Evidence on the impact of community health workers in the prevention, identification, and management of undernutrition amongst children under the age of five in conflict-affected or fragile settings: a systematic literature review

Background Malnutrition, specifically undernutrition, is a significant global challenge that contributes to nearly half of deaths in children under the age of five. The burden of undernutrition is disproportionately borne by conflict-affected, fragile settings (CAFS); children living in a conflict zone being more than twice as likely to suffer from malnourishment. Community health worker (CHW) models have been employed in CAFS to improve healthcare coverage and identify and treat illnesses. However, there lacks systematic evidence on the impact of CHW models in preventing, identifying, and managing child undernutrition in CAFS. We conducted this review to systematically evaluate evidence of CHW models in preventing, identifying, and managing undernutrition in children under the age of five in CAFS. Methodology This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting standards. The search strategy was developed using the Population-Intervention-Comparisons-Outcomes-Setting framework as a guide. Searches were performed using Ovid online database search platform, searching the databases of Ovid MEDLINE(R), COCHRANE, Embase Classic, Embase, Econlit, Global Health, SCOPUS, and Social Policy and Practice. Peer-reviewed publications were eligible for inclusion if they evaluated an intervention using a CHW model that aims to prevent, identify, or manage some form of undernutrition in children under five in a CAFS. Results We identified 25 studies—spanning 10 countries—that were included in the systematic review. CHW models were implemented alongside a variety of interventions, including behaviour change communication, supplementary foods, nutrition counselling, and integrated community health programmes. Key barriers in implementing successful CHW models include disruption of programmes due to active conflict, states of emergency, militancy, or political unrest; weak links between the community-based interventions and public health system; weak health system capacity that impeded referral and follow-ups; and cost of care and care-seeking. Key facilitators include CHWs’ connection to the community, close proximity of programmes to the community, supervision, and investment in high quality training and tools. Conclusions The findings suggest that CHW models may be effective, cost-effective, acceptable, feasible, and scalable in the prevention, identification, and management child undernutrition in CAFS. The study findings also confirmed a need for greater evidence in the field. These findings may inform policymaking, programme implementation, and design to strengthen best practices for CHW models addressing child undernutrition in CAFS

Bridging divisions in a war-torn state: Reflections on education and civicness in South Sudan

Despite civil war and economic crisis, the educational sector in South Sudan has made tentative gains since 2011. This paper explores the everyday governance of schools in South Sudan, and the struggles of teachers to deliver education amid violence and predation and with scarce resources. It presents an analysis of policy data on education coupled with the insights of researchers and teachers from seven locations in South Sudan, drawing on interviews and a dialogue conducted by a group of South Sudanese researchers (the Bridge Network), between November 2018 and July 2019. The paper highlights commonalities between the experiences of teachers and schools across South Sudan, including the consequences of underinvestment in teachers and schools, and suggests that the notion of education as a civic right – which South Sudan’s government has comprehensively failed to uphold – may well cut across the divisions of the conflict. It emphasises the initiatives and contributions of teachers, parents, and wider communities, highlighting some of the many ways in which reliance on local communities is built into the education system and contributes to sustaining it. The discussion builds the case for investment in teachers, schools, and educational resources not only as a public good in its own right, but also as a prerequisite for long term peace and security in South Sudan

Variation in pre-PCR processing of FFPE samples leads to discrepancies in BRAF and EGFR mutation detection: a diagnostic RING trial.

Aims Mutation detection accuracy has been described extensively; however, it is surprising that pre-PCR processing of formalin-fixed paraffin-embedded (FFPE) samples has not been systematically assessed in clinical context. We designed a RING trial to (i) investigate pre-PCR variability, (ii) correlate pre-PCR variation with EGFR/BRAF mutation testing accuracy and (iii) investigate causes for observed variation. Methods 13 molecular pathology laboratories were recruited. 104 blinded FFPE curls including engineered FFPE curls, cell-negative FFPE curls and control FFPE tissue samples were distributed to participants for pre-PCR processing and mutation detection. Follow-up analysis was performed to assess sample purity, DNA integrity and DNA quantitation. Results Rate of mutation detection failure was 11.9%. Of these failures, 80% were attributed to pre-PCR error. Significant differences in DNA yields across all samples were seen using analysis of variance (p<0.0001), and yield variation from engineered samples was not significant (p=0.3782). Two laboratories failed DNA extraction from samples that may be attributed to operator error. DNA extraction protocols themselves were not found to contribute significant variation. 10/13 labs reported yields averaging 235.8ng (95% CI 90.7 to 380.9) from cell-negative samples, which was attributed to issues with spectrophotometry. DNA measurements using Qubit Fluorometry demonstrated a median fivefold overestimation of DNA quantity by Nanodrop Spectrophotometry. DNA integrity and PCR inhibition were factors not found to contribute significant variation. Conclusions In this study, we provide evidence demonstrating that variation in pre-PCR steps is prevalent and may detrimentally affect the patient's ability to receive critical therapy. We provide recommendations for preanalytical workflow optimisation that may reduce errors in down-stream sequencing and for next-generation sequencing library generation

The Effects of Gas on Morphological Transformation in Mergers: Implications for Bulge and Disk Demographics

Transformation of disks into spheroids via mergers is a well-accepted element of galaxy formation models. However, recent simulations have shown that bulge formation is suppressed in increasingly gas-rich mergers. We investigate the global implications of these results in a cosmological framework, using independent approaches: empirical halo-occupation models (where galaxies are populated in halos according to observations) and semi-analytic models. In both, ignoring the effects of gas in mergers leads to the over-production of spheroids: low and intermediate-mass galaxies are predicted to be bulge-dominated (B/T~0.5 at <10^10 M_sun), with almost no bulgeless systems), even if they have avoided major mergers. Including the different physical behavior of gas in mergers immediately leads to a dramatic change: bulge formation is suppressed in low-mass galaxies, observed to be gas-rich (giving B/T~0.1 at <10^10 M_sun, with a number of bulgeless galaxies in good agreement with observations). Simulations and analytic models which neglect the similarity-breaking behavior of gas have difficulty reproducing the strong observed morphology-mass relation. However, the observed dependence of gas fractions on mass, combined with suppression of bulge formation in gas-rich mergers, naturally leads to the observed trends. Discrepancies between observations and models that ignore the role of gas increase with redshift; in models that treat gas properly, galaxies are predicted to be less bulge-dominated at high redshifts, in agreement with the observations. We discuss implications for the global bulge mass density and future observational tests.Comment: 14 pages, 11 figures, accepted to MNRAS (matched published version). A routine to return the galaxy merger rates discussed here is available at http://www.cfa.harvard.edu/~phopkins/Site/mergercalc.htm

Murine models of renal ischemia reperfusion injury: An opportunity for refinement using noninvasive monitoring methods

BACKGROUND: Renal ischemia reperfusion injury (R‐IRI) can cause acute kidney injury (AKI) and chronic kidney disease (CKD), resulting in significant morbidity and mortality. To understand the underlying mechanisms, reproducible small‐animal models of AKI and CKD are needed. We describe how innovative technologies for measuring kidney function noninvasively in small rodents allow successful refinement of the R‐IRI models, and offer the unique opportunity to monitor longitudinally in individual animals the transition from AKI to CKD. METHODS: Male BALB/c mice underwent bilateral renal pedicle clamping (AKI) or unilateral renal pedicle clamping with delayed contralateral nephrectomy (CKD) under isoflurane anesthetic. Transdermal GFR monitoring and multispectral optoacoustic tomography (MSOT) in combination with statistical analysis were used to identify and standardize variables within these models. RESULTS: Pre‐clamping anesthetic time was one of the most important predictors of AKI severity after R‐IRI. Standardizing pre‐clamping time resulted in a more predictably severe AKI model. In the CKD model, MSOT demonstrated initial improvement in renal function, followed by significant progressive reduction in function between weeks 2 and 4. Performing contralateral nephrectomy on day 14 enabled the development of CKD with minimal mortality. CONCLUSIONS: Noninvasive monitoring of global and individual renal function after R‐IRI is feasible and reproducible. These techniques can facilitate refinement of kidney injury models and enable the degree of injury seen in preclinical models to be translated to those seen in the clinical setting. Thus, future therapies can be tested in a clinically relevant, noninvasive manner

Molecular and genealogical characterization of the R1443X BRCA1 mutation in high-risk French-Canadian breast/ovarian cancer families

The Quebec population contains about six-million French Canadians, descended from the French settlers who colonized “Nouvelle-France” between 1608 and 1765. Although the relative genetic contribution of each of these founders is highly variable, altogether they account for the major part of the contemporary French-Canadian gene pool. This study was designed to analyze the role of this founder effect in the introduction and diffusion of the BRCA1 recurrent R1443X mutant allele. A highly conserved haplotype, observed in 18 French-Canadian families and generated using 17 microsatellite markers surrounding the BRCA1 locus, supports the fact that the R1443X mutation is a founder mutation in the Quebec population. We also performed haplotyping analysis of R1443X carriers on 19 other families from seven different nationalities; although the same alleles are shared for three markers surrounding the BRCA1 gene, distinct haplotypes were obtained in four families, suggesting multiple origins for the R1443X mutation. Ascending genealogies of the 18 French Canadian families and of controls were reconstructed on an average depth of 10 generations. We identified the founder couple with the highest probability of having introduced the mutation in the population. Based on the descending genealogy of this couple, we detected the presence of geographical concentration in the diffusion pattern of the mutation. This study demonstrates how molecular genetics and demogenetic analyses can complement each other to provide findings that could have an impact on public health. Moreover, this approach is certainly not unique to breast cancer genetics and could be used to understand other complex traits

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Partnering in oncogenetic research – the INHERIT BRCAs experience : opportunities and challenges

Today it is common to conduct research in collaboration with colleagues from different disciplines and institutions. The INterdisciplinary HEalth Research International Team on BReast CAncer susceptibility (INHERIT BRCAs), involves Canadian and international experts from diverse fields working with health service providers, patients and collaborators from the World Health Organization and other European networks. Evidence-based information and knowledge transfer drive our efforts to advance genomic research to understand the genetic basis of cancer susceptibility and treatment response. Several goals reveal the interdisciplinary team approach: (a) to estimate the prevalence and penetrance of BRCA1 and BRCA2 mutations and their deleterious impact upon different populations; (b) to pinpoint novel breast cancer susceptibility loci; (c) to assess the efficacy of clinical interventions; (d) to address changes in quality of life and health-related behaviour from the decision to undergo genetics testing and during follow-up; (e) to evaluate legal, social and ethical implications; and, finally; (f) to promote professional and public education by facilitating the transfer of research findings to clinical practice and informing policy makers. The lessons learned by the INHERIT research team and future challenges are presented

An intrinsically disordered proteins community for ELIXIR.

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are now recognised as major determinants in cellular regulation. This white paper presents a roadmap for future e-infrastructure developments in the field of IDP research within the ELIXIR framework. The goal of these developments is to drive the creation of high-quality tools and resources to support the identification, analysis and functional characterisation of IDPs. The roadmap is the result of a workshop titled "An intrinsically disordered protein user community proposal for ELIXIR" held at the University of Padua. The workshop, and further consultation with the members of the wider IDP community, identified the key priority areas for the roadmap including the development of standards for data annotation, storage and dissemination; integration of IDP data into the ELIXIR Core Data Resources; and the creation of benchmarking criteria for IDP-related software. Here, we discuss these areas of priority, how they can be implemented in cooperation with the ELIXIR platforms, and their connections to existing ELIXIR Communities and international consortia. The article provides a preliminary blueprint for an IDP Community in ELIXIR and is an appeal to identify and involve new stakeholders

Mergers in Lambda-CDM: Uncertainties in Theoretical Predictions and Interpretations of the Merger Rate

Different methodologies lead to order-of-magnitude variations in predicted galaxy merger rates. We examine and quantify the dominant uncertainties. Different halo merger rates and subhalo 'destruction' rates agree to within a factor ~2 given proper care in definitions. If however (sub)halo masses are not appropriately defined or are under-resolved, the major merger rate can be dramatically suppressed. The dominant differences in galaxy merger rates owe to baryonic physics. Hydrodynamic simulations without feedback and older models that do not agree with the observed galaxy mass function propagate factor ~5 bias in the resulting merger rates. However, if the model matches the galaxy mass function, properties of central galaxies are sufficiently converged to give small differences in merger rates. But variations in baryonic physics of satellites also have dramatic effects. The known problem of satellite 'over-quenching' in most semi-analytic models (SAMs), whereby SAM satellites are too efficiently stripped of gas, could lead to order-of-magnitude under-estimates of merger rates for low-mass, gas-rich galaxies. Fixing the satellite properties to observations tends to predict higher merger rates, but with factor ~2 empirical uncertainties. Choice of mass ratio definition matters: at low masses, most true major mergers (in baryonic/dynamical galaxy mass) will appear to be minor mergers in their stellar or luminosity mass ratio. Observations and models using these criteria may underestimate major merger rates by factors ~5. Orbital parameters and gas fractions also introduce factor ~3 differences in amount of bulge formed by mergers, even for fixed mass ratio encounters.Comment: 32 Pages, 15 figures, accepted to ApJ (revised to match accepted version and correct Fig. 12