Publications by authors named "David Lowe"

Introduction: Accurate evaluation of respiratory rate and pattern is important in health and disease; however, it can be challenging in children and babies due to small size and poor tolerability of existing monitoring equipment. This protocol outlines a study evaluating the feasibility of collecting respiratory data using a chest-worn accelerometer-based motion sensor in paediatric patients at risk of apnoea, respiratory failure and sudden death.

Methods And Analysis: This is an observational feasibility study over a 2-year period.

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RDE-3 adds poly UG tails to mRNAs targeted for silencing by the dsRNA-initiated RNA interference (RNAi) pathway. RDE-3 can also add p(UG) tails to some endogenous cellular mRNAs. Mechanisms directing RDE-3 to pUGylate specific mRNAs are not understood.

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Introduction: We describe the immunophenotyping and genetic analysis of HIV-uninfected apparently immunocompetent adults presenting with disseminated cryptococcosis. Cryptococci are environmentally ubiquitous fungi that may cause disseminated infection including meningitis. Cryptococcosis occurs predominantly in immunocompromised hosts and most commonly in the context of human immunodeficiency virus (HIV) infection.

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Introduction: Scotland has a drug death crisis. In 2023, 58% of drug-related deaths involved benzodiazepines. Novel benzodiazepines, predominantly bromazolam, are found in the drug "street valium", commonly used in Scotland.

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Aims: Echocardiography is a rate-limiting step in the timely diagnosis of heart failure (HF). Automated reporting of echocardiograms has the potential to streamline workflow. The aim of this study was to test the diagnostic accuracy of fully automated artificial intelligence (AI) analysis of images acquired using handheld echocardiography and its interchangeability with expert human-analysed cart-based echocardiograms in a real-world cohort with suspected HF.

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Randomized controlled trials (RCTs) remain the benchmark for assessing treatment effects but are limited to phenotypically narrow populations by design. We introduce a novel generative artificial intelligence (AI) driven emulation method that infers effect size through virtual clinical trials, which can emulate the RCT process and potentially extrapolate into wider populations. We validate the virtual trials by comparing the predicted impact of glucagon-like peptide-1 (GLP-1) agonists on HbA1c in type-2 diabetes (T2DM) with its true efficacy established in the LEAD-5 trial.

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Sera from patients with previous transplants, transfusions, and pregnancies may contain multiple Human Leukocyte Antigen (HLA)-specific antibodies recognizing various functional epitopes or eplets. The identification and verification of eplets in these high Panel Reactive Antibody (PRA) cases are important for understanding HLA antigenicity and potentially improving transplantation outcomes. For a particular high PRA case, we utilized adsorption and elution techniques using cells and HLA-specific magnetic beads to identify and verify eplets.

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RNA interference (RNAi) is a component of the innate immune systems of many eukaryotes, including . During RNAi in , the nucleotidyltransferase RDE-3 modifies the 3' termini of mRNAs with polyUG (pUG) tails, which recruit RNA-dependent RNA Polymerase (RdRP) enzymes that drive gene silencing by synthesizing antisense small interfering (si)RNAs. During normal growth and development, RDE-3 pUGylates transposon RNAs to silence transposons and protect genomic integrity.

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Background: The lack of international consensus on defining and categorising immunosuppression has undermined disease surveillance and patient care, particularly during the COVID-19 pandemic. To address this, a global expert panel was recruited to join the eDElphi STudy to fully defiINe and COVID-risk stratify ImmunosupprESsion (DESTINIES) and develop a COVID risk-stratified digital phenotype for 'adult immunosuppression' (the DESTINIES phenotype).

Methods: Panellists were presented with all medical diagnoses and procedures cited in prevailing immunosuppressed definitions; they evaluated their appropriateness for the DESTINIES phenotype and their risks for severe COVID-19 outcomes through anonymous online questionnaires and discussion.

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Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus transmitted sporadically from camels to humans. Most reported human Middle East respiratory syndrome (MERS) cases have occurred in or near the Arabian Peninsula. Limited human-to-human transmission can occur after close contact and has resulted in health care-associated outbreaks.

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Objectives: To assess outcomes in sotrovimab-treated immunocompromised patients in the United Kingdom.

Methods: Multicenter, prospective, observational, descriptive study in immunocompromised, non-hospitalized adults infected with SARS-CoV-2 who received intravenous sotrovimab 500 mg as standard-of-care (July 1, 2022-June 30, 2023; Omicron predominance). Virology analyses included determination of SARS-CoV-2 viral load, spike sequencing, and determination of amino-acid substitutions in the spike protein and sotrovimab epitope.

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Background: Chronic granulomatous disease (CGD) is a rare inborn error of immunity caused by mutations affecting individual components of the nicotinamide adenine dinucleotide phosphate oxidase complex. Resultant defective neutrophil function leads to infectious and inflammatory complications, resulting in reduced quality of life and survival. Although hematopoietic stem cell transplantation is a curative option, a significant proportion of patients are managed conservatively into adulthood.

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Objectives: To develop an early budget impact analysis of and inform future research on the national adoption of a commercially available artificial intelligence (AI) application to support clinicians reviewing radiographs for suspected fractures across National Health Service (NHS) emergency departments (ED) in England.

Methods: A decision tree framework was coded to assess a change in outcomes for suspected fractures in adults when AI fracture detection was integrated into the clinical workflow over a 1-year time horizon. Standard of care was the comparator scenario, and the ground truth reference cases were characterized by radiology report findings.

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Background: During the coronavirus disease 2019 (COVID-19) pandemic, many individuals developed persistent symptoms after COVID-19. The data on these long-term effects in the primary immunodeficiency (PID) community are limited.

Objective: This study aimed to understand long-term symptoms after COVID-19 in patients with PID, focusing on prevalence, risk factors, viral persistence, and the impact of COVID-19 on their health-related quality of life (HR-QoL).

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Background: The antiviral efficacy of molnupiravir against SARS-CoV-2 is controversial. Here, we develop a model integrating viral and immune dynamics to characterize the mechanism of action of molnupiravir in vivo and its impact on viral dynamics during and after treatment.

Methods: We analyzed data from the PANORAMIC trial, where 577 outpatients were randomized shortly after symptom onset to receive usual care or molnupiravir for 5 days, with viral and immunologic data collected within 2 weeks.

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A male infant presented with reduced oral intake, low-grade fever and postauricular erythema. Clinical examination revealed a soft, tender swelling posteroinferior to the mastoid tip with a dull tympanic membrane on otoscopy. Cross-sectional imaging did not show any evidence of middle ear infection or mastoiditis.

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Molnupiravir is an antiviral medicine that induces lethal copying errors during SARS-CoV-2 RNA replication. Molnupiravir reduced hospitalization in one pivotal trial by 50% and had variable effects on reducing viral RNA levels in three separate trials. We used mathematical models to simulate these trials and closely recapitulated their virologic outcomes.

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Article Synopsis
  • Allogeneic haematopoietic stem cell transplantation (alloHSCT) shows high survival rates (90% overall survival) in adolescents and adults with severe inborn errors of immunity (IEI), as assessed in a study of 82 patients.
  • The study found that pre-transplant immune dysregulation (measured by the IDDA v2.1 score) and the haematopoietic cell transplantation comorbidity index (HCT-CI) score significantly affected transplant outcomes, including overall survival and event-free survival.
  • Notably, a portion of patients with a high IDDA v2.1 score and low HCT-CI score indicates that existing risk assessments may underestimate the risks of alloHSCT, highlighting
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Heart Failure (HF) is common, with worldwide prevalence of 1%-3% and a lifetime risk of 20% for individuals 40 years or older. Despite its considerable health economic burden, techniques for early detection of HF in the general population are sparse. In this work we tested the hypothesis that a simple Transformer neural network, trained on comprehensive collection of secondary care data across the general population, can be used to prospectively (three-year predictive window) identify patients at an increased risk of first hospitalisation due to HF (HHF).

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During the 2022 and ongoing mpox outbreak, PCR diagnostics were already within the Laboratory Response Network (LRN) laboratories and additionally rapidly deployed to detect monkeypox (mpox) virus in patients and aid in accurate diagnosis. This accuracy is dependent on proper collection, shipment, and adherence to PCR procedure. This book chapter discusses effective collection, storage, and transportation for a real-time PCR to detect monkeypox virus nucleic acid.

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