Comparing In Vivo versus Simulation Training for Transnasal Endoscopy Skills

Fiberoptic endoscopic evaluations of swallowing (FEES) is as important of a swallowing evaluation as the videoflouroscopic swallow study, but far fewer speech-language pathologists are competent in its use (Ambika, Datta, Manjula, Warawantkar, & Thomas, 2019; Brady & Donzelli, 2013; Pisegna & Langmore, 2016). One hurdle in FEES training is the necessity of practicing transnasal endoscopy on volunteers. The primary aim of this study was to compare the learning effectiveness of practicing transnasal endoscopy via simulation with practice in vivo for a student’s first passes of the endoscope. The end goal of this study was to determine the most cost-effective and feasible means of teaching transnasal endoscopy to graduate clinicians. Twenty-one graduate students practiced transnasal endoscopy in one of three conditions: in vivo, high-fidelity lifelike simulation, low-fidelity non-lifelike simulation. The learning outcomes assessed were speed of endoscopy, student confidence, and simulated patients’ comfort and perception of student skill. There were no significant differences between conditions found for any of these measures. Students in all conditions became more confident after practicing endoscopy, and that confidence was predictive of procedure time. The results of this study indicate that practice with simulation may be an important first step in teaching endoscopy

The Utility of Peer-to-Peer Practice for Teaching Speech-Language Pathology Students Transnasal Endoscopy

Introduction: Transnasal flexible endoscopy (TNFE) is necessary for multiple assessments in speech-language pathology (SLP), but it is generally considered an advanced practice technique to be learned during clinical practice. As such, there is no standardized way that it is taught in training programs, leading to a substantial knowledge gap for new graduates. Though peer-to-peer practice has been discussed as an important step in training, it is not clear whether it confers additional benefits above and beyond simulation. This study sought to answer that question in the areas of student confidence, endoscopy speed, and motivation to pursue further TNFE experiences. Methods: Thirty-six SLP graduate students completed TNFE training and one of two practice conditions: simulation only or simulation with additional peer-to-peer practice. Outcome measures included confidence and comfort surveys, intrinsic motivation to complete an additional TNFE experience, and speed of TNFE. Results: No significant differences were found between the two groups for any measure, and consistently low effect sizes indicated there was little difference between groups. Conclusions: These results indicate that teaching TNFE through simulation may provide similar outcomes to peer-to-peer practice during the initial training that an SLP graduate program can provide. This adds to the literature indicating that TNFE simulation is a worthwhile addition to SLP programs

Genetic regulatory signatures underlying islet gene expression and type 2 diabetes

The majority of genetic variants associated with type 2 diabetes (T2D) are located outside of genes in noncoding regions that may regulate gene expression in disease-relevant tissues, like pancreatic islets. Here, we present the largest integrated analysis to date of high-resolution, high-throughput human islet molecular profiling data to characterize the genome (DNA), epigenome (DNA packaging), and transcriptome (gene expression). We find that T2D genetic variants are enriched in regions of the genome where transcription Regulatory Factor X (RFX) is predicted to bind in an islet-specific manner. Genetic variants that increase T2D risk are predicted to disrupt RFX binding, providing a molecular mechanism to explain how the genome can influence the epigenome, modulating gene expression and ultimately T2D risk

Allelic spectrum of the natural variation in CRP

With the recent completion of the International HapMap Project, many tools are in hand for genetic association studies seeking to test the common variant/common disease hypothesis. In contrast, very few tools and resources are in place for genotype–phenotype studies hypothesizing that rare variation has a large impact on the phenotype of interest. To create these tools for rare variant/common disease studies, much interest is being generated towards investing in re-sequencing either large sample sizes of random chromosomes or smaller sample sizes of patients with extreme phenotypes. As a case study for rare variant discovery in random chromosomes, we have re-sequenced ~1,000 chromosomes representing diverse populations for the gene C-reactive protein (CRP). CRP is an important gene in the fields of cardiovascular and inflammation genetics, and its size (~2 kb) makes it particularly amenable medical or deep re-sequencing. With these data, we explore several issues related to the present-day candidate gene association study including the benefits of complete SNP discovery, the effects of tagSNP selection across diverse populations, and completeness of dbSNP for CRP. Also, we show that while deep re-sequencing uncovers potentially medically relevant coding SNPs, these SNPs are fleetingly rare when genotyped in a population-based survey of 7,000 Americans (NHANES III). Collectively, these data suggest that several different types re-sequencing and genotyping approaches may be required to fully understand the complete spectrum of alleles that impact human phenotypes. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at http://dx.doi.org/10.1007/s00439-006-0160-y and is accessible for authorized users

The genetic regulatory signature of type 2 diabetes in human skeletal muscle

Type 2 diabetes (T2D) results from the combined effects of genetic and environmental factors on multiple tissues over time. Of the 4100 variants associated with T2D and related traits in genome-wide association studies (GWAS), >90% occur in non-coding regions, suggesting a strong regulatory component to T2D risk. Here to understand how T2D status, metabolic traits and genetic variation influence gene expression, we analyse skeletal muscle biopsies from 271 well-phenotyped Finnish participants with glucose tolerance ranging from normal to newly diagnosed T2D. We perform high-depth strand-specific mRNA-sequencing and dense genotyping. Computational integration of these data with epigenome data, including ATAC-seq on skeletal muscle, and transcriptome data across diverse tissues reveals that the tissue-specific genetic regulatory architecture of skeletal muscle is highly enriched in muscle stretch/super enhancers, including some that overlap T2D GWAS variants. In one such example, T2D risk alleles residing in a muscle stretch/super enhancer are linked to increased expression and alternative splicing of muscle-specific isoforms of ANK1.Peer reviewe

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Clinical evidence in speech-language pathology (Fissel Brannick et al., 2022)

Purpose: Two disparate models drive American speech-language pathologists’ views of evidence-based practice (EBP): the American Speech-Language-Hearing Association’s (2004a, 2004b) and Dollaghan’s (2007). These models discuss evidence derived from clinical practice but differ in the terms used, the definitions, and discussions of its role. These concepts, which we unify as clinical evidence, are an important part of EBP but lack consistent terminology and clear definitions in the literature. Our objective was to identify how clinical evidence is described in the field. Method: We conducted a scoping review to identify terms ascribed to clinical evidence and their descriptions. We searched the peer-reviewed, accessible, speech-language pathology intervention literature from 2005 to 2020. We extracted the terms and descriptions, from which three types of clinical evidence arose. We then used an open-coding framework to categorize positive and negative descriptions of clinical expertise and summarize the role of clinical evidence in decision making. Results: Seventy-eight articles included a description of clinical evidence. Across publications, a single term was used to describe disparate concepts, and the same concept was given different terms, yet the concepts that authors described clustered into three categories: clinical opinion, clinical expertise, and practice-based evidence, with each described as distinct from research evidence, and separate from the process of clinical decision making. Clinical opinion and clinical expertise were intrinsic to the clinician. Clinical opinion was insufficient and biased, whereas clinical expertise was a positive multidimensional construct. Practice-based evidence was extrinsic to the clinician—the local clinical data that clinicians generated. Good clinical decisions integrated multiple sources of evidence. Conclusions: These results outline a shared language for SLPs to discuss their clinical evidence with researchers, families, allied professionals, and each other. Clarification of the terminology, associated definitions, and the contributions of clinical evidence to good clinical decision-making informs EBP models in speech-language pathology. Supplemental Material S1. Corpus references.  Supplemental Material S2. Clinical evidence terms and sources.  Supplemental Material S3. Operational definitions and counts for clinical expertise categories and codes (N = 68). Supplemental Material S4. Operational definitions and counts for good clinical decision-making categories and codes (n = 53).  Fissel Brannick, S., Wolford, G. W., Wolford, L. L., Effron, K., & Buckler, J. (2022). What is clinical evidence in speech-language pathology? A scoping review. American Journal of Speech-Language Pathology. Advance online publication. https://doi.org/10.1044/2022_AJSLP-22-00203</p

A Type 2 Diabetes-Associated Functional Regulatory Variant in a Pancreatic Islet Enhancer at the ADCY5 Locus.

Molecular mechanisms remain unknown for most type 2 diabetes genome-wide association study identified loci. Variants associated with type 2 diabetes and fasting glucose levels reside in introns of ADCY5, a gene that encodes adenylate cyclase 5. Adenylate cyclase 5 catalyzes the production of cyclic AMP, which is a second messenger molecule involved in cell signaling and pancreatic β-cell insulin secretion. We demonstrated that type 2 diabetes risk alleles are associated with decreased ADCY5 expression in human islets and examined candidate variants for regulatory function. rs11708067 overlaps a predicted enhancer region in pancreatic islets. The type 2 diabetes risk rs11708067-A allele showed fewer H3K27ac ChIP-seq reads in human islets, lower transcriptional activity in reporter assays in rodent β-cells (rat 832/13 and mouse MIN6), and increased nuclear protein binding compared with the rs11708067-G allele. Homozygous deletion of the orthologous enhancer region in 832/13 cells resulted in a 64% reduction in expression level of Adcy5, but not adjacent gene Sec22a, and a 39% reduction in insulin secretion. Together, these data suggest that rs11708067-A risk allele contributes to type 2 diabetes by disrupting an islet enhancer, which results in reduced ADCY5 expression and impaired insulin secretion. Diabetes 2017 Sep; 66(9):2521-2530

Genetic regulatory signatures underlying islet gene expression and type 2 diabetes.

Genome-wide association studies (GWAS) have identified \u3e100 independent SNPs that modulate the risk of type 2 diabetes (T2D) and related traits. However, the pathogenic mechanisms of most of these SNPs remain elusive. Here, we examined genomic, epigenomic, and transcriptomic profiles in human pancreatic islets to understand the links between genetic variation, chromatin landscape, and gene expression in the context of T2D. We first integrated genome and transcriptome variation across 112 islet samples to produce dense cis-expression quantitative trait loci (cis-eQTL) maps. Additional integration with chromatin-state maps for islets and other diverse tissue types revealed that cis-eQTLs for islet-specific genes are specifically and significantly enriched in islet stretch enhancers. High-resolution chromatin accessibility profiling using assay for transposase-accessible chromatin sequencing (ATAC-seq) in two islet samples enabled us to identify specific transcription factor (TF) footprints embedded in active regulatory elements, which are highly enriched for islet cis-eQTL. Aggregate allelic bias signatures in TF footprints enabled us de novo to reconstruct TF binding affinities genetically, which support the high-quality nature of the TF footprint predictions. Interestingly, we found that T2D GWAS loci were strikingly and specifically enriched in islet Regulatory Factor X (RFX) footprints. Remarkably, within and across independent loci, T2D risk alleles that overlap with RFX footprints uniformly disrupt the RFX motifs at high-information content positions. Together, these results suggest that common regulatory variations have shaped islet TF footprints and the transcriptome and that a confluent RFX regulatory grammar plays a significant role in the genetic component of T2D predisposition. Proc Natl Acad Sci U S A 2017 Feb 28; 114(9):2301-2306