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White blood cell count (WBC) is unique among identified inflammatory predictors of chronic disease in that it is routinely measured in asymptomatic patients in the course of routine patient care. We led a genome-wide association analysis to identify variants associated with WBC levels in 13,923 subjects in the electronic Medical Records and Genomics (eMERGE) Network. We identified two regions of interest that were each unique to subjects of genetically determined ancestry to the African continent (AA) or to the European continent (EA). WBC varies among different ancestry groups. Despite being ancestry specific, these regions were identifiable in the combined analysis. In AA subjects, the region surrounding the Duffy antigen/chemokine receptor gene ( DARC ) on 1q21 exhibited significant association ( p value = 6.71e−55). These results validate the previously reported association between WBC and of the regulatory variant rs2814778 in the promoter region, which causes the Duffy negative phenotype (Fy−/−). A second missense variant (rs12075) is responsible for the two principal antigens, Fya and Fyb of the Duffy blood group system. The two variants, consisting of four alleles, act in concert to produce five antigens and subsequent phenotypes. We were able to identify the marginal and novel interaction effects of these two variants on WBC. In the EA subjects, we identified significantly associated SNPs tagging three separate genes in the 17q21 region: (1) GSDMA , (2) MED24 , and (3) PSMD3. Variants in this region have been reported to be associated with WBC, neutrophil count, and inflammatory diseases including asthma and Crohn’s disease.

The feasibility of using imperfectly phenotyped \"silver standard\" samples identified from electronic medical record diagnoses is considered in genetic association studies when these samples might be combined with an existing set of samples phenotyped with a gold standard technique. An analytic expression is derived for the power of a chi-square test of independence using either research-quality case/control samples alone, or augmented with silver standard data. The subset of the parameter space where inclusion of silver standard samples increases statistical power is identified. A case study of dementia subjects identified from electronic medical records from the Electronic Medical Records and Genomics (eMERGE) network, combined with subjects from two studies specifically targeting dementia, verifies these results.

This qualitative case study employed an existing framework (Chin, 2006) to examine teacher questioning strategies that promote students' higher-order thinking in science. The study explored the instruction of an experienced science teacher and a 10th grade Chemistry class that he taught in a Singapore school. Our methods included lesson observations, questionnaire and interviews. We found that the teacher frequently applied non-evaluative follow-up moves and supportive follow-up moves to student responses in episodes that students appeared to engage in science thinking through classroom talk. Non-evaluative follow-up moves included withhold evaluations, restatements and reformulations. Supportive follow-up moves were prompts that required students to elaborate or clarify their answers and to justify reasoning. Interview findings further suggested that the teacher prompts helped students to build on their science ideas and engaged them in thinking reflectively. We discussed implications for classroom practice to help teachers work towards the goal of nurturing lifelong learners.

We present a series of related robust optimization models for placing sensors in municipal water networks to detect contaminants that are maliciously or accidentally injected.We formulate sensor placement problems as mixed-integer programs, for which the objective coefficients are not known with certainty. We consider a restricted absolute robustness criteria that is motivated by natural restrictions on the uncertain data, and we define three robust optimization models that differ in how the coefficients in the objective vary. Under one set of assumptions there exists a sensor placement that is optimal for all admissible realizations of the coefficients. Under other assumptions, we can apply sorting to solve each worst-case realization efficiently, or we can apply duality to integrate the worst-case outcome and have one integer program. The most difficult case is where the objective parameters are bilinear, and we prove its complexity is NP-hard even under simplifying assumptions. We consider a relaxation that provides an approximation, giving an overall guarantee of nearoptimality when used with branch-and-bound search. We present preliminary computational experiments that illustrate the computational complexity of solving these robust formulations on sensor placement applications.

The feasibility of using imperfectly phenotyped \"silver standard\" samples identified from electronic medical record diagnoses is considered in genetic association studies when these samples might be combined with an existing set of samples phenotyped with a gold standard technique. An analytic expression is derived for the power of a chi-square test of independence using either research-quality case/control samples alone, or augmented with silver standard data. The subset of the parameter space where inclusion of silver standard samples increases statistical power is identified. A case study of dementia subjects identified from electronic medical records from the Electronic Medical Records and Genomics (eMERGE) network, combined with subjects from two studies specifically targeting dementia, verifies these results.

Heterosis is a centuries-old phenomenon that has been detected at the level of the gene by positive correlations between allozyme heterozygosity and various fitness-related traits. This study examined the effects of constant and fluctuating environments on heterosis vs. heterozygote inferiority measured as potence for six polymorphic loci in the earthworm Eisenia andrei. Neither heterosis nor heterozygote inferiority was promoted consistently by a fluctuating environment. The six loci responded differently to altered levels of soil temperature and/or moisture in both the constant and fluctuating environments. Potence was affected by interactions between locus and environment in the constant environments but not in the fluctuating environments. Fluctuation of the environment reduced the variation in the potence index observed in the constant environments, but it could not synchronize environmental effects on single loci efficiently enough to produce multilocus heterosis.