Showing papers by "Paul Morris published in 2020"

Angiography-Derived Fractional Flow Reserve: More or Less Physiology?

Abstract: Evidence robustly demonstrates that ischemia, rather than anatomy, is the optimal target for coronary revascularization. In the cardiac catheter laboratory, fractional flow reserve (FFR) and corresponding diastolic indices are regarded as the gold standard for physiological lesion assessment and ischemia detection (Table 1). Yet, despite a wealth of supporting data and indications in international guidelines, the use of FFR remains surprisingly low in the diagnostic assessment of coronary artery disease across the world.1, 2 To address this, multiple groups have developed methods for computing FFR from invasive angiography, without the need for passing a pressure wire or inducing hyperemia, thus removing the main barriers to uptake. Angiography‐derived FFR therefore has the potential to extend the benefits of physiological coronary lesion assessment to considerably more patients. Given the size of the interventional cardiology market, clinical and commercial motivation to deliver these tools as quickly as possible could hardly be greater. Several models are now approved as medical devices. Imminently, physicians and healthcare providers will have to decide whether to use these tools. But do they truly deliver physiology, and are they accurate enough? There are 3 particular areas of that deserve close scrutiny.

Predicting Binding from Screening Assays with Transformer Network Embeddings.

Abstract: Cheminformatics aims to assist in chemistry applications that depend on molecular interactions, structural characteristics, and functional properties The arrival of deep learning and the abundance

Genomic diversity of SARS-CoV-2 during early introduction into the United States National Capital Region

Abstract: Background: The early COVID-19 pandemic has been characterized by rapid global spread. In the United States National Capital Region, over 2,000 cases were reported within three weeks of its first detection in March 2020. We aimed to use genomic sequencing to understand the initial spread of SARS-CoV-2, the virus that causes COVID-19, in the region. By correlating genetic information to disease phenotype, we also aimed to gain insight into any correlation between viral genotype and case severity or transmissibility. Methods: We performed whole genome sequencing of clinical SARS-CoV-2 samples collected in March 2020 by the Johns Hopkins Health System, building on methods developed by the ARTIC network. We analyzed these regional SARS-CoV-2 genomes alongside detailed clinical metadata and the global phylogeny to understand early establishment of the virus within the region. Results: We analyzed 620 samples from the Johns Hopkins Health System collected between March 11-31, 2020, comprising 37.3% of the total cases in Maryland during this period. We selected 143 of these samples for sequencing, generating 114 complete viral genomes. These genomes belonged to all five major Nextstrain-defined clades, suggesting multiple introductions into the region and underscoring the diversity of the regional epidemic. We also found that clinically severe cases had genomes belonging to all of these clades. Conclusions: We established a pipeline for SARS-CoV-2 sequencing within the Johns Hopkins Health system, which enabled us to capture the significant viral diversity present in the region as early as March 2020. Efforts to control local spread of the virus were likely confounded by the number of introductions into the region early in the epidemic and interconnectedness of the region as a whole.

Developing Standards for Improved Data Quality and for Selecting Fit for Use Biodiversity Data

Abstract: The quality of biodiversity data publicly accessible via aggregators such as GBIF (Global Biodiversity Information Facility), the ALA (Atlas of Living Australia), iDigBio (Integrated Digitized Biocollections), and OBIS (Ocean Biogeographic Information System) is often questioned, especially by the research community. The Data Quality Interest Group, established by Biodiversity Information Standards (TDWG) and GBIF, has been engaged in four main activities: developing a framework for the assessment and management of data quality using a fitness for use approach; defining a core set of standardised tests and associated assertions based on Darwin Core terms; gathering and classifying user stories to form contextual-themed use cases, such as ‡ § | ¶ # ¤

Misunderstandings and omissions in textbook accounts of effect sizes

Abstract: There have been frequent attempts in psychology to reduce the reliance on null hypothesis significance testing (NHST) as the criterion for establishing the importance of results. Many authorities now recommend the reporting of effect sizes (ESs) as a supplement or alternative to NHST. However, there is extensive specialist literature highlighting problems associated with the use and interpretation of ESs. A review of the coverage of ESs in over 100 textbooks on statistical analysis in behavioural science revealed widespread neglect of ESs and the relevant critical issues that have widespread coverage in the more specialist literature. For example, many textbooks claim that ESs should be interpreted as a simple measure of the practical real-world importance of a result despite the fact that ESs are profoundly influenced by features of design and analysis strategy. We seek to highlight areas of misunderstanding about ESs found in the pedagogical literature in the light of the more specialist literature and make recommendations to researchers for the appropriate use and interpretation of ESs. This is critical as statistics textbooks have a crucial role in the education of researchers.

Arabidopsis ADC1 functions as an Nδ -acetylornithine decarboxylase.

Abstract: Polyamines are small aliphatic amines found in almost all organisms, ranging from bacteria to plants and animals. In most plants, putrescine, the metabolic precursor for longer polyamines, such as spermidine and spermine, is produced from arginine, with either agmatine or ornithine as intermediates. Here we show that Arabidopsis thaliana (Arabidopsis) arginine decarboxylase 1 (ADC1), one of the two known arginine decarboxylases in Arabidopsis, not only synthesizes agmatine from arginine, but also converts Nδ -acetylornithine to N-acetylputrescine. Phylogenetic analyses indicate that duplication and neofunctionalization of ADC1 and NATA1, the enzymes that synthesize Nδ -acetylornithine in Arabidopsis, co-occur in a small number of related species in the Brassicaceae. Unlike ADC2, which is localized in the chloroplasts, ADC1 is in the endoplasmic reticulum together with NATA1, an indication that these two enzymes have access to the same substrate pool. Together, these results are consistent with a model whereby NATA1 and ADC1 together provide a pathway for the synthesis of N-acetylputrescine in Arabidopsis.

Coronary Physiology Derived from Invasive Angiography: Will it be a Game Changer?

Abstract: There is a large body of evidence suggesting that having knowledge of the presence and extent of coronary atheroma and whether it is causing downstream myocardial ischaemia facilitates optimal diagnosis and management for patients presenting with chest pain. Despite this, the use of coronary pressure wire in routine practice is surprisingly low and routine assessment of all diseased vessels before making a bespoke management plan is rare. The advent of angiogram-derived models of physiology could change diagnostic practice completely. By offering routine assessment of the physiology of all the major epicardial coronary vessels, angiogram-derived physiology has the potential to radically modify current practice by facilitating more accurate patient-level, vessel-level, and even lesion-level decision-making. In this article, the authors review the current state of angiogram-derived physiology and speculate on its potential impact on clinical practice.

Structural and catalytic analysis of two diverse uridine phosphorylases in Phytophthora capsici.

Abstract: Uridine phosphorylase (UP) is a key enzyme of pyrimidine salvage pathways that enables the recycling of endogenous or exogenous-supplied pyrimidines and plays an important intracellular metabolic role. Here, we biochemically and structurally characterized two evolutionarily divergent uridine phosphorylases, PcUP1 and PcUP2 from the oomycete pathogen Phytophthora capsici. Our analysis of other oomycete genomes revealed that both uridine phosphorylases are present in Phytophthora and Pythium genomes, but only UP2 is seen in Saprolegnia spp. which are basal members of the oomycetes. Moreover, uridine phosphorylases are not found in obligate oomycete pathogens such as Hyaloperonospora arabidopsidis and Albugo spp. PcUP1 and PcUP2 are upregulated 300 and 500 fold respectively, within 90 min after infection of pepper leaves. The crystal structures of PcUP1 in ligand-free and in complex with uracil/ribose-1-phosphate, 2′-deoxyuridine/phosphate and thymidine/phosphate were analyzed. Crystal structure of this uridine phosphorylase showed strict conservation of key residues in the binding pocket. Structure analysis of PcUP1 with bound ligands, and site-directed mutagenesis of key residues provide additional support for the “push-pull” model of catalysis. Our study highlights the importance of pyrimidine salvage during the earliest stages of infection.

Suspicious for Malignancy Diagnoses on Pleural Effusion Cytology.

Abstract: Objectives A definitive diagnosis of malignancy may not be possible in pleural effusions. We report our experience with the diagnosis of suspicious for malignancy (SFM) in pleural effusion. Methods A search for pleural effusions diagnosed as SFM (2008-2018) was performed. Patient records and pathology reports were reviewed. Specimens were subdivided into groups depending on volume ( 400 mL). Diagnoses of malignant pleural effusion (MPE) served as controls. Results We identified 90 patients, with a mean age of 60.6 years. Diagnoses included suspicious for involvement by carcinoma/adenocarcinoma in 64.4%, leukemia/lymphoma in 15.6%, melanoma in 2.2%, sarcoma in 3.3%, germ cell tumor in 1.1%, and not otherwise specified in 13.3%. Immunostains were performed in 47.8% and considered inconclusive in 24%. Average sample volume was 419 mL. There was a statistically significant difference between the SFM vs MPE groups for volumes greater than 75 mL (P = .001, χ 2 test), with SFM having increased proportion of volumes greater than 400 mL, compared with the MPE group. There was no statistically significant difference in mean overall survival when the groups were compared (P = .49). Conclusions Samples with low cellularity, scant cell blocks, and inconclusive immunostains may contribute to a suspicious category diagnosis in pleural effusions.

Evaluating The Number of Trainable Parameters on Deep Maxout and LReLU Networks for Visual Recognition

Abstract: Object recognition research has made notable steps since the appearance of convolutional neural networks, and many activation functions have been proposed to enhance the classification performance of these networks. Maxout networks have achieved great success in many computer vision tasks, but there is limited information on whether an increase in the number of trainable parameters can increase the performance in Leaky Rectified Linear Unit (LReLU) networks compared to maxout networks. Our experiments compare LReLU, rectified linear unit, scaled exponential linear unit, and hyperbolic tangent to four maxout variants. We evaluate ReLU and LReLU with 2x, 3x and 6x the number of filters in each convolutional layer. We also evaluate ReLU, LReLU and maxout networks with approximately the same number of trainable parameters. Under equal conditions, we found that on average, across all datasets, LReLU performs better than any of the evaluated activation functions.

System for failure response advice based on diagnosed failures and their effect on planned activities

Abstract: A system and method of warning and planning failure responses using an automated failure response system including, providing an electro-mechanical system having mechanical and electrical components and providing a failure response system for diagnosing failures of the components. The failure response system then determines effects of said failures on carrying out system activities using the failure response system, quantifies a severity for each failure diagnosed by the failure response system, and identifies repairs for each component failure. The failure response system also prioritizes each failure of a component based on severity and then recommends which repairs should be prioritized as most urgent to keep the electro-mechanical system operational based upon the severity of the associated failures and the effects of their corresponding failure.