The Scientific Teaching Practices Survey for Undergraduate STEM Courses

The National Academies Summer Institutes on Undergraduate Education (SI) is a faculty development workshop in which STEM instructors are trained in the Scientific Teaching (ST) pedagogy and encouraged to implement its practices at their home institutions. While participants generally report positive experiences at the SI, it remains unclear how these experiences affect instructors’ teaching practices and associated student outcomes. As part of a larger effort to evaluate the SI, we developed a survey to gauge the frequencies of ST practices that could occur in undergraduate STEM courses. The ST Practices Survey is derived from the observable teaching practices described in the Scientific Teaching taxonomy (Couch et al., 2015). During survey development, we conducted interviews with a panel of experts, instructors, and students, and this input was used to make iterative revisions to the survey. After finalizing the survey, we administered the survey at 9 institutions with 62 instructors and 64 courses, with both instructors and students completing the survey for a given course. In this seminar, we will discuss the development, validity, reliability, factor structure, and implementation of the ST Practices Survey. (abstract only

The Scientific Teaching Practices Survey for Undergraduate STEM Courses

The National Academies Summer Institutes on Undergraduate Education (SI) is a faculty development workshop in which STEM instructors are trained in the Scientific Teaching (ST) pedagogy and encouraged to implement its practices at their home institutions. While participants generally report positive experiences at the SI, it remains unclear how these experiences affect instructors’ teaching practices and associated student outcomes. As part of a larger effort to evaluate the SI, we developed a survey to gauge the frequencies of ST practices that could occur in undergraduate STEM courses. The ST Practices Survey is derived from the observable teaching practices described in the Scientific Teaching taxonomy (Couch et al., 2015). During survey development, we conducted interviews with a panel of experts, instructors, and students, and this input was used to make iterative revisions to the survey. After finalizing the survey, we administered the survey at 9 institutions with 62 instructors and 64 courses, with both instructors and students completing the survey for a given course. In this seminar, we will discuss the development, validity, reliability, factor structure, and implementation of the ST Practices Survey. (abstract only

Resources for Teaching and Assessing the Vision and Change Biology Core Concepts

The Vision and Change report called for the biology community to mobilize around teaching the core concepts of biology. This essay describes a collection of resources developed by several different groups that can be used to respond to the report’s call to transform undergraduate education at both the individual course and departmental levels. First, we present two frameworks that help articulate the Vision and Change core concepts, the BioCore Guide and the Conceptual Elements (CE) Framework, which can be used in mapping the core concepts onto existing curricula and designing new curricula that teach the biology core concepts. Second, we describe how the BioCore Guide and the CE Framework can be used alongside the Partnership for Undergraduate Life Sciences Education curricular rubric as a way for departments to self-assess their teaching of the core concepts. Finally, we highlight three sets of instruments that can be used to directly assess student learning of the core concepts: the Biology Card Sorting Task, the Biology Core Concept Instruments, and the Biology—Measuring Achievement and Progression in Science instruments. Approaches to using these resources independently and synergistically are discussed

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases

Complex host genetics influence the microbiome in inflammatory bowel disease

Background: Human genetics and host-associated microbial communities have been associated independently with a wide range of chronic diseases. One of the strongest associations in each case is inflammatory bowel disease (IBD), but disease risk cannot be explained fully by either factor individually. Recent findings point to interactions between host genetics and microbial exposures as important contributors to disease risk in IBD. These include evidence of the partial heritability of the gut microbiota and the conferral of gut mucosal inflammation by microbiome transplant even when the dysbiosis was initially genetically derived. Although there have been several tests for association of individual genetic loci with bacterial taxa, there has been no direct comparison of complex genome-microbiome associations in large cohorts of patients with an immunity-related disease. Methods: We obtained 16S ribosomal RNA (rRNA) gene sequences from intestinal biopsies as well as host genotype via Immunochip in three independent cohorts totaling 474 individuals. We tested for correlation between relative abundance of bacterial taxa and number of minor alleles at known IBD risk loci, including fine mapping of multiple risk alleles in the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene exon. We identified host polymorphisms whose associations with bacterial taxa were conserved across two or more cohorts, and we tested related genes for enrichment of host functional pathways. Results: We identified and confirmed in two cohorts a significant association between NOD2 risk allele count and increased relative abundance of Enterobacteriaceae, with directionality of the effect conserved in the third cohort. Forty-eight additional IBD-related SNPs have directionality of their associations with bacterial taxa significantly conserved across two or three cohorts, implicating genes enriched for regulation of innate immune response, the JAK-STAT cascade, and other immunity-related pathways. Conclusions: These results suggest complex interactions between genetically altered host functional pathways and the structure of the microbiome. Our findings demonstrate the ability to uncover novel associations from paired genome-microbiome data, and they suggest a complex link between host genetics and microbial dysbiosis in subjects with IBD across independent cohorts. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0107-1) contains supplementary material, which is available to authorized users

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

A national cohort study and confidential enquiry to investigate ethnic disparities in maternal mortality

Background Ethnic disparities in maternal mortality were first documented in the UK in the early 2000s but are known to be widening. This project aimed to describe the women who died in the UK during or up to a year after the end of pregnancy, to compare the quality of care received by women from different aggregated ethnic groups, and to identify any structural or cultural biases or discrimination affecting their care. Methods National surveillance data was used to identify all 1894 women who died during or up to a year after the end of pregnancy between 2009 and 18 in the UK. Their characteristics and causes of death were described. A Confidential Enquiry was undertaken to describe the quality of care women received. The care of a stratified random sample of 54 women who died during or up to a year after the end of pregnancy between 2009 and 18, (18 from the aggregated group of Black women, 19 from the Asian aggregated group and 17 from the White aggregated group) was re-examined specifically to describe any structural or cultural biases or discrimination identified. Findings There were no major differences causes of death between women from different aggregated ethnic groups, with cardiovascular disease the leading cause of death in all groups. Multiple areas of bias were identified in the care women received, including lack of nuanced care (notable amongst women from Black aggregated ethnic groups who died), microaggressions (most prominent in the care of women from Asian aggregated ethnic groups who died) and clinical, social and cultural complexity (evident across all ethnic groups). Interpretation This confidential enquiry suggests that multiple structural and other biases exist in UK maternity care. Further research on the role of microaggressions is warranted. Funding This research is funded by the National Institute for Health Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Maternal and Neonatal Health and Care, PR-PRU-1217–21,202. MK is an NIHR Senior Investigator. SK is part funded and FCS fully funded by the National Institute for Health Research (NIHR) Applied Research Centre (ARC) West Midlands. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density.

INTRODUCTION: Mammographic density is an established breast cancer risk factor with a strong genetic component and can be increased in women using menopausal hormone therapy (MHT). Here, we aimed to identify genetic variants that may modify the association between MHT use and mammographic density. METHODS: The study comprised 6,298 postmenopausal women from the Mayo Mammography Health Study and nine studies included in the Breast Cancer Association Consortium. We selected for evaluation 1327 single nucleotide polymorphisms (SNPs) showing the lowest P-values for interaction (P int) in a meta-analysis of genome-wide gene-environment interaction studies with MHT use on risk of breast cancer, 2541 SNPs in candidate genes (AKR1C4, CYP1A1-CYP1A2, CYP1B1, ESR2, PPARG, PRL, SULT1A1-SULT1A2 and TNF) and ten SNPs (AREG-rs10034692, PRDM6-rs186749, ESR1-rs12665607, ZNF365-rs10995190, 8p11.23-rs7816345, LSP1-rs3817198, IGF1-rs703556, 12q24-rs1265507, TMEM184B-rs7289126, and SGSM3-rs17001868) associated with mammographic density in genome-wide studies. We used multiple linear regression models adjusted for potential confounders to evaluate interactions between SNPs and current use of MHT on mammographic density. RESULTS: No significant interactions were identified after adjustment for multiple testing. The strongest SNP-MHT interaction (unadjusted P int <0.0004) was observed with rs9358531 6.5kb 5' of PRL. Furthermore, three SNPs in PLCG2 that had previously been shown to modify the association of MHT use with breast cancer risk were found to modify also the association of MHT use with mammographic density (unadjusted P int <0.002), but solely among cases (unadjusted P int SNP×MHT×case-status <0.02). CONCLUSIONS: The study identified potential interactions on mammographic density between current use of MHT and SNPs near PRL and in PLCG2, which require confirmation. Given the moderate size of the interactions observed, larger studies are needed to identify genetic modifiers of the association of MHT use with mammographic density.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13058-015-0625-