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Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18 years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.

Human genetic variation affects the gut microbiota through a complex combination of environmental and host factors. Here we characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial metagenomes, and dietary and health records (prevalent and follow-up). We identified 567 independent SNP-taxon associations. Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis. Overall, we identify and characterize the intricate nature of host-microbiota interactions and their association with disease.

For Alzheimer's disease-a leading cause of dementia and global morbidity-improved identification of presymptomatic high-risk individuals and identification of new circulating biomarkers are key public health needs. Here, we tested the hypothesis that a polygenic predictor of risk for Alzheimer's disease would identify a subset of the population with increased risk of clinically diagnosed dementia, subclinical neurocognitive dysfunction, and a differing circulating proteomic profile. Using summary association statistics from a recent genome-wide association study, we first developed a polygenic predictor of Alzheimer's disease comprised of 7.1 million common DNA variants. We noted a 7.3-fold (95% CI 4.8 to 11.0; p < 0.001) gradient in risk across deciles of the score among 288,289 middle-aged participants of the UK Biobank study. In cross-sectional analyses stratified by age, minimal differences in risk of Alzheimer's disease and performance on a digit recall test were present according to polygenic score decile at age 50 years, but significant gradients emerged by age 65. Similarly, among 30,541 participants of the Mass General Brigham Biobank, we again noted no significant differences in Alzheimer's disease diagnosis at younger ages across deciles of the score, but for those over 65 years we noted an odds ratio of 2.0 (95% CI 1.3 to 3.2; p = 0.002) in the top versus bottom decile of the polygenic score. To understand the proteomic signature of inherited risk, we performed aptamer-based profiling in 636 blood donors (mean age 43 years) with very high or low polygenic scores. In addition to the well-known apolipoprotein E biomarker, this analysis identified 27 additional proteins, several of which have known roles related to disease pathogenesis. Differences in protein concentrations were consistent even among the youngest subset of blood donors (mean age 33 years). Of these 28 proteins, 7 of the 8 proteins with concentrations available were similarly associated with the polygenic score in participants of the Multi-Ethnic Study of Atherosclerosis. These data highlight the potential for a DNA-based score to identify high-risk individuals during the prolonged presymptomatic phase of Alzheimer's disease and to enable biomarker discovery based on profiling of young individuals in the extremes of the score distribution.

In this article, we offer an analysis of how institutions of higher education have responded to occurrences related to racism in educational contexts and the larger society. Since the initial drafting of this manuscript, continued police brutality and racially motivated tragedies have prompted protests and uprising across the US and the world, specifically after the killings of Ahmaud Arbery in Georgia, Breona Taylor in Kentucky, and George Floyd in Minnesota. This social unrest reflects the ways in which people respond when enough is enough. In addition, a number of schools across the P-20 landscape are engaging in discussions around equity and racism and responding in ways that address racist systems and policies. We conclude this article with a discussion of what institutions of higher education should aspire to in order to humanize the educational contexts for a more equitable and anti-racist society. We hope this discussion around past incidents provide a lens of possibilities for meaningful change; because as we knew when writing the initial draft, and as we still know, lives depend on it.

Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2), we observed slow but steady spatial spread, at about 100-200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2) produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transformation.

This article analyzes data from a qualitative practitioner-research case study in which four university faculty members attempted to disrupt the hegemonic domestication of candidates enrolled in an undergraduate teacher education program. During the semester prior to their student teaching, 16 candidates at a large public university in the southeastern U.S. enrolled in four content methods courses. Taught by the authors of this article, the curriculum of these courses emphasized social justice dimensions of teaching rather than just focusing on skills and strategies. Drawing from the multiple data sources, the authors highlight the possibilities and limitations of teacher education for social change and argue that greater resources are needed for teacher education to effect true social change.

Dengue viruses cause more human morbidity and mortality than any other arthropod-borne virus. Dengue prevention relies mainly on vector control; however, the failure of traditional methods has promoted the development of novel entomological approaches. Although use of the intracellular bacterium wolbachia to control mosquito populations was proposed 50 years ago, only in the past decade has its use as a potential agent of dengue control gained substantial interest. Here, we review evidence that supports a practical approach for dengue reduction through field release of wolbachia-infected mosquitoes and discuss the additional studies that have to be done before the strategy can be validated and implemented. A crucial next step is to assess the efficacy of wolbachia in reducing dengue virus transmission. We argue that a cluster randomised trial is at this time premature because choice of wolbachia strain for release and deployment strategies are still being optimised. We therefore present a pragmatic approach to acquiring preliminary evidence of efficacy through various complementary methods including a prospective cohort study, a geographical cluster investigation, virus phylogenetic analysis, virus surveillance in mosquitoes, and vector competence assays. This multipronged approach could provide valuable intermediate evidence of efficacy to justify a future cluster randomised trial.

Recently, the Vaccines to Vaccinate (v2V) initiative was reconfigured into the Partnership for Dengue Control (PDC), a multi-sponsored and independent initiative. This redirection is consistent with the growing consensus among the dengue-prevention community that no single intervention will be sufficient to control dengue disease. The PDC's expectation is that when an effective dengue virus (DENV) vaccine is commercially available, the public health community will continue to rely on vector control because the two strategies complement and enhance one another. Although the concept of integrated intervention for dengue prevention is gaining increasingly broader acceptance, to date, no consensus has been reached regarding the details of how and what combination of approaches can be most effectively implemented to manage disease. To fill that gap, the PDC proposed a three step process: (1) a critical assessment of current vector control tools and those under development, (2) outlining a research agenda for determining, in a definitive way, what existing tools work best, and (3) determining how to combine the best vector control options, which have systematically been defined in this process, with DENV vaccines. To address the first step, the PDC convened a meeting of international experts during November 2013 in Washington, DC, to critically assess existing vector control interventions and tools under development. This report summarizes those deliberations.

Researchers have argued that "job-embedded" professional learning is the most valuable model for teachers (Joyce & Showers, 2002). But there is little or no corresponding literature regarding job-embedded professional learning for literacy coaches. In this paper, the authors offer an example of one such model, the Coach-to-Coach Cycle, which has proven helpful to their own professional growth and development as coaches and which may support other coaches as well. Using transcribed snippets of coach-to-coach dialogue following a coaching post-observation conference with a teacher, the authors reflect on the successes and challenges facing coaches who wish to become co-investigators with teachers into their literacy instruction.

Primary and secondary education under capitalism serves as an ideological apparatus to construct productive workers who will participate in the extractive economy and consent to their own exploitation. However, some school children are marked as deficient--impaired, disabled, and mad--incapable of being good workers who facilitate capitalist accumulation. Just as capital banishes incapacitated workers to the reserve army of labor, so too do school children learn to "surplus" and "disable" their peers who do not meet school norms. In this paper, I use a revolutionary Marxist perspective to analyze empirical data from a grade 1 United States classroom where students were teasing a neurodivergent classmate and excluding her from participation. I explore how the teacher intervened by using critical literacy to design a curricular unit on hidden disabilities that would engage her students in transformative, disability justice, and how students built a community around their disabled peers. Along the way, I explore how disability is a relation under capitalism rather than an identity; how nature gives us diverse bodyminds but it is capitalism that disables us; how the education system in capitalist societies is a vehicle for the dissemination of ruling class ideologies of productivity; how some school children are surplused and labeled as incapable of being good workers who facilitate capitalist accumulation; and possible solutions--what educators, parents, caregivers, and others can do about it. [ABSTRACT FROM AUTHOR]