Surface exciton polariton enhanced Goos-Hänchen and Imbert-Fedorov shifts and their applications in refractive index sensing.

The spatial and angular Goos-Hänchen shifts (GHSs) and Imbert-Fedorov shifts (IFSs) are theoretically investigated in a modified Kretschmann-Raether configuration consisting of glass prism, J-aggregate cyanine dye, and air. With the excitation of surface excitation polaritons (SEPs), the spatial and angular GHSs and IFSs for the transverse magnetic polarized light are strongly enhanced around the resonant angle of SEP. A highly sensitive gas sensor based on the SEP enhanced GHS (or IFS) is proposed, which exhibits the refractive index sensitivity on the order of 106λ/RIU (or 105λ/RIU) (λ: illumination wavelength; RIU: refractive index unit) for the GHS- (or IFS-) based gas sensor, respectively.

High sensitivity gas sensor based on surface exciton polariton enhanced photonic spin Hall effect.

In this paper, the sub-wavelength transverse displacement of photonic spin Hall effect (PSHE) is significantly enhanced by the surface exciton polariton (SEP) for application in gas sensing. The transverse displacement of 14.4 times the wavelength of incident light is achieved with the SEP enhanced PSHE, which is about 3 times that of surface plasmon resonance enhanced PSHE. A gas sensor based on SEP enhanced PSHE is proposed for the detection of SO2, and the refractive index sensitivity of 6320.4 µm/RIU is obtained in the refractive index range from 1.00027281 to 1.00095981. These results undoubtedly demonstrate SEP to be a promising mechanism for PSHE enhancement, and open up new opportunities for highly sensitive gas sensing, biosensing, and chemical sensing.

Fractional modeling of urban growth with memory effects.

The previous urban growth model by L. M. A. Bettencourt was developed under the framework of a constant ß scaling law in an ordinary differential equation based model assuming instantaneous dynamic growth. In this paper, we improve the model by considering the memory effects based on fractional calculus. By testing this new fractional model to different urban attributes related to sustainable growth, such as congestion delay, water supply, and electricity consumption for selected countries (the USA, China, Singapore, Canada, Switzerland, New Zealand), this new model may provide better agreement to the annual population growth by numerically finding the optimal fractional parameter for different attributes. Based on the theoretical time-independent scaling of ß = 5 / 6 (sub-linear) and ß = 7 / 6 (super-linear), we also analyze the population growth of 42 countries from 1960 to 2018. Furthermore, time-dependent scaling law extracted from empirical data is shown to provide further improvements. With better agreement between this proposed fractional model and the collected empirical population growth data, useful parameters can be estimated. For example, the maintenance cost and additional cost related to the sustainable growth (for a given city's attribute) can be quantitatively determined for the informed decision and urban planning for the sustainable growth of cities.

Safety and effectiveness of switching to Abacavir/Lamivudine plus rilpivirine for maintenance therapy in virologically suppressed HIV-1 individuals in Singapore (SEALS).

BACKGROUND: The efficacy and tolerability of an antiretroviral regimen are important considerations for selection of HIV-1 infection maintenance therapy. Abacavir/lamivudine plus rilpivirine (ABC/3TC + RPV) has been shown in international studies to be effective and well-tolerated in virologically suppressed individuals. This study evaluated the effectiveness and safety of switching to ABC/3TC + RPV as maintenance therapy in virologically suppressed HIV-1 infected individuals in Singapore. METHODS: In this retrospective, single-centre study, we included individuals who were prescribed ABC/3TC + RPV, had HIV-1 viral load (VL) < 50 copies/ml immediately pre-switch, and had no documented history of resistance mutations or virologic failure to any of the components. The follow-up period was 48 ± 12 weeks. The primary outcome was the proportion of individuals who maintained virologic suppression of HIV-1 VL < 50 copies/ml at the end of follow-up period based on on-treatment analysis. The secondary outcomes were the resistance profiles associated with virologic failure, changes in immunologic and metabolic parameters, and the safety profile of ABC/3TC + RPV. RESULTS: A total of 222 individuals were included in the study. The primary outcome was achieved in 197 individuals [88.8%, 95% confidence interval: 83.7-92.4%]. There were 21 individuals (9.5%) who discontinued treatment for non-virologic reasons. The remaining 4 individuals experienced virologic failure, of whom, 3 of these individuals had developed emergent antiretroviral resistance and had HIV-1 VL > 500 copies/ml at the end of the 48 ± 12 weeks follow-up period. The remaining individual experienced sustained low level viremia and subsequently achieved viral suppression without undergoing resistance testing. A total of 49 adverse events were observed in 31 out of 222 individuals (14.0%), which led to 13 individuals discontinuing therapy. Neuropsychiatric adverse events were most commonly observed (53.1%). A statistically significant increase in CD4 was observed (p < 0.01), with a median absolute change of 31 cells/uL (interquartile range: - 31.50 to 140.75). No significant changes in lipid profiles were detected. CONCLUSION: ABC/3TC + RPV is a safe and effective switch option for maintenance therapy in virologically suppressed HIV-1 individuals with in Singapore.

Medicine in motion: Opportunities, challenges and data analytics-based solutions for traditional medicine integration into western medical practice.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional pharmacopeias have been developed by multiple cultures and evaluated for efficacy and safety through both historical/empirical iteration and more recently through controlled studies using Western scientific paradigms and an increasing emphasis on data science methodologies for network pharmacology. Traditional medicines represent likely sources of relatively inexpensive drugs for symptomatic management as well as potential libraries of new therapeutic approaches. Leveraging this potential requires hard evidence for efficacy that separates science from pseudoscience. MATERIALS AND METHODS: We performed a review of non-Western medical systems and developed case studies that illustrate the epistemological and practical translative barriers that hamper their transition to integration with Western approaches. We developed a new data analytics approach, in silico convergence analysis, to deconvolve modes of action, and potentially predict desirable components of TM-derived formulations based on computational consensus analysis across cultures and medical systems. RESULTS: Abstraction, simplification and altered dose and delivery modalities were identified as factors that influence actual and perceived efficacy once a medicine is moved from a non-Western to Western setting. Case studies on these factors highlighted issues with translation between non-Western and Western epistemologies, including those where epistemological and medicinal systems drive markets that can be epicenters for zoonoses such as the novel Coronavirus. The proposed novel data science approach demonstrated the ability to identify and predict desirable medicinal components for a test indication, pain. CONCLUSIONS: Relegation of traditional therapies to the relatively unregulated nutraceutical industry may lead healthcare providers and patients to underestimate the therapeutic potential of these medicines. We suggest three areas of emphasis for this field: First, vertical integration and embedding of traditional medicines into healthcare systems would subject them to appropriate regulation and evidence-based practice, as viable integrative implementation mode. Second, we offer a new Bradford-Hill-like framework for setting research priorities and evaluating efficacy, with the goal of rescuing potentially valuable therapies from the nutraceutical market and discrediting those that are pseudoscience. Third, data analytics pipelines offer new capacity to generate new types of TMS-inspired medicines that are rationally-designed based on integrated knowledge across cultures, and also provide an evaluative framework against which to test claims of fidelity and efficacy to TMS made for nutraceuticals.

Influenza vaccine failure in the tropics: a retrospective cohort study of waning effectiveness.

Influenza vaccine effectiveness (VE) wanes over the course of a temperate climate winter season but little data are available from tropical countries with year-round influenza virus activity. In Singapore, a retrospective cohort study of adults vaccinated from 2013 to 2017 was conducted. Influenza vaccine failure was defined as hospital admission with polymerase chain reaction-confirmed influenza infection 2-49 weeks after vaccination. Relative VE was calculated by splitting the follow-up period into 8-week episodes (Lexis expansion) and the odds of influenza infection in the first 8-week period after vaccination (weeks 2-9) compared with subsequent 8-week periods using multivariable logistic regression adjusting for patient factors and influenza virus activity. Records of 19 298 influenza vaccinations were analysed with 617 (3.2%) influenza infections. Relative VE was stable for the first 26 weeks post-vaccination, but then declined for all three influenza types/subtypes to 69% at weeks 42-49 (95% confidence interval (CI) 52-92%, P = 0.011). VE declined fastest in older adults, in individuals with chronic pulmonary disease and in those who had been previously vaccinated within the last 2 years. Vaccine failure was significantly associated with a change in recommended vaccine strains between vaccination and observation period (adjusted odds ratio 1.26, 95% CI 1.06-1.50, P = 0.010).

Different pathological processes for acute white matter lesions in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) has variable clinical presentations, prognoses, pathogeneses, and pathological patterns. We conducted a pathological review of acute MS-associated lesions that focused on the degree of axonal injury, myelin loss, and glial reaction to determine whether the observed demyelination was of the primary or secondary type. MATERIALS AND METHODS: After searching the records for a 15-year period at the London Health Sciences Centre Pathology Department, we identified 8 cases of surgical acute lesion biopsies in which clinical MS diagnoses were made before or after the biopsy. RESULTS: The white matter pathologies in these cases could be sorted into 3 morphological patterns. The first pattern, which represents typical demyelinated plaques, was observed in 4 cases and was characterised by nearly complete demyelination accompanied by variable degrees of axon preservation and axonal swelling. The second pattern was observed in 3 cases and was characterised by demyelinating lesions containing variable numbers of myelinated axons mixed with a few demyelinated axons and variable numbers of axonal swellings. The myelinated axons ranged from scattered fibres to bands of variable thickness, and the demyelination was a mixture of primary and secondary demyelination. The third pattern was observed in 1 case and was characterised by well-demarcated areas of reduced myelin staining and numerous apoptotic nuclei. Axonal staining revealed many fragmented axons with reduced myelin staining but no definitely demyelinated axons. CONCLUSIONS: This report shows that the predominant pathology underlying acute MS-related lesions is not limited to demyelination but can include axonal degeneration alone or in combination with primary demyelination which reflect different pathogenesis for these acute lesions.

Differential brain region-specific expression of MeCP2 and BDNF in Rett Syndrome patients: a distinct grey-white matter variation.

INTRODUCTION AND OBJECTIVES: Rett Syndrome (RTT) is a neurodevelopmental disorder caused by Methyl CpG Binding Protein 2 (MECP2) gene mutations. Previous studies of MeCP2 in the human brain showed variable and inconsistent mosaic-pattern immunolabelling, which has been interpreted as a reflection of activation-state variability. We aimed to study post mortem MeCP2 and BDNF (MeCP2 target) degradation and brain region-specific detection in relation to RTT pathophysiology. METHODS: We investigated MeCP2 and BDNF stabilities in non-RTT human brains by immunohistochemical labelling and compared them in three brain regions of RTT and controls. RESULTS: In surgically excised samples of human hippocampus and cerebellum, MeCP2 was universally detected. There was no significantly obvious difference between males and females. However, post mortem delay in autopsy samples had substantial influence on MeCP2 detection. Immunohistochemistry studies in RTT patients showed lower MeCP2 detection in glial cells of the white matter. Glial fibrillary acidic protein (GFAP) expression was also reduced in RTT brain samples without obvious change in myelin basic protein (MBP). Neurons did not show any noticeable decrease in MeCP2 detection. BDNF immunohistochemical detection showed an astroglial/endothelial pattern without noticeable difference between RTT and controls. CONCLUSIONS: Our findings indicate that MeCP2 protein is widely expressed in mature human brain cells at all ages. However, our data points towards a possible white matter abnormality in RTT and highlights the importance of studying human RTT brain tissues in parallel with research on animal and cell models of RTT.

Optical Kerr effect and third harmonic generation in topological Dirac/Weyl semimetal.

We study the nonlinear optical response generated by the massless Dirac quasiparticles residing around the topologically-protected Dirac/Weyl nodal points in three-dimensional (3D) topological semimetals. Analytical expressions of third-order interband nonlinear optical conductivities are obtained based on a quantum mechanical formalism which couples 3D Dirac fermions with multiple photons. Our results reveal that the massless Dirac fermions in three dimensions retains strong optical nonlinearity in terahertz frequency regime similar to the case of the two-dimensional Dirac fermions in graphene. At room temperature, the Kerr nonlinear refractive index and the harmonic generation susceptibility are found to be n2 = 10-11 ∼ 10-8 m2W-1 and χ(3) = 10-14 ∼ 10-8 m2V-2, respectively, in the few terahertz frequency regimes, which is comparable to graphene and orders of magnitudes stronger than many nonlinear crystals. Importantly, because 3D topological Dirac/Weyl semimetals possess bulk structural advantage not found in the strictly two-dimensional graphene, greater design flexibility and improved ease-of-fabrication in terms of photonic and optoelectronic device applications can be achieved. Our finding reveals the potential of 3D topological semimetals as a viable alternative to graphene for nonlinear optics applications.

Myrcene and terpene regulation of TRPV1.

Nociceptive Transient Receptor Potential channels such as TRPV1 are targets for treating pain. Both antagonism and agonism of TRP channels can promote analgesia, through inactivation and chronic desensitization. Since plant-derived mixtures of cannabinoids and the Cannabis component myrcene have been suggested as pain therapeutics, we screened terpenes found in Cannabis for activity at TRPV1. We used inducible expression of TRPV1 to examine TRPV1-dependency of terpene-induced calcium flux responses. Terpenes contribute differentially to calcium fluxes via TRPV1 induced by Cannabis-mimetic cannabinoid/terpenoid mixtures. Myrcene dominates the TRPV1-mediated calcium responses seen with terpenoid mixtures. Myrcene-induced calcium influx is inhibited by the TRPV1 inhibitor capsazepine and Myrcene elicits TRPV1 currents in the whole-cell patch-clamp configuration. TRPV1 currents are highly sensitive to internal calcium. When Myrcene currents are evoked, they are distinct from capsaicin responses on the basis of Imax and their lack of shift to a pore-dilated state. Myrcene pre-application and residency at TRPV1 appears to negatively impact subsequent responses to TRPV1 ligands such as Cannabidiol, indicating allosteric modulation and possible competition by Myrcene. Molecular docking studies suggest a non-covalent interaction site for Myrcene in TRPV1 and identifies key residues that form partially overlapping Myrcene and Cannabidiol binding sites. We identify several non-Cannabis plant-derived sources of Myrcene and other compounds targeting nociceptive TRPs using a data mining approach focused on analgesics suggested by non-Western Traditional Medical Systems. These data establish TRPV1 as a target of Myrcene and suggest the therapeutic potential of analgesic formulations containing Myrcene.

Reproductive factors and risk of total knee replacement due to severe knee osteoarthritis in women, the Singapore Chinese Health Study.

OBJECTIVES: Knee osteoarthritis (OA) is more common in women, and may be related to reproductive or hormonal factors. We evaluated these factors with the risk of total knee replacement (TKR) for severe knee OA among women. METHODS: The Singapore Chinese Health Study recruited 63,257 Chinese aged 45-74 years from 1993 to 1998, and among them, 35,298 were women. Information on height, weight, lifestyle factors, number of biological children, ages at menarche and menopause, and use of hormonal therapies was collected through interviews. Incident cases of TKR were identified via linkage with nationwide database. RESULTS: There were 1,645 women with TKR after mean follow-up of 14.8 years. Higher parity was associated with increased TKR risk in a stepwise manner (P for trend <0.001). Compared to nulliparous women, those with ≥5 children had the highest risk [hazard ratio (HR) 2.01, 95% confidence intervals (CIs) 1.50-2.70]. The effect of parity on TKR risk was significantly stronger among lean women compared to heavier women; HRs (95% CIs) for highest parity was 4.86 (2.22-10.63) for women with body mass index (BMI) <23 kg/m2 and 1.57 (1.14-2.14) for those ≥23 kg/m2 (P for interaction = 0.001). Earlier age at menarche and use of oral contraceptives were significantly associated with TKR in a stepwise manner (P for trend ≤0.002). Age at menopause and use of hormonal therapy were not associated with TKR risk. CONCLUSION: Higher parity, earlier age of menarche and use of oral contraceptives were associated with increased risk of TKR for severe knee OA among women.

Universal Scaling Laws in Schottky Heterostructures Based on Two-Dimensional Materials.

We identify a new universality in the carrier transport of two-dimensional (2D) material-based Schottky heterostructures. We show that the reversed saturation current (J) scales universally with temperature (T) as log(J/T^{ß})∝-1/T, with ß=3/2 for lateral Schottky heterostructures and ß=1 for vertical Schottky heterostructures, over a wide range of 2D systems including nonrelativistic electron gas, Rashba spintronic systems, single- and few-layer graphene, transition metal dichalcogenides, and thin films of topological solids. Such universalities originate from the strong coupling between the thermionic process and the in-plane carrier dynamics. Our model resolves some of the conflicting results from prior works and is in agreement with recent experiments. The universal scaling laws signal the breakdown of ß=2 scaling in the classic diode equation widely used over the past sixty years. Our findings shall provide a simple analytical scaling for the extraction of the Schottky barrier height in 2D material-based heterostructures, thus paving the way for both a fundamental understanding of nanoscale interface physics and applied device engineering.

Epidemiology of tuberculosis and HIV coinfections in Singapore, 2000-2014.

Cross-matching of records between Singapore's tuberculosis and HIV registries showed that 3.3% of individuals with tuberculosis (TB) were coinfected with HIV (2000-2014), the TB incidence among individuals with HIV infection was 1.65 per 100 person-years, and 53% of coinfections were diagnosed within 1 month of each other. The findings supported joint prevention programmes for early diagnosis and treatment.

Gout and risk of knee replacement for severe knee osteoarthritis in the Singapore Chinese Health Study.

OBJECTIVE: While cross-sectional and retrospective case-control studies suggest that gout is associated with knee osteoarthritis (KOA), no prospective study has evaluated the risk of total knee replacement (TKR) for KOA in association with gout. We prospectively evaluated the association between gout and the risk of TKR due to severe KOA. DESIGN: We used data from the Singapore Chinese Health Study (SCHS), a prospective cohort with 63,257 Chinese adults aged 45-74 years at recruitment (1993-1998). Self-report of physician-diagnosed gout was enquired at follow-up I interview (1999-2004) from 52,322 subjects. TKR cases for KOA after follow-up I were identified via linkage with nationwide hospital discharge database through 31 December 2011. Multivariable Cox proportional hazards regression model was applied with adjustment for potential risk factors of KOA. RESULTS: Among 51,858 subjects (22,180 men and 29,678 women) included in this analysis, after average 9.7 follow-up years, there were 1,435 cases of TKR. Gout was associated with 39% higher risk of TKR in women [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.08-1.79] but not in men (HR 0.78; 95% CI 0.49-1.23). The positive gout-TKR association in women remained after excluding participants with self-reported history of arthritis (HR 1.57; 95% CI 1.04-2.37). This association was stronger in women who were lean (body mass index [BMI] < 23 kg/m2) (HR 2.17; 95% CI 1.30-3.64) compared to their heavier counterparts (Pinteraction = 0.016). CONCLUSION: Gout is associated with risk of severe KOA, especially in lean women, suggesting the crystal arthritis may play a role in the pathogenesis or progression of OA.

Electrical transport and persistent photoconductivity in monolayer MoS2 phototransistors.

We study electrical transport properties in exfoliated molybdenum disulfide (MoS2) back-gated field effect transistors at low drain bias and under different illumination intensities. It is found that photoconductive and photogating effect as well as space charge limited conduction can simultaneously occur. We point out that the photoconductivity increases logarithmically with the light intensity and can persist with a decay time longer than 104 s, due to photo-charge trapping at the MoS2/SiO2 interface and in MoS2 defects. The transfer characteristics present hysteresis that is enhanced by illumination. At low drain bias, the devices feature low contact resistance of [Formula: see text] ON current as high as [Formula: see text] 105 ON-OFF ratio, mobility of ∼1 cm2 V-1 s-1 and photoresponsivity [Formula: see text].

Enhanced stability of filament-type resistive switching by interface engineering.

The uncontrollable rupture of the filament accompanied with joule heating deteriorates the resistive switching devices performance, especially on endurance and uniformity. To suppress the undesirable filaments rupture, this work presents an interface engineering methodology by inducing a thin layer of NiOx into a sandwiched Al/TaOx/ITO resistive switching device. The NiOx/TaOx interface barrier can confine the formation and rupture of filaments throughout the entire bulk structure under critical bias setups. The physical mechanism behind is the space-charge-limited conduction dominates in the SET process, while the Schottky emission dominates under the reverse bias.

Thermionic Energy Conversion Based on Graphene van der Waals Heterostructures.

Seeking for thermoelectric (TE) materials with high figure of merit (or ZT), which can directly converts low-grade wasted heat (400 to 500 K) into electricity, has been a big challenge. Inspired by the concept of multilayer thermionic devices, we propose and design a solid-state thermionic devices (as a power generator or a refrigerator) in using van der Waals (vdW) heterostructure sandwiched between two graphene electrodes, to achieve high energy conversion efficiency in the temperature range of 400 to 500 K. The vdW heterostructure is composed of suitable multiple layers of transition metal dichalcogenides (TMDs), such as MoS2, MoSe2, WS2 and WSe2. From our calculations, WSe2 and MoSe2 are identified as two ideal TMDs (using the reported experimental material's properties), which can harvest waste heat at 400 K with efficiencies about 7% to 8%. To our best knowledge, this design is the first in combining the advantages of graphene electrodes and TMDs to function as a thermionic-based device.

Pushing the limits of CMOS optical parametric amplifiers with USRN:Si7N3 above the two-photon absorption edge.

CMOS platforms operating at the telecommunications wavelength either reside within the highly dissipative two-photon regime in silicon-based optical devices, or possess small nonlinearities. Bandgap engineering of non-stoichiometric silicon nitride using state-of-the-art fabrication techniques has led to our development of USRN (ultra-silicon-rich nitride) in the form of Si7N3, that possesses a high Kerr nonlinearity (2.8 × 10-13 cm2 W-1), an order of magnitude larger than that in stoichiometric silicon nitride. Here we experimentally demonstrate high-gain optical parametric amplification using USRN, which is compositionally tailored such that the 1,550 nm wavelength resides above the two-photon absorption edge, while still possessing large nonlinearities. Optical parametric gain of 42.5 dB, as well as cascaded four-wave mixing with gain down to the third idler is observed and attributed to the high photon efficiency achieved through operating above the two-photon absorption edge, representing one of the largest optical parametric gains to date on a CMOS platform.

A large common-source outbreak of norovirus gastroenteritis in a hotel in Singapore, 2012.

An outbreak of gastroenteritis affected 453 attendees (attack rate 28·5%) of six separate events held at a hotel in Singapore. Active case detection, case-control studies, hygiene inspections and microbial analysis of food, environmental and stool samples were conducted to determine the aetiology of the outbreak and the modes of transmission. The only commonality was the food, crockery and cutlery provided and/or handled by the hotel's Chinese banquet kitchen. Stool specimens from 34 cases and 15 food handlers were positive for norovirus genogroup II. The putative index case was one of eight norovirus-positive food handlers who had worked while they were symptomatic. Several food samples and remnants tested positive for Escherichia coli or high faecal coliforms, aerobic plate counts and/or total coliforms, indicating poor food hygiene. This large common-source outbreak of norovirus gastroenteritis was caused by the consumption of contaminated food and/or contact with contaminated crockery or cutlery provided or handled by the hotel's Chinese banquet kitchen.