Deworming and Development: Asking the Right Questions, Asking the Questions Right

Two billion people are infected with intestinal worms. In many areas, the majority of schoolchildren are infected, and the World Health Organization (WHO) has called for school-based mass deworming. The key area for debate is not whether deworming medicine works—in fact, the medical literature finds that treatment is highly effective, and thus the standard of care calls for treating any patient known to harbor an infection. As the authors of the Cochrane systematic review point out, a critical issue in evaluating current soil-transmitted helminth policies is whether the benefits of deworming exceed the costs or whether it would be more prudent to use the money for other purposes. While in general we think the Cochrane approach is very valuable, we argue below that many of the underlying studies of deworming suffer from three critical methodological problems: treatment externalities in dynamic infection systems, inadequate measurement of cognitive outcomes and school attendance, and sample attrition. We then argue that the currently available evidence from studies that address these issues is consistent with the consensus view expressed by other reviews and by policymakers that deworming is a very cost-effective way to increase school participation and has a high benefit to cost ratio.Economic

Active flow control systems architectures for civil transport aircraft

Copyright @ 2010 American Institute of Aeronautics and AstronauticsThis paper considers the effect of choice of actuator technology and associated power systems architecture on the mass cost and power consumption of implementing active flow control systems on civil transport aircraft. The research method is based on the use of a mass model that includes a mass due to systems hardware and a mass due to the system energy usage. An Airbus A320 aircraft wing is used as a case-study application. The mass model parameters are based on first-principle physical analysis of electric and pneumatic power systems combined with empirical data on system hardware from existing equipment suppliers. Flow control methods include direct fluidic, electromechanical-fluidic, and electrofluidic actuator technologies. The mass cost of electrical power distribution is shown to be considerably less than that for pneumatic systems; however, this advantage is reduced by the requirement for relatively heavy electrical power management and conversion systems. A tradeoff exists between system power efficiency and the system hardware mass required to achieve this efficiency. For short-duration operation the flow control solution is driven toward lighter but less power-efficient systems, whereas for long-duration operation there is benefit in considering heavier but more efficient systems. It is estimated that a practical electromechanical-fluidic system for flow separation control may have a mass up to 40% of the slat mass for a leading-edge application and 5% of flap mass for a trailing-edge application.This work is funded by the Sixth European Union Framework Programme as part of the AVERT project (Contract No. AST5-CT-2006-030914

Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants

Infiltration efficiency and subsurface water processes of a sustainable drainage system and consequences to flood management

With increased intensity rainfall events globally and urban expansion decreasing permeable surfaces, there is an increasing problem of urban flooding. This study aims to better understand rainfall infiltration into a Sustainable Drainage System (SuDS) permeable pavement, compared with an adjacent Green Area of made ground, in relationship to groundwater levels below both areas. Both areas were instrumented with soil water content and matric potential sensors and four shallow boreholes were instrumented with groundwater level sensors. Surface infiltration rates were measured using a double‐ring infiltrometer. Results showed that average infiltration rates of the SuDS (1,925 mm/hr) were significantly higher than the Green Area (56 mm/hr). The SuDS was well designed to transfer rainfall rapidly to the aquifer below, where groundwater levels rapidly rose within 1 hr of a 1 in 30 year event (32.8 mm/hr). In comparison, soil compaction of the made ground Green Area decreased infiltration rates, but still enabled the majority of rainfall events to infiltrate. The aquifer below the Green Area responded more slowly, as lower matrix potentials facilitated water retention in the soil profile, slowing water draining to the aquifer. This work reiterates the importance of ensuring a 1 m separation depth between the base of the SuDS infiltration zone and aquifer depth

Long-Term Impact of Malaria Chemoprophylaxis on Cognitive Abilities and Educational Attainment: Follow-Up of a Controlled Trial

OBJECTIVES: We investigated the long-term impact of early childhood malaria prophylaxis on cognitive and educational outcomes. DESIGN: This was a household-based cluster-controlled intervention trial. SETTING: The study was conducted in 15 villages situated between 32 km to the east and 22 km to the west of the town of Farafenni, the Gambia, on the north bank of the River Gambia. PARTICIPANTS: A total of 1,190 children aged 3–59 mo took part in the trial. We traced 579 trial participants (291 in the prophylaxis group and 288 in the placebo group) in 2001, when their median age was 17 y 1 mo (range 14 y 9 mo to 19 y 6 mo). INTERVENTIONS: Participants received malaria chemoprophylaxis (dapsone/pyrimethamine) or placebo for between one and three malaria transmission seasons from 1985 to 1987 during the controlled trial. At the end of the trial, prophylaxis was provided for all children under 5 y of age living in the study villages. OUTCOME MEASURES: The outcome measures were cognitive abilities, school enrolment, and educational attainment (highest grade reached at school). RESULTS: There was no significant overall intervention effect on cognitive abilities, but there was a significant interaction between intervention group and the duration of post-trial prophylaxis (p = 0.034), with cognitive ability somewhat higher in the intervention group among children who received no post-trial prophylaxis (treatment effect = 0.2 standard deviations [SD], 95% confidence interval [CI] −0.03 to 0.5) and among children who received less than 1 y of post-trial prophylaxis (treatment effect = 0.4 SD, 95% CI 0.1 to 0.8). The intervention group had higher educational attainment by 0.52 grades (95% CI = −0.041 to 1.089; p = 0.069). School enrolment was similar in the two groups. CONCLUSIONS: The results are suggestive of a long-term effect of malaria prophylaxis on cognitive function and educational attainment, but confirmatory studies are needed

Improving educational achievement and anaemia of school children: design of a cluster randomised trial of school-based malaria prevention and enhanced literacy instruction in Kenya

BACKGROUND: Improving the health of school-aged children can yield substantial benefits for cognitive development and educational achievement. However, there is limited experimental evidence on the benefits of school-based malaria prevention or how health interventions interact with other efforts to improve education quality. This study aims to evaluate the impact of school-based malaria prevention and enhanced literacy instruction on the health and educational achievement of school children in Kenya. DESIGN: A factorial, cluster randomised trial is being implemented in 101 government primary schools on the coast of Kenya. The interventions are (i) intermittent screening and treatment of malaria in schools by public health workers and (ii) training workshops and support for teachers to promote explicit and systematic literacy instruction. Schools are randomised to one of four groups: receiving either (i) the malaria intervention alone; (ii) the literacy intervention alone; (iii) both interventions combined; or (iv) control group where neither intervention is implemented. Children from classes 1 and 5 are randomly selected and followed up for 24 months. The primary outcomes are educational achievement and anaemia, the hypothesised mediating variables through which education is affected. Secondary outcomes include malaria parasitaemia, school attendance and school performance. A nested process evaluation, using semi-structured interviews, focus group discussion and a stakeholder analysis will investigate the community acceptability, feasibility and cost-effectiveness of the interventions. DISCUSSION: Across Africa, governments are committed to improve health and education of school-aged children, but seek clear policy and technical guidance as to the optimal approach to address malaria and improved literacy. This evaluation will be one of the first to simultaneously evaluate the impact of health and education interventions in the improvement of educational achievement. Reflection is made on the practical issues encountered in conducting research in schools in Africa. TRIAL REGISTRATION: National Institutes of Health NCT00878007

Identifying an essential package for school-age child health: economic analysis

This chapter presents the investment case for providing an integrated package of essential health services for children attending primary schools in low- and middle- income countries (LMICs). In doing so, it builds on chapter 20 in this volume (Bundy, Schultz, and others 2017), which presents a range of relevant health services for the school- age population and the economic rationale for adminis- tering them through educational systems. This chapter identifies a package of essential health services that low- and middle-income countries (LMICs) can aspire to implement through the primary and secondary school platforms. In addition, the chapter considers the design of such programs, including targeting strategies. Upper- middle-income countries and high-income countries (HICs) typically aim to implement such interventions on a larger scale and to include and promote additional health services relevant to their populations. Studies have docu- mented the contribution of school health interventions to a range of child health and educational outcomes, partic- ularly in the United States (Durlak and others 2011; Murray and others 2007; Shackleton and others 2016). Health services selected for the essential package are those that have demonstrated benefits and relevance for children in LMICs. The estimated costs of implementation are drawn from the academic literature. The concept of a package of essential school health interventions and its justification through a cost-benefit perspective was pioneered by Jamison and Leslie (1990). As chapter 20 notes, health services for school-age children can promote educational outcomes, including access, attendance, and academic achievement, by mitigat- ing earlier nutrition and health deprivations and by addressing current infections and nutritional deficiencies (Bundy, Schultz, and others 2017). This age group is partic- ularly at risk for parasitic helminth infections (Jukes, Drake, and Bundy 2008), and malaria has become prevalent in school-age populations as control for younger children delays the acquisition of immunity from early childhood to school age (Brooker and others 2017). Furthermore, school health services are commonly viewed as a means for build- ing and reinforcing healthy habits to lower the risk of non- communicable disease later in life (Bundy 2011). This chapter focuses on packages and programs to reach school-age children, while the previous chapter, chapter 24 (Horton and Black 2017), focuses on early childhood inter- ventions, and the next chapter, chapter 26 (Horton and others 2017), focuses on adolescent interventions. These packages are all part of the same continuum of care from age 5 years to early adulthood, as discussed in chapter 1 (Bundy, de Silva, and others 2017). A particular emphasis of the economic rationale for targeting school-age children is to promote their health and education while they are in the process of learning; many of the interventions that are part of the package have been shown to yield substantial benefits in educational outcomes (Bundy 2011; Jukes, Drake, and Bundy 2008). They might be viewed as health interventions that leverage the investment in education. Schools are an effective platform through which to deliver the essential package of health and nutrition ser- vices (Bundy, Schultz, and others 2017). Primary enroll- ment and attendance rates increased substantially during the Millennium Development Goals era, making schools a delivery platform with the potential to reach large num- bers of children equitably. Furthermore, unlike health centers, almost every community has a primary school, and teachers can be trained to deliver simple health inter- ventions, resulting in the potential for high returns for relatively low costs by using the existing infrastructure. This chapter identifies a core set of interventions for children ages 5–14 years that can be delivered effectively through schools. It then simulates the returns to health and education and benchmarks them against the costs of the intervention, drawing on published estimates. The invest- ment returns illustrate the scale of returns provided by school-based health interventions, highlighting the value of integrated health services and the parameters driving costs, benefits, and value for money (the ratio of benefits to costs). Countries seeking to introduce such a package need to undertake context-specific analyses of critical needs to ensure that the package responds to the specific local needs

Nutrition issues in Codex: health claims, nutrient reference values and WTO agreements: a conference report

BACKGROUND: Codex documents may be used as educational and consensus materials for member governments. Also, the WTO SPS Agreement recognizes Codex as the presumptive international authority on food issues. Nutrient bioavailability is a critical factor in determining the ability of nutrients to provide beneficial effects. Bioavailability also influences the quantitative dietary requirements that are the basis of nutrient intake recommendations and NRVs. HEALTH CLAIMS: Codex, EFSA and some national regulatory authorities have established guidelines or regulations that will permit several types of health claims. The scientific basis for claims has been established by the US FDA and EFSA, but not yet by Codex. Evidence-based nutrition differs from evidence-based medicine, but the differences are only recently gaining recognition. Health claims on foods may provide useful information to consumers, but many will interpret the information to mean that they can rely upon the food or nutrient to eliminate a disease risk. NUTRIENT REFERENCE VALUES: NRVs are designed to provide a quantitative basis for comparing the nutritive values of foods, helping to illustrate how specific foods fit into the overall diet. The INL-98 and the mean of adult male and female values provide NRVs that are sufficient when used as targets for individual intakes by most adults. WORLD TRADE ORGANIZATION AGREEMENTS: WTO recognizes Codex as the primary international authority on food issues. Current regulatory schemes based on recommended dietary allowances are trade restrictive. A substantial number of decisions by the EFSA could lead to violation of WTO agreements

Mathematical modeling and comparison of protein size distribution in different plant, animal, fungal and microbial species reveals a negative correlation between protein size and protein number, thus providing insight into the evolution of proteomes

<p>Abstract</p> <p>Background</p> <p>The sizes of proteins are relevant to their biochemical structure and for their biological function. The statistical distribution of protein lengths across a diverse set of taxa can provide hints about the evolution of proteomes.</p> <p>Results</p> <p>Using the full genomic sequences of over 1,302 prokaryotic and 140 eukaryotic species two datasets containing 1.2 and 6.1 million proteins were generated and analyzed statistically. The lengthwise distribution of proteins can be roughly described with a gamma type or log-normal model, depending on the species. However the shape parameter of the gamma model has not a fixed value of 2, as previously suggested, but varies between 1.5 and 3 in different species. A gamma model with unrestricted shape parameter described best the distributions in ~48% of the species, whereas the log-normal distribution described better the observed protein sizes in 42% of the species. The gamma restricted function and the sum of exponentials distribution had a better fitting in only ~5% of the species. Eukaryotic proteins have an average size of 472 aa, whereas bacterial (320 aa) and archaeal (283 aa) proteins are significantly smaller (33-40% on average). Average protein sizes in different phylogenetic groups were: Alveolata (628 aa), Amoebozoa (533 aa), Fornicata (543 aa), Placozoa (453 aa), Eumetazoa (486 aa), Fungi (487 aa), Stramenopila (486 aa), Viridiplantae (392 aa). Amino acid composition is biased according to protein size. Protein length correlated negatively with %C, %M, %K, %F, %R, %W, %Y and positively with %D, %E, %Q, %S and %T. Prokaryotic proteins had a different protein size bias for %E, %G, %K and %M as compared to eukaryotes.</p> <p>Conclusions</p> <p>Mathematical modeling of protein length empirical distributions can be used to asses the quality of small ORFs annotation in genomic releases (detection of too many false positive small ORFs). There is a negative correlation between average protein size and total number of proteins among eukaryotes but not in prokaryotes. The %GC content is positively correlated to total protein number and protein size in prokaryotes but not in eukaryotes. Small proteins have a different amino acid bias than larger proteins. Compared to prokaryotic species, the evolution of eukaryotic proteomes was characterized by increased protein number (massive gene duplication) and substantial changes of protein size (domain addition/subtraction).</p