55 results on '"Lim LK"'
Search Results
2. Outcome of a grocery voucher incentive scheme for low-income tuberculosis patients on directly observed therapy in Singapore
- Author
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Chua, AP, primary, Lim, LK, additional, Ng, H, additional, Chee, CB, additional, and Wang, YT, additional
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- 2015
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3. Maternal body mass index in the first trimester and risk of caesarean section in nulliparous women in spontaneous labour
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Bergholt, T, Lim, LK, Jørgensen, Jan Stener, and Robson, MS
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- 2007
4. Intra-articular glucocorticoid injections in patients with juvenile idiopathic arthritis in a Singapore hospital
- Author
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Leow, OM, primary, Lim, LK, additional, Ooi, PL, additional, Shek, LP, additional, Ang, EY, additional, and Son, MB, additional
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- 2014
- Full Text
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5. Maternal body mass index in the first trimester and risk of cesarean delivery in nulliparous women in spontaneous labor.
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Bergholt, T, Lim, LK, Jørgensen, JS, Robson, MS, Bergholt, T, Lim, LK, Jørgensen, JS, and Robson, MS
- Published
- 2007
6. Maternal body mass index in the first trimester and risk of cesarean delivery in nulliparous women in spontaneous labor.
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Bergholt T, Lim LK, Jørgensen JS, and Robson MS
- Abstract
A 6-year prospective observational cohort study of 4341 women in London compared the incidence of cesarean delivery with maternal body mass index. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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7. Mesoscopic fluctuations in entanglement dynamics.
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Lim LK, Lou C, and Tian C
- Abstract
Understanding fluctuation phenomena plays a dominant role in the development of many-body physics. The time evolution of entanglement is essential to a broad range of subjects in many-body physics, ranging from exotic quantum matter to quantum thermalization. Stemming from various dynamical processes of information, fluctuations in entanglement evolution differ conceptually from out-of-equilibrium fluctuations of traditional physical quantities. Their studies remain elusive. Here we uncover an emergent random structure in the evolution of the many-body wavefunction in two classes of integrable-either interacting or noninteracting-lattice models. It gives rise to out-of-equilibrium entanglement fluctuations which fall into the paradigm of mesoscopic fluctuations of wave interference origin. Specifically, the entanglement entropy variance obeys a universal scaling law in each class, and the full distribution displays a sub-Gaussian upper and a sub-Gamma lower tail. These statistics are independent of both the system's microscopic details and the choice of entanglement probes, and broaden the class of mesoscopic universalities. They have practical implications for controlling entanglement in mesoscopic devices., (© 2024. The Author(s).)
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- 2024
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8. The yield of tuberculosis contact investigation on relapsed TB patients and analysis of associated risk factors: Singapore's experience.
- Author
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Kyaw WM, Lim LK, Tay JY, Cutter JL, and Ng DHL
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- Humans, Contact Tracing, Retrospective Studies, Singapore epidemiology, Tuberculosis epidemiology, Tuberculosis diagnosis, Mycobacterium tuberculosis, Latent Tuberculosis epidemiology
- Abstract
The yield of contact investigation on relapsed tuberculosis (TB) cases can guide strategies and resource allocation in the TB control programme. We conducted a retrospective cohort study to review the yield of contact investigation in relapsed TB cases and identify factors associated with TB infection (TBI) among close contacts of relapsed TB cases notified between 2018 and 2022 in Singapore. TB infection positivity was higher among contacts of relapsed cases which were culture-positive for Mycobacterium tuberculosis complex compared to those who were only polymerase chain reaction (PCR)-positive (14.8% vs. 12.3%). On multivariate analysis, after adjusting for age and gender of the index, gender, and existing comorbidities of contacts, factors independently associated with TBI were culture and smear positivity of the index (AOR 1.41, 95%CI 1.02-1.94), higher odds with every 10 years of increase in age compared to contacts below aged 30, contacts who were not Singapore residents (AOR 2.09, 95%CI 1.46-2.97), and household contacts (AOR 2.19, 95%CI 1.44-3.34). Although the yield of screening was higher for those who were culture-positive compared to only PCR-positive relapsed cases, contact tracing for only PCR-positive cases may still be important in a country with moderate TB incidence, should resources allow.
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- 2024
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9. Heterogenous antibody and T-cell responses to SARS-CoV-2 mRNA vaccines among immunocompromised young people.
- Author
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Lu L, Chan CY, Chan-Ng PPL, Than M, Tan PSY, Lim LK, Teo S, Lau PY, Ng KH, Ang EY, Karthik SV, Aw MM, Tambyah PA, Yap HK, and Lee BW
- Subjects
- Humans, Adolescent, COVID-19 Vaccines, T-Lymphocytes, Antibodies, SARS-CoV-2 genetics, COVID-19 prevention & control
- Published
- 2023
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10. Yield of Cardiac Magnetic Resonance Imaging in a Preparticipation Cohort of Young Asian Males With T Wave Inversion.
- Author
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Thiagarajan N, Ho WHH, Lim DYZ, Loo WTW, Shen G, Sundar V, Lim HY, Lim LK, Chua TSJ, Lim PCY, Tang HC, Koh CH, Yeo TJ, and Chong DTT
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- Male, Humans, Magnetic Resonance Imaging, Cohort Studies, Electrocardiography, Mass Screening methods, Athletes, Arrhythmias, Cardiac, Death, Sudden, Cardiac
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- 2022
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11. Janus kinase inhibition in induction treatment of anti-MDA5 juvenile dermatomyositis-associated rapidly progressive interstitial lung disease.
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Chan Ng PLP, Mopur A, Goh DYT, Ramamurthy MB, Lim MTC, Lim LK, Ooi PL, and Ang EY
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- Child, Dermatomyositis complications, Humans, Lung Diseases, Interstitial diagnostic imaging, Lung Diseases, Interstitial etiology, Lung Diseases, Interstitial pathology, Male, Remission Induction methods, Dermatomyositis drug therapy, Janus Kinase Inhibitors administration & dosage, Lung Diseases, Interstitial drug therapy, Piperidines administration & dosage, Pyrimidines administration & dosage
- Abstract
Tofacitinib has an important role in pediatric rapidly progressive interstitial lung disease (ILD) associated with juvenile dermatomyositis (JDM), an otherwise potentially fatal condition. It may be useful in induction of remission and can be used safely to maintain remission. Serum ferritin and interleukin-18 are useful markers for tracking activity and response of JDM-associated ILD., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)
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- 2022
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12. Irreducible anteromedial radial head fracture-dislocation: value of pre-operative magnetic resonance imaging.
- Author
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Lim LK and Beh J
- Abstract
We describe a case of an anteromedial fracture-dislocation of the radial head in an adult patient, which was initially irreducible using closed means, and remained challenging to reduce despite open surgery. Further advanced CT/MRI revealed entrapment of the radial head due to the interposition of the brachialis tendon posteriorly, thereby preventing sustained reduction. While three other cases of irreducible anteromedial radial head dislocation due to the brachialis tendon have been reported in the English surgical literature, none of the imaging findings have been described in the radiological literature. Only one other case published in a surgical journal briefly demonstrated pre-operative MRI imaging. We would like to share the value of pre-operative MRI in this rare presentation, which would be helpful in diagnosing not only cases with interposition of the brachialis tendon, but potentially other types of soft tissue interposition which also limit closed reduction. To the best of the authors' knowledge, this would be the first report on the imaging findings in a radiological journal. Awareness of this phenomenon would assist radiologists in the diagnosis and management of this rare condition., (© 2021 The Authors. Published by the British Institute of Radiology.)
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- 2020
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13. A "BREACH" Too Far: Exertional Rhabdomyolysis in the Elbow Flexor Muscles.
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Lim LK, Sia DSY, Hallinan JTPD, and Zhang J
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- Acute Disease, Adult, Elbow Joint pathology, Humans, Male, Muscle, Skeletal pathology, Physical Exertion, Rhabdomyolysis etiology, Elbow Joint diagnostic imaging, Muscle, Skeletal diagnostic imaging, Rhabdomyolysis diagnostic imaging, Weight Lifting
- Published
- 2019
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14. Elastic Scattering Time of Matter Waves in Disordered Potentials.
- Author
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Richard J, Lim LK, Denechaud V, Volchkov VV, Lecoutre B, Mukhtar M, Jendrzejewski F, Aspect A, Signoles A, Sanchez-Palencia L, and Josse V
- Abstract
We report on an extensive study of the elastic scattering time τ_{s} of matter waves in optical disordered potentials. Using direct experimental measurements, numerical simulations, and comparison with the first-order Born approximation based on the knowledge of the disorder properties, we explore the behavior of τ_{s} over more than 3 orders of magnitude, ranging from the weak to the strong scattering regime. We study in detail the location of the crossover and, as a main result, we reveal the strong influence of the disorder statistics, especially on the relevance of the widely used Ioffe-Regel-like criterion kl_{s}∼1. While it is found to be relevant for Gaussian-distributed disordered potentials, we observe significant deviations for laser speckle disorders that are commonly used with ultracold atoms. Our results are crucial for connecting experimental investigation of complex transport phenomena, such as Anderson localization, to microscopic theories.
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- 2019
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15. Two-Year Clinical and Functional Outcomes of an Asian Cohort at Ultra-High Risk of Psychosis.
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Chan CT, Abdin E, Subramaniam M, Tay SA, Lim LK, and Verma S
- Abstract
Background: To determine the 2-year clinical and functional outcomes of an Asian cohort at ultra-high risk (UHR) of psychosis. Method: This was a longitudinal study with a follow-up period of 2 years on 255 help-seeking adolescents and young adults at UHR of psychosis managed by a multi-disciplinary mental health team in Singapore. Clients received case management, psychosocial, and pharmacological treatment as appropriate. Data comprising symptom and functional outcomes were collected over the observation period by trained clinicians and psychiatrists. Results: The 2-year psychosis transition rate was 16.9%, with a median time to transition of 168 days. After 2 years, 14.5% of the subjects had persistent at-risk symptoms while 7.5% developed other non-psychotic psychiatric disorders. 38.4% of the cohort had recovered and was discharged from mental health services. The entire cohort's functioning improved as reflected by an increase in the score of the Social and Occupational Functioning Assessment Scale during the follow-up period. Predictors to psychosis transition included low education level, baseline unemployment, a history of violence, and brief limited intermittent psychotic symptoms, while male gender predicted the persistence of UHR state, or the development of non-psychotic disorders. Conclusion: Use of the current UHR criteria allows us to identify individuals who are at imminent risk of developing not just psychosis, but also those who may develop other mental health disorders. Future research should include identifying the needs of those who do not transition to psychosis, while continuing to refine on ways to improve the UHR prediction algorithm for psychosis.
- Published
- 2019
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16. Winding Vector: How to Annihilate Two Dirac Points with the Same Charge.
- Author
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Montambaux G, Lim LK, Fuchs JN, and Piéchon F
- Abstract
The merging or emergence of a pair of Dirac points may be classified according to whether the winding numbers which characterize them are opposite (+- scenario) or identical (++ scenario). From the touching point between two parabolic bands (one of them can be flat), two Dirac points with the same winding number emerge under appropriate distortion (interaction, etc.), following the ++ scenario. Under further distortion, these Dirac points merge following the +- scenario, that is corresponding to opposite winding numbers. This apparent contradiction is solved by the fact that the winding number is actually defined around a unit vector on the Bloch sphere and that this vector rotates during the motion of the Dirac points. This is shown here within the simplest two-band lattice model (Mielke) exhibiting a flat band. We argue on several examples that the evolution between the two scenarios is general.
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- 2018
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17. The role of chronic viral hepatitis on tuberculosis treatment interruption.
- Author
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Chua AP, Lim LK, Gan SH, Chee CB, and Wang YT
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- Adult, Aged, Antitubercular Agents adverse effects, Chemical and Drug Induced Liver Injury diagnosis, Chemical and Drug Induced Liver Injury epidemiology, Directly Observed Therapy, Female, Hepatitis B diagnosis, Hepatitis C diagnosis, Humans, Liver Function Tests, Logistic Models, Male, Middle Aged, Multivariate Analysis, Prevalence, Risk Assessment, Risk Factors, Singapore epidemiology, Time Factors, Tuberculosis epidemiology, Coinfection, Hepatitis B epidemiology, Hepatitis C epidemiology, Tuberculosis drug therapy
- Abstract
Background: Tuberculosis (TB) drug-induced liver injury (TB-DILI) usually occurs within 8 weeks of anti-tuberculosis drug initiation. In Singapore, we suspected that the onset of TB drug-induced transaminitis may be confounded with hepatitis C virus (HCV) and hepatitis B (HBV) virus co-infection., Objective: To determine the impact of HCV/HBV co-infection on the course of treatment in patients with TB treatment interrupted due to transaminitis., Design: TB patients with treatment interruption during 2013-2014 were identified through the Singapore national TB registry. Case notes of those with transaminitis were perused., Results: Of 3860 TB patients notified, 140 had suspected TB-DILI. Of these, respectively 20/140 (14.3%) and 16/140 (11.4%) were HCV- or HBV-positive. The median time to treatment interruption/transaminitis was 5 weeks vs. 9.9 weeks and 9.6 weeks for transaminitis patients without chronic liver disease and with HCV/HBV co-infection ( P < 0.01). Multivariate logistic regression analysis revealed that having HCV/HBV co-infection was associated with treatment interruption occurring beyond 8 weeks (adjusted OR [aOR] 4.06, 95%CI 1.28-12.85); HCV transaminitis patients were more likely to take 10 months to complete anti-tuberculosis treatment (aOR 5.11, 95%CI 1.21-21.67) than those without chronic liver disease., Conclusion: TB treatment interruption due to transaminitis in HCV/HBV co-infected patients occurred later than in those without liver disease. Most had completed 2 months of pyrazinamide-containing intensive phase treatment before the onset of transaminitis.
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- 2018
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18. Time-resolved characteristics of deuteron-beam generated by plasma focus discharge.
- Author
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Lim LK, Yap SL, and Bradley DA
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- Equipment Design, Microscopy, Time and Motion Studies, Deuterium, Plasma Gases
- Abstract
The plasma focus device discussed herein is a Z-pinch pulsed-plasma arrangement. In this, the plasma is heated and compressed into a cylindrical column, producing a typical density of > 1025 particles/m3 and a temperature of (1-3) × 107 oC. The plasma focus has been widely investigated as a radiation source, including as ion-beams, electron-beams and as a source of x-ray and neutron production, providing considerable scope for use in a variety of technological situations. Thus said, the nature of the radiation emission depends on the dynamics of the plasma pinch. In this study of the characteristics of deuteron-beam emission, in terms of energy, fluence and angular distribution were analyzed. The 2.7 kJ plasma focus discharge has been made to operate at a pressure of less than 1 mbar rather than at its more conventional operating pressure of a few mbar. Faraday cup were used to determine deuteron-beam energy and deuteron-beam fluence per shot while CR-39 solid-state nuclear track detectors were employed in studying the angular distribution of deuteron emission. Beam energy and deuteron-beam fluence per shot have been found to be pressure dependent. The largest value of average deuteron energy measured for present conditions was found to be (52 ± 7) keV, while the deuteron-beam fluence per shot was of the order of 1015 ions/m2 when operated at a pressure of 0.2 mbar. The deuteron-beam emission is in the forward direction and is observed to be highly anisotropic.
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- 2018
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19. Highly sensitive and scalable AAO-based nano-fibre SERS substrate for sensing application.
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Lim LK, Ng BK, Fu CY, Tobing LYM, and Zhang DH
- Abstract
Well-ordered periodic nanostructures are excellent substrates for many surface-enhanced Raman spectroscopy (SERS) applications. Conventional fabrication approaches such as high precision electron beam lithography or focused ion beam produce high resolution nano-features with great reproducibility at the expense of low throughput. In this work, a highly sensitive and scalable AAO-nano-fibre (ANF) SERS substrate is demonstrated by optimising the second anodisation time of the standard two-step anodisation of aluminium and performing an additional wet etching step on the resulting AAO substrate. The optimised ANF substrate exhibits SERS sensitivity that surpasses the AAO nanoholes and the metal-film-on-nanoparticles substrates. A detection limit of 0.1 nM is achieved with a signal-to-noise ratio of 2.6-3 using a low excitation power of 0.1 mW. The ANF substrate exhibits an enhancement factor of 9.28 × 106 and a standard deviation of no more than 8%. The results indicate that the highly sensitive and scalable ANF substrate is a promising substrate for commercial SERS application.
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- 2017
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20. Pseudospin Vortex Ring with a Nodal Line in Three Dimensions.
- Author
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Lim LK and Moessner R
- Abstract
We present a model of a topological semimetal in three dimensions whose energy spectrum exhibits a nodal line acting as a vortex ring; this in turn is linked by a pseudospin structure akin to that of a smoke ring. Contrary to a Weyl point node spectrum, the vortex ring gives rise to Skyrmionic pseudospin patterns in cuts on both sides of the nodal ring plane; this pattern covers the full Brillouin zone, thus leading to a fully extended chiral Fermi arc and a new, "maximal," anomalous Hall effect in a 3D semimetal. Tuning a model parameter shrinks the vortex ring until it vanishes, giving way to a pair of Weyl nodes of opposite chirality. This establishes a connection between two distinct momentum-space topologies-that of a vortex ring (a circle of singularity) and a monopole-antimonopole pair (two point singularities). We present the model both as a low-energy continuum and a two-band tight-binding lattice model. Its simplicity permits an analytical computation of its Landau level spectrum.
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- 2017
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21. Independent Mobility Achieved through a Wireless Brain-Machine Interface.
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Libedinsky C, So R, Xu Z, Kyar TK, Ho D, Lim C, Chan L, Chua Y, Yao L, Cheong JH, Lee JH, Vishal KV, Guo Y, Chen ZN, Lim LK, Li P, Liu L, Zou X, Ang KK, Gao Y, Ng WH, Han BS, Chng K, Guan C, Je M, and Yen SC
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- Algorithms, Animals, Behavior, Animal, Macaca fascicularis, Motor Neurons cytology, Software, Brain-Computer Interfaces, Movement, Wireless Technology
- Abstract
Individuals with tetraplegia lack independent mobility, making them highly dependent on others to move from one place to another. Here, we describe how two macaques were able to use a wireless integrated system to control a robotic platform, over which they were sitting, to achieve independent mobility using the neuronal activity in their motor cortices. The activity of populations of single neurons was recorded using multiple electrode arrays implanted in the arm region of primary motor cortex, and decoded to achieve brain control of the platform. We found that free-running brain control of the platform (which was not equipped with any machine intelligence) was fast and accurate, resembling the performance achieved using joystick control. The decoding algorithms can be trained in the absence of joystick movements, as would be required for use by tetraplegic individuals, demonstrating that the non-human primate model is a good pre-clinical model for developing such a cortically-controlled movement prosthetic. Interestingly, we found that the response properties of some neurons differed greatly depending on the mode of control (joystick or brain control), suggesting different roles for these neurons in encoding movement intention and movement execution. These results demonstrate that independent mobility can be achieved without first training on prescribed motor movements, opening the door for the implementation of this technology in persons with tetraplegia., Competing Interests: The authors have declared that no competing interests exist.
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- 2016
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22. Support for Wellness Achievement Programme (SWAP): clinical and demographic characteristics of young people with at-risk mental state in Singapore.
- Author
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Tay SA, Yuen S, Lim LK, Pariyasami S, Rao S, Poon LY, and Verma S
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- Comorbidity, Demography, Female, Humans, Male, Psychotherapy, Psychotic Disorders diagnosis, Psychotic Disorders drug therapy, Risk Assessment, Singapore epidemiology, Young Adult, Anxiety Disorders epidemiology, Depression epidemiology, Early Medical Intervention, Psychotic Disorders epidemiology, Psychotic Disorders therapy
- Abstract
Aim: Individuals with at-risk mental state (ARMS) experience subtle changes in thinking, behaviour and emotion before their first psychotic episode. Research has shown intervention provided during this period could delay, reduce, or even prevent the conversion to psychosis. In March 2008, the Support for Wellness Achievement Programme (SWAP) was launched for the assessment and treatment of patients with ARMS in Singapore. This paper examines the sociodemographic and clinical characteristics of patients at baseline., Methods: In total, 384 patients were screened and 155 were accepted into the service. All patients were evaluated using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Severity of psychopathology was assessed by Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and levels of functioning were assessed using the Social and Occupational Functioning Assessment Scale (SOFAS)., Results: The mean age of the patients was 21.0 years (standard deviation (SD) = 3.5) and 69.7% were men, 42.6% had a relative with a mental health problem and 69.8% met the criterion solely for the attenuated symptoms group. The mean PANSS total score was 48.9 (SD = 10.8). There was also a high rate of comorbidity with 34.8% having depression and 20.0% had anxiety disorders. The mean baseline SOFAS score was 51.5 (SD = 9.8), indicating moderate impairment in their functioning., Conclusion: These preliminary findings have highlighted that our data are similar to other ARMS programmes, and in addition to the management of ARMS, there is a need to treat both the comorbidities and impairment in social occupational functioning., (© 2014 Wiley Publishing Asia Pty Ltd.)
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- 2015
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23. Time series analysis of demographic and temporal trends of tuberculosis in Singapore.
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Wah W, Das S, Earnest A, Lim LK, Chee CB, Cook AR, Wang YT, Win KM, Ong ME, and Hsu LY
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- Adolescent, Adult, Aged, Aged, 80 and over, Forecasting, Humans, Incidence, Middle Aged, Models, Theoretical, Retrospective Studies, Singapore epidemiology, Socioeconomic Factors, Time Factors, Young Adult, Demography trends, Emigrants and Immigrants statistics & numerical data, Population Groups statistics & numerical data, Tuberculosis epidemiology
- Abstract
Background: Singapore is an intermediate tuberculosis (TB) incidence country, with a recent rise in TB incidence from 2008, after a fall in incidence since 1998. This study identified population characteristics that were associated with the recent increase in TB cases, and built a predictive model of TB risk in Singapore., Methods: Retrospective time series analysis was used to study TB notification data collected from 1995 to 2011 from the Singapore Tuberculosis Elimination Program (STEP) registry. A predictive model was developed based on the data collected from 1995 to 2010 and validated using the data collected in 2011., Results: There was a significant difference in demographic characteristics between resident and non-resident TB cases. TB risk was higher in non-residents than in residents throughout the period. We found no significant association between demographic and macro-economic factors and annual incidence of TB with or without adjusting for the population-at-risk. Despite growing non-resident population, there was a significant decrease in the non-resident TB risk (p < 0.0001). However, there was no evidence of trend in the resident TB risk over this time period, though differences between different demographic groups were apparent with ethnic minorities experiencing higher incidence rates., Conclusion: The study found that despite an increasing size of non-resident population, TB risk among non-residents was decreasing at a rate of about 3% per year. There was an apparent seasonality in the TB reporting.
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- 2014
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24. Mass and chirality inversion of a Dirac cone pair in Stückelberg interferometry.
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Lim LK, Fuchs JN, and Montambaux G
- Abstract
We show that a Stückelberg interferometer made of two massive Dirac cones can reveal information on band eigenstates such as the chirality and mass sign of the cones. For a given spectrum with two gapped cones, we propose several low-energy Hamiltonians differing by their eigenstates properties. The corresponding interband transition probability is affected by such differences in its interference fringes being shifted by a new phase of geometrical origin. This phase can be a useful bulk probe for topological band structures realized with artificial crystals.
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- 2014
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25. Surveillance of tuberculosis treatment outcomes of Singapore citizens and permanent residents, 2002-2011.
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Chee CB, Lim LK, KhinMar KW, Han KY, Gan SH, Cutter J, Ooi PL, and Wang YT
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- Cause of Death, Directly Observed Therapy, Emigration and Immigration, Humans, Incidence, Patient Dropouts, Population Surveillance, Singapore epidemiology, Time Factors, Treatment Outcome, Tuberculosis diagnosis, Tuberculosis mortality, Antitubercular Agents therapeutic use, Emigrants and Immigrants, Medication Adherence, Residence Characteristics, Tuberculosis drug therapy
- Abstract
Setting: Singapore, which had a tuberculosis (TB) incidence rate of 41 per 100,000 resident population in 2011., Objective: To report the outcomes of Singapore citizens and permanent residents treated for TB from 2002 to 2011., Methods: A computerised treatment surveillance module (TSM) was launched in 2001 to track the progress and outcome of TB patients nationally. Physicians were required to submit an electronic or paper return for every patient at each clinic visit. Treatment adherence, drugs prescribed, treatment delivery mode and final outcome, specified as 'completed treatment', 'lost to follow-up', 'death', 'transferred out', 'permanent cessation of treatment' and 'still on treatment/no final outcome', were captured. Quarterly cohort outcomes at 12-15 months after starting treatment were combined to generate annual treatment outcomes., Results: Treatment completion rates increased from 73.4% to 82.8%. The proportion of patients lost to follow-up decreased from 3.4% to 1.7%, while that of patients still on treatment or with no final outcome decreased from 10.5% to 4.4%. The death rate ranged between 10.2% and 11.7%; the majority were not attributed to TB., Conclusion: TB treatment completion among Singapore citizens and permanent residents has improved since 2002 as the likely result of the TSM and other initiatives introduced over the past decade.
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- 2014
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26. Can CT angiography rule out aneurysmal subarachnoid haemorrhage in CT scan-negative subarachnoid haemorrhage patients?
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Lim LK, Dowling RJ, Yan B, and Mitchell PJ
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- Angiography, Digital Subtraction, Humans, Intracranial Aneurysm diagnostic imaging, Cerebral Angiography methods, Subarachnoid Hemorrhage diagnostic imaging, Tomography, X-Ray Computed methods
- Abstract
Current management guidelines for CT scan-negative subarachnoid haemorrhage (SAH) patients recommend cerebral digital subtraction angiography (DSA). We aimed to investigate the utility of CT angiography (CTA) as a substitute for DSA in these patients. We included patients who presented with SAH confirmed by spectrophotometric xanthochromia analysis of cerebrospinal fluid (CSF) whereby the CT scan was negative. Electronic records were reviewed to collect data on non-contrast CT scan, CTA and DSA results. Patients without DSA or with other explanations for CSF xanthochromia were excluded. Sixty-three patients with CT scan-negative SAH were included. The diagnosis of SAH was confirmed by CSF analysis. All 63 patients underwent both DSA and CTA. Using DSA as the benchmark, CTA demonstrated a negative predictive value, positive predictive value, sensitivity and specificity of 98%, 82%, 90% and 96%, respectively, for the detection of intracranial aneurysms. CTA correctly identified patients in whom there were no underlying aneurysms responsible for SAH, with one patient with suspected dissection referred for further evaluation using MRI and DSA., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
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- 2014
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27. Notified tuberculosis among Singapore residents by ethnicity, 2002-2011.
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Lim LK, Enarson DA, Reid AJ, Satyanarayana S, Cutter J, Kyi Win KM, Chee CB, and Wang YT
- Abstract
Setting: The National Tuberculosis Programme in Singapore where, among resident cases, higher tuberculosis (TB) rates have been reported in ethnic Malays., Objective: To describe the socio-demographic and clinical characteristics of resident TB cases by ethnicity, and to assess whether Malays differ from other groups in terms of the above parameters., Design: Cross-sectional review of records from the tuberculosis registry's electronic database., Results: Among 15 622 resident cases notified, 72.2% were Chinese, 18.7% Malay, 5.8% Indian and 2.9% were from other minorities. Compared to other ethnicities, Malays were more likely to be incarcerated at the time of notification (odds ratio [OR] 3.70, 95%CI 3.03-4.52) and clustered at the same residential address (OR 1.65, 95%CI 1.44-1.89), but were less likely to be aged ≥65 years (OR 0.61, 95%CI 0.54-0.70) or to reside in high-cost housing (OR 0.11, 95%CI 0.07-0.17). In terms of disease characteristics, more Malays had diabetes mellitus (OR 1.54, 1.37-1.73), a highly-positive acid-fast bacilli smear (OR 1.64, 95%CI 1.47-1.83) and cavitary disease on chest X-ray (OR 1.41, 95%CI 1.28-1.55)., Conclusion: Compared to other ethnicities, reported TB cases among Malays were more severe and were likely to be more infectious. Increased vigilance in case management and contact investigations, as well as an improvement in the socio-economic conditions of this community, are required to reduce TB rates in this ethnic group.
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- 2013
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28. Molecular epidemiology of Mycobacterium tuberculosis complex in Singapore, 2006-2012.
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Lim LK, Sng LH, Win W, Chee CB, Hsu LY, Mak E, Earnest A, Ong ME, Cutter J, and Wang YT
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- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Infant, Newborn, Male, Middle Aged, Molecular Epidemiology, Mycobacterium tuberculosis physiology, Singapore epidemiology, Tuberculosis transmission, Young Adult, Mycobacterium tuberculosis genetics, Tuberculosis epidemiology
- Abstract
Background: Tuberculosis remains common in Singapore, increasing in incidence since 2008. We attempted to determine the molecular epidemiology of Mycobacterium tuberculosis complex (MTC) isolates locally, identifying major circulating genotypes and obtaining a glimpse of transmission dynamics., Methodology: Non-duplicate MTC isolates archived between 2006 and 2012 at the larger clinical tuberculosis laboratory in Singapore were sampled for spoligotyping and MIRU-VNTR typing, with case data obtained from the Singapore Tuberculosis Elimination Program registry database. Isolates between 2008 and 2012 were selected because of either multidrug-resistance or potential epidemiological linkage, whereas earlier isolates were randomly selected. Separate analyses were performed for the early (2006-2007) and later (2008-2012) study phases in view of potential selection bias., Principal Findings: A total of 1,612 MTC isolates were typed, constituting 13.1% of all culture-positive tuberculosis cases during this period. Multidrug-resistance was present in 91 (5.6%) isolates - higher than the national prevalence in view of selection bias. The majority of isolates belonged to the Beijing (45.8%) and EAI (22.8%) lineages. There were 347 (30.7%) and 133 (27.5%) cases clustered by combined spoligotyping and MIRU-VNTR typing from the earlier and later phases respectively. Patients within these clusters tended to be of Chinese ethnicity, Singapore resident, and have isolates belonging to the Beijing lineage. A review of prior contact investigation results for all patients with clustered isolates failed to reveal epidemiological links for the majority, suggesting either unknown transmission networks or inadequate specificity of the molecular typing methods in a country with a moderate incidence of tuberculosis., Conclusion: Our work demonstrates that Singapore has a large and heterogeneous distribution of MTC strains, and with possible cross-transmission over the past few years based on our molecular typing results. A universal MTC typing program coupled with enhanced contact investigations may be useful in further understanding the transmission dynamics of tuberculosis locally.
- Published
- 2013
- Full Text
- View/download PDF
29. Support for Wellness Achievement Programme (SWAP): A service for individuals with at-risk mental state in singapore.
- Author
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Rao S, Pariyasami S, Tay SA, Lim LK, Yuen S, Poon LY, Lee H, and Verma S
- Subjects
- Humans, Mental Disorders, Mental Health Services, Risk, Singapore, Achievement, Health Promotion
- Published
- 2013
30. Bloch-Zener oscillations across a merging transition of Dirac points.
- Author
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Lim LK, Fuchs JN, and Montambaux G
- Abstract
Bloch oscillations are a powerful tool to investigate spectra with Dirac points. By varying band parameters, Dirac points can be manipulated and merged at a topological transition toward a gapped phase. Under a constant force, a Fermi sea initially in the lower band performs Bloch oscillations and may Zener tunnel to the upper band mostly at the location of the Dirac points. The tunneling probability is computed from the low-energy universal Hamiltonian describing the vicinity of the merging. The agreement with a recent experiment on cold atoms in an optical lattice is very good.
- Published
- 2012
- Full Text
- View/download PDF
31. Specialist pediatric dialysis nursing improves outcomes in children on chronic peritoneal dialysis.
- Author
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Gunasekara WD, Ng KH, Chan YH, Aragon E, Foong PP, Lau YW, Lim LK, Liew CW, Yeo WS, and Yap HK
- Subjects
- Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Peritoneal Dialysis adverse effects, Peritonitis epidemiology, Peritonitis etiology, Treatment Outcome, Pediatric Nursing statistics & numerical data, Peritoneal Dialysis nursing
- Abstract
Chronic peritoneal dialysis (PD) for children in Singapore was instituted in 1988 at the National University Hospital with adult nurses providing dialysis services during the first 10 years. In 1998, a specialist pediatric dialysis nursing team was recruited. This study was conducted to determine the impact of dialysis nursing service on PD-related outcomes during the two nursing periods. Comparing the adult (group 1) and pediatric (group 2) nursing periods, the peritonitis rate was significantly higher in group 1 (RR 1.90; 95%CI 1.27-2.84), and this association did not weaken after adjusting for age, gender, and exit site infections. Exit site infection rate (RR 2.16; 95%CI 1.44-3.23), risk of peritonitis during the first year (RR 3.65; 95%CI 1.68-7.90), and multiple peritonitis attacks (RR 2.45; 95%CI 1.32-4.55) were higher in group 1. The peritonitis rates for adult patients cared for by the same adult nurses declined sharply from 1.05 episodes per patient-year between 1989 and 1992 to 0.41 episodes per patient-year between 1995 and 1997, however the corresponding pediatric rates did not change (1.48 to 1.06 episodes per patient-year, respectively) until the second era when specialized pediatric nurses were available. In conclusion, establishment of a specialist pediatric dialysis nursing team resulted in significant improvement in infection-related PD outcomes.
- Published
- 2010
- Full Text
- View/download PDF
32. Developing the "NUS Tummy Dummy", a low-cost simulator to teach medical students to perform the abdominal examination.
- Author
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Mahaboob S, Lim LK, Ng CL, Ho QY, Leow ME, and Lim EC
- Subjects
- Humans, Singapore, Teaching methods, Abdomen physiology, Manikins, Physical Examination methods, Students, Medical
- Published
- 2010
33. Simulating inadequate dialysis and its correction using an individualized patient-derived nomogram.
- Author
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Lee AJ, Kho K, Chia KS, Oi TL, Yap C, Foong PP, Lau YW, Lim LK, Aragon E, Liew CW, and Yap HK
- Subjects
- Adolescent, Creatinine blood, Creatinine urine, Female, Glucose pharmacokinetics, Humans, Kinetics, Longitudinal Studies, Male, Metabolic Clearance Rate, Models, Statistical, Monitoring, Physiologic, Peritoneum metabolism, Prescriptions, Therapy, Computer-Assisted, Urea blood, Urea urine, Computer Simulation, Nomograms, Patient Compliance, Peritoneal Dialysis, Peritoneal Dialysis, Continuous Ambulatory
- Abstract
Computerized kinetic modeling is a valuable automated peritoneal dialysis (APD) prescription tool for optimizing dialysis adequacy. However, non-compliance results in failure to achieve adequacy targets. The aim of this study was to determine if a nomogram could estimate dialysis compensations for shortfalls in simulated non-compliant patients, such that total weekly urea clearance (Kt/V(urea)) targets are met. Individualized nomograms comprising a series of curves were derived from PD Adequest (ver. 2.0)-predicted Kt/V(urea) data (r (2 ) > 0.99) for different APD prescriptions. The nomogram was then used to estimate the (Nomogram-computed) average of the daily Kt/V(urea) in 14 patients. The study comprised three 1-month phases. Patients were compliant to dialysis in phase I, where Adequest-predicted Kt/V(urea) showed good agreement with both measured (r (I) = 0.72), and Nomogram-computed values (r (I) > 0.99) (p < 0.001). Conversely, in non-compliant phase II, Nomogram-computed values were lower than Adequest-predicted values (p < 0.002). In phase III, the nomogram estimated prescription adjustments required to compensate for shortfalls, such that there was significantly less difference between Nomogram-computed and Adequest-predicted Kt/V(urea) than in phase II (p = 0.005). Thus, despite non-compliance, predicted Kt/V(urea) targets were attained using the nomogram to adjust the daily APD prescriptions. This concept is potentially useful for patients desiring to compensate for inadvertent shortfalls, rather than for 'truly non-compliant' patients.
- Published
- 2009
- Full Text
- View/download PDF
34. Use of a T cell interferon-gamma release assay to evaluate tuberculosis risk in newly qualified physicians in Singapore healthcare institutions.
- Author
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Chee CB, Lim LK, Barkham TM, Koh DR, Lam SO, Shen L, and Wang YT
- Subjects
- Adult, BCG Vaccine administration & dosage, Female, Humans, Male, Personnel, Hospital, Risk Factors, Singapore, Students, Medical, Tuberculin Test methods, Tuberculosis prevention & control, Young Adult, Interferon-gamma blood, Mycobacterium tuberculosis immunology, T-Lymphocytes immunology, Tuberculosis diagnosis
- Abstract
Background: Surveillance for latent tuberculosis in high-risk groups such as healthcare workers is limited by the nonspecificity of the tuberculin skin test (TST) in BCG-vaccinated individuals. The Mycobacterium tuberculosis antigen-specific interferon-gamma release assays (IGRAs) show promise for more accurate latent tuberculosis detection in such groups., Objective: To compare the utility of an IGRA, the T-SPOT.TB assay, with that of the TST in healthcare workers with a high rate of BCG vaccination., Methods: Two hundred seven medical students from 2 consecutive cohorts underwent the T-SPOT.TB test and the TST in their final year of study. Subjects with negative baseline test results underwent repeat testing after working for 1 year as junior physicians in Singapore's public hospitals., Results: The baseline TST result was an induration 10 mm or greater in diameter in 177 of the 205 students who returned to have their TST results evaluated (86.3%), while the baseline T-SPOT.TB assay result was positive in 9 (4.3%) of the students. Repeat T-SPOT.TB testing in 182 baseline-negative subjects showed conversion in 9 (4.9%). A repeat TST in 18 subjects with baseline-negative TST results did not reveal any TST result conversion., Conclusions: The high rate of positive baseline TST results in our BCG-vaccinated healthcare workers renders the TST unsuitable as a surveillance tool in this tuberculosis risk group. Use of an IGRA has enabled the detection and treatment of latent tuberculosis in this group. Our T-SPOT.TB conversion rate highlights the need for greater tuberculosis awareness and improved infection control practices in our healthcare institutions.
- Published
- 2009
- Full Text
- View/download PDF
35. Acceptance of information and communication technologies for healthcare delivery: a SingHealth Polyclinics study.
- Author
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Luo N, Koh WP, Ng WY, Yau JW, Lim LK, Sim SS, and Tay EG
- Subjects
- Adult, Aged, Cross-Sectional Studies, Female, Humans, Interviews as Topic, Male, Middle Aged, Physician-Patient Relations, Singapore, Surveys and Questionnaires, Attitude to Computers, Communication, Delivery of Health Care, Internet statistics & numerical data, Patients
- Abstract
Objective: This study aimed to determine the prevalence of short message system (SMS) and internet usage in patients visiting the SingHealth Polyclinics and to measure patients' acceptance of using these technologies in healthcare delivery., Materials and Methods: A representative sample of patients visiting the 9 SingHealth Polyclinics were interviewed in-person by trained medical students. Collected information included demographic characteristics, access to and usage of mobile phone/SMS and internet, as well as acceptance and concerns on using these technologies in primary healthcare delivery., Results: Among 705 patients surveyed (mean age: 54.6 years, female: 50.6%, response rate: 92%), 407 (57.7%) were SMS users and 158 (22.4%) were internet users. Two hundred and eighty-four of 412 SMS and/or internet users (40.3% of the entire sample) were comfortable with the use of these technologies in healthcare delivery. Malay or Indian ethnicity, better education, and visiting the clinic for acute symptoms or screening were factors positively associated with willingness to use such technologies. The main concerns associated with the use of SMS and internet in healthcare delivery were preference for in-person consultation with a doctor (23.5%), reduced patient-doctor interaction (23.0%), and increased healthcare cost (20.8%)., Conclusion: The present prevalence of SMS and internet usage among patients visiting the SingHealth Polyclinics and their concerns towards use of these technologies in healthcare delivery do not support current widespread implementation of services entailing SMS and internet in the study sites.
- Published
- 2009
36. Staggered-vortex superfluid of ultracold bosons in an optical lattice.
- Author
-
Lim LK, Smith CM, and Hemmerich A
- Abstract
We show that the dynamics of cold bosonic atoms in a two-dimensional square optical lattice produced by a bichromatic light-shift potential is described by a Bose-Hubbard model with an additional effective staggered magnetic field. In addition to the known uniform superfluid and Mott insulating phases, the zero-temperature phase diagram exhibits a novel kind of finite-momentum superfluid phase, characterized by a quantized staggered rotational flux. An extension for fermionic atoms leads to an anisotropic Dirac spectrum, which is relevant to graphene and high-T(c) superconductors.
- Published
- 2008
- Full Text
- View/download PDF
37. Electrohydrodynamic atomization for biodegradable polymeric particle production.
- Author
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Xie J, Lim LK, Phua Y, Hua J, and Wang CH
- Subjects
- Electrochemistry, Microscopy, Electron, Scanning, Microspheres, Nebulizers and Vaporizers, Particle Size, Salts chemistry, Surface Properties, Surface-Active Agents chemistry, Nanoparticles chemistry, Polymers chemistry
- Abstract
Electrohydrodynamic atomization (EHDA) has many applications such as electrospray ionization in mass spectroscopy, electrospray deposition of thin films, pharmaceutical productions, and polymeric particle fabrications for drug encapsulation. In the present study, EHDA was employed to produce biodegradable polymeric micro- and nanoparticles. The effects of processing parameters such as polymer concentration, flow rate, surfactants, organic salt, and setup configurations on the size and morphology of polymeric particles were investigated systematically. By changing the various processing parameters, controllable particle shape and size can be achieved. PLGA nanoparticles with size of around 250 nm can be obtained by using organic salts to increase the conductivity of the spraying solution even at a relatively high flow rate. A higher flow rate has the advantage of producing a stable cone spray and can be easily reproduced. Solid and porous particles can be fabricated using different experimental setups to control the organic solvent evaporation rate. Also, paclitaxel, a model antineoplastic drug, was encapsulated in polymeric particles which can be employed for controlled release applications. In short, EHDA is a promising technique to fabricate polymeric micro- or nanoparticles which can be used in drug delivery systems.
- Published
- 2006
- Full Text
- View/download PDF
38. Monitoring of dengue viruses in field-caught Aedes aegypti and Aedes albopictus mosquitoes by a type-specific polymerase chain reaction and cycle sequencing.
- Author
-
Chow VT, Chan YC, Yong R, Lee KM, Lim LK, Chung YK, Lam-Phua SG, and Tan BT
- Subjects
- Animals, Humans, Larva virology, Prospective Studies, Singapore epidemiology, Aedes virology, Dengue epidemiology, Dengue Virus isolation & purification, Disease Outbreaks, Insect Vectors, Polymerase Chain Reaction methods
- Abstract
Virologic surveillance for dengue through the detection of the prevalent serotype(s) circulating in the human population during inter- and intra-epidemic periods constitutes a reliable sentinel system for dengue outbreaks. We have applied a rapid and sensitive, semi-nested, reverse transcription-polymerase chain reaction (RT-PCR) assay using nonstructural protein 3 gene primers for the type-specific-detection of dengue viruses in artificially infected and in field-caught adult Aedes mosquitoes. In laboratory experiments, the assay was sensitive enough to detect one virus-infected mosquito head in pools of up to 59 uninfected heads. In a prospective field study conducted from April 1995 to July 1996, female adult Ae. aegypti and Ae. albopictus mosquitoes were caught from selected dengue-sensitive areas in Singapore and assayed by RT-PCR. Approximately 20% of 309 mosquito pools were positive for dengue viruses. Of the 23 RT-PCR-positive Ae. aegypti pools (containing 1-17 mosquitoes each), 18 pools (78.3%) were positive for dengue 1 virus. There were 40 RT-PCR-positive Ae. albopictus pools (containing 1-33 mosquitoes each) of which 31 (77.5%) were positive for dengue 1 virus. The predominant virus type responsible for the current dengue epidemic since 1995 was also dengue 1. The geographic locations of the virus-infected mosquitoes correlated with the residences or workplaces of patients within dengue outbreak areas. A total of 43.5% of the positive Ae. aegypti pools and 25.0% of the positive Ae. albopictus pools contained only a single mosquito. Both Aedes species showed similar overall minimum infection rates of 57.6 and 50 per 1,000 mosquitoes. Infected Ae. aegypti were detected as early as six weeks before the start of the dengue outbreaks in 1995 and 1996. However, infected Ae. albopictus appeared later, when the number of cases was increasing. Virologic surveillance by RT-PCR for detecting dengue virus-infected Aedes mosquitoes in the field may serve as an early warning monitoring system for dengue outbreaks.
- Published
- 1998
- Full Text
- View/download PDF
39. Syntaxin 12, a member of the syntaxin family localized to the endosome.
- Author
-
Tang BL, Tan AE, Lim LK, Lee SS, Low DY, and Hong W
- Subjects
- Amino Acid Sequence, Base Sequence, Cell Line, Cloning, Molecular, Membrane Proteins genetics, Microscopy, Fluorescence, Molecular Sequence Data, Open Reading Frames, Protein Binding, Qa-SNARE Proteins, SNARE Proteins, Endosomes metabolism, Membrane Proteins metabolism, Vesicular Transport Proteins
- Abstract
We have cloned a new member of the syntaxin family of proteins. The open reading frame encodes a polypeptide of 272 amino acids with potential coiled-coil domains and a C-terminal hydrophobic tail. Northern blot analysis showed that the transcript is fairly ubiquitous. A soluble recombinant form of the polypeptide without the hydrophobic region binds to alpha-SNAP (soluble N-ethylmaleimide-sensitive factor attachment protein) and syndet/SNAP-23 in vitro. Polyclonal antibody raised against the recombinant protein recognized a 39-kDa protein in the membrane fraction of cell lysates. Indirect immunofluorescence studies using the polyclonal antibody showed that the protein is localized to intracellular membrane structures. Selective permeabilization studies with digitonin and saponin indicate that the epitope(s) recognized by the antibody is expose to the cytoplasm, consistent with the predicted orientation characteristic of SNAP receptor molecules. Morphological alterations of the staining pattern of the protein with brefeldin A and wortmannin treatment indicate that the protein is localize to the endosome. The cDNA we have cloned apparently corresponded to three previously described expressed sequence tags named as syntaxins 12, 13, and 14, respectively. We therefore propose to retain the name syntaxin 12 for this protein.
- Published
- 1998
- Full Text
- View/download PDF
40. Cyclic AMP and the regulation of prostaglandin production by macrophages.
- Author
-
Lim LK, Hunt NH, Eichner RD, and Weidemann MJ
- Subjects
- 8-Bromo Cyclic Adenosine Monophosphate, Animals, Aspirin pharmacology, Bucladesine pharmacology, Calcimycin pharmacology, Cholera Toxin pharmacology, Cyclic AMP analogs & derivatives, Cyclic AMP pharmacology, Indomethacin pharmacology, Kinetics, Macrophages drug effects, Rats, Verapamil pharmacology, Cyclic AMP metabolism, Macrophages metabolism, Prostaglandins biosynthesis
- Abstract
The ionophore A23187 (6.7 microM) increased the rates of formation of prostaglandins and cyclic AMP in suspensions of thioglycollate-elicited rat peritoneal macrophages. Both effects were inhibited by the calmodulin blocker trifluoperazine (50 microM) and the calcium channel blocker verapamil (500 microM). Inhibitors of phospholipase A2 and cyclo-oxygenase also blocked both actions of A23187. The stimulated prostaglandin formation was markedly reduced when the cells were preincubated with 8-bromo-cyclic AMP (1mM), dibutyryl cyclic AMP (1mM) or cholera toxin (500ng/ml). Addition of exogenous arachidonic acid (30 microM) alleviated this inhibition. We propose that the effect of A23187 on macrophages includes a 'self-limiting' mechanism whereby newly-synthesized prostaglandins can inhibit, via cyclic AMP, a step(s) prior to the transformation of arachidonic acid and thus modulate their own production.
- Published
- 1983
- Full Text
- View/download PDF
41. Fine needle aspiration biopsy, serum beta 2-microglobulin, and urine thromboxane in renal allografts.
- Author
-
Lim LK, Alijani MR, and Foegh ML
- Subjects
- Humans, Kidney pathology, Predictive Value of Tests, Sensitivity and Specificity, Biopsy, Needle, Graft Rejection, Kidney Transplantation, Thromboxane B2 urine, beta 2-Microglobulin analysis
- Published
- 1989
42. Adenine nucleotides directly stimulate pertussis toxin.
- Author
-
Lim LK, Sekura RD, and Kaslow HR
- Subjects
- Adenosine Diphosphate Ribose metabolism, Adenylyl Imidodiphosphate pharmacology, Animals, Brain Chemistry, Cattle, Cholera Toxin metabolism, NAD+ Nucleosidase metabolism, Pertussis Toxin, Serum Albumin, Bovine metabolism, Tubulin metabolism, Virulence Factors, Bordetella, Adenine Nucleotides pharmacology, Bacterial Toxins metabolism
- Abstract
Both cholera toxin and pertussis toxin catalyzed ADP-ribosylation of purified bovine brain tubulin. The effect of cholera toxin was evident in the absence or presence of nucleotides. In contrast, pertussis toxin required adenine nucleotides for its ADP-ribosylating activity. ATP, ATP gamma S, App(NH)p, deoxy-ATP, and ADP all supported pertussis toxin-catalyzed ADP-ribosylations in the absence or presence of EDTA, suggesting that nucleotide hydrolysis was not involved. Adenine nucleotides also promoted pertussis toxin-catalyzed ADP-ribosylation of heat-treated bovine serum albumin. This result suggests that adenine nucleotides directly affect pertussis toxin. ATP stimulation of pertussis toxin-catalyzed hydrolysis of NAD to ADP-ribose supports this hypothesis.
- Published
- 1985
43. Reactive oxygen production, arachidonate metabolism and cyclic AMP in macrophages.
- Author
-
Lim LK, Hunt NH, and Weidemann MJ
- Subjects
- 8-Bromo Cyclic Adenosine Monophosphate, Animals, Arachidonic Acid, Aspirin pharmacology, Bucladesine pharmacology, Calcimycin pharmacology, Cyclic AMP analogs & derivatives, Cyclic AMP pharmacology, Dinoprostone, Indomethacin pharmacology, Kinetics, Luminescent Measurements, Macrophages drug effects, Prostaglandins E pharmacology, Rats, Verapamil pharmacology, Arachidonic Acids metabolism, Cyclic AMP metabolism, Macrophages metabolism, Oxygen metabolism
- Abstract
Chemiluminescence was used as an indicator of the production of reactive oxygen species by thioglycollate-elicited rat peritoneal macrophages stimulated by A23187. This action of the ionophore was inhibited by bromophenacyl bromide and nordihydroguaiaretic acid, inhibitors of the phospholipase A2 and lipoxygenase enzymes, respectively. The cyclo-oxygenase inhibitors, indomethacin and aspirin, did not diminish the light output. Preincubation of the cells with the 8-bromo- or dibutyryl analogues of cyclic AMP or with the cyclic AMP-phosphodiesterase inhibitors theophylline and RO-20-1724, or with PGE2, inhibited the A23187-evoked chemiluminescence. The results suggest that he lipoxygenase pathway of arachidonic acid metabolism may make a significant contribution to reactive oxygen production. This process may be modulated, and its duration limited, by cyclic AMP-mediated actions of prostaglandins, which are products of the cyclo-oxygenation of arachidonate.
- Published
- 1983
- Full Text
- View/download PDF
44. Activation of cyclic AMP-dependent protein kinase in macrophages.
- Author
-
Hunt NH, Lim LK, Eichner RD, Buffinton GD, and Weidemann MJ
- Subjects
- Acetophenones pharmacology, Animals, Aspirin pharmacology, Calcimycin pharmacology, Enzyme Activation, Indomethacin pharmacology, Kinetics, Rats, Thioglycolates pharmacology, Macrophages enzymology, Protein Kinases metabolism
- Abstract
The activity of cyclic AMP-dependent protein kinase (cyclic AMP-PK) was significantly higher (P less than 0.001) in thioglycollate-elicited than in resident rat peritoneal macrophages. The activity ratio of the enzyme (its activity in the absence of added cyclic AMP divided by that in the presence of 5 microM cyclic AMP) was similar in the two cell types. The divalent ion ionophore A23187 induced a rapid increase in the activity ratio of cyclic AMP-PK in both macrophage types. This effect was blocked by pretreating the cells with indomethacin or aspirin (inhibitors of cyclo-oxygenase) and bromo-phenacyl bromide (an inhibitor of phospholipase A2), implicating the synthesis of a prostanoid as an intermediary step. Prostaglandin (PG) E2, 8-bromo cyclic AMP and cholera toxin, all of which inhibit chemiluminescence and/or PG formation in macrophages, increased the activity ratio of cyclic AMP-PK in these cells. We propose that the activation of cyclic AMP-PK plays a central role in the response of macrophages to both endogenously-generated and exogenously added PGE.
- Published
- 1984
- Full Text
- View/download PDF
45. Glycogen synthesis in resident and thioglycollate-elicited rat peritoneal exudate cells.
- Author
-
Eichner RD, Lim LK, and Hunt NH
- Subjects
- Animals, Ascitic Fluid, Biotransformation, Enzyme Activation drug effects, Glucose metabolism, Glycogen Synthase metabolism, In Vitro Techniques, Kinetics, Male, Rats, Glycogen biosynthesis, Macrophages metabolism, Thioglycolates pharmacology
- Abstract
The values of the A0.5 for glucose-6-P, apparent Km for UDPglucose and -/+glucose-6-P activity ratio are similar for glycogen synthase derived from rat resident and thioglycollate-elicited peritoneal macrophages; the specific activity is 7-fold higher for the enzyme from thioglycollate-elicited macrophages. The rate of incorporation of [14C]glucose into macrophage glycogen is 7-fold greater in the elicited population that that in the resident one; the values of the S0.5 for glucose are similar. The in vitro activation of glycogen synthase proceeds at a greater rate and extent for the enzyme from elicited macrophages; thus, phosphatase activity may be reduced in resident macrophages relative to that in thioglycollate-elicited ones.
- Published
- 1983
- Full Text
- View/download PDF
46. Therapeutic ultrasound and the liver in vivo: action and possible mechanisms.
- Author
-
Saad AH, Bahakim HM, Helmi A, Bashandi AM, and Lim LK
- Subjects
- Alanine Transaminase blood, Animals, Aspartate Aminotransferases blood, Blood Proteins analysis, Body Temperature, Cholesterol blood, Creatine Kinase blood, Hemolysis, Infrared Rays adverse effects, Rats, Rats, Inbred Strains, Liver injuries, Ultrasonic Therapy adverse effects
- Abstract
This paper reports on the effects of therapeutic ultrasound upon the liver in vivo. Exposure of the liver of rats to therapeutic ultrasound at a frequency of 0.87 MHz results in intravascular haemolysis which is dependent upon the product of the intensity and the exposure duration (energy deposited within the liver). The resulting structural change (noted when a spatial peak intensity of 1.25 W/cm2 was applied for a duration of 10 min) is a lesion which has four zones. The severity of the injury increased across the four zones when scanning towards the ischaemic area. The biochemical changes observed included an increase in aspartate transaminase, alanine transferase, creatinine kinase and cholesterol and a decrease in total protein and albumin. Healing processes reversed the structural changes after 72 h which was also reflected in the plasma biochemical profile. Exposure of the liver to infrared radiation resulted in haemolysis but not the biochemical or structural alterations observed following sonication suggesting a mechanism for ultrasound action other than heating alone.
- Published
- 1986
- Full Text
- View/download PDF
47. Evidence that in chick embryos destruction of hepatic microsomal cytochrome P-450 haem is a general mechanism of induction of delta-aminolaevulinate synthase by porphyria-causing drugs.
- Author
-
Lim LK, Srivastava G, Brooker JD, May BK, and Elliott WH
- Subjects
- Allylisopropylacetamide pharmacology, Animals, Chick Embryo, Deferoxamine pharmacology, Dicarbethoxydihydrocollidine pharmacology, Enzyme Induction drug effects, Hemin pharmacology, Microsomes, Liver drug effects, Phenobarbital pharmacology, Porphyrias chemically induced, Proadifen pharmacology, 5-Aminolevulinate Synthetase biosynthesis, Cytochrome P-450 Enzyme System metabolism, Heme metabolism, Microsomes, Liver enzymology
- Abstract
A variety of prophyrinogenic compounds were tested for their effect in ovo on chick-embryo liver microsomal cytochrome P-450 haem concentration and mitochondrial delta-aminolaevulinate synthase activity. With all drugs tested, there was a 30--50% decrease in cytochrome P-450 haem concentration within 1 h of treatment, and this was closely followed by an increase in delta-aminolaevulinate synthase activity. The relationship was independent of the extent of enzyme induction and is consistent with the proposal that drug-mediated destruction of cytochrome P-450 haem is the primary mechanism of induction of delta-aminolaevulinate synthase. After induction, synthesis of delta-aminolaevulinate synthase could be maintained by inhibiting further haem synthesis. These studies suggest that induction of porphyria is a combination of two distinct processes: (a) induction of delta-aminolaevulinate synthase synthesis by destruction of cytochrome P-450 haem and consequent depletion of cellular free haem; (b) maintenance of continued delta-aminolaevulinate synthase synthesis by preventing replenishment of cellular haem either by inhibiting haem synthesis and/or by promoting continuous removal of newly synthesized haem.
- Published
- 1980
- Full Text
- View/download PDF
48. Reactive-oxygen formation and its relationship to prostaglandin and cyclic AMP production by zymosan-treated rat peritoneal macrophages.
- Author
-
Lim LK, Hunt NH, and Weidemann MJ
- Subjects
- Animals, Arachidonic Acids antagonists & inhibitors, Cells, Cultured, Female, Macrophages metabolism, Rats, Rats, Inbred Strains, Cyclic AMP biosynthesis, Macrophages drug effects, Oxygen metabolism, Prostaglandins biosynthesis, Zymosan pharmacology
- Abstract
Addition of zymosan (20 particles/cell) to suspensions of resident rat peritoneal macrophages caused an increase in the concns of prostaglandins and cyclic AMP. Preincubation of the cells with inhibitors of arachidonate metabolism led to inhibition of prostaglandin, but not of cyclic AMP, formation, which suggested that the two processes may occur independently of each other in phagocytosing cells. The luminol-dependent chemiluminescence associated with the addition of zymosan to the cells consisted of a minor, Ca2+-dependent, glucose-independent component and a major, glucose-dependent, Ca2+-independent component. Only the minor, Ca2+-dependent component appeared to be related to the lipoxygenation of arachidonic acid. Close examination of the production of prostaglandins and cyclic AMP and of chemiluminescence after zymosan addition, indicated that the expanded pool of endogenous cyclic AMP was probably not a negative modulator of the other two processes, although they remained susceptible to inhibition by exogenously-added cyclic AMP analogues or PGE2. The events induced by zymosan may be relevant to the physiological roles of prostaglandins during the inflammatory response.
- Published
- 1985
- Full Text
- View/download PDF
49. Structure-activity analysis of the activation of pertussis toxin.
- Author
-
Kaslow HR, Lim LK, Moss J, and Lesikar DD
- Subjects
- ADP Ribose Transferases, Adenosine pharmacology, Enzyme Activation, Macromolecular Substances, Ribonucleotides pharmacology, Structure-Activity Relationship, NAD+ Nucleosidase metabolism, Pentosyltransferases metabolism, Pertussis Toxin, Virulence Factors, Bordetella pharmacology
- Abstract
Bordetella pertussis, the causative agent of whooping cough, releases pertussis toxin in an inactive form. The toxin consists of an A protomer containing one S1 peptide subunit and a B oligomer containing several other peptide subunits. The toxin binds to cells via the B oligomer, and the S1 subunit is activated and expresses ADP-ribosyltransferase and NAD glycohydrolase activities. Treatment of purified toxin with dithiothreitol (DTT) in vitro increases both activities. ATP and the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) synergistically reduce the A0.5 (activation constant) for DTT from greater than 100 mM to 200 microM. We studied the structure-activity relationships of activators of the toxin. In the presence of CHAPS (1%) and DTT (10 mM) the following compounds increased the NAD glycohydrolase activity of the toxin with the following A0.5's in microM and fraction of the ATP effect in parentheses: ATP, 0.2 (1.0); ADP, 6 (0.8); UTP, 15 (0.7); GTP, 35 (0.6); pyrophosphate, 45 (0.7); triphosphate, 60 (0.6); tetraphosphate, greater than or equal to 170 (greater than or equal to 0.4). Thus, the polyphosphate moiety is sufficient to stimulate the toxin, and the adenosine moiety confers upon ATP its extraordinary affinity for the toxin. Phospholipid and detergents could substitute for CHAPS in the activation of the toxin. Glutathione substituted for DTT with an A0.5 of 2 mM, a concentration within the range found in eucaryotic cells. Thus, membrane lipids and cellular concentrations of glutathione and ATP are sufficient to activate pertussis toxin without the need for a eucaryotic enzymatic process.
- Published
- 1987
- Full Text
- View/download PDF
50. Effect of the 5-lipoxygenase inhibitors EP 10045 and EP 10161 on cardiac graft cellular infiltrate and thromboxane formation.
- Author
-
Lim LK, Khirabadi BS, Braquet P, Ramwell PW, and Foegh ML
- Subjects
- Animals, Cyclosporins pharmacology, Leukocytes pathology, Myocardium immunology, Myocardium pathology, Rats, Arachidonate Lipoxygenases antagonists & inhibitors, Benzopyrans pharmacology, Catechols pharmacology, Chromans pharmacology, Graft Rejection drug effects, Heart Transplantation, Lipoxygenase Inhibitors, Sulfides pharmacology, Thromboxane B2 biosynthesis
- Published
- 1988
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