The keeping of livestock has been posited as a risk factor for the emergence of zoonoses and the ... more The keeping of livestock has been posited as a risk factor for the emergence of zoonoses and the spread of antimicrobial resistance. However, quantitative evidence regarding the major sources of pathogenic and drug-resistant bacteria and transmission routes between hosts remains lacking. In the largest epidemiological study of this nature to date, we sampled Escherichia coli from humans, livestock, food, wildlife and the environment of 99 households across Nairobi, Kenya to gain a deeper understanding of sharing of bacteria among hosts and potential reservoirs. By analysing whole genome sequencing data from 1,338 E. coli isolates, we reconstruct sharing patterns for the sampled E. coli and its antimicrobial resistance determinants. We find that the diversity and sharing patterns of E. coli is heavily structured by household, which is the primary epidemiological interface for bacterial strain sharing. Strain sharing within households was strongly shaped by host type. We also find evi...
Collaborative (HIC) has established a cohort of individuals with chronic hepatitis B virus (HBV) ... more Collaborative (HIC) has established a cohort of individuals with chronic hepatitis B virus (HBV) infection in secondary care in the UK, providing a resource for translational research. • The dataset comprises >6000 individuals (99% adults aged 18-88, 1% children aged 1-17) with diverse ethnicities (32% Asian, 23% Black, 30% White and 15% mixed or other ethnic groups) from six NHS Trusts across England, representing data collected between August 1994 and October 2021. • The dataset is populated with routinely collected clinical data captured from electronic patient record (EPR) systems; follow-up frequency of each individual depends on clinical practice, with a median of 5.1 (IQR: 2.8-8.0) years. • Data on demographics, laboratory tests, antiviral treatment, elastography scores, imaging/biopsy reports, death information and potential risk factors for liver disease have been collected. • Over time, the cohort will continue to grow in size, average follow-up duration will increase and more NHS Trusts will participate. • This dataset offers important opportunities for epidemiological studies and biomedical informatics research, as well as characterizing an HBV population for clinical trials, including external collaborations with industry.
Quantitative evidence for the risk of zoonoses and the spread of antimicrobial resistance remains... more Quantitative evidence for the risk of zoonoses and the spread of antimicrobial resistance remains lacking. Here, as part of the UrbanZoo project, we sampled Escherichia coli from humans, livestock and peri-domestic wildlife in 99 households across Nairobi, Kenya, to investigate its distribution among host species in this rapidly developing urban landscape. We performed whole-genome sequencing of 1,338 E. coli isolates and found that the diversity and sharing patterns of E. coli were heavily structured by household and strongly shaped by host type. We also found evidence for inter-household and inter-host sharing and, importantly, between humans and animals, although this occurs much less frequently. Resistome similarity was differently distributed across host and household, consistent with being driven by shared exposure to antimicrobials. Our results indicate that a large, epidemiologically structured sampling framework combined with WGS is needed to uncover strain-sharing events a...
ObjectivesCOVID-19 is a heterogeneous disease, and many reports have described variations in demo... more ObjectivesCOVID-19 is a heterogeneous disease, and many reports have described variations in demographic, biochemical and clinical features at presentation influencing overall hospital mortality. However, there is little information regarding longitudinal changes in laboratory prognostic variables in relation to disease progression in hospitalised patients with COVID-19.Design and settingThis retrospective observational report describes disease progression from symptom onset, to admission to hospital, clinical response and discharge/death among patients with COVID-19 at a tertiary centre in South East England.ParticipantsSix hundred and fifty-one patients treated for SARS-CoV-2 between March and September 2020 were included in this analysis. Ethical approval was obtained from the HRA Specific Review Board (REC 20/HRA/2986) for waiver of informed consent.ResultsThe majority of patients presented within 1 week of symptom onset. The lowest risk patients had low mortality (1/45, 2%), an...
Objectives Dexamethasone has now been incorporated into the standard of care for COVID-19 hospita... more Objectives Dexamethasone has now been incorporated into the standard of care for COVID-19 hospital patients. However, larger intensive care unit studies have failed to show discernible improvements in mortality in the most recent wave. We aimed to investigate the impacts of these factors on disease outcomes in a UK hospital study. Methods This retrospective observational study reports patient characteristics, interventions and outcomes in COVID-19 patients from a UK teaching hospital; cohort 1, pre 16th June-2020 (pre-dexamethasone); cohort 2, 17th June to 30th November-2020 (post-dexamethasone, pre-VOC 202012/01 as dominant strain); cohort 3, 1st December-2020 to 3rd March-2021 (during establishment of VOC202012/01 as dominant strain). Results Dexamethasone treatment was more common in cohorts 2 and 3 (42.7% and 51.6%) compared with cohort 1 (2.5%). After adjusting for risk, odds of death within 28 days were 2-fold lower in cohort 2 vs 1 (OR:0.47,[0.27,0.79],p=0.006). Mortality was higher cohort 3 vs 2 (20% vs 14%); but not significantly different to cohort 1 (OR: 0.86,[0.64, 1.15],p=0.308). Conclusions The real world finding of lower mortality following dexamethasone supports the published trial evidence and highlights ongoing need for research with introduction of new and ongoing concern of new COVID-19 variants.
Introduction-The Birth of a Brain Child Apple, Inc. started out as an idea of one man. This man w... more Introduction-The Birth of a Brain Child Apple, Inc. started out as an idea of one man. This man was Steve Jobs. Jobs and his friend, Steve Wozniak, were two high school drop outs living in the Silicon Valley with extremely innovative and intelligent minds (Santa Clara Historical Society, 2012). The pair teamed up, while working for Hewlett Packard, to start Apple, Inc. from the basement of Jobs' home (Santa Clara Historical Society, 2012). The pair created the first Apple computer on April 1, 1976 (Santa Clara Historical Society, 2012). The rest, as they say, is history. The creation of that first computer-and subsequently the birth of Steve Jobs' brain child-is what started Jobs and Wozniak on the path that has now revolutionized the way that many people all over the world use a computer, search the internet, listen to music, and even talk on the phone. Apple, Inc. is the perfect example of how a dream became a reality-one step at a time.
Genome informatics. International Conference on Genome Informatics, 2004
In this paper, we propose a graph-based method to measure the similarity between chemical compoun... more In this paper, we propose a graph-based method to measure the similarity between chemical compounds described by 2D form. Our main idea is to measure the similarity between two compounds based on edges, nodes, and connectivity of their common subgraphs. We applied the proposed similarity measure in combination with a clustering method to more than eleven thousand compounds in the chemical compound database KEGG/LIGAND and discovered that compound clusters with highly similar structure compounds that share common names, take part in the same pathways, and have the same requirement of enzymes in reactions. Furthermore, we discovered the surprising sameness between pathway modules identified by clusters of similar structure compounds and that identified by genomic contexts, namely, operon structures of enzyme genes.
We present some preliminary results on the whole genome analysis of an anonymous Kinh Vietnamese ... more We present some preliminary results on the whole genome analysis of an anonymous Kinh Vietnamese (KHV) individual that was deeply sequenced to 34-fold using the Illumina sequencing technology. The sequenced genome covered 99.85% of the human reference genome (GRCh37). We discovered (1) 3408825 single polymorphism nucleotides (SNPs) of which 41396 (1.2%) were novel, (2) 654024 short indels of which 35263 (5.4%) were novel, i.e. not present in the dbSNP and 1000 genomes project databases. We also detected 10611 large SVs (the length ≥ 100bp) of four types, i.e. large indels (90.6%), the inter-chromosomal translocations (3.1%), the inversions (3.4%) and the intra-chromosomal translocations (2.9%). This study is our initial step toward large-scale projects on Vietnamese population.
Background and aimsTo determine the impact of the COVID-19 pandemic on the population with chroni... more Background and aimsTo determine the impact of the COVID-19 pandemic on the population with chronic Hepatitis B virus (HBV) infection under hospital follow-up in the UK, we quantified the coverage and frequency of measurements of biomarkers used for routine surveillance (ALT and HBV viral load).MethodsWe used anonymised electronic health record data from the National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) pipeline representing five UK NHS Trusts.ResultsWe report significant reductions in surveillance of both biomarkers during the pandemic compared to pre-COVID years, both in terms of the proportion of patients who had ≥1 measurement annually, and the mean number of measurements per patient.ConclusionsFurther investigation is required to determine whether these disruptions will be associated with increased rates of adverse chronic HBV outcomes.
Conclusion Telephone triage demonstrated that primary care compliance with national TWW guidance ... more Conclusion Telephone triage demonstrated that primary care compliance with national TWW guidance was low. Risk stratification via telephone triage resulted in more appropriate investigations and earlier detection of non-upper GI cancer with less unnecessary endsocopies. Crucially, the majority of cancers diagnosed were not UGI, and would have been missed on STT endoscopy alone. During short term follow up no delayed cancer diagnoses were made. This study suggests telephone triage is an effective tool to reduce endoscopy waiting lists whilst carefully utilising radiological resources.
PurposeThe National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) w... more PurposeThe National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) was established to enable re-use of routinely collected clinical data across National Health Service (NHS) Trusts in the United Kingdom to support translational research. Viral hepatitis is one of the first five exemplar themes and hepatitis B virus (HBV) is the current focus of the theme. The NIHR HIC HBV dataset, derived from the central data repository of NIHR HIC viral hepatitis theme, aims to describe and characterise HBV infection in secondary care in the United Kingdom, and provides a resource for translational research.ParticipantsThe dataset comprises >5000 individuals (99% adults aged ≥18, 1% children aged <18) with chronic HBV (CHB) infection from five NHS Trusts across England, representing clinical data collected between August 1994 and August 2021.Findings to dateData on demographics, laboratory tests, antiviral treatment, elastography scores, imaging/biopsy reports, d...
IntroductionThe COVID-19 pandemic caused by SARS-CoV-2 places immense worldwide demand on healthc... more IntroductionThe COVID-19 pandemic caused by SARS-CoV-2 places immense worldwide demand on healthcare services. Earlier identification of patients at risk of severe disease may allow intervention with experimental targeted treatments, mitigating the course of their disease and reducing critical care service demand.Methods and analysisThis prospective observational study of patients tested or treated for SARS-CoV-2, who are under the care of the tertiary University Hospital Southampton NHS Foundation Trust (UHSFT), captured data from admission to discharge; data collection commenced on 7 March 2020. Core demographic and clinical information, as well as results of disease-defining characteristics, was captured and recorded electronically from hospital clinical record systems at the point of testing. Manual data were collected and recorded by the clinical research team for assessments which are not part of the structured electronic healthcare record, for example, symptom onset date. The...
Objectives Previous studies have suggested that SARS-CoV-2 viral load, measured on upper respirat... more Objectives Previous studies have suggested that SARS-CoV-2 viral load, measured on upper respiratory tract samples at presentation to hospital using PCR Cycle threshold (Ct) value, has prognostic utility. However, these studies have not comprehensively adjusted for factors known to be intimately related to viral load. We aimed to evaluate the association between Ct value at admission and patient outcome whilst adjusting carefully for covariates. Methods We evaluated the association between Ct value at presentation and the outcomes of ICU admission and death, in patients hospitalised during the first wave of the pandemic in Southampton, UK. We adjusted for covariates including age, duration of illness and antibody sero-status, measured by neutralisation assay. Results 185 patients were analysed, with a median [IQR] Ct value of 27.9 [22.6-32.1]. On univariate analysis the Ct value at presentation was associated with the risk of both ICU admission and death. In addition, Ct value significantly differed according to age, the duration of illness at presentation and antibody sero-status. On multivariate analysis, Ct value was independently associated with risk of death (aOR 0.84, 95% CI 0.72-0.96; p = 0.011) but not ICU admission (aOR 1.04, 95% CI 0.93-1.16; p = 0.507). Neutralising antibody status at presentation was not associated with mortality or ICU admission (aOR 10.62, 95% CI 0.47-889; p = 0.199 and aOR 0.46, 95% CI 0.10-2.00; p = 0.302, respectively). Conclusions SARS-CoV-2 Ct value on admission to hospital was independently associated with mortality, when comprehensively adjusting for other factors and could be used for risk stratification.
The keeping of livestock has been posited as a risk factor for the emergence of zoonoses and the ... more The keeping of livestock has been posited as a risk factor for the emergence of zoonoses and the spread of antimicrobial resistance. However, quantitative evidence regarding the major sources of pathogenic and drug-resistant bacteria and transmission routes between hosts remains lacking. In the largest epidemiological study of this nature to date, we sampled Escherichia coli from humans, livestock, food, wildlife and the environment of 99 households across Nairobi, Kenya to gain a deeper understanding of sharing of bacteria among hosts and potential reservoirs. By analysing whole genome sequencing data from 1,338 E. coli isolates, we reconstruct sharing patterns for the sampled E. coli and its antimicrobial resistance determinants. We find that the diversity and sharing patterns of E. coli is heavily structured by household, which is the primary epidemiological interface for bacterial strain sharing. Strain sharing within households was strongly shaped by host type. We also find evi...
Collaborative (HIC) has established a cohort of individuals with chronic hepatitis B virus (HBV) ... more Collaborative (HIC) has established a cohort of individuals with chronic hepatitis B virus (HBV) infection in secondary care in the UK, providing a resource for translational research. • The dataset comprises >6000 individuals (99% adults aged 18-88, 1% children aged 1-17) with diverse ethnicities (32% Asian, 23% Black, 30% White and 15% mixed or other ethnic groups) from six NHS Trusts across England, representing data collected between August 1994 and October 2021. • The dataset is populated with routinely collected clinical data captured from electronic patient record (EPR) systems; follow-up frequency of each individual depends on clinical practice, with a median of 5.1 (IQR: 2.8-8.0) years. • Data on demographics, laboratory tests, antiviral treatment, elastography scores, imaging/biopsy reports, death information and potential risk factors for liver disease have been collected. • Over time, the cohort will continue to grow in size, average follow-up duration will increase and more NHS Trusts will participate. • This dataset offers important opportunities for epidemiological studies and biomedical informatics research, as well as characterizing an HBV population for clinical trials, including external collaborations with industry.
Quantitative evidence for the risk of zoonoses and the spread of antimicrobial resistance remains... more Quantitative evidence for the risk of zoonoses and the spread of antimicrobial resistance remains lacking. Here, as part of the UrbanZoo project, we sampled Escherichia coli from humans, livestock and peri-domestic wildlife in 99 households across Nairobi, Kenya, to investigate its distribution among host species in this rapidly developing urban landscape. We performed whole-genome sequencing of 1,338 E. coli isolates and found that the diversity and sharing patterns of E. coli were heavily structured by household and strongly shaped by host type. We also found evidence for inter-household and inter-host sharing and, importantly, between humans and animals, although this occurs much less frequently. Resistome similarity was differently distributed across host and household, consistent with being driven by shared exposure to antimicrobials. Our results indicate that a large, epidemiologically structured sampling framework combined with WGS is needed to uncover strain-sharing events a...
ObjectivesCOVID-19 is a heterogeneous disease, and many reports have described variations in demo... more ObjectivesCOVID-19 is a heterogeneous disease, and many reports have described variations in demographic, biochemical and clinical features at presentation influencing overall hospital mortality. However, there is little information regarding longitudinal changes in laboratory prognostic variables in relation to disease progression in hospitalised patients with COVID-19.Design and settingThis retrospective observational report describes disease progression from symptom onset, to admission to hospital, clinical response and discharge/death among patients with COVID-19 at a tertiary centre in South East England.ParticipantsSix hundred and fifty-one patients treated for SARS-CoV-2 between March and September 2020 were included in this analysis. Ethical approval was obtained from the HRA Specific Review Board (REC 20/HRA/2986) for waiver of informed consent.ResultsThe majority of patients presented within 1 week of symptom onset. The lowest risk patients had low mortality (1/45, 2%), an...
Objectives Dexamethasone has now been incorporated into the standard of care for COVID-19 hospita... more Objectives Dexamethasone has now been incorporated into the standard of care for COVID-19 hospital patients. However, larger intensive care unit studies have failed to show discernible improvements in mortality in the most recent wave. We aimed to investigate the impacts of these factors on disease outcomes in a UK hospital study. Methods This retrospective observational study reports patient characteristics, interventions and outcomes in COVID-19 patients from a UK teaching hospital; cohort 1, pre 16th June-2020 (pre-dexamethasone); cohort 2, 17th June to 30th November-2020 (post-dexamethasone, pre-VOC 202012/01 as dominant strain); cohort 3, 1st December-2020 to 3rd March-2021 (during establishment of VOC202012/01 as dominant strain). Results Dexamethasone treatment was more common in cohorts 2 and 3 (42.7% and 51.6%) compared with cohort 1 (2.5%). After adjusting for risk, odds of death within 28 days were 2-fold lower in cohort 2 vs 1 (OR:0.47,[0.27,0.79],p=0.006). Mortality was higher cohort 3 vs 2 (20% vs 14%); but not significantly different to cohort 1 (OR: 0.86,[0.64, 1.15],p=0.308). Conclusions The real world finding of lower mortality following dexamethasone supports the published trial evidence and highlights ongoing need for research with introduction of new and ongoing concern of new COVID-19 variants.
Introduction-The Birth of a Brain Child Apple, Inc. started out as an idea of one man. This man w... more Introduction-The Birth of a Brain Child Apple, Inc. started out as an idea of one man. This man was Steve Jobs. Jobs and his friend, Steve Wozniak, were two high school drop outs living in the Silicon Valley with extremely innovative and intelligent minds (Santa Clara Historical Society, 2012). The pair teamed up, while working for Hewlett Packard, to start Apple, Inc. from the basement of Jobs' home (Santa Clara Historical Society, 2012). The pair created the first Apple computer on April 1, 1976 (Santa Clara Historical Society, 2012). The rest, as they say, is history. The creation of that first computer-and subsequently the birth of Steve Jobs' brain child-is what started Jobs and Wozniak on the path that has now revolutionized the way that many people all over the world use a computer, search the internet, listen to music, and even talk on the phone. Apple, Inc. is the perfect example of how a dream became a reality-one step at a time.
Genome informatics. International Conference on Genome Informatics, 2004
In this paper, we propose a graph-based method to measure the similarity between chemical compoun... more In this paper, we propose a graph-based method to measure the similarity between chemical compounds described by 2D form. Our main idea is to measure the similarity between two compounds based on edges, nodes, and connectivity of their common subgraphs. We applied the proposed similarity measure in combination with a clustering method to more than eleven thousand compounds in the chemical compound database KEGG/LIGAND and discovered that compound clusters with highly similar structure compounds that share common names, take part in the same pathways, and have the same requirement of enzymes in reactions. Furthermore, we discovered the surprising sameness between pathway modules identified by clusters of similar structure compounds and that identified by genomic contexts, namely, operon structures of enzyme genes.
We present some preliminary results on the whole genome analysis of an anonymous Kinh Vietnamese ... more We present some preliminary results on the whole genome analysis of an anonymous Kinh Vietnamese (KHV) individual that was deeply sequenced to 34-fold using the Illumina sequencing technology. The sequenced genome covered 99.85% of the human reference genome (GRCh37). We discovered (1) 3408825 single polymorphism nucleotides (SNPs) of which 41396 (1.2%) were novel, (2) 654024 short indels of which 35263 (5.4%) were novel, i.e. not present in the dbSNP and 1000 genomes project databases. We also detected 10611 large SVs (the length ≥ 100bp) of four types, i.e. large indels (90.6%), the inter-chromosomal translocations (3.1%), the inversions (3.4%) and the intra-chromosomal translocations (2.9%). This study is our initial step toward large-scale projects on Vietnamese population.
Background and aimsTo determine the impact of the COVID-19 pandemic on the population with chroni... more Background and aimsTo determine the impact of the COVID-19 pandemic on the population with chronic Hepatitis B virus (HBV) infection under hospital follow-up in the UK, we quantified the coverage and frequency of measurements of biomarkers used for routine surveillance (ALT and HBV viral load).MethodsWe used anonymised electronic health record data from the National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) pipeline representing five UK NHS Trusts.ResultsWe report significant reductions in surveillance of both biomarkers during the pandemic compared to pre-COVID years, both in terms of the proportion of patients who had ≥1 measurement annually, and the mean number of measurements per patient.ConclusionsFurther investigation is required to determine whether these disruptions will be associated with increased rates of adverse chronic HBV outcomes.
Conclusion Telephone triage demonstrated that primary care compliance with national TWW guidance ... more Conclusion Telephone triage demonstrated that primary care compliance with national TWW guidance was low. Risk stratification via telephone triage resulted in more appropriate investigations and earlier detection of non-upper GI cancer with less unnecessary endsocopies. Crucially, the majority of cancers diagnosed were not UGI, and would have been missed on STT endoscopy alone. During short term follow up no delayed cancer diagnoses were made. This study suggests telephone triage is an effective tool to reduce endoscopy waiting lists whilst carefully utilising radiological resources.
PurposeThe National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) w... more PurposeThe National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) was established to enable re-use of routinely collected clinical data across National Health Service (NHS) Trusts in the United Kingdom to support translational research. Viral hepatitis is one of the first five exemplar themes and hepatitis B virus (HBV) is the current focus of the theme. The NIHR HIC HBV dataset, derived from the central data repository of NIHR HIC viral hepatitis theme, aims to describe and characterise HBV infection in secondary care in the United Kingdom, and provides a resource for translational research.ParticipantsThe dataset comprises >5000 individuals (99% adults aged ≥18, 1% children aged <18) with chronic HBV (CHB) infection from five NHS Trusts across England, representing clinical data collected between August 1994 and August 2021.Findings to dateData on demographics, laboratory tests, antiviral treatment, elastography scores, imaging/biopsy reports, d...
IntroductionThe COVID-19 pandemic caused by SARS-CoV-2 places immense worldwide demand on healthc... more IntroductionThe COVID-19 pandemic caused by SARS-CoV-2 places immense worldwide demand on healthcare services. Earlier identification of patients at risk of severe disease may allow intervention with experimental targeted treatments, mitigating the course of their disease and reducing critical care service demand.Methods and analysisThis prospective observational study of patients tested or treated for SARS-CoV-2, who are under the care of the tertiary University Hospital Southampton NHS Foundation Trust (UHSFT), captured data from admission to discharge; data collection commenced on 7 March 2020. Core demographic and clinical information, as well as results of disease-defining characteristics, was captured and recorded electronically from hospital clinical record systems at the point of testing. Manual data were collected and recorded by the clinical research team for assessments which are not part of the structured electronic healthcare record, for example, symptom onset date. The...
Objectives Previous studies have suggested that SARS-CoV-2 viral load, measured on upper respirat... more Objectives Previous studies have suggested that SARS-CoV-2 viral load, measured on upper respiratory tract samples at presentation to hospital using PCR Cycle threshold (Ct) value, has prognostic utility. However, these studies have not comprehensively adjusted for factors known to be intimately related to viral load. We aimed to evaluate the association between Ct value at admission and patient outcome whilst adjusting carefully for covariates. Methods We evaluated the association between Ct value at presentation and the outcomes of ICU admission and death, in patients hospitalised during the first wave of the pandemic in Southampton, UK. We adjusted for covariates including age, duration of illness and antibody sero-status, measured by neutralisation assay. Results 185 patients were analysed, with a median [IQR] Ct value of 27.9 [22.6-32.1]. On univariate analysis the Ct value at presentation was associated with the risk of both ICU admission and death. In addition, Ct value significantly differed according to age, the duration of illness at presentation and antibody sero-status. On multivariate analysis, Ct value was independently associated with risk of death (aOR 0.84, 95% CI 0.72-0.96; p = 0.011) but not ICU admission (aOR 1.04, 95% CI 0.93-1.16; p = 0.507). Neutralising antibody status at presentation was not associated with mortality or ICU admission (aOR 10.62, 95% CI 0.47-889; p = 0.199 and aOR 0.46, 95% CI 0.10-2.00; p = 0.302, respectively). Conclusions SARS-CoV-2 Ct value on admission to hospital was independently associated with mortality, when comprehensively adjusting for other factors and could be used for risk stratification.
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