Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases

Development of point-of-care bioassays for renal function marker-creatinine

Creatinine is an important diagnostic compound in determining renal and muscular dysfunction. There is an urgent necessity of rapid and simple creatinine assays for point-of-care (POC) applications. In this thesis, novel creatinine lateral-flow bioassays and electrochemical biosensor have been developed. An enzymatic bar-code lateral-flow creatinine test has been demonstrated. A unique approach that involves both 3,3’,5,5’-tetramethylbenzidine (TMB) diffusion and horseradish peroxidase (HRP) kinetics is presented. The hydrophobic TMB tends to form micro-crystals on the hydrophilic polyester pad. The large size of TMB crystals results in their delay in release, which in turn generates a decrease of reaction time on successive lines. Accordingly, a bar-code result in three distinct lines is generated. The assay expresses creatinine concentration at micromole range and is applicable to both urine and serum samples. Creatinine competitive immunochromatographic (IC) lateral-flow assays using colloidal gold and HRP as signal generator are implemented. The use of HRP as label offers a lower detection limit (3 μM) compared to colloidal gold (88 μM). The HRP-labeled IC assay is further devised into bar-code and one-step format by two unique approaches. The bar-code assay is based on the progressive decrease in the amount of anti-creatinine antibody immobilized on successive lines. The decrease in amount of free creatinine-HRP conjugate bound to antibodies immobilized on nitrocellulose (NC) membrane is therefore more significant in sequence. The one-step IC assay is constructed by incorporating glucose oxidase (GOD) and TMB pads to the IC setup. The delay in TMB release compared to GOD and creatinine-HRP conjugate effectively prevents the simultaneous occurrence of HRP reaction and competitive antigen-antibody binding. Multi-wall carbon nanotube (MWCNT)-modified sarcosine and creatinine layer-by-layer (LbL) electrochemical biosensors are described. In the presence of ferrocene carboxylic acid (FCA) as a diffusive electron mediator, an enhanced electroanalytical performance at lower working potential (0.37 vs. Ag/AgC1) is achieved. It is believed that the simple design of our developed creatinine bioassays will provide platforms for portable POC devices in decentralized detection

Industrialization in Singapore - The role of the Jurong Town Corporation in planning and control.

Singapore always prides herself to be the harmonized multi-racial country. Despite the differences in cultural, racial and social backgrounds, remarkable results have been achieved. It is believed that industrialization has spearheaded the whole economic development process in Singapore. The architect behind the industrialization is the Jurong Town Corporation. Our project aims to analyze the contribution of the JTC to the Singapore economic development process, with respect to six selected aspects

Development of enzyme-based bar code-style lateral-flow assay for hydrogen peroxide determination

A unique approach of developing a bar code version of lateral-flow enzymatic-based assay for the semiquantification of hydrogen peroxide is described. The proposed assay system is mainly composed of a goat anti-mouse IgG-horseradish peroxidase conjugate (Gt anti-M IgG-HRP)-coated nitrocellulose (NC) membrane and a peroxidase substrate pad. Unlike the bar code immunochromatographic assay which depends on the stepwise capture of analyte, the principle of enzyme-based bar code lateral-flow assay is based on the different reaction time on successive lines due to the delay in 3,3',5,5'-tetramethylbenzidine (TMB) release. Hydrogen peroxide (H2O2) acts as a limiting factor which controls the rate of the enzymatic conversion of TMB to blue color complex. The system expresses the concentration of H2O2 in micromole range as three distinct ladder bars in 9 min therefore without the need of any reading device. The major advantages of this assay are its easily readable result, and also its simplicity and low-cost in production offers a cheaper alternative for testing those expensive biosensors might not be available to the third world countries. By incorporating with H2O2-generating oxidoreductases, the assay can be further extended to detect a variety of analytes with clinical and environmental importance. Glucose was chosen to be the model analyte where the proposed system gave signal response at between 5 mu M and 100 mu M. (C) 2008 Elsevier B.V. All rights reserved

Development of a creatinine enzyme-based bar-code-style lateral-flow assay

A lateral-flow, enzyme-based, bar-code assay for creatinine employing the concept of combination of diffusion and kinetics controlled has been developed. Unlike the traditional bar-code version of immunochromatographic assay, which depends on the stepwise capture of colorimetric tracer-labeled antibody-antigen complex by the immobilized antibody on each successive line, the principle of our proposed assay is based on the delay in TMB release and its diffusion in combination with horseradish peroxidase kinetics. Hydrogen peroxide (H2O2) produced from enzymatic reactions acts as a limiting factor, which controls the rate of conversion of TMB to blue color complex. The assay takes advantage of giving ladder bar result therefore without the need of any reading device. Depending on the amount of enzymes used, the assay can be one (9 min) or two steps (19 min). The strip assay semiquantitatively measures creatinine concentrations ranging from 0 to 400 mu M. Thirty urine samples and thirty serum samples were tested, and the assay showed 90.0\% and 86.7\% agreement compared with conventional Jaffe method, respectively. This assay provides a tool for quick identification of creatinine for patients without the requirement of any instrument

Common chronic health problems and life satisfaction among Macau elderly people

Aim: Most elderly people live with one or more health problems and their quality of life is affected. This study aimed to compare life satisfaction of elderly people living with common chronic medical illness compared with those without these health conditions in order to identify conditions that most affect life satisfaction of elderly people living in the community. Method: The data was collected by a questionnaire survey of 529 elderly living in community dwellings of Macau using a single measure of life satisfaction and self-reported common chronic medical illness diagnosed by a physician. A purposeful stratified random sampling method was used. Independent sample t-tests were conducted to compare participants who had a health condition to those without a health condition. Results: Respondents who indicated the lowest life satisfaction were those with fracture after the age of 60, eye illness, chronic bronchitis/emphysema, and metabolic arthritis/arthritis. For men, prostate problems was also significantly related to low life satisfaction. Conclusion: Lowest life satisfaction was reported among Macau elderly people living with mobility related chronic medical illness. Policies and practices should pay more attention to mobility related health problems or issues of elderly people, such as eye health and neuromuscular weaknesses

From incubation, engagement, to decline : the role of social media in Hong Kong's Umbrella movement

In 2014, Hong Kong witnessed the rise of a significant social movement, known as the Umbrella Movement. Like other social protests in recent times, social media is assumed to have played a major role in the Umbrella Movement’s inception and development. This thesis critically examines that assumption by analyzing which forms of social media were most frequently used in the movement and demonstrates how the role of different social media varied through the different stages of the movement — from incubation and engagement, to decline. By adopting a qualitative approach, with the use of semi-structured interviews with ten protestors, we argue that social media harnessed the growth of the movement effectively by mobilizing resources and modifying the formation of protest organizations during the incubation and engagement stages; at the same time, however, social media also contributed to the rapid decline of the movement, which failed to sustain the participation of individuals. Online interaction via social media, unlike physical participation in a social movement, could not foster the necessary trust and solidarity among participants. This thesis highlights the limitations of social media, which failed to sustain and even arguably facilitated participants’ disengagement from Hong Kong’s Umbrella Movement.published_or_final_versionCriminologyMasterMaster of Social Science

Help-seeking and antibiotic prescribing for acute cough in a Chinese primary care population: a prospective multicentre observational study

Acute cough is a common reason to prescribe antibiotics in primary care. This study aimed to explore help-seeking and antibiotic prescribing for acute cough in Chinese primary care population. This is a prospective multicentre observational study that included adults presenting with acute cough. Clinicians recorded patients' presenting symptoms, examination findings and medication prescription. Patients completed symptom diaries for up to 28 days by charting their symptom severity and recovery. Adjusted binary logistic regression models identified factors independently associated with antibiotic prescription. Primary care clinicians (n=19) recruited 455 patients. A total of 321 patients (70.5%) returned their completed symptom diaries. Concern about illness severity (41.6%) and obtaining a prescription for symptomatic medications (45.9%), rather than obtaining a prescription for antibiotics, were the main reasons for consulting. Antibiotics were prescribed for 6.8% (n=31) of patients, of which amoxicillin was the most common antimicrobial prescribed (61.3%), as it was associated with clinicians' perception of benefit from antibiotic treatment (odds ratio (OR): 25.9, 95% confidence interval (CI): 6.7-101.1), patients' expectation for antibiotics (OR: 5.1, 95% CI: 1.7-11.6), anticipation (OR: 5.1, 95% CI: 1.6-15.0) and request for antibiotics (OR 15.7, 95% CI: 5.0-49.4), as well as the severity of respiratory symptoms (cough, sputum, short of breath and wheeze OR: 2.7-3.7, all P<0.05). There was a significant difference in antibiotic prescription rates between private primary care clinicians and public primary care clinicians (17.4 vs 1.6%, P=0.00). Symptomatic medication was prescribed in 98.0% of patients. Mean recovery was 9 days for cough and 10 days for all symptoms, which was not significantly associated with antibiotic treatment. Although overall antibiotic-prescribing rates were low, there was a higher rate of antibiotic prescribing among private primary care clinicians, which warrants further exploration and scope for education and interventio

Single-Nucleotide Variations, Insertions/Deletions and Copy Number Variations in Myelodysplastic Syndrome during Disease Progression Revealed by a Single-Cell DNA Sequencing Platform

Myelodysplastic syndrome (MDS) is a clonal myeloid neoplasm characterized by ineffective hematopoiesis, cytopenia, dysplasia, and clonal instability, leading to leukemic transformation. Hypomethylating agents are the mainstay of treatment in higher-risk MDS. However, treatment resistance and disease transformation into acute myeloid leukemia (AML) is observed in the majority of patients and is indicative of a dismal outcome. The residual cell clones resistant to therapy or cell clones acquiring new genetic aberrations are two of the key events responsible for drug resistance. Bulk tumor sequencing often fails to detect these rare subclones that confer resistance to therapy. In this study, we employed a single-cell DNA (sc-DNA) sequencing approach to study the clonal heterogeneity and clonal evolution in two MDS patients refractory to HMA. In both patients, different single nucleotide variations (SNVs) or insertions and deletions (INDELs) were detected with bulk tumor sequencing. Rare cell clones with mutations that are undetectable by bulk tumor sequencing were detected by sc-DNA sequencing. In addition to SNVs and short INDELs, this study also revealed the presence of a clonal copy number loss of DNMT3A, TET2, and GATA2 as standalone events or in association with the small SNVs or INDELs detected during HMA resistance and disease progression

Comparison of double-bag and Y-set disconnect systems in continuous ambulatory peritoneal dialysis: A randomized prospective multicenter study

We performed a multicenter, single-blinded, prospective randomized study on the use of a double-bag disconnect system (B) versus a Y-set disconnect system (Y). The peritonitis rate, exit site infection, clinical outcome, and patients' acceptance to the procedure were assessed. A total of 120 new end- stage renal failure patients of three regional hospitals were randomized: 60 each to the B and the Y systems. The results of 60 patients on the B system and 51 on the Y system were analyzable. They were followed up for a median of 16 months. Peritonitis rates for the B and the Y systems were 33.5 and 29.4 patient-months per episode, respectively. Exit site infection rates for the B and Y systems were 17.4 and 16.0 patient-months per episode, respectively. Four catheters were removed in each group. Patients on the B system were hospitalized for 2.1 days per patient per year related to peritonitis and exit site infection, and those on the Y system were hospitalized for 1.2 days. There was no significant difference between the B and Y systems in the incidences of peritonitis (all causes and those due to coagulase-negative staphylococci), exit site infection, and in hospitalization days. However, there was a higher percentage of gram-positive infections in the Y system (52%) than in the B system (32%) and a lower percentage of gram-negative infections in the Y system (16%) than in the B system (32%). Patients on the B system had a better acceptance of the procedure than patients on the Y system, as assessed by a six-item, 10-point questionnaire (total score, 43.1 ± 10.2 v 37.6 ± 9.4; P < 0.005 at 1 month; 44.6 ± 9.1 v 39.8 ± 8.6; P < 0.01 at 6 months). From this study, it is concluded that the B and Y systems are similar in the incidences of peritonitis and exit site infection, although the B system is better accepted by patients. This is probably the first multicenter randomized study comparing the double-bag and Y-set disconnect system using only new patients who had never used other systems of continuous ambulatory peritoneal dialysis.link_to_subscribed_fulltex