Multilingual assessment of early child development: Analyses from repeated observations of children in Kenya.

In many low- and middle-income countries, young children learn a mother tongue or indigenous language at home before entering the formal education system where they will need to understand and speak a country's official language(s). Thus, assessments of children before school age, conducted in a nation's official language, may not fully reflect a child's development, underscoring the importance of test translation and adaptation. To examine differences in vocabulary development by language of assessment, we adapted and validated instruments to measure developmental outcomes, including expressive and receptive vocabulary. We assessed 505 2-to-6-year-old children in rural communities in Western Kenya with comparable vocabulary tests in three languages: Luo (the local language or mother tongue), Swahili, and English (official languages) at two time points, 5-6 weeks apart, between September 2015 and October 2016. Younger children responded to the expressive vocabulary measure exclusively in Luo (44%-59% of 2-to-4-year-olds) much more frequently than did older children (20%-21% of 5-to-6-year-olds). Baseline receptive vocabulary scores in Luo (ß = 0.26, SE = 0.05, p < 0.001) and Swahili (ß = 0.10, SE = 0.05, p = 0.032) were strongly associated with receptive vocabulary in English at follow-up, even after controlling for English vocabulary at baseline. Parental Luo literacy at baseline (ß = 0.11, SE = 0.05, p = 0.045) was associated with child English vocabulary at follow-up, while parental English literacy at baseline was not. Our findings suggest that multilingual testing is essential to understanding the developmental environment and cognitive growth of multilingual children.

Monitoring and evaluating the impact of national school-based deworming in Kenya: study design and baseline results.

BACKGROUND: An increasing number of countries in Africa and elsewhere are developing national plans for the control of neglected tropical diseases. A key component of such plans is school-based deworming (SBD) for the control of soil-transmitted helminths (STHs) and schistosomiasis. Monitoring and evaluation (M&E) of national programmes is essential to ensure they are achieving their stated aims and to evaluate when to reduce the frequency of treatment or when to halt it altogether. The article describes the M&E design of the Kenya national SBD programme and presents results from the baseline survey conducted in early 2012. METHODS: The M&E design involves a stratified series of pre- and post-intervention, repeat cross-sectional surveys in a representative sample of 200 schools (over 20,000 children) across Kenya. Schools were sampled based on previous knowledge of STH endemicity and were proportional to population size. Stool (and where relevant urine) samples were obtained for microscopic examination and in a subset of schools; finger-prick blood samples were collected to estimate haemoglobin concentration. Descriptive and spatial analyses were conducted. The evaluation measured both prevalence and intensity of infection. RESULTS: Overall, 32.4% of children were infected with at least one STH species, with Ascaris lumbricoides as the most common species detected. The overall prevalence of Schistosoma mansoni was 2.1%, while in the Coast Province the prevalence of S. haematobium was 14.8%. There was marked geographical variation in the prevalence of species infection at school, district and province levels. The prevalence of hookworm infection was highest in Western Province (25.1%), while A. lumbricoides and T. trichiura prevalence was highest in the Rift Valley (27.1% and 11.9%). The lowest prevalence was observed in the Rift Valley for hookworm (3.5%), in the Coast for A. lumbricoides (1.0%), and in Nyanza for T. trichiura (3.6%). The prevalence of S. mansoni was most common in Western Province (4.1%). CONCLUSIONS: The current findings are consistent with the known spatial ecology of STH and schistosome infections and provide an important empirical basis on which to evaluate the impact of regular mass treatment through the school system in Kenya.

A systems approach to mapping DNA damage response pathways.

Failure of cells to respond to DNA damage is a primary event associated with mutagenesis and environmental toxicity. To map the transcriptional network controlling the damage response, we measured genomewide binding locations for 30 damage-related transcription factors (TFs) after exposure of yeast to methyl-methanesulfonate (MMS). The resulting 5272 TF-target interactions revealed extensive changes in the pattern of promoter binding and identified damage-specific binding motifs. As systematic functional validation, we identified interactions for which the target changed expression in wild-type cells in response to MMS but was nonresponsive in cells lacking the TF. Validated interactions were assembled into causal pathway models that provide global hypotheses of how signaling, transcription, and phenotype are integrated after damage.

Discovering regulatory and signalling circuits in molecular interaction networks.

MOTIVATION: In model organisms such as yeast, large databases of protein-protein and protein-DNA interactions have become an extremely important resource for the study of protein function, evolution, and gene regulatory dynamics. In this paper we demonstrate that by integrating these interactions with widely-available mRNA expression data, it is possible to generate concrete hypotheses for the underlying mechanisms governing the observed changes in gene expression. To perform this integration systematically and at large scale, we introduce an approach for screening a molecular interaction network to identify active subnetworks, i.e., connected regions of the network that show significant changes in expression over particular subsets of conditions. The method we present here combines a rigorous statistical measure for scoring subnetworks with a search algorithm for identifying subnetworks with high score. RESULTS: We evaluated our procedure on a small network of 332 genes and 362 interactions and a large network of 4160 genes containing all 7462 protein-protein and protein-DNA interactions in the yeast public databases. In the case of the small network, we identified five significant subnetworks that covered 41 out of 77 (53%) of all significant changes in expression. Both network analyses returned several top-scoring subnetworks with good correspondence to known regulatory mechanisms in the literature. These results demonstrate how large-scale genomic approaches may be used to uncover signalling and regulatory pathways in a systematic, integrative fashion.

Cytoscape: a software environment for integrated models of biomolecular interaction networks.

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.