Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
1,537
result(s) for
"Lo, Christine"
Sort by:
Machine learning application for the prediction of SARS-CoV-2 infection using blood tests and chest radiograph
Triaging and prioritising patients for RT-PCR test had been essential in the management of COVID-19 in resource-scarce countries. In this study, we applied machine learning (ML) to the task of detection of SARS-CoV-2 infection using basic laboratory markers. We performed the statistical analysis and trained an ML model on a retrospective cohort of 5148 patients from 24 hospitals in Hong Kong to classify COVID-19 and other aetiology of pneumonia. We validated the model on three temporal validation sets from different waves of infection in Hong Kong. For predicting SARS-CoV-2 infection, the ML model achieved high AUCs and specificity but low sensitivity in all three validation sets (AUC: 89.9–95.8%; Sensitivity: 55.5–77.8%; Specificity: 91.5–98.3%). When used in adjunction with radiologist interpretations of chest radiographs, the sensitivity was over 90% while keeping moderate specificity. Our study showed that machine learning model based on readily available laboratory markers could achieve high accuracy in predicting SARS-CoV-2 infection.
Journal Article
Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson’s disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The ‘Exenatide-PD3’ study
IntroductionParkinson’s disease (PD) is a common neurodegenerative disorder with substantial morbidity. No disease-modifying treatments currently exist. The glucagon like peptide-1 receptor agonist exenatide has been associated in single-centre studies with reduced motor deterioration over 1 year. The aim of this multicentre UK trial is to confirm whether these previous positive results are maintained in a larger number of participants over 2 years and if effects accumulate with prolonged drug exposure.Methods and analysisThis is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial of exenatide at a dose of 2 mg weekly in 200 participants with mild to moderate PD. Treatment duration is 96 weeks. Randomisation is 1:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96 weeks.The primary outcome is the comparison of Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 motor subscore in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Secondary outcomes will compare the change between groups among other motor, non-motor and cognitive scores. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups using a mixed model, adjusting for baseline scores. Secondary outcomes will be summarised between treatment groups using summary statistics and appropriate statistical tests to assess for significant differences.Ethics and disseminationThis trial has been approved by the South Central-Berkshire Research Ethics Committee and the Health Research Authority. Results will be disseminated in peer-reviewed journals, presented at scientific meetings and to patients in lay-summary format.Trial registration numbersNCT04232969, ISRCTN14552789.
Journal Article
The language of solitude : a novel
Starting over in Hong Kong after a devastating family tragedy, journalist Paul Leibovitz investigates a mysterious illness in a remote village outside Shanghai, where he discovers that a powerful chemical conglomerate is polluting a local lake.
Book
Marijuana and chronic obstructive lung disease: a population-based study
Our aim was to determine the combined and independent effects of tobacco and marijuana smoking on respiratory symptoms and chronic obstructive pulmonary disease (COPD) in the general population.
We surveyed a random sample of 878 people aged 40 years or older living in Vancouver, Canada, about their respiratory history and their history of tobacco and marijuana smoking. We performed spirometric testing before and after administration of 200 μg of salbutamol. We examined the association between tobacco and marijuana smoking and COPD.
The prevalence of a history of smoking in this sample was 45.5% (95% confidence interval [CI] 42.2%–48.8%) for marijuana use and 53.1% (95% CI 49.8%–56.4%) for tobacco use. The prevalence of current smoking (in the past 12 months) was 14% for marijuana use and 14% for tobacco use. Compared with nonsmokers, participants who reported smoking only tobacco, but not those who reported smoking only marijuana, experienced more frequent respiratory symptoms (odds ratio [OR] 1.50, 95% CI 1.05–2.14) and were more likely to have COPD (OR 2.74, 95% CI 1.66–4.52). Concurrent use of marijuana and tobacco was associated with increased risk (adjusted for age, asthma and comorbidities) of respiratory symptoms (OR 2.39, 95% CI 1.58–3.62) and COPD (OR 2.90, 95% CI 1.53–5.51) if the lifetime dose of marijuana exceeded 50 marijuana cigarettes. The risks of respiratory symptoms and of COPD were related to a synergistic interaction between marijuana and tobacco.
Smoking both tobacco and marijuana synergistically increased the risk of respiratory symptoms and COPD. Smoking only marijuana was not associated with an increased risk of respiratory symptoms or COPD.
Une version française de ce résumé est disponible à l'adresse www.cmaj.ca/cgi/content/full/180/8/814/DC1
CMAJ 2009;180(8):814-20
Journal Article
Epidemiology and introduction to the clinical presentation of Wilson disease
Our understanding of the epidemiology of Wilson disease has steadily grown since Sternlieb and Scheinberg's first prevalence estimate of 5 per million individuals in 1968. Increasingly sophisticated genetic techniques have led to revised genetic prevalence estimates of 142 per million. Various population isolates exist where the prevalence of Wilson disease is higher still, the highest being 885 per million from within the mountainous region of Rucar in Romania. In Sardinia, where the prevalence of Wilson disease has been calculated at 370 per million births, six mutations account for around 85% of Wilson disease chromosomes identified. Significant variation in the patterns of presentation may however exist, even between individuals carrying the same mutations. At either extremes of presentation are an 8-month-old infant with abnormal liver function tests and individuals diagnosed in their eighth decade of life. Three main patterns of presentation have been recognized – hepatic, neurologic, and psychiatric – prompting their presentation to a diverse range of specialists. Deviations in the family history from the anticipated autosomal-recessive mode of inheritance, with apparent “pseudodominance” and mechanisms of inheritance that include uniparental isodisomy (the inheritance of both chromosomal copies from a single parent), may all further cloud the diagnosis. It can therefore take the efforts of an astute clinician with a high clinical index of suspicion to clinch the diagnosis of this eminently treatable condition.
Book Chapter
Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA
Liquid biopsy is a valuable precision oncology tool that is increasingly used as a non-invasive approach to identify biomarkers, detect resistance mutations, monitor disease burden, and identify early recurrence. The Tempus xF liquid biopsy assay is a 105-gene, hybrid-capture, next-generation sequencing (NGS) assay that detects single-nucleotide variants, insertions/deletions, copy number variants, and chromosomal rearrangements. Here, we present extensive validation studies of the xF assay using reference standards, cell lines, and patient samples that establish high sensitivity, specificity, and accuracy in variant detection. The Tempus xF assay is highly concordant with orthogonal methods, including ddPCR, tumor tissue-based NGS assays, and another commercial plasma-based NGS assay. Using matched samples, we developed a dynamic filtering method to account for germline mutations and clonal hematopoiesis, while significantly decreasing the number of false-positive variants reported. Additionally, we calculated accurate circulating tumor fraction estimates (ctFEs) using the Off-Target Tumor Estimation Routine (OTTER) algorithm for targeted-panel sequencing. In a cohort of 1,000 randomly selected cancer patients who underwent xF testing, we found that ctFEs correlated with disease burden and clinical outcomes. These results highlight the potential of serial testing to monitor treatment efficacy and disease course, providing strong support for incorporating liquid biopsy in the management of patients with advanced disease.
Journal Article
Exploration of whether socioeconomic factors affect the results of priority setting partnerships: updating the top 10 research priorities for the management of Parkinson’s in an international setting
ObjectivesExplore whether socioeconomic differences of patients affect the prioritisation of pre-existing research questions and explore the agreement between healthcare professionals (HCP) and patients in priority setting partnerships (PSPs).Design and settingProspective, three centre survey across UK (400 participants), Tuebingen (176 participants) and Luxembourg (303 participants). People with Parkinson’s (PwP), research participants, relatives and HCP associated with three Parkinson’s cohort studies were invited to participate, along with linked centres (clinical care settings, research groups, charities). Responders were encouraged to pass on the survey to friends/families/carers.MethodsThe survey involved rating the importance of research questions on a Likert scale, allowing for the generation of one new question participants felt was particularly important. Collection of demographic information allowed for comparisons of priorities across a range of socioeconomic variables; the top 10 research priorities for each group were then compared. Questions added by participants were subject to a thematic analysis.Results879 participants completed the survey (58% PwP, 22% family/friends, 13% HCP, 4% carers). Finding the best form of physiotherapy for PwP was the number one priority across the majority of analyses. HCP were the only subgroup not to place physiotherapy in the top 10. Factors most likely to affect prioritisation in PwP included educational level, presence of carer support and disease duration. There was little difference between other socioeconomic categories.ConclusionsSocioeconomic factors modestly influenced some research priority ratings but did not significantly affect the top priority in most comparisons. Future studies must ensure patients from a range of socioeconomic backgrounds are recruited, ensuring results generalisable to the public while also identifying any key disparities in prioritisation. PSP should also take care that HCP do not skew results during prioritisation of questions, as in this study the most important priority to patients was not identified by professionals.
Journal Article
Lexicon for Clonal Hematopoiesis in Liquid Biopsy
Historically, clonal hematopoiesis (CH) has been recognized as a confounder of cell‐free DNA (cfDNA) testing. Recent evidence now demonstrates the role of CH as a risk factor in health, generating distinct sources of cfDNA that can be leveraged for liquid biopsy diagnostics. Nonetheless, gaps in standardization challenge the advancement of such diagnostics from development to regulatory approval, through clinical trials, and ultimately, to routine implementation. In 2024, the Blood Profiling Atlas in Cancer (BLOODPAC) Consortium, a collaborative infrastructure for developing standards and best practices for liquid biopsy assays, established the CH/clonal hematopoiesis of indeterminate potential (CHIP) Working Group to address the need for accurate identification and removal of CH from liquid biopsy results. As a first step to support the interpretability of CH/CHIP results, the Working Group developed this lexicon to standardize terms and provide a unified vocabulary related to CH and liquid biopsy, DNA sequencing tests, biomarkers, and clinical use cases, facilitating communication within the field. BLOODPAC's CH/CHIP Working Group believes that terminology agreement across these various stakeholders can improve communication in the field and unify future data collection efforts across studies.
Journal Article