Although investigations have shown that closing live poultry markets (LPMs) is highly effective i... more Although investigations have shown that closing live poultry markets (LPMs) is highly effective in controlling human influenza A (H7N9) infections, many of the urban LPMs were shut down, but rural LPMs remained open. This study aimed to compare the proportional changes between urban and rural infections in the Zhejiang province from 2013 to 2017 by analyzing the exposure histories of human cases. All laboratory-confirmed cases of H7N9 from 2013 (the first wave) to 2017 (the fifth wave) in the Zhejiang province of China were analyzed. Urban and rural infections were defined based on the locations of poultry exposure (direct and indirect) in urban areas (central towns) and rural areas (towns and villages on the outskirts of cities). A Chi-square trend test was used to compare the proportional trend between urban and rural infections over time and logistic regression was used to obtain the odds ratio by years. From 2013 to 2017, a statistically significant trend in rural infections was...
In a new influenza pandemic, travel data such as arrival times of cases seeded by the originating... more In a new influenza pandemic, travel data such as arrival times of cases seeded by the originating country can be regarded as a combination of the epidemic size and the mobility networks of infections connecting the originating country with other regions. It can be a complete and timely source for estimating the basic reproduction number (R 0 ), a key indicator of disease transmissibility. In this study, we developed a likelihood-based method using arrival times of infected cases in different countries to estimate R 0 for influenza pandemics. A simulation was conducted to assess the performance of the proposed method. We further applied the method to the outbreak of the influenza pandemic A/H1N1 in Mexico. In the numerical application, the estimated R 0 was equal to 1.69 with a 95% confidence interval (1.65, 1.73). For the simulation results, the estimations were robust to the decline of travel rate and other parameter assumptions. Nevertheless, the estimates were moderately sensitiv...
Breath mass spectrometry is a useful tool for identifying important compounds associated with hea... more Breath mass spectrometry is a useful tool for identifying important compounds associated with health. However, there have been few studies that have explored human exhaled breath by full-scan mass spectrometry as a non-invasive method for medical diagnosis, which may be attributed to the difficulties resulting from multicollinearity and small sample sizes relative to a large number of product ions. In this study, breath samples from 54 chronic kidney disease patients were analyzed by selected ion flow tube mass spectrometry in the full-scan mode. With the signal intensities of product ions, we developed a novel and robust algorithm, iterative PCA with intensity screening (IPS), to build linear models for estimating important clinical parameters of chronic kidney disease. It has been shown that IPS provided good estimations in cross-validated samples, and furthermore the identified product ions could have direct medical relevance to the disease. The study demonstrated the potential o...
Genetic data consists of a wide range of marker types, including common, low frequency, and rare ... more Genetic data consists of a wide range of marker types, including common, low frequency, and rare variants. Multiple genetic markers and their interactions play central roles in the heritability of complex disease. In this study, we propose an algorithm that uses a stratified variable selection design by genetic architectures and interaction effects, achieved by a data-set adaptive W-test. The polygenic sets in all strata were integrated to form a classification rule. The algorithm was applied to the Critical Assessment of Genome Interpretation 4 bipolar challenge sequencing data. The prediction accuracy was 60% using genetic markers on an independent test set. We found that epistasis among common genetic variants contributed most substantially to prediction precision. However, the sample size was not large enough to draw conclusions for the lack of predictability of low frequency variants and their epistasis. This article is protected by copyright. All rights reserved.
Glycaemic goals are not achieved in most patients with type II diabetes mellitus (T2DM), especial... more Glycaemic goals are not achieved in most patients with type II diabetes mellitus (T2DM), especially in those with long disease duration and taking multiple oral antidiabetic drugs (OAD). We aimed to investigate the effectiveness of individualized homeopathic treatment in glycaemic control. Retrospective cohort study. At least 6 months of individualized homeopathic treatment at a private homeopathic centre in Hong Kong. Twenty-seven adults aged 37-84 years were treated with individualized homeopathic remedies between 2012 and 2015. Published data on 40 T2DM patients under standard conventional treatment in Hong Kong were used as a control. Change in fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) at 12-month or the last follow-up, whichever is earlier. Compared with the conventional treatment only group, the homeopathy group had higher baseline FPG (p = 0.044), and more patients had a long (>20 years) duration of diabetes (p = 0.006), and a history of cardiac events (p = 0.022). The mean difference in FPG in the homeopathy group was significantly greater than in the control after 12 months: -2.24 mmol/L (95% confidence interval [CI]: -3.47 to -1.01) vs 0.16 mmol/L (95% CI: -1.72 to 2.04), p = 0.001. The mean difference in glycated haemoglobin (HbA1c) was also significantly greater, -1.11% (95% CI: -2.17 to -0.05) vs 0.08% (95% CI: -1.37 to 1.53), p = 0.046. Poorer baseline glycaemic control was associated with better outcome (r = -0.750, p < 0.001), but not the duration of diabetes (r = 0.058, p = 0.772). The improvement was robust to sensitivity analyses. Individualized homeopathic treatment was associated with better glycaemic control compared with standard conventional treatment alone.
Increasing amounts of whole exome or genome sequencing data present the challenge of analysing ra... more Increasing amounts of whole exome or genome sequencing data present the challenge of analysing rare variants with extremely small minor allele frequencies. Various statistical tests have been proposed, which are specifically configured to increase power for rare variants by conducting the test within a certain bin, such as a gene or a pathway. However, a gene may contain from several to thousands of markers, and not all of them are related to the phenotype. Combining functional and non-functional variants in an arbitrary genomic region could impair the testing power. We propose a Zoom-Focus algorithm (ZFA) to locate the optimal testing region within a given genomic region. It can be applied as a wrapper function in existing rare variant association tests to increase testing power. The algorithm consists of two steps. In the first step, Zooming, a given genomic region is partitioned by an order of two, and the best partition is located. In the second step, Focusing, the boundaries of the zoomed region are refined. Simulation studies showed that ZFA substantially increased the statistical power of rare variants' tests, including the SKAT, SKAT-O, burden test and the W-test. The algorithm was applied on real exome sequencing data of hypertensive disorder, and identified biologically relevant genetic markers to metabolic disorders that were undetectable by a gene-based method. The proposed algorithm is an efficient and powerful tool to enhance the power of association study for whole exome or genome sequencing data. The ZFA software is available at: http://www2.ccrb.cuhk.edu.hk/statgene/software.html. [email protected]. Supplementary data are available at Bioinformatics online.
Although evidence has shown that supplementary immunization activity (SIA) campaigns greatly redu... more Although evidence has shown that supplementary immunization activity (SIA) campaigns greatly reduce the incidence of measles, their effects on disease transmissibility have seldom been monitored. A great decrease in the number of cases may be a false signal of early success towards measles elimination to policy makers. By interpreting the transmissibility in two different post-SIA periods in Hubei, China, the current study showed sustained measles transmissions despite a reduced number of cases. Two population-based cross-sectional serological surveys of measles antibodies were conducted in Hubei province in mid-2010 and mid-2011 after the implementation of SIAs. Immunoglobulin G (IgG) antibodies against measles were measured by enzyme-linked immunosorbent assay (ELISA). Based on the estimated age-specific susceptibility levels, the effective reproduction number (R), a key indicator of disease transmissibility, was determined by the next generation matrix in transmission model. The ...
Selected ion flow tube-mass spectrometry (SIFT-MS) provides rapid, non-invasive measurements of a... more Selected ion flow tube-mass spectrometry (SIFT-MS) provides rapid, non-invasive measurements of a full-mass scan of volatile compounds in exhaled breath. Although various studies have suggested that breath metabolites may be indicators of human disease status, many of these studies have included few breath samples and large numbers of compounds, limiting their power to detect significant metabolites. This study employed a least absolute shrinkage and selective operator (LASSO) approach to SIFT-MS data of breath samples to preliminarily evaluate the ability of exhaled breath findings to monitor the efficacy of dialysis in hemodialysis patients. A process of model building and validation showed that blood creatinine and urea concentrations could be accurately predicted by LASSO-selected masses. Using various precursors, the LASSO models were able to predict creatinine and urea concentrations with high adjusted R-square (>80%) values. The correlation between actual concentrations and concentrations predicted by the LASSO model (using precursor H3O(+)) was high (Pearson correlation coefficient  =  0.96). Moreover, use of full mass scan data provided a better prediction than compounds from selected ion mode. These findings warrant further investigations in larger patient cohorts. By employing a more powerful statistical approach to predict disease outcomes, breath analysis using SIFT-MS technology could be applicable in future to daily medical diagnoses.
Human Enterovirus A71 (EV-A71) is one of the severest enteroviruses that causes hand, foot, and m... more Human Enterovirus A71 (EV-A71) is one of the severest enteroviruses that causes hand, foot, and mouth disease (HFMD) among children. This study identified the mutations of EV-A71 VP1 amino acid residues over a number of years and explored the possible association of identified mutations and HFMD epidemic outbreaks in Shenzhen, China. A total of 3,760 stool specimens were collected from HFMD patients by Shenzhen Centers for Disease Control and Prevention (CDC) between 1998 and 2013. In total 289 VP1 strains were sequenced in this study, genetic sequences were obtained, and amino acids mutation frequency was calculated. There were 2,040 China nationwide sequences downloaded from Genebank as replication data. In our samples, 1036 subjects (27.6%) were EV-A71 infected. Three amino acid positions on VP1 protein were found to have high mutation prevalence. These are Q22H, S283T, and A289H. Site 22 showed a fast mutation fixation in the year 2008, at the time of the large scale epidemic ou...
International Journal of Environmental Research and Public Health, 2015
Compared with temperate areas, the understanding of seasonal variations of influenza infections i... more Compared with temperate areas, the understanding of seasonal variations of influenza infections is lacking in subtropical and tropical regions. Insufficient information about viral activity increases the difficulty of forecasting the disease burden and thus hampers official preparation efforts. Here we identified potential meteorological factors that drove the seasonal variations in influenza infections in a subtropical city, Hong Kong. We fitted the meteorological data and influenza mortality data from 2002 to 2009 in a Susceptible-Infected-Recovered model. From the results, air temperature was a common significant driver of seasonal patterns and cold temperature was associated with an increase in transmission intensity for most of the influenza epidemics. Except 2004, the fitted models with significant meteorological factors could account for more than 10% of the variance in additional to the null model. Rainfall was also found to be a significant driver of seasonal influenza, although results were less robust. The identified meteorological indicators could alert officials to take appropriate control measures for influenza epidemics, such as enhancing vaccination activities before cold seasons. Further studies are required to fully justify the associations.
Proceedings of the National Academy of Sciences, 2007
Trisomy 21 is the most common reason that women opt for prenatal diagnosis. Conventional prenatal... more Trisomy 21 is the most common reason that women opt for prenatal diagnosis. Conventional prenatal diagnostic methods involve the sampling of fetal materials by invasive procedures such as amniocentesis. Screening by ultrasonography and biochemical markers have been used to risk-stratify pregnant women before definitive invasive diagnostic procedures. However, these screening methods generally target epiphenomena, such as nuchal translucency, associated with trisomy 21. It would be ideal if noninvasive genetic methods were available for the direct detection of the core pathology of trisomy 21. Here we outline an approach using digital PCR for the noninvasive detection of fetal trisomy 21 by analysis of fetal nucleic acids in maternal plasma. First, we demonstrate the use of digital PCR to determine the allelic imbalance of a SNP on PLAC4 mRNA, a placenta-expressed transcript on chromosome 21, in the maternal plasma of women bearing trisomy 21 fetuses. We named this the digital RNA SNP strategy. Second, we developed a nonpolymorphism-based method for the noninvasive prenatal detection of trisomy 21. We named this the digital relative chromosome dosage (RCD) method. Digital RCD involves the direct assessment of whether the total copy number of chromosome 21 in a sample containing fetal DNA is overrepresented with respect to a reference chromosome. Even without elaborate instrumentation, digital RCD allows the detection of trisomy 21 in samples containing 25% fetal DNA. We applied the sequential probability ratio test to interpret the digital PCR data. Computer simulation and empirical validation confirmed the high accuracy of the disease classification algorithm.
Background: During the early stages of a new influenza pandemic, travel restriction is an immedia... more Background: During the early stages of a new influenza pandemic, travel restriction is an immediate and non-pharmaceutical means of retarding incidence growth. It extends the time frame of effective mitigation, especially when the characteristics of the emerging virus are unknown. In the present study, we used the 2009 influenza A pandemic as a case study to evaluate the impact of regulating air, sea, and land transport. Other government strategies, namely, antivirals and hospitalizations, were also evaluated.
Transactions of The Royal Society of Tropical Medicine and Hygiene, 2015
Smoking is an important risk factor of TB. However, no studies have been conducted to identify TB... more Smoking is an important risk factor of TB. However, no studies have been conducted to identify TB cases from smokers. We assessed the process and initial impact of active case finding among smokers at primary care facilities in a setting with high smoking rates and TB burden. A prospective quasi-experimental study was conducted in para-urban communities in Yunnan China between September 2013 and June 2014. Smokers attending primary care facilities in the intervention group were prescribed chest X-rays if they had diabetes or TB symptoms, or were elders or close contacts of TB patients. Those with X-rays suggestive of TB were referred to TB dispensaries for diagnosis. Passive case finding was practiced in the control group. In the intervention group, we screened 471 smokers with high risks of TB, of whom 73% took chest X-ray examinations. Eight TB cases were diagnosed, reflecting a 1.7% yield rate of all screened smokers. Smokers with diabetes (OR 6.003, 95% CI 1.057-34.075) were more likely to have TB compared with those without. In total, the intervention group reported significantly higher TB notification rate compared with the control group (38.6 vs 22.9 per 100 000, p=0.016). Active case finding among smokers with high risks of TB was feasible and contributed to improved notification rates.
Environmental health : a global access science source, Jan 19, 2013
Numerous studies have found associations between extreme temperatures and human mortality but rel... more Numerous studies have found associations between extreme temperatures and human mortality but relatively few studies have been done in sub-tropical and tropical cities, especially in Asia. In this study we examine the impact of cold temperatures, cold waves and other meteorological and environmental variables on cool season mortality in 2 subtropical Asian cities. Separate analysis of daily mortality time-series from Hong Kong and Taipei using Generalized Additive Models with natural mortality as the outcome daily mean temperature as the main explanatory variable and relative humidity, solar radiation, wind speed, pollutants (nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), respirable suspended particulates (PM(10)), ozone (O(3)), seasonality and day of the week controlled as potential confounders. Lags up to 35 days were considered for temperature, and distributed lag models were used to determine the number of lags for final models. Subgroup analyses were also done by gender, age...
This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG... more This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG35156 in addition to sorafenib in patients with advanced hepatocellular carcinoma (HCC), as compared with sorafenib alone. Eligible patients were randomly assigned in a 2:1 ratio to receive AEG35156 (300 mg weekly intravenous infusion) in combination with sorafenib (400 mg twice daily orally) or sorafenib alone. The primary endpoint was progression-free survival (PFS). Other endpoints include overall survival (OS), objective response rates (ORR), and safety profile. A total of 51 patients were enrolled; of them, 48 were evaluable. At a median follow-up of 16.2 months, the median PFS and OS were 4.0 months (95% CI, 1.2-4.1) and 6.5 months (95% CI, 3.9-11.5) for combination arm, and 2.6 (95% CI, 1.2-5.4) and 5.4 months (95% CI, 4.3-11.2) for sorafenib arm. Patients who had the study treatment interrupted or had dose modifications according to protocol did significantly better, in terms of PFS and OS, than those who had no dose reduction in combination arm and those in sorafenib arm. The ORR based on Choi and RECIST criteria were 16.1% and 9.7% in combination arm, respectively. The ORR was 0 in control arm. One drug-related serious adverse event of hypersensitivity occurred in the combination arm, whereas 2 gastrointestinal serious adverse events in the sorafenib arm. AEG35156 in combination with sorafenib showed additional activity in terms of ORR and was well tolerated. The benefit on PFS is moderate but more apparent in the dose-reduced subgroups.
Background: Cardiovascular disease (CVD) is a major cause of death in China. Despite government e... more Background: Cardiovascular disease (CVD) is a major cause of death in China. Despite government efforts, the majority of hypertensive and diabetic patients in China do not receive proper treatment. Reducing CVD events requires long-term care that is proactive, patient-centred, community-based, and sustainable. We have designed a package of interventions for patients at high risk of CVD to be implemented by family doctors based in township hospitals (providers of primary care) in rural Zhejiang, China. This trial aims to determine whether the systematic CVD risk reduction package results in reduced CVD events among patients at risk of CVD compared with usual care, and whether the package is cost-effective and suitable for routine implementation and scale-up.
Although investigations have shown that closing live poultry markets (LPMs) is highly effective i... more Although investigations have shown that closing live poultry markets (LPMs) is highly effective in controlling human influenza A (H7N9) infections, many of the urban LPMs were shut down, but rural LPMs remained open. This study aimed to compare the proportional changes between urban and rural infections in the Zhejiang province from 2013 to 2017 by analyzing the exposure histories of human cases. All laboratory-confirmed cases of H7N9 from 2013 (the first wave) to 2017 (the fifth wave) in the Zhejiang province of China were analyzed. Urban and rural infections were defined based on the locations of poultry exposure (direct and indirect) in urban areas (central towns) and rural areas (towns and villages on the outskirts of cities). A Chi-square trend test was used to compare the proportional trend between urban and rural infections over time and logistic regression was used to obtain the odds ratio by years. From 2013 to 2017, a statistically significant trend in rural infections was...
In a new influenza pandemic, travel data such as arrival times of cases seeded by the originating... more In a new influenza pandemic, travel data such as arrival times of cases seeded by the originating country can be regarded as a combination of the epidemic size and the mobility networks of infections connecting the originating country with other regions. It can be a complete and timely source for estimating the basic reproduction number (R 0 ), a key indicator of disease transmissibility. In this study, we developed a likelihood-based method using arrival times of infected cases in different countries to estimate R 0 for influenza pandemics. A simulation was conducted to assess the performance of the proposed method. We further applied the method to the outbreak of the influenza pandemic A/H1N1 in Mexico. In the numerical application, the estimated R 0 was equal to 1.69 with a 95% confidence interval (1.65, 1.73). For the simulation results, the estimations were robust to the decline of travel rate and other parameter assumptions. Nevertheless, the estimates were moderately sensitiv...
Breath mass spectrometry is a useful tool for identifying important compounds associated with hea... more Breath mass spectrometry is a useful tool for identifying important compounds associated with health. However, there have been few studies that have explored human exhaled breath by full-scan mass spectrometry as a non-invasive method for medical diagnosis, which may be attributed to the difficulties resulting from multicollinearity and small sample sizes relative to a large number of product ions. In this study, breath samples from 54 chronic kidney disease patients were analyzed by selected ion flow tube mass spectrometry in the full-scan mode. With the signal intensities of product ions, we developed a novel and robust algorithm, iterative PCA with intensity screening (IPS), to build linear models for estimating important clinical parameters of chronic kidney disease. It has been shown that IPS provided good estimations in cross-validated samples, and furthermore the identified product ions could have direct medical relevance to the disease. The study demonstrated the potential o...
Genetic data consists of a wide range of marker types, including common, low frequency, and rare ... more Genetic data consists of a wide range of marker types, including common, low frequency, and rare variants. Multiple genetic markers and their interactions play central roles in the heritability of complex disease. In this study, we propose an algorithm that uses a stratified variable selection design by genetic architectures and interaction effects, achieved by a data-set adaptive W-test. The polygenic sets in all strata were integrated to form a classification rule. The algorithm was applied to the Critical Assessment of Genome Interpretation 4 bipolar challenge sequencing data. The prediction accuracy was 60% using genetic markers on an independent test set. We found that epistasis among common genetic variants contributed most substantially to prediction precision. However, the sample size was not large enough to draw conclusions for the lack of predictability of low frequency variants and their epistasis. This article is protected by copyright. All rights reserved.
Glycaemic goals are not achieved in most patients with type II diabetes mellitus (T2DM), especial... more Glycaemic goals are not achieved in most patients with type II diabetes mellitus (T2DM), especially in those with long disease duration and taking multiple oral antidiabetic drugs (OAD). We aimed to investigate the effectiveness of individualized homeopathic treatment in glycaemic control. Retrospective cohort study. At least 6 months of individualized homeopathic treatment at a private homeopathic centre in Hong Kong. Twenty-seven adults aged 37-84 years were treated with individualized homeopathic remedies between 2012 and 2015. Published data on 40 T2DM patients under standard conventional treatment in Hong Kong were used as a control. Change in fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) at 12-month or the last follow-up, whichever is earlier. Compared with the conventional treatment only group, the homeopathy group had higher baseline FPG (p = 0.044), and more patients had a long (>20 years) duration of diabetes (p = 0.006), and a history of cardiac events (p = 0.022). The mean difference in FPG in the homeopathy group was significantly greater than in the control after 12 months: -2.24 mmol/L (95% confidence interval [CI]: -3.47 to -1.01) vs 0.16 mmol/L (95% CI: -1.72 to 2.04), p = 0.001. The mean difference in glycated haemoglobin (HbA1c) was also significantly greater, -1.11% (95% CI: -2.17 to -0.05) vs 0.08% (95% CI: -1.37 to 1.53), p = 0.046. Poorer baseline glycaemic control was associated with better outcome (r = -0.750, p < 0.001), but not the duration of diabetes (r = 0.058, p = 0.772). The improvement was robust to sensitivity analyses. Individualized homeopathic treatment was associated with better glycaemic control compared with standard conventional treatment alone.
Increasing amounts of whole exome or genome sequencing data present the challenge of analysing ra... more Increasing amounts of whole exome or genome sequencing data present the challenge of analysing rare variants with extremely small minor allele frequencies. Various statistical tests have been proposed, which are specifically configured to increase power for rare variants by conducting the test within a certain bin, such as a gene or a pathway. However, a gene may contain from several to thousands of markers, and not all of them are related to the phenotype. Combining functional and non-functional variants in an arbitrary genomic region could impair the testing power. We propose a Zoom-Focus algorithm (ZFA) to locate the optimal testing region within a given genomic region. It can be applied as a wrapper function in existing rare variant association tests to increase testing power. The algorithm consists of two steps. In the first step, Zooming, a given genomic region is partitioned by an order of two, and the best partition is located. In the second step, Focusing, the boundaries of the zoomed region are refined. Simulation studies showed that ZFA substantially increased the statistical power of rare variants' tests, including the SKAT, SKAT-O, burden test and the W-test. The algorithm was applied on real exome sequencing data of hypertensive disorder, and identified biologically relevant genetic markers to metabolic disorders that were undetectable by a gene-based method. The proposed algorithm is an efficient and powerful tool to enhance the power of association study for whole exome or genome sequencing data. The ZFA software is available at: http://www2.ccrb.cuhk.edu.hk/statgene/software.html. [email protected]. Supplementary data are available at Bioinformatics online.
Although evidence has shown that supplementary immunization activity (SIA) campaigns greatly redu... more Although evidence has shown that supplementary immunization activity (SIA) campaigns greatly reduce the incidence of measles, their effects on disease transmissibility have seldom been monitored. A great decrease in the number of cases may be a false signal of early success towards measles elimination to policy makers. By interpreting the transmissibility in two different post-SIA periods in Hubei, China, the current study showed sustained measles transmissions despite a reduced number of cases. Two population-based cross-sectional serological surveys of measles antibodies were conducted in Hubei province in mid-2010 and mid-2011 after the implementation of SIAs. Immunoglobulin G (IgG) antibodies against measles were measured by enzyme-linked immunosorbent assay (ELISA). Based on the estimated age-specific susceptibility levels, the effective reproduction number (R), a key indicator of disease transmissibility, was determined by the next generation matrix in transmission model. The ...
Selected ion flow tube-mass spectrometry (SIFT-MS) provides rapid, non-invasive measurements of a... more Selected ion flow tube-mass spectrometry (SIFT-MS) provides rapid, non-invasive measurements of a full-mass scan of volatile compounds in exhaled breath. Although various studies have suggested that breath metabolites may be indicators of human disease status, many of these studies have included few breath samples and large numbers of compounds, limiting their power to detect significant metabolites. This study employed a least absolute shrinkage and selective operator (LASSO) approach to SIFT-MS data of breath samples to preliminarily evaluate the ability of exhaled breath findings to monitor the efficacy of dialysis in hemodialysis patients. A process of model building and validation showed that blood creatinine and urea concentrations could be accurately predicted by LASSO-selected masses. Using various precursors, the LASSO models were able to predict creatinine and urea concentrations with high adjusted R-square (>80%) values. The correlation between actual concentrations and concentrations predicted by the LASSO model (using precursor H3O(+)) was high (Pearson correlation coefficient  =  0.96). Moreover, use of full mass scan data provided a better prediction than compounds from selected ion mode. These findings warrant further investigations in larger patient cohorts. By employing a more powerful statistical approach to predict disease outcomes, breath analysis using SIFT-MS technology could be applicable in future to daily medical diagnoses.
Human Enterovirus A71 (EV-A71) is one of the severest enteroviruses that causes hand, foot, and m... more Human Enterovirus A71 (EV-A71) is one of the severest enteroviruses that causes hand, foot, and mouth disease (HFMD) among children. This study identified the mutations of EV-A71 VP1 amino acid residues over a number of years and explored the possible association of identified mutations and HFMD epidemic outbreaks in Shenzhen, China. A total of 3,760 stool specimens were collected from HFMD patients by Shenzhen Centers for Disease Control and Prevention (CDC) between 1998 and 2013. In total 289 VP1 strains were sequenced in this study, genetic sequences were obtained, and amino acids mutation frequency was calculated. There were 2,040 China nationwide sequences downloaded from Genebank as replication data. In our samples, 1036 subjects (27.6%) were EV-A71 infected. Three amino acid positions on VP1 protein were found to have high mutation prevalence. These are Q22H, S283T, and A289H. Site 22 showed a fast mutation fixation in the year 2008, at the time of the large scale epidemic ou...
International Journal of Environmental Research and Public Health, 2015
Compared with temperate areas, the understanding of seasonal variations of influenza infections i... more Compared with temperate areas, the understanding of seasonal variations of influenza infections is lacking in subtropical and tropical regions. Insufficient information about viral activity increases the difficulty of forecasting the disease burden and thus hampers official preparation efforts. Here we identified potential meteorological factors that drove the seasonal variations in influenza infections in a subtropical city, Hong Kong. We fitted the meteorological data and influenza mortality data from 2002 to 2009 in a Susceptible-Infected-Recovered model. From the results, air temperature was a common significant driver of seasonal patterns and cold temperature was associated with an increase in transmission intensity for most of the influenza epidemics. Except 2004, the fitted models with significant meteorological factors could account for more than 10% of the variance in additional to the null model. Rainfall was also found to be a significant driver of seasonal influenza, although results were less robust. The identified meteorological indicators could alert officials to take appropriate control measures for influenza epidemics, such as enhancing vaccination activities before cold seasons. Further studies are required to fully justify the associations.
Proceedings of the National Academy of Sciences, 2007
Trisomy 21 is the most common reason that women opt for prenatal diagnosis. Conventional prenatal... more Trisomy 21 is the most common reason that women opt for prenatal diagnosis. Conventional prenatal diagnostic methods involve the sampling of fetal materials by invasive procedures such as amniocentesis. Screening by ultrasonography and biochemical markers have been used to risk-stratify pregnant women before definitive invasive diagnostic procedures. However, these screening methods generally target epiphenomena, such as nuchal translucency, associated with trisomy 21. It would be ideal if noninvasive genetic methods were available for the direct detection of the core pathology of trisomy 21. Here we outline an approach using digital PCR for the noninvasive detection of fetal trisomy 21 by analysis of fetal nucleic acids in maternal plasma. First, we demonstrate the use of digital PCR to determine the allelic imbalance of a SNP on PLAC4 mRNA, a placenta-expressed transcript on chromosome 21, in the maternal plasma of women bearing trisomy 21 fetuses. We named this the digital RNA SNP strategy. Second, we developed a nonpolymorphism-based method for the noninvasive prenatal detection of trisomy 21. We named this the digital relative chromosome dosage (RCD) method. Digital RCD involves the direct assessment of whether the total copy number of chromosome 21 in a sample containing fetal DNA is overrepresented with respect to a reference chromosome. Even without elaborate instrumentation, digital RCD allows the detection of trisomy 21 in samples containing 25% fetal DNA. We applied the sequential probability ratio test to interpret the digital PCR data. Computer simulation and empirical validation confirmed the high accuracy of the disease classification algorithm.
Background: During the early stages of a new influenza pandemic, travel restriction is an immedia... more Background: During the early stages of a new influenza pandemic, travel restriction is an immediate and non-pharmaceutical means of retarding incidence growth. It extends the time frame of effective mitigation, especially when the characteristics of the emerging virus are unknown. In the present study, we used the 2009 influenza A pandemic as a case study to evaluate the impact of regulating air, sea, and land transport. Other government strategies, namely, antivirals and hospitalizations, were also evaluated.
Transactions of The Royal Society of Tropical Medicine and Hygiene, 2015
Smoking is an important risk factor of TB. However, no studies have been conducted to identify TB... more Smoking is an important risk factor of TB. However, no studies have been conducted to identify TB cases from smokers. We assessed the process and initial impact of active case finding among smokers at primary care facilities in a setting with high smoking rates and TB burden. A prospective quasi-experimental study was conducted in para-urban communities in Yunnan China between September 2013 and June 2014. Smokers attending primary care facilities in the intervention group were prescribed chest X-rays if they had diabetes or TB symptoms, or were elders or close contacts of TB patients. Those with X-rays suggestive of TB were referred to TB dispensaries for diagnosis. Passive case finding was practiced in the control group. In the intervention group, we screened 471 smokers with high risks of TB, of whom 73% took chest X-ray examinations. Eight TB cases were diagnosed, reflecting a 1.7% yield rate of all screened smokers. Smokers with diabetes (OR 6.003, 95% CI 1.057-34.075) were more likely to have TB compared with those without. In total, the intervention group reported significantly higher TB notification rate compared with the control group (38.6 vs 22.9 per 100 000, p=0.016). Active case finding among smokers with high risks of TB was feasible and contributed to improved notification rates.
Environmental health : a global access science source, Jan 19, 2013
Numerous studies have found associations between extreme temperatures and human mortality but rel... more Numerous studies have found associations between extreme temperatures and human mortality but relatively few studies have been done in sub-tropical and tropical cities, especially in Asia. In this study we examine the impact of cold temperatures, cold waves and other meteorological and environmental variables on cool season mortality in 2 subtropical Asian cities. Separate analysis of daily mortality time-series from Hong Kong and Taipei using Generalized Additive Models with natural mortality as the outcome daily mean temperature as the main explanatory variable and relative humidity, solar radiation, wind speed, pollutants (nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), respirable suspended particulates (PM(10)), ozone (O(3)), seasonality and day of the week controlled as potential confounders. Lags up to 35 days were considered for temperature, and distributed lag models were used to determine the number of lags for final models. Subgroup analyses were also done by gender, age...
This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG... more This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG35156 in addition to sorafenib in patients with advanced hepatocellular carcinoma (HCC), as compared with sorafenib alone. Eligible patients were randomly assigned in a 2:1 ratio to receive AEG35156 (300 mg weekly intravenous infusion) in combination with sorafenib (400 mg twice daily orally) or sorafenib alone. The primary endpoint was progression-free survival (PFS). Other endpoints include overall survival (OS), objective response rates (ORR), and safety profile. A total of 51 patients were enrolled; of them, 48 were evaluable. At a median follow-up of 16.2 months, the median PFS and OS were 4.0 months (95% CI, 1.2-4.1) and 6.5 months (95% CI, 3.9-11.5) for combination arm, and 2.6 (95% CI, 1.2-5.4) and 5.4 months (95% CI, 4.3-11.2) for sorafenib arm. Patients who had the study treatment interrupted or had dose modifications according to protocol did significantly better, in terms of PFS and OS, than those who had no dose reduction in combination arm and those in sorafenib arm. The ORR based on Choi and RECIST criteria were 16.1% and 9.7% in combination arm, respectively. The ORR was 0 in control arm. One drug-related serious adverse event of hypersensitivity occurred in the combination arm, whereas 2 gastrointestinal serious adverse events in the sorafenib arm. AEG35156 in combination with sorafenib showed additional activity in terms of ORR and was well tolerated. The benefit on PFS is moderate but more apparent in the dose-reduced subgroups.
Background: Cardiovascular disease (CVD) is a major cause of death in China. Despite government e... more Background: Cardiovascular disease (CVD) is a major cause of death in China. Despite government efforts, the majority of hypertensive and diabetic patients in China do not receive proper treatment. Reducing CVD events requires long-term care that is proactive, patient-centred, community-based, and sustainable. We have designed a package of interventions for patients at high risk of CVD to be implemented by family doctors based in township hospitals (providers of primary care) in rural Zhejiang, China. This trial aims to determine whether the systematic CVD risk reduction package results in reduced CVD events among patients at risk of CVD compared with usual care, and whether the package is cost-effective and suitable for routine implementation and scale-up.
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Papers by Ka Chun Chong