Likelihood of Spontaneous Conversion of Atrial Fibrillation to Sinus Rhythm

AbstractObjectives. We sought to determine the likelihood and predictors of spontaneous conversion to sinus rhythm of recent-onset atrial fibrillation (symptoms <72 h).Background. Although spontaneous conversion of recent-onset atrial fibrillation is common, the likelihood and clinical and echocardiographic predictors have not been fully defined. Such data would be important for management of patients in whom early cardioversion is desired: Cardioversion could be delayed in patients with a high likelihood of spontaneous conversion, and it could be expeditiously pursued if spontaneous conversion is unlikely.Methods. We screened 1,822 consecutive adults admitted to the hospital with atrial fibrillation and prospectively identified 356 patients (45% male, mean age ± SD 68 ± 16 years) with atrial fibrillation of <72-h duration. The occurrence of spontaneous conversion to sinus rhythm and clinical and echocardiographic data were identified through retrospective chart review.Results. Spontaneous conversion to sinus rhythm occurred in 68% of the study group (n = 242; 95% confidence interval [CI] 63% to 73%). Among patients with spontaneous conversion, the total duration of atrial fibrillation was <24 h in 159 (66%), 24 to 48 h in 42 (17%) and >48 h in 41 (17%) (p < 0.001). Logistic regression analysis of clinical data identified presentation <24 h from onset of symptoms as the only predictor of spontaneous conversion (odds ratio 1.8, 95% CI 1.4 to 2.4, p < 0.0001). Normal left ventricular systolic function was more common among patients with spontaneous conversion (p = 0.03), but it was not an independent predictor of conversion. Left atrial dimension was similar between groups.Conclusions. Spontaneous conversion to sinus rhythm occurs in almost 70% of patients presenting with atrial fibrillation of <72-h duration. Presentation with symptoms of <24-h duration is the best predictor of spontaneous conversion

Providing Reliability Services through Demand Response: A Prelimnary Evaluation of the Demand Response Capabilities of Alcoa Inc.

Demand response is the largest underutilized reliability resource in North America. Historic demand response programs have focused on reducing overall electricity consumption (increasing efficiency) and shaving peaks but have not typically been used for immediate reliability response. Many of these programs have been successful but demand response remains a limited resource. The Federal Energy Regulatory Commission (FERC) report, 'Assessment of Demand Response and Advanced Metering' (FERC 2006) found that only five percent of customers are on some form of demand response program. Collectively they represent an estimated 37,000 MW of response potential. These programs reduce overall energy consumption, lower green house gas emissions by allowing fossil fuel generators to operate at increased efficiency and reduce stress on the power system during periods of peak loading. As the country continues to restructure energy markets with sophisticated marginal cost models that attempt to minimize total energy costs, the ability of demand response to create meaningful shifts in the supply and demand equations is critical to creating a sustainable and balanced economic response to energy issues. Restructured energy market prices are set by the cost of the next incremental unit of energy, so that as additional generation is brought into the market, the cost for the entire market increases. The benefit of demand response is that it reduces overall demand and shifts the entire market to a lower pricing level. This can be very effective in mitigating price volatility or scarcity pricing as the power system responds to changing demand schedules, loss of large generators, or loss of transmission. As a global producer of alumina, primary aluminum, and fabricated aluminum products, Alcoa Inc., has the capability to provide demand response services through its manufacturing facilities and uniquely through its aluminum smelting facilities. For a typical aluminum smelter, electric power accounts for 30% to 40% of the factory cost of producing primary aluminum. In the continental United States, Alcoa Inc. currently owns and/or operates ten aluminum smelters and many associated fabricating facilities with a combined average load of over 2,600 MW. This presents Alcoa Inc. with a significant opportunity to respond in areas where economic opportunities exist to help mitigate rising energy costs by supplying demand response services into the energy system. This report is organized into seven chapters. The first chapter is the introduction and discusses the intention of this report. The second chapter contains the background. In this chapter, topics include: the motivation for Alcoa to provide demand response; ancillary service definitions; the basics behind aluminum smelting; and a discussion of suggested ancillary services that would be particularly useful for Alcoa to supply. Chapter 3 is concerned with the independent system operator, the Midwest ISO. Here the discussion examines the evolving Midwest ISO market structure including specific definitions, requirements, and necessary components to provide ancillary services. This section is followed by information concerning the Midwest ISO's classifications of demand response parties. Chapter 4 investigates the available opportunities at Alcoa's Warrick facility. Chapter 5 involves an in-depth discussion of the regulation service that Alcoa's Warrick facility can provide and the current interactions with Midwest ISO. Chapter 6 reviews future plans and expectations for Alcoa providing ancillary services into the market. Last, chapter 7, details the conclusion and recommendations of this paper

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data

Abstract: Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe