Evaluating the accuracy and use of continuous glucose monitoring in hospitalized patients: a systematic review and meta-analysis

Introduction: Glycemic variability in hospitalized patients is associated with poor clinical outcomes, longer length of stay, and increased cost. Advances in subcutaneous continuous glucose monitoring (CGM) technology may reduce glycemic excursions and improve clinical outcomes in hospitalized patients, yet CGM is not used due to a lack of evidence on accuracy. The objective of this study was to review and summarize the evidence on the accuracy of CGM in hospitalized, diabetic patients. Methods: A search was conducted for literature evaluating CGM accuracy in hospitalized, diabetic patients. Relevant studies were identified through full-text review and data was extracted for analysis. The primary outcome was any reported measure of accuracy. Descriptive analysis of data was performed but pooling of primary outcomes was not feasible due to the heterogeneity and nature of reported outcomes. Results: Systematic review returned 302 results, with 9 studies meeting inclusion criteria. All included studies assessed CGM accuracy using fingerstick blood glucose measurement as a reference. Reported measures of accuracy (# reporting) included mean absolute relative difference (MARD) (6), coefficient of variation (4), bias (2), and Clarke Error Grid analysis (7). MARD ranged from 9.4% to 14.9% though direction of deviation differed across studies and blood glucose ranges. Discussion: There is considerable variation in the analytic techniques used to assess CGM accuracy in the inpatient population. Outcome measures used to assess CGM data cannot be pooled using traditional meta-analysis methods. Reporting guidelines are necessary to make data comparable and determine the suitability of CGM for use in hospitalized patients

Satisfaction with teledermatology in an underserved urban shelter setting

Problem Statement: People experiencing homelessness (PEH) face disproportionate access to dermatologic care. Teledermatology is a platform that may improve access to medical care in underserved communities. The literature is lacking on this topic. Project Aim: The purpose of this quality improvement initiative is to evaluate patient and provider satisfaction with teledermatology in an urban shelter setting. Satisfaction surveys will be distributed over one year to provide measurable data that are determinate (designed to highlight multiple satisfaction metrics, numerically), concise (designed with functionality and efficiency in mind) and relevant (validated across multiple studies).https://jdc.jefferson.edu/medposters/1021/thumbnail.jp

A thin layer angiogenesis assay: a modified basement matrix assay for assessment of endothelial cell differentiation

BACKGROUND: Basement matrices such as Matrigel™ and Geltrex™ are used in a variety of cell culture assays of anchorage-dependent differentiation including endothelial cell tube formation assays. The volumes of matrix recommended for these assays (approximately 150 μl/cm(2)) are costly, limit working distances for microscopy, and require cell detachment for subsequent molecular analysis. Here we describe the development and validation of a thin-layer angiogenesis (TLA) assay for assessing the angiogenic potential of endothelial cells that overcomes these limitations. RESULTS: Geltrex™ basement matrix at 5 μl/cm(2) in 24-well (10 μl) or 96-well (2 μl) plates supports endothelial cell differentiation into tube-like structures in a comparable manner to the standard larger volumes of matrix. Since working distances are reduced, high-resolution single cell microscopy, including DIC and confocal imaging, can be used readily. Using MitoTracker dye we now demonstrate, for the first time, live mitochondrial dynamics and visualise the 3-dimensional network of mitochondria present in differentiated endothelial cells. Using a standard commercial total RNA extraction kit (Qiagen) we also show direct RNA extraction and RT-qPCR from differentiated endothelial cells without the need to initially detach cells from their supporting matrix. CONCLUSIONS: We present here a new thin-layer assay (TLA) for measuring the anchorage-dependent differentiation of endothelial cells into tube-like structures which retains all the characteristics of the traditional approach but with the added benefit of a greatly lowered cost and better compatibility with other techniques, including RT-qPCR and high-resolution microscopy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-014-0041-5) contains supplementary material, which is available to authorized users

Climate Change Adaptation Planning for Cultural Heritage, a National Scale Methodology

Ireland’s Climate Action and Low Carbon Development Act 2015 established the requirement for a National Adaptation Framework (NAF) composed of 9 sectoral plans, of which Built and Archaeological Heritage is one. All the plans were written according to the six step process outlined in Sectoral Planning Guidelines for Climate Change Adaptation produced by the Department of Communications, Climate Action and Environment (DCCAE, 2018) which is also the government department charged with coordinating the NAF. This article summarises the application of the methodology to heritage resources in Ireland, the issues encountered and the results achieved. The plan was informed by existing research and incorporated expert, stakeholder and public consultation throughout the process. It also closely considered published plans from other sectors in order to aid consistency within the NAF and to ensure cross-cutting issues were highlighted. Of the many potential impacts of climate change, those identified as priorities for adaptation planning in Ireland were flooding (inland & coastal), storm damage, coastal erosion, soil movement (landslip or erosion), changing burial preservation conditions, pests and mould, wildfires, and maladaptation. Goals, objectives and an action plan were developed commensurate with the five-year term of the plan, but also initiating a long-term strategic vision. A monitoring strategy was developed to monitor progress, identify problems and inform improvements to the adaptation plan as part of an iterative process. Much work is being done on the topic of climate change and cultural heritage but it is believed that when Ireland adopted its national adaptation plan for cultural heritage in October 2019 it was the first government to do so

Conserved motifs reveal details of ancestry and structure in the small tim chaperones of the mitochondrial intermembrane space

The mitochondrial inner and outer membranes are composed of a variety of integral membrane proteins, assembled into the membranes posttranslationally. The small translocase of the inner mitochondrial membranes (TIMs) are a group of ∼10 kDa proteins that function as chaperones to ferry the imported proteins across the mitochondrial intermembrane space to the outer and inner membranes. In yeast, there are 5 small TIM proteins: Tim8, Tim9, Tim10, Tim12, and Tim13, with equivalent proteins reported in humans. Using hidden Markov models, we find that many eukaryotes have proteins equivalent to the Tim8 and Tim13 and the Tim9 and Tim10 subunits. Some eukaryotes provide "snapshots" of evolution, with a single protein showing the features of both Tim8 and Tim13, suggesting that a single progenitor gene has given rise to each of the small TIMs through duplication and modification. We show that no "Tim12" family of proteins exist, but rather that variant forms of the cognate small TIMs have been recently duplicated and modified to provide new functions: the yeast Tim12 is a modified form of Tim10, whereas in humans and some protists variant forms of Tim9, Tim8, and Tim13 are found instead. Sequence motif analysis reveals acidic residues conserved in the Tim10 substrate-binding tentacles, whereas more hydrophobic residues are found in the equivalent substrate-binding region of Tim13. The substrate-binding region of Tim10 and Tim13 represent structurally independent domains: when the acidic domain from Tim10 is attached to Tim13, the Tim8–Tim13¹⁰ complex becomes essential and the Tim9–Tim10 complex becomes dispensable. The conserved features in the Tim10 and Tim13 subunits provide distinct binding surfaces to accommodate the broad range of substrate proteins delivered to the mitochondrial inner and outer membranes

Finding the Balance: Creating an open, sustainable future for OU

Today’s scholars have more publishing options available to them than ever before. In addition to traditional publishing venues, open publishing has become a viable and practicable option for communicating research to ever broadening audiences. This breadth of publishing options focuses new attention on the way business models, accessibility, copyright and intellectual property, and research dissemination are envisioned. Moreover, these considerations have important and pressing implications for OU faculty members and graduate students who are authors, readers, reviewers, editors, society associates, and advisory board members dependent upon effective scholarly communication for professional development and advancement. Scholars are on the cusp of a transformative shift toward a more sustainable system of scholarly communication. In 2019 the University Libraries Committee convened a Scholarly Communication Taskforce to examine these issues. The Taskforce met during the 2019-2020 and will continue their work through the spring of 2022. The Taskforce has met monthly to discuss selected readings and how these scholarly communication topics will effect their colleagues and students in their colleges and departments.The Taskforce's work culminated in this report "Finding the Balance: Creating an Open Sustainable Future for OU," to be presented to the OU community. For more information, visit the Taskforce website at https://bit.ly/SCTFReport.N

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

A Combined Pathway and Regional Heritability Analysis Indicates NETRIN1 Pathway is Associated with Major Depressive Disorder

AbstractBackgroundGenome-wide association studies (GWASs) of major depressive disorder (MDD) have identified few significant associations. Testing the aggregation of genetic variants, in particular biological pathways, may be more powerful. Regional heritability analysis can be used to detect genomic regions that contribute to disease risk.MethodsWe integrated pathway analysis and multilevel regional heritability analyses in a pipeline designed to identify MDD-associated pathways. The pipeline was applied to two independent GWAS samples [Generation Scotland: The Scottish Family Health Study (GS:SFHS, N = 6455) and Psychiatric Genomics Consortium (PGC:MDD) (N = 18,759)]. A polygenic risk score (PRS) composed of single nucleotide polymorphisms from the pathway most consistently associated with MDD was created, and its accuracy to predict MDD, using area under the curve, logistic regression, and linear mixed model analyses, was tested.ResultsIn GS:SFHS, four pathways were significantly associated with MDD, and two of these explained a significant amount of pathway-level regional heritability. In PGC:MDD, one pathway was significantly associated with MDD. Pathway-level regional heritability was significant in this pathway in one subset of PGC:MDD. For both samples the regional heritabilities were further localized to the gene and subregion levels. The NETRIN1 signaling pathway showed the most consistent association with MDD across the two samples. PRSs from this pathway showed competitive predictive accuracy compared with the whole-genome PRSs when using area under the curve statistics, logistic regression, and linear mixed model.ConclusionsThese post-GWAS analyses highlight the value of combining multiple methods on multiple GWAS data for the identification of risk pathways for MDD. The NETRIN1 signaling pathway is identified as a candidate pathway for MDD and should be explored in further large population studies