Supporting the quality of measurement and evaluation in education

The impetus for the development of a measurement and evaluation team for Robert Morris University, School of Nursing and Health Sciences (SNHS), was to foster faculty and administration commitment in enhancing the quality of measurement and evaluation processes. Many of the SNHS faculty members had experienced incidents of academic inconsistencies with student exam protocols. The measurement and evaluation team was charged to define the goals for faculty to use evidence-based assessment and evaluation strategies that are appropriate for the learner and learning goals, support use of evaluation data to measure the achievement of designated outcomes, and promote curricular excellence through the use of assessment and evaluation data and policies to enhance the teaching and learning process. This paper examines the results of surveys of undergraduate students, proctors, and faculty within the SNHS regarding new exam protocols, the implementation of the protocols, and their success

Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer

Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR ≤ 0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P = 2.2 × 10− 4, replication P = 0.01), and PYGL (discovery P = 2.3 × 10− 4, replication P = 6.7 × 10− 4). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P < 0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci. © 2019, The Author(s)

Correction to: Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer (Human Genetics, (2019), 138, 4, (307-326), 10.1007/s00439-019-01989-8)

Every author has erroneously been assigned to the affiliation “62”. The affiliation 62 belongs to the author Graham Casey. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature

NOD-Like Receptors-Pivotal Guardians of the Immunological Integrity of Barrier Organs

NOD-like receptors (NLRs) exert pivotal roles in innate immunity as sensors of exogenous or endogenous cellular danger signals. The NLR protein family has a characteristic domain architecture comprising a central nucleotide binding and oligomerization domain (NOD), an N-terminal effector binding domain and C-terminal leucine-rich repeats (LRRs). Mutations in NLR genes are genetically associated with a number of chronic inflammatory diseases of barrier organs. In this chapter, we focus on the influence of NLR regulation and function in the complex pathophysiology of mucosal homeostasis. The understanding of NLR biology may guide our future understanding of how the interaction between the human genome and the metagenome of transient and resident microbiota precipitates into chronic inflammatory disorders, such as Crohn's disease or atopy

Discovery of common and rare genetic risk variants for colorectal cancer

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10 −8 , bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development. © 2018, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10−8), breast and ovarian cancer (rg = 0.24, p = 7 × 10−5), breast and lung cancer (rg = 0.18, p =1.5 × 10−6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10−4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis