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Severe and moderate acute malnutrition (SAM and MAM) affect more than 50 million children worldwide yet 80% of these children do not access care. The Combined Protocol for Acute Malnutrition Study (ComPAS) trial assessed the effectiveness of a simplified, combined SAM/MAM protocol for children aged 6-59 months and found non-inferior recovery compared to standard care. To further inform policy, this study assessed post-discharge outcomes of children treated with this novel protocol in Kenya. Six 'combined' protocol clinics treated SAM and MAM children using an optimised mid-upper arm circumference (MUAC)-based dose of ready-to-use therapeutic food (RUTF). Six 'standard care' clinics treated SAM with weight-based RUTF rations; MAM with ready-to-use supplementary food (RUSF). Four months post-discharge, we assessed anthropometry, recent history of illness, and body composition by bioelectrical impedance analysis. Data was analysed using multivariable linear regression, adjusted for age, sex and allowing for clustering by clinic. We sampled 850 children (median age 18 months, IQR 15-23); 44% of the original trial sample in Kenya. Children treated with the combined protocol had similar anthropometry, fat-free mass, fat mass, skinfold thickness z-scores, and frequency of common illnesses 4 months post-discharge compared the standard protocol. Mean subscapular skinfold z-scores were close to the global norm (standard care: 0.24; combined 0.27). There was no significant difference in odds of relapse between protocols (SAM, 3% vs 3%, OR = 1.0 p = 0.75; MAM, 10% vs 12%, OR = 0.90 p = 0.34). Despite the lower dosage of RUTF for most SAM children in the combined protocol, their anthropometry and relapse rates at 4 months post-discharge were similar to standard care. MAM children treated with RUTF had similar body composition to those treated with RUSF and neither group exhibited excess adiposity. These results add further evidence that a combined protocol is as effective as standard care with no evidence of adverse effects post-discharge. A simplified, combined approach could treat more children, stretch existing resources further, and contribute to achieving Sustainable Development Goal Two.

Systematic reviews have highlighted that repeated severe wasting after receiving treatment is likely to be common, but standardised measurement is needed urgently. The Council of Research & Technical Advice for Acute Malnutrition (CORTASAM) released recommendations on standard measurement of relapse (wasting within 6 months after exiting treatment as per recommended discharge criteria), regression (wasting within 6 months after exiting treatment before reaching recommended discharge criteria) and reoccurrence (wasting after 6 months of exit from treatment as per recommended discharge criteria). We provide a theoretical framework of post‐treatment relapse and regression to severe wasting to guide discussions, risk factor analyses, and development and evaluations of interventions. This framework highlights that there are factors that may impact risk of relapse and regression in addition to the impact of contextual factors associated with incidence and reoccurrence of severe wasting more generally. Factors hypothesised to be associated with relapse and regression relate specifically to the nutrition and health status of the child on admission to, during and exit from treatment and treatment interventions, platforms and approaches as well as type of exit from treatment (e.g., before reaching recommended criteria). These factors influence whether children reach full recovery, and poorer nutritional and immunological status at exit from treatment are more proximate determinants of risk of severe wasting after treatment, although post‐treatment interventions may modify risks. The evidence base for many of these factors is weak. Our framework can guide research to improve our understanding of risks of relapse and regression and how to prevent them and inform programmes on what data to collect to evaluate relapse. Implementation research is needed to operationalise results in programmes and reduce post‐treatment severe wasting at scale.

IntroductionEstimates of incident cases of severe wasting among young children are not available for most settings but are needed for optimal planning of treatment programmes and burden estimation. To improve programme planning, global guidance recommends a single ‘incidence correction factor’ of 1.6 be applied to available prevalence estimates to account for incident cases. This study aimed to update estimates of the incidence correction factor to improve programme planning and inform the approach to burden estimation for severe wasting.MethodsA global call was issued for secondary data from severe wasting treatment programmes including prevalence, population size, programme admission and programme coverage through a UNICEF-led effort. Site-specific incidence correction factors were calculated as the number of incident cases (annual programme admissions/programme coverage) divided by the number of prevalent cases (prevalence*population size). Estimates were aggregated by country, region and overall using inverse-variance weighted random-effects meta-analysis.ResultsWe estimated incidence correction factors from 352 sites in 20 countries. Estimates aggregated by country ranged from 1.3 (Nigeria) to 30.1 (Burundi). Excluding implausible values, the overall incidence correction factor was 3.6 (95% CI 3.4 to 3.9).ConclusionOur results suggest that incidence correction factors vary between sites and that the burden of severe wasting will often be underestimated using the currently recommended incidence correction factor of 1.6. Application of updated incidence correction factors represents a simple way to improve programme planning when incidence data are not available and could inform the approach to burden estimation.

Background Acute malnutrition is currently divided into severe (SAM) and moderate (MAM) based on level of wasting. SAM and MAM currently have separate treatment protocols and products, managed by separate international agencies. For SAM, the dose of treatment is allocated by the child’s weight. A combined and simplified protocol for SAM and MAM, with a standardised dose of ready-to-use therapeutic food (RUTF), is being trialled for non-inferior recovery rates and may be more cost-effective than the current standard protocols for treating SAM and MAM. Method This is the protocol for the economic evaluation of the ComPAS trial, a cluster-randomised controlled, non-inferiority trial that compares a novel combined protocol for treating uncomplicated acute malnutrition compared to the current standard protocol in South Sudan and Kenya. We will calculate the total economic costs of both protocols from a societal perspective, using accounting data, interviews and survey questionnaires. The incremental cost of implementing the combined protocol will be estimated, and all costs and outcomes will be presented as a cost-consequence analysis. Incremental cost-effectiveness ratio will be calculated for primary and secondary outcome, if statistically significant. Discussion We hypothesise that implementing the combined protocol will be cost-effective due to streamlined logistics at clinic level, reduced length of treatment, especially for MAM, and reduced dosages of RUTF. The findings of this economic evaluation will be important for policymakers, especially given the hypothesised non-inferiority of the main health outcomes. The publication of this protocol aims to improve rigour of conduct and transparency of data collection and analysis. It is also intended to promote inclusion of economic evaluation in other nutrition intervention studies, especially for MAM, and improve comparability with other studies. Trial Registration ISRCTN 30393230 , date: 16/03/2017.

Background Program decision-making to prevent and treat acute malnutrition in an emergency can be hampered by a lack of accessible and relevant overviews of directly available robust research evidence. There is often evidence from related settings such as from low-income countries, but this is dispersed across many databases, may be inaccessible and requires assessment of its relevance to the humanitarian setting. We describe a process whereby a multi-disciplinary, international group of specialists worked together to build relevant and effective collections of available systematic reviews on acute malnutrition, published and disseminated as online collections, to improve access to the evidence and concise, synthesised, relevant up to date evidence for programming. By describing this process, we hope to inspire other professional groups to take part in similar multi-stakeholder, multi-disciplinary projects. Objectives This project was designed to make the evidence from relevant systematic reviews about malnutrition as accessible as possible to support evidence-based decision-making and to guide future research on the prevention and treatment of acute malnutrition in humanitarian emergencies. Methods Between March 2017 and March 2018, a large group (21 volunteers and stakeholders) with different backgrounds collaborated to review and curate collections of systematic reviews of interventions for the prevention and treatment of moderate and severe acute malnutrition relevant to humanitarian emergencies. The methodology loosely followed general guidance for overviews of systematic reviews with a pre-defined question (formulated using the PICOS format) and search strategies applied to multiple databases. Pairs of collaborators first screened the search yields to identify potentially eligible reviews, where after other pairs screened the list of potentially eligible reviews for relevance and thus included in the final collections. Results Search strategies were run in 12 databases, in the week of 15 September 2017, yielding a total of 4646 records after de-duplication. At this point, Cochrane reviews ( n  = 463) and non-Cochrane reviews ( n  = 4183) were separated and handled by different teams to compile three linked collections, namely the Evidence Aid Collection, consisting of relevant non-Cochrane reviews, and two Cochrane Special Collections, consisting of relevant Cochrane reviews, one for prevention and the other for treatment of acute malnutrition. The collections were published on the Evidence Aid website on 12 March 2018 and Cochrane website in August 2018. Discussion Through this collaboration, we have successfully generated three collections of systematic reviews to guide prevention and management of acute malnutrition in humanitarian emergencies: an Evidence Aid collection of non-Cochrane reviews, and two Cochrane Special Collections of Cochrane reviews. These collections provide accessible synthesised evidence that can be used to inform decision-making on strategies and policies in the humanitarian emergency and disaster risk reduction sectors and to guide future research by identifying gaps in robust evidence and areas that are under-researched. These collections did not set out to assess methodological quality, appraise in detail what the reviews found or summarise the evidence, but rather to curate the identified relevant systematic reviews into online resources for others to use. This unique collaboration of different individuals, organisations and stakeholders, and the collation of robust evidence can be repeated for other subjects, and Evidence Aid is eager to support new collections around other topics relevant to humanitarian emergencies.

An estimated 49.5 million children under five years of age are wasted. There is a lack of robust studies on effective interventions to prevent wasting. The aim of this study was to identify and prioritise the main outstanding research questions in relation to wasting prevention to inform future research agendas. A research prioritisation exercise was conducted following the Child Health and Nutrition Research Initiative method. Identified research gaps were compiled from multiple sources, categorised into themes and streamlined into forty research questions by an expert group. A survey was then widely circulated to assess research questions according to four criteria. An overall research priority score was calculated to rank questions. The prioritised questions have a strong focus on interventions. The importance of the early stages of life in determining later experiences of wasting was highlighted. Other important themes included the identification of at-risk infants and young children early in the progression of wasting and the roles of existing interventions and the health system in prevention. These results indicate consensus to support more research on the pathways to wasting encompassing the in-utero environment, on the early period of infancy and on the process of wasting and its early identification. They also reinforce how little is known about impactful interventions for the prevention of wasting. This exercise provides a five-year investment case for research that could most effectively improve on-the-ground programmes to prevent child wasting and inform supportive policy change.

Background: Child wasting is highly prevalent, with around 49.5 million children under five years affected globally. More evidence is needed to inform the scale up of effective treatment of wasted children worldwide. The aim of this study was to identify and prioritise the main outstanding research questions relating to the treatment of wasting to inform future research agendas. Methods: A research prioritisation exercise was undertaken using the Child Health and Nutrition Research Initiative method. Research gaps were identified from multiple sources, grouped in themes and condensed into a list of 53 research areas by a group of experts. An online survey was developed and circulated globally to individuals working in the global nutrition sector. Participants evaluated each research area according to four agreed criteria. Research areas were then ranked according to an overall research priority score. Results: A total of 394 individuals from 63 countries participated in the survey. Research areas prioritised by the group focused on the effective detection and diagnosis of 'high risk' wasted children in the community; provision of a continuum of care; and early life course interventions. The group also prioritised evidence to inform guidance on the impatient management of wasted children with diarrhoea; prevention of post-treatment relapse and mortality; and the optimisation of ready-to-use therapeutic foods in treatment programmes. Conclusions: Critical gaps in our understanding of the treatment of wasting must be filled to inform guidance, policy and programming to ensure that all wasted children receive the treatment services that they need. A coordinated research agenda across treatment and prevention is urgently needed to maximise the impact of funding investments towards the meeting of global targets to reduce child wasting.

The plant-specific translation initiation complex eIFiso4F is encoded by three genes in Arabidopsis (Arabidopsis thaliana)—genes encoding the cap binding protein eIFiso4E (eifiso4e) and two isoforms of the large subunit scaffolding protein eIFiso4G (i4g1 and i4g2). To quantitate phenotypic changes, a phenomics platform was used to grow wild-type and mutant plants (i4g1, i4g2, i4e, i4g1 x i4g2, and i4g1 x i4g2 x i4e [i4f]) under various light conditions. Mutants lacking both eIFiso4G isoforms showed the most obvious phenotypic differences from the wild type. Two-dimensional differential gel electrophoresis and mass spectrometry were used to identify changes in protein levels in plants lacking eIFiso4G. Four of the proteins identified as measurably decreased and validated by immunoblot analysis were two light harvesting complex binding proteins 1 and 3, Rubisco activase, and carbonic anhydrase. The observed decreased levels for these proteins were not the direct result of decreased transcription or protein instability. Chlorophyll fluorescence induction experiments indicated altered quinone reduction kinetics for the double and triple mutant plants with significant differences observed for absorbance, trapping, and electron transport. Transmission electron microscopy analysis of the chloroplasts in mutant plants showed impaired grana stacking and increased accumulation of starch granules consistent with some chloroplast proteins being decreased. Rescue of the i4g1 x i4g2 plant growth phenotype and increased expression of the validated proteins to wild-type levels was obtained by overexpression of eIFiso4G1. These data suggest a direct and specialized role for eIFiso4G in the synthesis of a subset of plant proteins.

The relation between reading ability and phonological coding and awareness (PCA) skills in individuals who are severely and profoundly deaf was investigated with a metaanalysis. From an initial set of 230 relevant publications, 57 studies were analyzed that experimentally tested PCA skills in 2,078 deaf participants. Half of the studies found statistically significant evidence for PCA skills and half did not. A subset of 25 studies also tested reading proficiency and showed a wide range of effect sizes. Overall PCA skills predicted 11% of the variance in reading proficiency in the deaf participants. Other possible modulating factors, such as task type and reading grade level, did not explain the remaining variance. In 7 studies where it was measured, language ability predicted 35% of the variance in reading proficiency. These meta-analytic results indicate that PCA skills are a low to moderate predictor of reading achievement in deaf individuals and that other factors, most notably language ability, have a greater influence on reading development, as has been found to be the case in the hearing population.

Children typically acquire their native language naturally and spontaneously at a very young age. The emergence of early grammar can be predicted from children's vocabulary size and composition (Bates et al., 1994; Bates, Bretherton & Snyder, 1998; Bates & Goodman, 1997). One central question in language research is understanding what causes the changes in early language acquisition. Some researchers argue that the qualitative and quantitative shifts in word learning simply reflect the changing character of the child's cognitive maturity (for example, Gentner, 1982), while others argue that the trajectory of early language acquisition is driven by the child's growing familiarity with the language (Gillette, Gleitman, Gleitman & Lederer, 1999; Snedeker & Gleitman, 2004). These hypotheses are difficult to adjudicate because language acquisition in virtually all hearing children begins from birth and occurs simultaneously with cognitive development and brain maturation. The acquisition of sign languages, in contrast, is frequently delayed until older ages. In the USA, over 90% of deaf children are born to hearing parents who do not use sign language (Schein, 1989). As a result, deaf children are often exposed to sign language as a first language at a range of ages well beyond infancy (Mayberry, 2007). In rare cases, some deaf individuals are isolated from all linguistic input until adolescence when they start receiving special services and begin to learn sign language through immersion (Morford, 2003). Case studies of language acquisition in such extreme late first-language (L1) learners provide a unique opportunity to investigate first-language learning. The current study investigates three cases of young teens who are in the early stages of acquiring American Sign Language (ASL) as a first language, to determine what first-language acquisition in adolescence looks like.