very cost‐effective in each of the four countries.Table Most of the interventions – with the exception of the public provision of complementary food for the prevention of moderate acute malnutrition – are ‘very cost‐effective’ when considered individually Table . Across 7The criteria for highest burden of stunting are country specific as follows: stunting rates greater than 45% and severe stunting greater than 25% (DRC); stunting rates greater than 40% ; and 13 States with stunting rates greater than 35% (Nigeria). This scenario was not estimated for Togo. (2) scale‐up only the most cost‐effective interventions or (3) scale‐up the most cost‐effective interventions in the highest burden regions. Table Finally, we compared the full national coverage scenario with more limited scale‐up scenarios that (1) target only the regions with highest burden of stunting,et al. et al. This paper contributes to the existing literature on the cost of scaling up nutrition interventions  and very cost‐effective in the other two (Nigeria and Togo), it is nevertheless between two and eight times more costly per DALY averted than the next least cost‐effective intervention. Therefore, in countries like the four examined here, where fiscal and capacity constraints will limit scale‐up, certain expensive interventions – such as the public provision of complementary foods – may be a lower priority. Furthermore, issues of governance, accountability and supply logistics will all put pressure on the cost and complicate the scale‐up of the public provision of complementary foods.The cost per DALY and other outcomes were consistent in magnitude but varied slightly across the four countries. Overall, the cost per outcome was the highest in Mali  and lowest in Togo  and DRC . The differences between countries are driven mostly by the differences in unit costs of the specific interventions and, to a much smaller extent, by the differences in the baseline coverage in and, consequently, cost of filling the coverage gaps and its impact on morbidity and mortality.Scaling up high‐impact interventions  was the most cost‐effective strategy. Whether these interventions were scaled up nationwide or only in the highest burden regions did not affect their cost‐effectiveness by much. However, there was a large total cost differential between the two scenarios, and therefore in most cases, the selection between the two scale‐up scenarios hinges mainly on the availability of public resources for scaling up nutrition interventions. These results are not counterintuitive. However, they demonstrate that data‐based planning that incorporates both local need, current coverage of interventions and economic analysis is needed to ensure that investment in nutrient has the greatest possible impact. This is particularly important given the severe resource constraints faced by countries with high burdens of malnutrition.et al. At present, rigorous country estimates of the costs and benefits of nutrition investments similar to those available for some sub‐Saharan countries do not exist for South Asia. The one analysis in Bangladesh estimated that the $1.3–1.7bn cost of implementing a comprehensive package of interventions to improve health status of child under 2 years of age was much smaller than the $10bn loss to GDP because of productivity losses resulting from inaction . Coverage rates of micronutrient supplement programmes are low: only 24% of pregnant women take iron–folic acid supplements during pregnancy; only 68% of children age 6–59 months receive vitamin A supplementation; and only 70% of the South Asia population uses iodized salt (International Food Policy Research Institute et al. 8There are two schools of thought as to why there is currently very little evidence. Some believe that there is little evidence of impact of agricultural interventions on nutrition outcomes because indeed they have no effect. This is referred to as the ‘agriculture–nutrition disconnect’. Another school of thought is that very few agricultural interventions have been designed such as to have an impact on nutrition and so the lack of evidence is inevitable. However, if these interventions were indeed designed to have an impact on nutrition, they could become critical mechanisms for building the evidence base for nutrition‐sensitive programming. Second, compared with nutrition‐specific interventions, estimating and attributing the costs of nutrition‐sensitive interventions is more complex because these interventions have multiple objectives, improved nutrition outcomes being only one of them. Notwithstanding these limitations, the availability of costing information is crucial to assess cost‐effectiveness of these interventions and is needed to engage other sectors in planning for nutritional effects.Although the results reported here are limited to ‘nutrition‐specific’ interventions delivered through the health sector, multisectoral ‘nutrition‐sensitive’ actions through agriculture sector, social protection, water and sanitation and poverty reduction programmes have the potential to strengthen nutritional outcomes in several ways (Ruel South Asia is home to the largest number of children stunted worldwide.Stunting leads to increased mortality and morbidity, poor educational outcomes, lost earnings and reductions in national economic productivity, yet nutrition investments are among the most cost‐effective development actions.Analysis of four sub-Saharan countries finds that the scaling up of a set of 10 key nutrition interventions is highly cost-effective and most are very cost‐effective when considered individually.Rigorous estimations of the costs and benefits of nutrition investments are an important next step in all South Asian countries in order to drive political commitment and action.Despite overwhelming evidence of the debilitating costs of stunting, minimal resources are allocated to stunting reduction in South Asia, and where resources are allocated, these are often not focused on scaling up the most cost‐effective interventions. This is largely because stunting in South Asia continues to be invisible to and unrecognized by families, communities and especially policymakers. An appreciation of the economic costs described here can help to make stunting a more ‘visible’ challenge to development. Rigorous estimations of the costs, benefits and cost‐effectiveness of nutrition investments need to be an important next step in all South Asian countries in order to drive political commitment and action and to maximize allocative efficiencies. Knowing how many interventions would cost to scale‐up, what results these might deliver, and how to maximize the effectiveness of the investments provides governments with guidance to prioritize the most cost‐effective interventions as well as with cost‐effective ways of scaling up the interventions over time, thereby maximizing both technical and allocative efficiencies. Furthermore, these rigorous analyses are necessary to leverage new financing from both domestic budgets and overseas development aid.The authors declare that they have no conflicts of interest.MS conceptualized and led the project. MS, JDE and JK designed the research. JDE and JK conducted the analysis and wrote the paper. All authors edited and approved the final paper.