Dengue Virus Surveillance for Early Warning, Singapore

In Singapore, after a major outbreak of dengue in 2005, another outbreak occurred in 2007. Laboratory-based surveillance detected a switch from dengue virus serotype 1 (DENV-1) to DENV-2. Phylogenetic analysis showed a clade replacement within DENV-2 cosmopolitan genotype, which accompanied the predominant serotype switch, and cocirculation of multiple genotypes of DENV-3

Large-scale evolutionary surveillance of the 2009 H1N1 influenza A virus using resequencing arrays

In April 2009, a new influenza A (H1N1 2009) virus emerged that rapidly spread around the world. While current variants of this virus have caused widespread disease, particularly in vulnerable groups, there remains the possibility that future variants may cause increased virulence, drug resistance or vaccine escape. Early detection of these virus variants may offer the chance for increased containment and potentially prevention of the virus spread. We have developed and field-tested a resequencing kit that is capable of interrogating all eight segments of the 2009 influenza A(H1N1) virus genome and its variants, with added focus on critical regions such as drug-binding sites, structural components and mutation hotspots. The accompanying base-calling software (EvolSTAR) introduces novel methods that utilize neighbourhood hybridization intensity profiles and substitution bias of probes on the microarray for mutation confirmation and recovery of ambiguous base queries. Our results demonstrate that EvolSTAR is highly accurate and has a much improved call rate. The high throughput and short turn-around time from sample to sequence and analysis results (30 h for 24 samples) makes this kit an efficient large-scale evolutionary biosurveillance tool

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Characterisation of the self-incompatibility related F-box proteins of Nicotiana alata

© 2015 Dr. Poh Ling KohSelf-incompatibility is a genetically encoded barrier to self-fertilisation found in some plant species. In solanaceous plants such as Nicotiana alata self-incompatibility is controlled by a highly allelic single locus known as the S locus (Newbigin et al., 1993). Fertilisation is prevented when the S allele expressed by the haploid pollen grain matches either of the S alleles expressed by the diploid female reproductive tissue or style. The only known products of the N. alata S locus are a style-specific extracellular ribonuclease called the S-RNase and a family of 10 pollen-expressed F-box protein genes called the DD genes (Wheeler and Newbigin 2007). S-RNases determine the allelic identity of the style and in Petunia inflata, another self-incompatible member of the Solanaceae, a family of DD-related genes called S locus F-box or SLF genes regulates S allele identity in pollen (Kubo et al., 2010). Although it now appears that pollen identity in solanaceous plants is determined through the action of several genes, as described by Kubo et al’s (2010) collaborative non-self recognition model, when this thesis began it was thought that only one gene, encoding a determinant factor known as pollen S, was involved (McCubbin et al., 1997; Newbign et al., 2008). As the hypothesis was that N. alata pollen S was encoded by a DD gene or related sequence, this thesis began with the aim of discovering whether there were any more DD genes expressed in N. alata pollen and which of the 10 (or more) DD genes encoded the pollen S determinant. Chapter 1 reviews the literature relevant to this study and sets out the thesis aims. Chapter 2 describes the use of next generation sequencing of N. alata pollen grain RNA to identify DDs and other RNase-based SI related transcripts reported by other studies. As the N. alata genome has not been sequenced an RNA-Seq bioinformatics pipeline was developed for de novo transcriptome assembly. The assembled pollen grain transcriptome was validated using bioinformatic and molecular approaches and searched using the sequences implicated by other studies in the self-incompatibility response of solanaceous plants (Hua and Kao, 2006; Zhao et al., 2010). F-box proteins are a component of the SCF (Skp1-Cullin-F-box protein) complex that takes ubiquitin from the E2 ubiquitin-conjugating enzyme and transfers it to a substrate protein or target. F-box proteins such as DD/SLF bind to the substrate protein and give the SCF complex its unique specificity (Petroski and Deshaies, 2005; Vierstra 2009). Two novel DD/SLF transcripts were identified in the transcriptome, as well as transcripts of other genes suggested to encode components of the SLF-containing SCF complex. Some of the work described in this chapter contributed to the paper by Lampugnani et al. (2013). Because SLFs are F-box proteins their main function in the self-incompatibility response is presumably to bind to and ubiquitylate the S-RNase, leading to degradation by the 26S proteasome pathway (Sijacic et al., 2004). Chapter 3 reports on experiments designed to identify the N. alata pollen S determinant using recombinant DD/SLF and S-RNase proteins produced in E. coli, and an in vitro binding assay similar to that described by Hua and Kao (2006) for Petunia SLFs. A major problem for the binding assay was obtaining recombinant proteins in a largely soluble and intact or full-length form – the proteins were usually insoluble and had undergone degradation – but even so the in vitro assay failed to consistently detect binding between SLF and S-RNase. An alternative assay was developed that used antibodies specific for one of the protein partners to immunoprecipitate the other partner (the Co-IP assay). As reproducible binding of SLF and S-RNase could be detected in a Co-IP assay that used recombinant SLF proteins in E. coli extracts and native S-RNases from N. alata stylar extracts, further experiments aimed at production of enriched, soluble SLF/DD proteins were planned. Chapter 4 describes work focussed on refolding the insoluble DD and SLF proteins into a soluble and enriched form for use in the Co-IP assay and biophysical characterization. Protein folding is not a routine procedure but many studies have successfully rescued misfolded proteins by this approach. This chapter reports the production of soluble, enriched SLF/DD proteins from which the N-terminal F-box motif had been deleted. These truncated SLF/DD proteins could still interact specifically with N. alata S-RNases, suggesting that F-box motif is not necessary for this interaction. Biophysical characterization of SLF/DD proteins by circular dichroism analysis suggested they had a large component of β-sheet, which is consistent with the six-bladed beta-propeller structure predicted from theoretical modeling. However the high content of β-sheet was also consistent with the presence of amyloids, misfolded globular proteins composed of intermolecular arrays of parallel β-sheets (Nelson et al., 2005). As analytical ultracentrifugation of the resolubilised SLF/DD proteins detected polydispersed oligomers, it seems likely that refolding had resulted in amyloid formation that were nonetheless still functional, based on their ability to bind to S-RNases. Chapter 5, the final chapter, summarises the work in the rest of the thesis and suggests some productive areas for further research

The effect of budgetary participation in the information asymmetry/budget satisfaction relationship under task uncertainty

86 p.The objective of this paper is to examine the role budgetary participation plays in the relationship between information asymmetry and budget satisfaction, under the effects of high and low task uncertainty. A random sample was picked out of 500 companies from both the public and private sectors in Singapore. Targeted respondents were lower level managers in charge of budgetary matters. Related studies have suggested that budgetary participation has a positive influence on the level of budget satisfaction experienced by managers. The results of this study support the hypothesis that budgetary participation enhances satisfaction but find no significant difference in the effect of budgetary participation in the information asymmetry/budget satisfaction relationship under the conditions of high and low task uncertainty. This implies that budgetary participation is a universal criterion for budget satisfaction.ACCOUNTANC

Study on the differences in buying behaviour between teenagers and their parents.

We are interested in understanding the way teenagers acquire skills, knowledge and attitudes relevant to their functioning as consumers.BUSINES

A study on the differences in buying behaviour between teenagers and their parents.

We are interested in understanding the way teenagers acquire skills, knowledge and attitudes relevant to their functioning as consumers. There are two aspects to consumer socialisation : • First, we are interested in establishing who are the main external sources of influences. These external sources of influences help reduce consumers feeling of uncertainty when they purchase a product for the first time or make a purchase that could have major consequences. External search often begins with an intimate primary groups such as family members or close friends. The secondary groups often consulted are colleagues, neighbours, and/or sales persons. • Secondly, we would look at the teenagers’ development as consumers. We had found at what age and for what product categories are they most capable of making purchase decisions. Furthermore, we have looked at the intergenerational influences that occured when teenagers and their parents made purchase decisions. All these findings are then related to the marketing system in the Singapore context.BUSINES

Left atrial phasic function in older adults is associated with fibrotic and low-grade inflammatory pathways

Introduction: Concomitant risk factors challenge the mechanistic understanding of cardiac aging. We determined the degree to which the left atrial function could be distinguished by advanced cardiac magnetic resonance (CMR) imaging in older adults and assessed associations between the left atrial function and the plasma biomarkers related to biological aging and cardiovascular disease [serum monocyte chemoattractant protein-1 (MCP1), matrix metallopeptidase 9 (MMP-9), B-type natriuretic peptides (BNPs), galectin-3 (Gal-3), high-sensitivity cardiac troponin I (hsTn1), high-sensitivity C-reactive protein (hs-CRP), and soluble urokinase plasminogen activator receptor (sUPAR)]. Methods: Among a cross-sectional population-based cohort of older adults, longitudinal LA strain including reservoir strain (ϵs), conduit strain (ϵe), and booster strain (ϵa) as well as peak strain rates (SRs, SRe, SRa) were determined using CMR and studied in association with blood biomarkers. Results: We studied 243 community adults (42.8% female, mean age 70.3 ± 9.5 years). In bivariate analysis, ϵe and SRe were reduced in gradation with increasing risk factors (all p values <0.0001). Corresponding levels of sUPAR (ng/mL) were quantitatively higher in older adults with <2 risk factors (2.5 ± 1.6 vs. 1.7 ± 1.3, p = 0.0005), in those with ≥2 risk factors (3.3 ± 2.4 vs. 1.7 ± 1.3, p < 0.0001), compared to young adults; including between older adults with ≥2 risk factors and older adults with <2 risk factors (3.3 ± 2.4 vs. 2.5 ± 1.6, p = 0.017). Based on multivariate analysis, sUPAR was significantly associated with both ϵe (OR 1.52, p = 0.006) and SRe decline (OR 1.5, p = 0.019). The associations between Gal-3 and ϵe reduction (OR 1.2, p = 0.022) and between BNP and SRe decline were generally weaker (OR 1.03, p = 0.027). The addition of sUPAR to a model consisting of age, risk factors, Gal-3, and BNPs increased the area under the curve of ϵe from 0.72 to 0.77 (p = 0.015). Conclusion: By advanced CMR imaging, a panel of circulating biomarkers comprising galectin, MMP-9 and sUPAR were associated with left atrial dysfunction in older adults. Higher levels of Gal-3 and MMP-9 may be suggestive of fibrotic mechanisms in left atrial aging while impairments in left atrial strain seen in association with circulating sUPAR may be related to immune activation in the left atrium in response to left atrial remodeling and fibrotic processes.Nanyang Technological UniversityNational Medical Research Council (NMRC)Published versionThe Cardiac Aging Study has received funding support from the National Medical Research Council of Singapore (MOH000153), Hong Leong Foundation, Duke-NUS Medical School, Estate of Tan Sri Khoo Teck Puat and Singhealth Foundation. Those participants recruited from the Singapore Chinese Health Study were supported by the United States National Institutes of Health (NIH R01 CA144034 and UM1 CA182876). The CMR imaging analysis was partially supported by National Medical Research Council of Singapore (NMRC/OFIRG/0018/2016). The Nanyang Assistant Professorship from Nanyang Technological University funded the work done by Dr. Christine Cheung. W.-P. Koh is supported by the National Medical Research Council, Singapore (MOH-CSASI19nov-0001). The funders had no role in the design and conduct of the study; collection; management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript