HARVESTMAN: a framework for hierarchical feature learning and selection from whole genome sequencing data.

BACKGROUND: Supervised learning from high-throughput sequencing data presents many challenges. For one, the curse of dimensionality often leads to overfitting as well as issues with scalability. This can bring about inaccurate models or those that require extensive compute time and resources. Additionally, variant calls may not be the optimal encoding for a given learning task, which also contributes to poor predictive capabilities. To address these issues, we present HARVESTMAN, a method that takes advantage of hierarchical relationships among the possible biological interpretations and representations of genomic variants to perform automatic feature learning, feature selection, and model building. RESULTS: We demonstrate that HARVESTMAN scales to thousands of genomes comprising more than 84 million variants by processing phase 3 data from the 1000 Genomes Project, one of the largest publicly available collection of whole genome sequences. Using breast cancer data from The Cancer Genome Atlas, we show that HARVESTMAN selects a rich combination of representations that are adapted to the learning task, and performs better than a binary representation of SNPs alone. We compare HARVESTMAN to existing feature selection methods and demonstrate that our method is more parsimonious-it selects smaller and less redundant feature subsets while maintaining accuracy of the resulting classifier. CONCLUSION: HARVESTMAN is a hierarchical feature selection approach for supervised model building from variant call data. By building a knowledge graph over genomic variants and solving an integer linear program , HARVESTMAN automatically and optimally finds the right encoding for genomic variants. Compared to other hierarchical feature selection methods, HARVESTMAN is faster and selects features more parsimoniously.

Thermochromic Polymer Film Sensors for Detection of Incipient Thermal Damage in Carbon Fiber⁻Epoxy Composites.

Carbon fiber⁻epoxy composites have become prevalent in the aerospace industry where mechanical properties and light weight are at a premium. The significant non-destructive evaluation challenges of composites require new solutions, especially in detecting early-stage, or incipient, thermal damage. The initial stages of thermal damage are chemical rather than physical, and can cause significant reduction in mechanical properties well before physical damage becomes detectable in ultrasonic testing. Thermochromic fluorescent probe molecules have the potential to sense incipient thermal damage more accurately than traditional inspection methods. We have designed a molecule which transitions from a colorless, non-fluorescent state to a colorful, highly fluorescent state when exposed to temperature⁻time combinations that can cause damage in composites. Moreover, this molecule can be dispersed in a polymer film and attached to composite parts as a removable sensor. This work presents an evaluation of the sensor performance of this thermochromic film in comparison to ultrasonic C-scan as a method to detect incipient thermal damage in one of the most widely used carbon fiber⁻epoxy composite systems. Composite samples exposed to varying thermal exposures were used to evaluate the fluorescent thermal sensor films, and the results are compared to the results of ultrasonic imaging and short-beam shear tests for interlaminar shear strength.

Coverage and Utilization in Food Fortification Programs: Critical and Neglected Areas of Evaluation.

The need for evidence to inform nutrition program design and implementation has long been recognized, yet the generation and use of evidence for program decision making has lagged. The results of the coverage surveys reported in this supplement highlight some of the strengths and areas for improvement of current population-based (i.e., staple foods and condiments) and targeted (e.g., foods for infants and young children) fortification programs. Among other topics, the results identify a few striking successful fortification programs whereby the majority of the food vehicle used is fortifiable and fortified, and coverage is equitable among those classified as vulnerable and not. Other programs have great potential based on very high use of a fortifiable food vehicle, including in most cases among the vulnerable, but that potential is not currently reached because of low compliance with fortification requirements. Programs were also identified whereby the food vehicle has limited potential to make public health contributions to micronutrient intake, given the low proportions of the population who consume the food vehicle in general or who consume the fortifiable food vehicle. Four key lessons were learned: 1) the potential for impact of food fortification depends on the appropriate choice of food fortification vehicle but also on the proportion of the food vehicle consumed that is fortifiable; 2) the design of fortification programs should be informed by the magnitude and distribution of inadequate intake and deficiency and consumption of fortifiable foods, and part of micronutrient deficiency control strategies to ensure coordination with other programs; 3) effective quality control of fortification levels in foods urgently needs strengthening, including the many governance and other policy factors that influence the capacity, resources, and commitment to do this; 4) periodic review of the assumptions related to dietary patterns that underpin food fortification is needed to ensure continual safe and impactful programs.

Integrating Vitamin A Supplementation at 6 months into the Expanded Program of Immunization in Sierra Leone.

Since 2004, twice-yearly mass vitamin A supplementation (VAS) has equitably reached over 85% of children 6-59 months old in Sierra Leone. However infants who turn 6 months after the event may wait until they are 11 months old to receive their first dose. The effectiveness of integrating VAS at 6 months into the Expanded Program of Immunization (EPI) in a revised child health card was studied. Health facilities matched according to staff cadre and work load were assigned to provide either a 'mini package' of VAS and infant and young child feeding (IYCF), a 'full package' of VAS, IYCF and family planning (FP), or 'child health card' only. 400 neonates were enrolled into each group, caregivers given the new child health card and followed until they were 12 months old. More infants in the full: 74.5% and mini: 71.7% group received VAS between 6 and 7 months of age compared with the new CH card only group: 60.2% (p = 0.002, p < 0.001 respectively). FP commodities were provided to 44.5% of caregivers in the full compared with <2.5% in the mini and new child health card only groups (p < 0.0001). Integration of VAS within the EPI schedule achieved >60% coverage for infants between 6 and 7 months of age. Provision of FP and/or IYCF further improved coverage. Funding was provided by the Canadian Department of Foreign Affairs, Trade and Development who had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Comparison of the estimated cost-effectiveness of preventive and therapeutic zinc supplementation strategies for reducing child morbidity and mortality in sub-Saharan Africa.

BACKGROUND: Zinc supplementation of young children in lower-income countries reduces morbidity from diarrhea and pneumonia and all-cause mortality, but the most cost-effective approach for distributing zinc supplements is unknown. OBJECTIVE: To examine the potential impact of four possible strategies for delivering zinc supplements on disease prevention and deaths averted among children 6 to 59 months of age in sub-Saharan Africa. METHODS: We analyzed different zinc supplementation strategies to assess their likely impact on morbidity and mortality of preschool children in sub-Saharan Africa and to estimate their possible costs. RESULTS: Preventive zinc supplementation reduces diarrhea incidence by 27% among children 12 to 59 months of age, pneumonia incidence by 21% among children 6 to 59 months of age, and all-cause mortality by 18% among children 12 to 59 months of age. The likely average total program costs of zinc supplementation programs were estimated from the outlays of existing service delivery platforms, such as child health days, community-based nutrition programs, and clinic-based treatment of diarrhea, assuming different levels of coverage and target age ranges of children. CONCLUSIONS: We found that the average total costs per life saved ranged from approximately US$462 to US$3,111, and the most cost-effective interventions were weekly or intermittent preventive zinc supplementation, because of the possibility of high coverage and fewer supplements required. Empirical data from zinc supplementation programs will be needed to confirm these estimates.

Results of Fortification Rapid Assessment Tool (FRAT) surveys in sub-Saharan Africa and suggestions for future modifications of the survey instrument.

BACKGROUND: Food fortification has been increasingly recognized as a promising approach to prevent micronutrient deficiencies. The Fortification Rapid Assessment Tool (FRAT) was developed to assist public health program managers to acquire the information needed to implement an effective mass food fortification program. Multiple countries have conducted FRAT surveys, but information on results and experiences with the FRAT tool has been available only at the national level. OBJECTIVE: To summarize the findings of the FRAT surveys previously conducted in sub-Saharan Africa. METHODS: Surveys from 12 sub-Saharan African countries (Burkina Faso, Cameroon, Congo, Guinea, Malawi, Mali, Mauritania, Mozambique, Niger, Rwanda, Senegal, Uganda) were identified. Information on consumption patterns for wheat flour, vegetable oil, sugar, and bouillon cubes was reviewed and summarized. RESULTS: Most surveys found that a moderate to high proportion of women reported consuming wheat flour (48% to 93%), vegetable oil (44% to 98%), sugar (55% to 99%), and bouillon cubes (79% to 99%) in the past 7 days, although consumption was more common and more frequent in urban areas than in rural areas. Similarly, the reported amounts consumed during the previous 24 hours were generally higher in urban settings. CONCLUSIONS: The FRAT instrument has been successfully used in multiple countries, and the results obtained have helped in planning national food fortification programs. However, the recommended sampling scheme may need to be reconsidered, and the guidelines should be revised to clarify important aspects of fieldworker training, implementation, data analysis and interpretation, and reporting of the results.

The role of nutrition in integrated programs to control neglected tropical diseases.

There are strong and direct relationships between undernutrition and the disease caused by infectious organisms, including the diverse pathogens labeled as neglected tropical diseases (NTDs). Undernutrition increases the risk of infection, the severity of disease and the risk that children will die, while the physical damage, loss of appetite, and host responses during chronic infection can contribute substantially to undernutrition. These relationships are often synergistic. This opinion article examines the role of nutrition in controlling NTDs and makes the point that mass drug treatment--the major strategy currently proposed to control several diseases--is crucial to controlling disease and transmission, but is only the start of the process of physical recovery. Without adequate energy and nutrients to repair damaged tissues or recover lost growth and development, the benefits of treatment may not be evident quickly; the effects of control programs may be not appreciated by beneficiaries; while vulnerability to reinfection and disease may not be reduced. There is substantial potential for nutritional interventions to be added to large-scale programs to deliver drug treatments and thereby contribute, within a broad strategy of public health interventions and behavior change activities, to controlling and preventing NTDs in populations, and to restoring their health.

Thriving public-private partnership to fortify cooking oil in the West African Economic and Monetary Union (UEMOA) to control vitamin A deficiency: Faire Tache d'Huile en Afrique de l'Ouest.

BACKGROUND: In sub-Saharan Africa, more than 42% of children are at risk for vitamin A deficiency, and control of vitamin A deficiency will prevent more than 600,000 child deaths annually. In the West African Economic and Monetary Union (UEMOA), an estimated 54.3% of preschool-age children are vitamin A deficient and 13% of pregnant women have night blindness. OBJECTIVE: To project the achievements of this West African coalition. METHODS: This article documents the achievements, challenges, and lessons learned associated with the development of a public-private partnership to fortify vegetable oil in West Africa through project reports and industry assessments. RESULTS: National-level food consumption surveys identified cooking oil as a key vehicle for vitamin A. Stakeholders therefore advocated for the production of fortified vegetable oil at large scale, supported industrial assessments, and reinforced the capacity of cooking oil industries to implement vitamin A fortification through effective coordination of public and private partnerships tied with standards, regulations, and social marketing. Strong alliances for food fortification were established at the regional and national levels. Stakeholders also developed policies, adopted directives, built capacity, implemented social marketing, and monitored quality enforcement systems to sustain fortification for maximum public health impact. The synergy created resulted from the unique and complementary core competencies of all the partners under effective coordination. The initiative began with the 8 UEMOA member countries and now includes all 15 countries of the Economic Community of West African States (ECOWAS), plus Cameroon, Tanzania, and Mozambique, forming a sub-Saharan Africa-wide initiative on food fortification. All members of the Professional Association of Cooking Oil Industries of the West African Economic and Monetary Union (AIFO-UEMOA) now fortify edible oil with vitamin A. Through multisector cooperation, an estimated 70% of the population has access to vitamin A-fortified edible oil in participating countries. CONCLUSIONS: Sustainable fortification of cooking oil is now a reality in all UEMOA countries.

A multi-micronutrient beverage enhances the vitamin A and zinc status of Nigerian primary schoolchildren.

Schoolchildren in Nigeria are rarely targeted by micronutrient interventions. We completed a 6-mo, double-blind, placebo-controlled trial to determine the effects of a multi-micronutrient beverage on biochemical and anthropometric indicators of nutritional status among schoolchildren participating in a pilot school feeding program in Nasarawa State, Nigeria. Children received 1 of 2 interventions 5 d/wk during school hours: 1) 250 mL/d of a multi-micronutrient beverage that included vitamin A, iron, and zinc (micronutrient); or 2) an isoenergetic control beverage (control). At baseline, 566 children 5-13 y old were randomized to groups (micronutrient: n = 288; control: n = 278). Height, weight, hemoglobin, and serum concentrations of C-reactive protein, ferritin, retinol, and zinc were measured at baseline and at the end of the study. A total of 270 children in the micronutrient group and 264 children in the control group completed the study. Self-reports of vomiting increased in both groups at 6 mo; however, the prevalence tended to be greater in the micronutrient group (21%) compared to the control group (14%) (P = 0.06). Biochemical changes were greater in the micronutrient group compared to control for serum retinol (0.10 ± 0.02 µmol/L vs. 0.02 ± 0.02 µmol/L; P = 0.016) and zinc (1.0 ± 0.2 µmol/L vs. 0.6 ± 0.2 µmol/L; P = 0.031). The intervention did not significantly affect hemoglobin or serum ferritin concentrations. The cost effectiveness of the intervention needs to be further evaluated, as does the efficacy of the beverage on anemia and indicators of iron status.

Excellent outcomes for adults who experienced early standardized treadmill training during acute phase of recovery from stroke: a case series.

OBJECTIVE: To describe gait outcomes, including assistive device use and incidence of falls, in a group of adults post stroke who received early standardized treadmill training (ESTT) in the acute phase of rehabilitation. DESIGN: A case series of 18 individuals post stroke with varied lesion size, location, and comorbidities. SETTING: Inpatient rehabilitation unit. INTERVENTION: Daily 30-minute sessions of ESTT initiated before overground training in the acute rehabilitation period. OUTCOME MEASURES: Three-dimensional gait analysis, 6-minute walk test (6MWT), assistive device inventory, and fall history. RESULTS: Gait analysis revealed better temporal and spatial symmetry than have been previously documented. Twelve participants walked at speeds of greater than 0.80 m/s and 10 walked without the use of an assistive device or orthoses. Mean 6MWT distance was 322.42 m (±114.33). Thirteen participants (72%) reported no falls over a 6-month period. CONCLUSION: These outcomes far surpass the current data reported in the literature for this patient population and were achieved by the application of an intervention that was feasible in the acute rehabilitation setting.

Control of neglected tropical diseases needs a long-term commitment.

BACKGROUND: Neglected tropical diseases are widespread, particularly in sub-Saharan Africa, affecting over 2 billion individuals. Control of these diseases has gathered pace in recent years, with increased levels of funding from a number of governmental or non-governmental donors. Focus has currently been on five major 'tool-ready' neglected tropical diseases (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis and trachoma), using a package of integrated drug delivery according to the World Health Organization guidelines for preventive chemotherapy. DISCUSSION: Success in controlling these neglected tropical diseases has been achieved in a number of countries in recent history. Experience from these successes suggests that long-term sustainable control of these diseases requires: (1) a long-term commitment from a wider range of donors and from governments of endemic countries; (2) close partnerships of donors, World Health Organization, pharmaceutical industries, governments of endemic countries, communities, and non-governmental developmental organisations; (3) concerted action from more donor countries to provide the necessary funds, and from the endemic countries to work together to prevent cross-border disease transmission; (4) comprehensive control measures for certain diseases; and (5) strengthened primary healthcare systems as platforms for the national control programmes and capacity building through implementation of the programmes. CONCLUSIONS: The current level of funding for the control of neglected tropical diseases has never been seen before, but it is still not enough to scale up to the 2 billion people in all endemic countries. While more donors are sought, the stakeholders must work in a coordinated and harmonised way to identify the priority areas and the best delivery approaches to use the current funds to the maximum effect. Case management and other necessary control measures should be supported through the current major funding streams in order to achieve the objectives of the control of these diseases. For a long-term and sustainable effort, control of neglected tropical diseases should also be integrated into national primary healthcare systems.

How countries can reduce child stunting at scale: lessons from exemplar countries.

BACKGROUND: Child stunting and linear growth faltering have declined over the past few decades and several countries have made exemplary progress. OBJECTIVES: To synthesize findings from mixed methods studies of exemplar countries to provide guidance on how to accelerate reduction in child stunting. METHODS: We did a qualitative and quantitative synthesis of findings from existing literature and 5 exemplar country studies (Nepal, Ethiopia, Peru, Kyrgyz Republic, Senegal). Methodology included 4 broad research activities: 1) a series of descriptive analyses of cross-sectional data from demographic and health surveys and multiple indicator cluster surveys; 2) multivariable analysis of quantitative drivers of change in linear growth; 3) interviews and focus groups with national experts and community stakeholders and mothers; and 4) a review of policy and program evolution related to nutrition. RESULTS: Several countries have dramatically reduced child stunting prevalence, with or without closing geographical, economic, and other population inequalities. Countries made progress through interventions from within and outside the health sector, and despite significant heterogeneity and differences in context, contributions were comparable from health and nutrition sectors (40% of change) and other sectors (50%), previously called nutrition-specific and -sensitive strategies. Improvements in maternal education, maternal nutrition, maternal and newborn care, and reductions in fertility/reduced interpregnancy intervals were strong contributors to change. A roadmap to reducing child stunting at scale includes several steps related to diagnostics, stakeholder consultations, and implementing direct and indirect nutrition interventions related to the health sector and nonhealth sector . CONCLUSIONS: Our results show that child stunting reduction is possible even in diverse and challenging contexts. We propose that our framework of organizing nutrition interventions as direct/indirect and inside/outside the health sector should be considered when mapping causal pathways of child stunting and planning interventions and strategies to accelerate stunting reduction to achieve the 2030 Sustainable Development Goals.

Using RNA sample titrations to assess microarray platform performance and normalization techniques.

We have assessed the utility of RNA titration samples for evaluating microarray platform performance and the impact of different normalization methods on the results obtained. As part of the MicroArray Quality Control project, we investigated the performance of five commercial microarray platforms using two independent RNA samples and two titration mixtures of these samples. Focusing on 12,091 genes common across all platforms, we determined the ability of each platform to detect the correct titration response across the samples. Global deviations from the response predicted by the titration ratios were observed. These differences could be explained by variations in relative amounts of messenger RNA as a fraction of total RNA between the two independent samples. Overall, both the qualitative and quantitative correspondence across platforms was high. In summary, titration samples may be regarded as a valuable tool, not only for assessing microarray platform performance and different analysis methods, but also for determining some underlying biological features of the samples.

The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements.

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings.

Galvanizing action: conclusions and next steps for mainstreaming zinc interventions in public health programs.

This paper summarizes the results of the foregoing reviews of the impact of different intervention strategies designed to enhance zinc nutrition, including supplementation, fortification, and dietary diversification or modification. Current evidence indicates a beneficial impact of such interventions on zinc status and zinc-related functional outcomes. Preventive zinc supplementation reduces the incidence of diarrhea and acute lower respiratory tract infection among young children, decreases mortality of children over 12 months of age, and increases growth velocity. Therapeutic zinc supplementation during episodes of diarrhea reduces the duration and severity of illness. Zinc fortification increases zinc intake and total absorbed zinc, and recent studies are beginning to confirm a positive impact of zinc fortification on indicators of population zinc status. To assist with the development of zinc intervention programs, more information is needed on the prevalence of zinc deficiency in different countries, and rigorous evaluations of the effectiveness of large-scale zinc intervention programs should be planned. Recommended steps for scaling up zinc intervention programs, with or without other micronutrients, are described. In summary, there is now clear evidence of the benefit of selected interventions to reduce the risk of zinc deficiency, and a global commitment is urgently needed to conduct systematic assessments of population zinc status and to develop interventions to control zinc deficiency in the context of existing public health and nutrition programs.

Preventive zinc supplementation among infants, preschoolers, and older prepubertal children.

Zinc supplementation trials carried out among children have produced variable results, depending on the specific outcomes considered and the initial characteristics of the children who were enrolled. We completed a series of meta-analyses to examine the impact of preventive zinc supplementation on morbidity; mortality; physical growth; biochemical indicators of zinc, iron, and copper status; and indicators of behavioral development, along with possible modifying effects of the intervention results. Zinc supplementation reduced the incidence of diarrhea by approximately 20%, but the impact was limited to studies that enrolled children with a mean initial age greater than 12 months. Among the subset of studies that enrolled children with mean initial age greater than 12 months, the relative risk of diarrhea was reduced by 27%. Zinc supplementation reduced the incidence of acute lower respiratory tract infections by approximately 15%. Zinc supplementation yielded inconsistent impacts on malaria incidence, and too few trials are currently available to allow definitive conclusions to be drawn. Zinc supplementation had a marginal 6% impact on overall child mortality, but there was an 18% reduction in deaths among zinc-supplemented children older than 12 months of age. Zinc supplementation increased linear growth and weight gain by a small, but highly significant, amount. The interventions yielded a consistent, moderately large increase in mean serum zinc concentrations, and they had no significant adverse effects on indicators of iron and copper status. There were no significant effects on children's behavioral development, although the number of available studies is relatively small. The available evidence supports the need for intervention programs to enhance zinc status to reduce child morbidity and mortality and to enhance child growth. Possible strategies for delivering preventive zinc supplements are discussed.

Locomotor treadmill training with partial body-weight support before overground gait in adults with acute stroke: a pilot study.

OBJECTIVE: To investigate the impact of locomotor treadmill training with partial body-weight support (BWS) before the initiation of overground gait for adults less than 6 weeks poststroke. DESIGN: Parallel group, posttest only. SETTING: Inpatient rehabilitation center. PARTICIPANTS: Adults after first stroke admitted to an inpatient rehabilitation unit: treadmill group (n=7) and comparison group (n=7). INTERVENTIONS: Locomotor treadmill training with partial BWS or traditional gait training methods. MAIN OUTCOME MEASURES: Gait kinematics, symmetry, velocity, and endurance at least 6 months postinsult. RESULTS: Data from 3-dimensional gait analysis and 6-minute walk test (6MWT) supported improved gait for adults postacute stroke who practiced gait on a treadmill before walking over ground. Gait analysis showed increased knee flexion during swing and absence of knee hyperextension in stance for the treadmill group. In addition, more normal ankle kinematics at initial contact and terminal stance were observed in the treadmill group. Improved gait symmetry in the treadmill group was confirmed by measures of single support time, hip flexion at initial contact, maximum knee flexion, and maximum knee extension during stance. The treadmill group also walked further and faster in the 6MWT than the comparison group. CONCLUSIONS: Application of locomotor treadmill training with partial BWS before overground gait training may be more effective in establishing symmetric and efficient gait in adults postacute stroke than traditional gait training methods in acute rehabilitation.