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In anticipation of the new Proton Therapy Centre in Singapore at 2020, the medical physicists and physicists in NCCS and NUS have come together to do several preparation/preliminary works. Of which, one of the most important programme is to develop the Monte Carlo simulation capability using GEANT4 toolkit. We simulated the entire beam delivery and nozzle based on specifications given by Hitachi. The results of the Energy-Range curves in water phantom together with spot size in air agrees well with measurement data provided by Hitachi. We will show the complete methodology of simulation leading up to the comparison with measurement data. There were 3 main aspects we focused on—(1) The choice of physics models, (2) The determination of initial proton phase space based on Twiss parameters from beam profile measurement and (3) The choice of cut-off energy and step size. This simulation is important for the commissioning of the Proton Therapy System and the methodology presented will be helpful for other upcoming centers who are interested in doing the same.

Current Treatment Planning System uses advanced optimization algorithm with Dose Calculation Engine to optimize the dose delivered to the tumor to maximize the tumor-killing potential while limiting the side-effects to the normal tissues. Working in parallel, there are various radiobiology simulation programs being developed by different research groups to quantify biological endpoints such as Double Strand Breaks (DBSs) yield and Chromosome Aberration (CA) induced by different radiation types. In this paper, we conduct a novel preliminary work to combine these two areas to determine DSB yields in a 3D CT geometry. Our preliminary result shows that the position of the Bragg Peak determined from dose deposition differs from the position of maximal DSB yields. The difference can range from 0 to 1 mm, hence showing that dose is not entirely indicative of biological damage in tissue.

It is known that high energy protons in proton therapy generate secondary particles. Of which, secondary neutrons are a main concern as they deposit out-of-field doses and can have long-term health effects on cancer patients. In this paper, the energy, 3-D spatial and angular distribution of the production yield of neutrons is scored along the proton beam path in different types of tissue medium. The degree of biological damage is then quantified through factoring in the relative biological effectiveness of neutrons. This systematic study involved simulating 70, 150 and 200 MeV proton beam transport in various tissue compositions with the GEANT4 code. System specifications of the Hitachi proton therapy system were used in this study. Simulation results showed that the neutrons are forward facing and are generally emitted at a preferential angle. With considerations on the RBE variation with neutron’s energy, the spatial and angular distribution of the production of lethal neutrons were identified along the proton track. Non-trivial relations between biological damage in different tissue medium were observed. Such comprehensive simulation studies have not been reported and this input information can be useful for treatment planning in reducing out-of-field neutron dose in sensitive organs.

Purpose: To investigate the potential impact of anatomic change in the treatment of locally advanced oropharyngeal cancer with proton pencil beam scanning. Materials and Methods: Ten patients with locally advanced oropharyngeal cancer who previously received intensity-modulated radiation therapy (IMRT) and synchronous chemotherapy underwent replanning by using RapidArc IMRT and proton pencil beam scanning. Deformable image registration deformed the planning computed tomography (CT), target volumes, and organs at risk (OARs) contours onto each weekly cone-beam CT scan. Target and OARs volumes were reviewed and modified. Treatment plans were forward calculated onto each corrected cone-beam CT scan and dose-volume histograms produced for targets and OARs volumes. Results: Proton pencil beam scanning compared with RapidArc IMRT achieved lower mean doses to the contralateral parotid gland (14.8 Gy versus 20.6 Gy, P

The asymmetric synthesis of 3-alkyl-3-hydroxyindolin-2-ones via direct aldol reaction of isatin with ketones catalyzed by natural amino acid salts is described, in which the phenylalanine lithium salt was found to be the best catalyst. This strategy was then applied to a variety of isatin and ketone substrates and the corresponding aldol products were obtained in excellent yields (up to 97%) with good to excellent enantioselectivities (up to 90%).

A series of novel teraryl oxazolidinone compounds was designed, synthesized, and evaluated for their antimicrobial activity and toxicities. The compounds with aromatic N-heterocyclic substituents at the 4-position of pyrazolyl ring showed better antibacterial activity against the tested bacteria than other compounds with different patterns of substitution. Among all potent compounds, 10f exhibited promising safety profile in MTT assays and in hERG K(+) channel inhibition test. Furthermore, its phosphate was found to be highly soluble in water (47.1 mg/mL), which is beneficial for the subsequent in vivo test. In MRSA systemic infection mice models, 10f phosphate exerted significantly improved survival protection compared with linezolid. The compound also demonstrated high oral bioavailability (F = 99.1%). Moreover, from the results of in vivo toxicology experiments, 10f phosphate would be predicted to have less bone marrow suppression.

We conducted a pediatric seroprevalence study of dengue virus (DENV) infection in Singapore, a dengue endemic city-state. Residual sera from 1,200 Singapore residents aged 1-17 years seen in two hospitals between 2008 and 2010 were tested for anti-DENV IgG antibodies. The overall seroprevalence was 10.4% (95%CI: 8.7-12.1%). There had been a marked decline in seroprevalence in the 15-19-year age group over the last three decades, while the prevalence in the 1-5-year olds (12.6%) was significantly higher than that of the 1996-1997 pediatric survey (0.8%). The overall dengue seroprevalence in children and adolescents remained low.

A series of scutellarein-O-alkylamine derivatives were designed, synthesized and tested as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good multifunctional activities. Among them, compound 16d demonstrated significant metal chelating properties, moderate acetylcholinesterase (AChE) inhibitory and anti-oxidative activity, and excellent inhibitory effects on self-induced Aβ(1-42) aggregation, Cu(2+)-induced Aβ(1-42) aggregation, human AChE-induced Aβ(1-40) aggregation and disassembled Cu(2+)-induced aggregation of the well-structured Aβ(1-42) fibrils. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that 16d binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Moreover, compound 16d showed a good protective effect against H2O2-induced PC12 cell injury, with low toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test showed this compound significantly reversed scopolamine-induced memory deficit in mice. Thus, 16d was shown to be an interesting multifunctional lead compound worthy of further study.

Automatic vehicle navigation is commonly used in today's world with the proliferation of low-cost GNSS receivers. However, positioning inaccuracies inherent to GNSS-based positioning can reduce the application coverage. Areas such as urban canyons with limited satellite view and poor PDOP (position dilution of precision) could cause significant positioning errors. To complement the inefficacy of positioning in such urban environment, we conducted a study into the effectiveness of using WIFI fingerprinting technology to complement GNSS-based positioning for vehicle positioning in an urban environment. WIFI fingerprinting positioning complements well with GNSS-based positioning in that although there is limited satellite view in urban environment, there are an abundance of WIFI signals. In this paper, we present the results of our study conducted in the Singapore Jurong Lake District. Data collection of WIFI signals were performed using an Android APP running on a mobile device by driving around the area. The WIFI signal data are then processed and stored in a WIFI fingerprint database. A navigation APP was developed to compute the vehicle position based on measured WIFI signals and WIFI fingerprint data from the database. The vehicle position can then be displayed on a map live, just like a GNSS-based navigation device. We studied two methods of fingerprinting-based positioning. The first method uses the kNN method in which WIFI signal strengths information is taken into the positioning computation. The second method uses a simpler approach without using signal strengths. The positioning accuracies obtained using these two methods of WIFI fingerprinting are discussed. The results showed that WIFI fingerprinting-based positioning may be a feasible complement to GNSS in providing positioning for vehicle navigation in an urban environment.

While the effect of physical activity on knee osteoarthritis (KOA) remains controversial, how sitting and sleep durations affect KOA is unknown. We evaluated the association between durations of physical activity, sitting and sleep, and incidence of total knee replacement (TKR) due to severe KOA.We used data from the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese, aged 45-74 years at recruitment from 1993-1998. Height, weight, lifestyle factors, hours of sitting and sleep per day, and hours of moderate activity, strenuous sports or vigorous work per week were assessed through in-person interviews using structured questionnaires. Incident cases of TKR were identified via record linkage with nationwide hospital discharge database.Compared to those with0.5 hour/week of moderate physical activity, participants with ≥5 hour/week had increased risk of TKR risk [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.00-1.35]. Conversely, duration of sitting activities, especially sitting at work, was associated with reduced risk in a stepwise manner. Compared to4 hour/day of sitting, those with ≥12 hour/day had the lowest risk (HR 0.76, 95% CI 0.60-0.96, p for trend = 0.02). Sleep duration was inversely associated with reduced risk of TKR in a dose-dependent manner; compared to those with sleep ≤ 5 hour/day, participants with ≥ 9 hour/day had the lowest risk (HR 0.55, 95% CI) 0.43-0.70, p for trend0.001).While prolonged sitting or sleeping duration could be associated with reduced risk of severe KOA, extended duration of physical activity could be associated with increased risk.

Objectives While the effect of physical activity on knee osteoarthritis (KOA) remains controversial, how sitting and sleep durations affect KOA is unknown. We evaluated the association between durations of physical activity, sitting and sleep, and incidence of total knee replacement (TKR) due to severe KOA. Methods We used data from the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese, aged 45–74 years at recruitment from 1993–1998. Height, weight, lifestyle factors, hours of sitting and sleep per day, and hours of moderate activity, strenuous sports or vigorous work per week were assessed through in-person interviews using structured questionnaires. Incident cases of TKR were identified via record linkage with nationwide hospital discharge database. Results Compared to those with

Singapore is a tropical country with influenza seasons occurring bi-annually. We compared the profile of severely ill patients with laboratory confirmed influenza A(H1N1)pdm09 infection in Singapore during the pandemic and post-pandemic periods, and studied their risk factors associated with mortality.Three periods were defined for this study; pandemic period from 18 June to 29 August 2009, early post-pandemic period from 30 August 2009 to 12 February 2010, and late post-pandemic period from 13 February to 10 August 2010.A total of 172 severely ill patients were admitted to hospitals from 18 June 2009 to 10 August 2010, of whom 23.8% died. The median age in the late post-pandemic period was significantly older than that in the early post-pandemic period (52 years versus 35 years, P=0.02). The median age of patients who died was significantly older than those who survived (52 years versus 44 years, P0.01). The median length of stay under intensive care in the late post-pandemic period was twice that in the early post-pandemic (6 days versus 3 days, P=0.045). The proportion who died in the late post-pandemic period was more than 2.5 times that in the early post-pandemic period (29.8% versus 11.1%, P=0.043).Severely ill patients were of older age in the late post-pandemic period. Older age was also significantly associated with mortality. It is important to maintain heightened vigilance and continue the surveillance of severely ill patients with influenza post-pandemic, so that patients with suspected infections could be promptly identified for early diagnosis and treatment.

Objectives We determined the seroprevalence of chikungunya virus (CHIKV) infection in the adult resident population in Singapore following local outbreaks of chikungunya fever (CHIKF) in 2008–2009. Methods Our cross-sectional study involved residual sera from 3,293 adults aged 18–79 years who had participated in the National Health Survey in 2010. Sera were tested for IgG antibodies against CHIKV and dengue virus (DENV) and neutralizing antibodies against CHIKV. Results The prevalence of CHIKV-neutralizing antibodies among Singapore residents aged 18–79 years was 1.9% (95% confidence interval: 1.4%– 2.3%). The CHIKV seroprevalence was highest in the elderly aged 70–79 years at 11.5%, followed by those aged 30–39 years at 3.1%. Men had significantly higher CHIKV seroprevalence than women (2.5% versus 1.3%, p = 0.01). Among the three main ethnic groups, Indians had the highest seroprevalence (3.5%) compared to Chinese (1.6%) and Malays (0.7%) (p = 0.02 and p = 0.01, respectively). Multivariable logistic regression identified adults aged 30–39 years and 70–79 years, men, those of Indian ethnicity and ethnic minority groups, and residence on ground floor of public and private housing apartments as factors that were significantly associated with a higher likelihood of exposure to CHIKV. The overall prevalence of anti-DENV IgG antibodies was 56.8% (95% CI: 55.1%– 58.5%), while 1.5% (95% CI: 1.1%– 2.0%) of adults possessed both neutralizing antibodies against CHIKV and IgG antibodies against DENV. Conclusions Singapore remains highly susceptible to CHIKV infection. There is a need to maintain a high degree of vigilance through disease surveillance and vector control. Findings from such serological study, when conducted on a regular periodic basis, could supplement surveillance to provide insights on CHIKV circulation in at-risk population., Author summary The prevalence of neutralizing antibodies against chikungunya virus (CHIKV) was low at 1.9% among resident adults in Singapore after local outbreaks in 2008–2009. Adults aged 30–39 years and 70–79 years, men, those of Indian ethnicity and ethnic minority groups, and residence on ground floor of public and private housing apartments were significantly associated with a higher likelihood of exposure to CHIKV.

When a vehicle makes a turn at a traffic junction, and views of oncoming vehicles and pedestrians are obstructed by other vehicles, some drivers would inch forward to get a better view — which could result in dangerous situations. The Junction Safety System is designed to provide information to drivers to help them navigate traffic junctions safely. The system sends out messages to On-Board-Units installed in the vehicles to warn the drivers when oncoming vehicles and at-risk pedestrians are detected. To evaluate the effectiveness of the system, a trial was conducted with public buses in Singapore. The trial consisted of two groups of buses to determine the effect of introducing the system — one group was installed with warning displays, and the other group was not installed with warning displays. System message latency and accuracy are also reported in this paper. The results showed that the Junction Safety System can improve the safety of drivers navigating a traffic junction.

The incidence of traffic violations caused by public transportation demonstrates the importance of investigating alternative forms of road safety intervention. In this paper, we report on a two-month field trial in which three HMI (human-machine interface) prototypes were evaluated with 47 bus drivers in Singapore. This was done to understand how warning messages might improve junction safety for public buses. Via semi-structured interviews and video analysis, the study evaluated driver perceptions of the HMIs, as well as whether the display of different warning messages had any measurable impact on driving behaviour. Overall, the results identified stronger preferences for more context-specific information, which aided the drivers by improving the road visibility around traffic obstructions and blind spots. An interpretation of these results, in addition to recommendations for future work is provided.

There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01–0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m2). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m2 for each Mb of total deletion burden (P = 2.5 × 10−10, 6.0 × 10−5, and 2.9 × 10−3). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders., Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.

With the rapid progress of fiber lasers, there is increasing demand to develop optical waveguides providing large fundamental mode (FM) effective areas. Several of these fibers possess structural features, beyond the traditional core and cladding of a step-index fiber, in order to suppress higher-order modes (HOMs); however, their mode filtering capabilities are limited by imperfections in fabrication. In this work, we propose an approach based on Monte Carlo method that takes into account practical fabrication tolerances to determine the fabrication yields of complex fiber designs. Importantly, for a fiber design to be viable in applications, it must not only perform well optically, but also be robust against fabrication imperfections. We applied the methodology to an exemplary 33-μm W-type fiber, and assume independent uniform distributions of ±10% in all dimensions and numerical apertures (NAs). In total, 500 fabrication iterations are simulated, and the cumulative yield that simultaneously satisfies α FM hom > 10 dB/m and A eff, fm > 400 μm2 is found to be 21.6% ± 3.6% (95% confidence level) across coil radii between 10.2 cm and 27.0 cm. We expect this methodology to be particularly useful in predicting yields of fibers whose properties are based on resonant coupling (i.e. 3C and anti-resonant fibers), where imperfections in fabrication modify their resonance conditions.

Introduction: High levels of toxicities have been observed when docetaxel is administered at the standard dose of 75 mg/m2 every 3 weeks (Q3W) in the real-world treatment of Asian patients with metastatic castrate-resistant prostate cancer (CRPC). This study aimed to evaluate the efficacy and tolerability of 2 attenuated regimens more widely used in an Asian setting to minimise toxicity – 60 mg/m2 Q3W and weekly docetaxel (20 mg/m2 to 35 mg/m2). Materials and Methods: Medical records of 89 CRPC patients between December 2003 and April 2013 were reviewed. Pairwise statistical analysis was performed, comparing efficacy and safety outcomes of 75 mg/m2 Q3W and weekly docetaxel with 60 mg/m2 Q3W. Treatment endpoints used were prostate-specific antigen (PSA) response (decrease of ≥50% from baseline), pain improvement after cycle 2, overall survival, time to disease progression and radiological response. Results: Patients who received docetaxel at 75 mg/m2 Q3W were younger than those who received 60 mg/m2 Q3W (62 years and 66 years, respectively; P = 0.0489). Both groups had similar response rates. Compared with patients on 60 mg/m2Q3W, more patients on weekly regimens were symptomatic at baseline (63.2% and 87.5%, respectively; P = 0.0173). Longer overall survival was observed in the 60 mg/m2 Q3W arm than the weekly docetaxel arm (16.9 months and 10.6 months, respectively; P = 0.0131), though other measures of response did not differ significantly. Conclusion: Our data supports the use of 60 mg/m2 Q3W docetaxel which has similar efficacy and an acceptable toxicity profile compared to the standard 75 mg/m2 Q3W regimen. Weekly docetaxel has significant palliative benefits among symptomatic patients despite lower overall survival. Key words: Chemotherapy, Genitourinary, Toxicity

Infectious diseases claim millions of lives every year, but with the advent of drug resistance, therapeutic options to treat infections are inadequate. There is now an urgent need to develop new and effective treatments. Nitroimidazoles are a class of antimicrobial drugs that have remarkable broad spectrum activity against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. While nitroimidazoles were discovered in the 1950s, there has been renewed interest in their therapeutic potential, particularly for the treatment of parasitic infections and tuberculosis. In this review, we summarize different classes of nitroimidazoles that have been described in the literature in the past five years, from approved drugs and clinical candidates to examples undergoing preclinical or early stage development. The relatively "nonspecific" mode of action and resistance mechanisms of nitromidazoles are discussed, and contemporary strategies to facilitate nitroimidazole drug development are highlighted.

Probe vehicle data, also known as floating car data or connected vehicle data, is the data collected from GPS-enabled sensors on vehicles. With the advancement in wireless communications and localization technologies, more and more vehicles are expected to be equipped with such sensors. Existing studies only focus on using small-scale probe vehicle data. In this paper, we are interested in developing a real-time parallel stream processing framework to extract traffic flow KPIs from large-scale probe vehicle data. The developed framework is implemented using Apache Storm on Amazon AWS, and can process one million probe vehicle messages per second. Various design considerations, such as data partition and delay processing are discussed. To evaluate the performance of stream processing framework, simulated probe vehicle data based on the actual traffic flows in Jurong Lake District (JLD) of Singapore, is generated using the microscopic simulation software VISSIM. The JLD data is replicated multiple times to represent the one million population of vehicles in Singapore. GPS errors and communication delays are added to represent the real situations before the data is fed to stream processing module. The estimated KPIs from our stream processing model are validated against the ground truth values under different penetration levels.

A facile method to synthesize various 1,2-disubstituted benzimidazoles is developed. It is suggested that formation of a Meisenheimer adduct between the substrate, amine, and solvent aids the N-arylation process. The generality of the protocol is demonstrated by the efficient reactions involving numerous substituents ranging from electron-withdrawing groups to electron-donating groups.

Background: Incense burning is common in many parts of the world. Although it is perceived that particulate matter from incense smoke is deleterious to health, there is no epidemiologic evidence linking domestic exposure to cardiovascular mortality. Objective: We examined the association between exposure to incense burning and cardiovascular mortality in the Singapore Chinese Health Study. Methods: We enrolled a total of 63,257 Singapore Chinese 45–74 years of age during 1993–1998. All participants were interviewed in person to collect information about lifestyle behaviors, including the practice of burning incense at home. We identified cardiovascular deaths via record linkage with the nationwide death registry through 31 December 2011. Results: In this cohort, 76.9% were current incense users, and most of the current users (89.9%) had burned incense daily for ≥ 20 years. Relative to noncurrent users, current users had a 12% higher risk of cardiovascular mortality [multivariable adjusted hazard ratio (HR) = 1.12; 95% CI: 1.04, 1.20]. The HR was 1.19 (95% CI: 1.03, 1.37) for mortality due to stroke and 1.10 (95% CI: 1.00, 1.21) for mortality due to coronary heart disease. The association between current incense use and cardiovascular mortality appeared to be limited to participants without a history of cardiovascular disease at baseline (HR = 1.16; 95% CI: 1.07, 1.26) but not linked to those with a history (HR = 1.00; 95% CI: 0.86, 1.17). In addition, the association was stronger in never-smokers (HR = 1.12; 95% CI: 1.02, 1.23) and former smokers (HR = 1.19; 95% CI: 1.00, 1.42) than in current smokers (HR = 1.05; 95% CI: 0.91, 1.22). Conclusions: Long-term exposure to incense burning in the home environment was associated with an increased risk of cardiovascular mortality in the study population. Citation: Pan A, Clark ML, Ang LW, Yu MC, Yuan JM, Koh WP. 2014. Incense use and cardiovascular mortality among Chinese in Singapore: The Singapore Chinese Health Study. Environ Health Perspect 122:1279–1284; http://dx.doi.org/10.1289/ehp.1307662

Non-coherent ultra-wideband (UWB) transceiver employing energy detector suffers from degradation in output SNR due to the squarer. A burst mode super-regenerative UWB transceiver which can recover the received signal to rail-to-rail with relatively fewer post-amplification stages is proposed. Unlike other super-regenerative receiver architectures that use oscillator, the proposed architecture employs a positive feedback loop to achieve the super-regeneration of received signal and thus eliminates the need for external resonator or quench signal. The transceiver is suitable for low data rate sensor networks application covering spectrum of 3-5 GHz. Manufactured in CMOS 0.18-μm technology, the transceiver occupies an area of 2.2 mm × 2 mm. By exploiting the duty cycle and the transceiver on-time through the burst mode operation for a given data rate of 1 Mbps, it can achieve transmitter energy efficiency of 0.671 nJ/bit and receiver energy efficiency of 3.54 nJ/bit.

In this study, a series of novel naphthalene compounds were synthesized and screened for their antidepressant-like activities in vitro and in vivo. Their values for two descriptors (ClogP, tPSA) of the blood-brain barrier (BBB) were calculated for early assessment of the central nervous system (CNS) drug-likeness. Seven of them (6d, 6i, 6k, 6o, 6p, 6s and 6t) demonstrated potential protective effects on corticosterone-induced lesion of PC12 cells although they cannot repair the irreversible oxidant injury to PC12 cells by hydrogen peroxide. Compounds with promising neurorestorative activities (6k, 6o and 6p) were further evaluated for their in vivo effects by forced swim test (FST) and open field test (OFT) in C57 mice models. The FST results showed that compounds 6k, 6o and 6p remarkably reduced the immobility time of the tested mice. Among them, compound 6k was the most potent one, much more effective than Agomelatine and comparable to Fluoxetine. The OFT results showed that mice treated with compound 6k traveled a longer distance than those treated with Agomelatine or Fluoxetine, indicating a better general locomotor activity. The paper also proposed a possible binding mode of compound 6k with glucocorticoid receptor by docking study. The in vitro cytotoxicity data on HEK293 and L02 cells suggested compound 6k to be a promising antidepressant candidate for subsequent investigation.

SummaryPurposeData on the effects of cigarette smoking with osteoarthritis (OA) are inconsistent and no study has examined the effect of smoking cessation. We examined smoking status, duration, dosage and cessation in association with risk of total knee replacement (TKR) for severe knee OA among elderly Chinese in Singapore.MethodsWe used data from the Singapore Chinese Health Study, a population-based prospective cohort of 63,257 Chinese men and women aged 45–74 years during enrollment between 1993 and 1998. Detailed information on smoking, current diet and lifestyle factors were obtained through in person interviews. As of 31 December 2011, 1,973 incident TKR cases for severe knee OA had been identified via linkage with nationwide hospital discharge database. We used Cox regression methods to examine smoking in relation to TKR risk with adjustment for age, gender, education, body mass index (BMI), comorbidities and physical activity level.ResultsCompared to never smokers, current smokers had a 51% decrease in risk of TKR [Hazards ratio (HR) = 0.49; 95% confidence interval (CI) = 0.40–0.60]. Among current smokers, there was a very strong dose-dependent association between increasing duration and dosage of smoking with decreasing risk of TKR (P for trend

Background To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. Objective We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. Methods We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). Results At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10 −9 ) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10 −8 ). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP . Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10 −7 ) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10 −6 ). Conclusion By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency.

Summary Objective To understand the seroepidemiology of varicella zoster virus (VZV) in the Singaporean population, based on a paediatric survey conducted in 2008–2010 and the 2010 National Health Survey. The findings were compared with previous studies carried out in 1989–1990, 1993, 1998, and 2004. Methods The paediatric survey involved 1200 subjects; residual diagnostic serum samples were collected from Singapore residents aged 1–17 years at two hospitals. The adult survey involved 3293 subjects; residual serum samples were obtained from Singapore residents aged 18–79 years who had participated in the 2010 National Health Survey. Results The seroprevalence in children under 5 years of age increased from 4% in 1989/1990 to 11.7% in 1998 and 33.2% in 2008–2010. For children aged 5–14 years, the corresponding seroprevalences were 22.8%, 59.5%, and 58.0%. The seroprevalence in children aged 5–14 years in 2008–2010 was not significantly different from that in 1998 ( p =0.721). Among Singapore adults over 25 years of age, the seroprevalence remained consistently high at around 88% from 1998/1990 to 2010. Conclusions Nearly two-thirds of pre-school children, 39.5% of primary school children, and 29% of adolescents aged 13–17 years are susceptible to VZV infection. At this level of immunity, it can be expected that outbreaks will continue to occur unless the varicella vaccine is introduced into the national childhood immunization programme.

Vitamin D deficiency is associated with chronic lung disease. We have previously shown in an in vivo mouse model that maternal vitamin D deficiency is associated with alterations in early life lung structure and function. However, there are limited data to support a relationship between maternal vitamin D deficiency during the early stages of lung development and postnatal lung function in human populations.To assess the association between maternal vitamin D deficiency, postnatal lung function, and asthmatic status in a longitudinal birth cohort.Serum was collected at 16 to 20 weeks' gestation at the time of recruitment in a community-based prospective birth cohort for measurement of vitamin D (25[OH]D). Lung function was assessed by spirometry according to American Thoracic Society guidelines in children at 6 and 14 years of age. Demographic and clinical history data were collected by questionnaire at recruitment and at the follow-up visits.FVC Z-scores in both sexes (β, 0.007 [95% confidence interval (CI), 0.001-0.013]; P = 0.02) and FEV1 Z-scores in girls (β, 0.007 [95% CI, 0.001-0.013]; P = 0.02) were positively associated with maternal serum 25(OH)D at 6 years of age. These associations were mostly absent at 14 years of age. Maternal vitamin D deficiency was positively associated with asthma at 6 years of age but only in boys (odds ratio, 3.03 [95% CI, 1.02-9.02]; P = 0.04).This study supports the notion that vitamin D deficiency during lung development may impact on postnatal lung growth and increase the risk of developing lung disease.

A series of genistein derivatives with carbon spacer-linked alkylbenzylamines were designed, synthesized and tested as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good acetylcholinesterase (AChE) inhibitory activity, with moderate-to-good anti-oxidative activity. Specifically, compounds 10b, 19d and 25d exhibited significant inhibition of β-amyloid (Aβ) aggregation and exhibited metal chelating properties. In particular, 25d inhibited: self-induced Aβ₁₋₄₂ aggregation, Cu(2+)-induced Aβ₁₋₄₂ aggregation, and human AChE-induced Aβ₁₋₄₀ aggregation by 35%, 77.8%, and 36.2%, respectively. Moreover, both kinetic analysis of AChE inhibition and the molecular modeling study suggested that 25d binds simultaneously to catalytic active site and peripheral anionic site of AChE. More importantly, compound 25d disassembled the well-structured Aβ fibrils generated by Cu(2+)-induced Aβ aggregation by 72.1%. Furthermore, the step-down passive avoidance test showed this compound significantly reversed scopolamine-induced memory deficit in mice. These results suggest that 25d may be a promising multifunctional agent for AD treatment.

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31513690/ We describe the epidemiological characteristics, pattern of circulation, and geographical distribution of influenza B viruses and its lineages using data from the Global Influenza B Study. We included over 1.8 million influenza cases occurred in thirty-one countries during 2000-2018. We calculated the proportion of cases caused by influenza B and its lineages; determined the timing of influenza A and B epidemics; compared the age distribution of B/Victoria and B/Yamagata cases; and evaluated the frequency of lineage-level mismatch for the trivalent vaccine. The median proportion of influenza cases caused by influenza B virus was 23.4%, with a tendency (borderline statistical significance, p = 0.060) to be higher in tropical vs. temperate countries. Influenza B was the dominant virus type in about one every seven seasons. In temperate countries, influenza B epidemics occurred on average three weeks later than influenza A epidemics; no consistent pattern emerged in the tropics. The two B lineages caused a comparable proportion of influenza B cases globally, however the B/Yamagata was more frequent in temperate countries, and the B/Victoria in the tropics (p = 0.048). B/Yamagata patients were significantly older than B/Victoria patients in almost all countries. A lineage-level vaccine mismatch was observed in over 40% of seasons in temperate countries and in 30% of seasons in the tropics. The type B virus caused a substantial proportion of influenza infections globally in the 21st century, and its two virus lineages differed in terms of age and geographical distribution of patients. These findings will help inform health policy decisions aiming to reduce disease burden associated with seasonal influenza. info:eu-repo/semantics/publishedVersion

Biological uncertainty remains one of the main sources of uncertainties in proton therapy, and is encapsulated in a scalar quantity known as relative biological effective (RBE). It is currently recognised that a constant RBE of 1.1 is not consistent with radiobiological experiment and may lead to sub-optimal exploitation of the benefits of proton therapy. To overcome this problem, several RBE models have been developed, and in most of these models, there is a dependence of RBE on dose-averaged linear energy transfer (LET), [Formula: see text]. In this work, we show that the [Formula: see text] estimation in these models during the data-fitting (or parameter estimation) phase could be subjected to a huge uncertainty due to not taking into account cellular materials during simulation, and this uncertainty can propagate down to the resulting RBE models. The dosimetric impact of this [Formula: see text] uncertainty is then evaluated on a simple clinical spread out Bragg peak (SOBP) and a prostate example. Our simulation shows that [Formula: see text] uncertainty due to the use of water as cellular material is non-negligible under low [Formula: see text] and low dose (2 Gy), and can be neglected otherwise. Thus, this study indicates that further dose and range margins may be required for low [Formula: see text] target under low dose. This is due to greater uncertainties in RBE model associated with incomplete knowledge of cellular composition for [Formula: see text] computation.

Experimental and epidemiologic data suggest that carotenoids in vegetables and fruits may benefit bone health due to their antioxidant properties. The relationship between dietary total and specific carotenoids, as well as vegetables and fruits, and risk of hip fracture was examined among Chinese in Singapore. We used data from the Singapore Chinese Health Study, a prospective cohort of 63,257 men and women who were of ages 45 to 74 years between 1993 and 1998. At recruitment, subjects were interviewed on lifestyle factors and medical history. Usual diet was measured using a validated food frequency questionnaire. During a mean follow-up of 9.9 years, we identified 1630 hip fracture incident cases. Among men, consumption of vegetables was associated with lower hip fracture risk. Similarly, dietary total carotenoids and specific carotenoids, α-carotene, β-carotene, and lutein/zeaxanthin were inversely associated with hip fracture risk. Compared to men in the lowest quartile of nutrient density, men in the highest quartile had statistically significant 26% to 39% risk reduction (all p for trend

In pursuit of utilizing combinatorial peptide libraries on beads, rapid and robust screening is one of the key steps for the success of high-throughput process. We have introduced improved structural features that greatly facilitate a MALDI-MS/MS-based sequencing, associated with easy and fast synthesis and analysis of such libraries. Whilst commonly used MS-based analysis involves in sophisticated procedures such as ladder synthesis, encoding tags are not required in our MS/MS-based sequencing platform. Fragment peaks in an acquired MS/MS should be outstanding in line with correct identification of parent mass in the preceding MS. To meet these requirements a one-bead-one-compound (OBOC) peptide library was designed by placing a positively charged arginine at C-terminus. As well as enhancing the overall ionization efficiency, arginine appended in all y-ion fragments generates a series of doublet peaks under MS/MS environments, which can speed up the sequencing process in conjunction with high accuracy. It is another strong benefit that the designed library significantly suppresses the adverse formation of sodium ion adducts, which seriously jeopardizes the sequencing, especially of peptides containing negatively charged amino acids. A peptide library constructed with D-amino acids was applied to screening against a clinically significant biomarker, C-reactive protein (CRP). Through the screening of focused libraries narrowed down from a comprehensive library, several hexamer peptide ligands were successfully identified and their binding affinity and specificity towards CRP were validated by surface plasmon resonance (SPR) and dot blot experiments.