Impact of a rapid access chest pain clinic in Singapore to improve evaluation of new-onset chest pain.

BACKGROUND: Chest pain (CP) accounts for 5% of emergency department (ED) visits, unplanned hospitalisations and costly admissions. Conversely, outpatient evaluation requires multiple hospital visits and longer time to complete testing. Rapid access chest pain clinics (RACPCS) are established in the UK for timely, cost-effective CP assessment. This study aims to evaluate the feasibility, safety, clinical and economic benefits of a nurse-led RACPC in a multiethnic Asian country. METHODS: Consecutive CP patients referred from a polyclinic to the local general hospital were recruited. Referring physicians were left to their discretion to refer patients to the ED, RACPC (launched in April 2019) or outpatients. Patient demographics, diagnostic journey, clinical outcomes, costs, HEART (History, ECG, Age, Risk Factors, Troponin) scores and 1-year overall mortality were recorded. RESULTS: 577 CP patients (median HEAR score of 2.0) were referred; 237 before the launch of RACPC. Post RACPC, fewer patients were referred to the ED (46.5% vs 73.9%, p < 0.01), decreased adjusted bed days for CP, more non-invasive tests (46.8 vs 39.2 per 100 referrals, p = 0.07) and fewer invasive coronary angiograms (5.6 vs 12.2 per 100 referrals, p < 0.01) were performed. Time from referral to diagnosis was shortened by 90%, while requiring 66% less visits (p < 0.01). System cost to evaluate CP was reduced by 20.7% and all RACPC patients were alive at 12 months. CONCLUSIONS: An Asian nurse-led RACPC expedited specialist evaluation of CP with less visits, reduced ED attendances and invasive testing whilst saving costs. Wider implementation across Asia would significantly improve CP evaluation.

Spectral control of nonclassical light pulses using an integrated thin-film lithium niobate modulator.

Manipulating the frequency and bandwidth of nonclassical light is essential for implementing frequency-encoded/multiplexed quantum computation, communication, and networking protocols, and for bridging spectral mismatch among various quantum systems. However, quantum spectral control requires a strong nonlinearity mediated by light, microwave, or acoustics, which is challenging to realize with high efficiency, low noise, and on an integrated chip. Here, we demonstrate both frequency shifting and bandwidth compression of heralded single-photon pulses using an integrated thin-film lithium niobate (TFLN) phase modulator. We achieve record-high electro-optic frequency shearing of telecom single photons over terahertz range (±641 GHz or ±5.2 nm), enabling high visibility quantum interference between frequency-nondegenerate photon pairs. We further operate the modulator as a time lens and demonstrate over eighteen-fold (6.55 nm to 0.35 nm) bandwidth compression of single photons. Our results showcase the viability and promise of on-chip quantum spectral control for scalable photonic quantum information processing.

Surface Plasmon Enhanced Upconversion Fluorescence in Short-Wave Infrared for In Vivo Imaging of Ovarian Cancer.

Short-wave infrared (SWIR; 850-1700 nm) upconversion fluorescence enables "autofluorescence-free" imaging with minimal tissue scattering, yet it is rarely explored due to the lack of strongly emissive SWIR upconversion fluorophores. In this work, we apply SWIR upconversion fluorescence for in vivo imaging with exceptional image contrast. Gold nanorods (AuNRs) are used to enhance the SWIR upconversion emission of small organic dyes, forming a AuNR-dye nanocomposite (NC). A maximal enhancement factor of ∼1320, contributed by both excitation and radiative decay rate enhancement, is achieved by varying the dye-to-AuNR ratio. In addition, the upconversion emission intensity of both free dyes and AuNR-dye NCs depends linearly on the excitation power, indicating that the upconversion emission mechanism remains unchanged upon enhancement, and it involves one-photon absorption. Moreover, the SWIR upconversion emission shows a significantly higher signal contrast than downconversion emission in the same emission window in a nonscattering medium. Finally, we apply the surface plasmon enhanced SWIR upconversion fluorescence for in vivo imaging of ovarian cancer, demonstrating high image contrast and low required dosage due to the suppressed autofluorescence.

Spectrally separable photon-pair generation in dispersion engineered thin-film lithium niobate.

Existing nonlinear-optic implementations of pure, unfiltered heralded single-photon sources do not offer the scalability required for densely integrated quantum networks. Additionally, lithium niobate has hitherto been unsuitable for such use due to its material dispersion. We engineer the dispersion and the quasi-phasematching conditions of a waveguide in the rapidly emerging thin-film lithium niobate platform to generate spectrally separable photon pairs in the telecommunications band. Such photon pairs can be used as spectrally pure heralded single-photon sources in quantum networks. We estimate a heralded-state spectral purity of >94% based on joint spectral intensity measurements. Further, a joint spectral phase-sensitive measurement of the unheralded time-integrated second-order correlation function yields a heralded-state purity of (86±5)%.

Experimental Demonstration of Conjugate-Franson Interferometry.

Franson interferometry is a well-known quantum measurement technique for probing photon-pair frequency correlations that is often used to certify time-energy entanglement. We demonstrate, for the first time, the complementary technique in the time basis called conjugate-Franson interferometry. It measures photon-pair arrival-time correlations, thus providing a valuable addition to the quantum toolbox. We obtain a conjugate-Franson interference visibility of 96±1% without background subtraction for entangled photon pairs generated by spontaneous parametric down-conversion. Our measured result surpasses the quantum-classical threshold by 25 standard deviations and validates the conjugate-Franson interferometer (CFI) as an alternative method for certifying time-energy entanglement. Moreover, the CFI visibility is a function of the biphoton's joint temporal intensity, and is therefore sensitive to that state's spectral phase variation: something that is not the case for Franson interferometry or Hong-Ou-Mandel interferometry. We highlight the CFI's utility by measuring its visibilities for two different biphoton states: one without and the other with spectral phase variation, observing a 21% reduction in the CFI visibility for the latter. The CFI is potentially useful for applications in areas of photonic entanglement, quantum communications, and quantum networking.

Identifying COVID-19 cases in outpatient settings.

Case identification is an ongoing issue for the COVID-19 epidemic, in particular for outpatient care where physicians must decide which patients to prioritise for further testing. This paper reports tools to classify patients based on symptom profiles based on 236 severe acute respiratory syndrome coronavirus 2 positive cases and 564 controls, accounting for the time course of illness using generalised multivariate logistic regression. Significant symptoms included abdominal pain, cough, diarrhoea, fever, headache, muscle ache, runny nose, sore throat, temperature between 37.5 and 37.9 °C and temperature above 38 °C, but their importance varied by day of illness at assessment. With a high percentile threshold for specificity at 0.95, the baseline model had reasonable sensitivity at 0.67. To further evaluate accuracy of model predictions, leave-one-out cross-validation confirmed high classification accuracy with an area under the receiver operating characteristic curve of 0.92. For the baseline model, sensitivity decreased to 0.56. External validation datasets reported similar result. Our study provides a tool to discern COVID-19 patients from controls using symptoms and day from illness onset with good predictive performance. It could be considered as a framework to complement laboratory testing in order to differentiate COVID-19 from other patients presenting with acute symptoms in outpatient care.

Single-photon frequency shifting with a quadrature phase-shift keying modulator.

Deterministic frequency manipulation of single photons is an essential tool for quantum communications and quantum networks. We demonstrate a 15.65 GHz frequency shift for classical and nonclassical light using a commercially available quadrature phase-shift keying modulator. The measured spectrum of frequency-shifted single photons indicates a high carrier-to-sideband ratio of 30 dB. We illustrate our frequency shifter's utility in quantum photonics by performing Hong-Ou-Mandel quantum interference between two photons whose initial frequency spectra overlap only partially, and showing visibility improvement from 62.7 to 89.1% after one of the photons undergoes a corrective frequency shift.

Seeing around corners with edge-resolved transient imaging.

Non-line-of-sight (NLOS) imaging is a rapidly growing field seeking to form images of objects outside the field of view, with potential applications in autonomous navigation, reconnaissance, and even medical imaging. The critical challenge of NLOS imaging is that diffuse reflections scatter light in all directions, resulting in weak signals and a loss of directional information. To address this problem, we propose a method for seeing around corners that derives angular resolution from vertical edges and longitudinal resolution from the temporal response to a pulsed light source. We introduce an acquisition strategy, scene response model, and reconstruction algorithm that enable the formation of 2.5-dimensional representations-a plan view plus heights-and a 180∘ field of view for large-scale scenes. Our experiments demonstrate accurate reconstructions of hidden rooms up to 3 meters in each dimension despite a small scan aperture (1.5-centimeter radius) and only 45 measurement locations.

Resolving Photon Numbers Using a Superconducting Nanowire with Impedance-Matching Taper.

Time- and number-resolved photon detection is crucial for quantum information processing. Existing photon-number-resolving (PNR) detectors usually suffer from limited timing and dark-count performance or require complex fabrication and operation. Here, we demonstrate a PNR detector at telecommunication wavelengths based on a single superconducting nanowire with an integrated impedance-matching taper. The taper provides a kΩ load impedance to the nanowire, making the detector's output amplitude sensitive to the number of photon-induced hotspots. The prototyping device was able to resolve up to four absorbed photons with 16.1 ps timing jitter and <2 c.p.s. device dark count rate. Its exceptional distinction between single- and two-photon responses is ideal for high-fidelity coincidence counting and allowed us to directly observe bunching of photon pairs from a single output port of a Hong-Ou-Mandel interferometer. This detector architecture may provide a practical solution to applications that require high timing resolution and few-photon discrimination.

Large-alphabet encoding for higher-rate quantum key distribution.

The manipulation of high-dimensional degrees of freedom provides new opportunities for more efficient quantum information processing. It has recently been shown that high-dimensional encoded states can provide significant advantages over binary quantum states in applications of quantum computation and quantum communication. In particular, high-dimensional quantum key distribution enables higher secret-key generation rates under practical limitations of detectors or light sources, as well as greater error tolerance. Here, we demonstrate high-dimensional quantum key distribution capabilities both in the laboratory and over a deployed fiber, using photons encoded in a high-dimensional alphabet to increase the secure information yield per detected photon. By adjusting the alphabet size, it is possible to mitigate the effects of receiver bottlenecks and optimize the secret-key rates for different channel losses. This work presents a strategy for achieving higher secret-key rates in receiver-limited scenarios and marks an important step toward high-dimensional quantum communication in deployed fiber networks.

Indistinguishable single-mode photons from spectrally engineered biphotons.

We use pulsed spontaneous parametric down-conversion in KTiOPO 4, with a Gaussian phase-matching function and a transform-limited Gaussian pump, to achieve near-unity spectral purity in heralded single photons at telecommunication wavelength. Theory shows that these phase-matching and pump conditions are sufficient to ensure that a biphoton state with a circularly symmetric joint spectral intensity profile is transform limited and factorable. We verify the heralded-state spectral purity in a four-fold coincidence measurement by performing Hong-Ou-Mandel interference between two independently generated heralded photons. With a mild spectral filter we obtain an interference visibility of 98.4±1.1% which corresponds to a heralded-state purity of 99.2%. Our heralded photon source is potentially an essential resource for measurement-based quantum information processing and quantum network applications.

Comparing monovalent and combination hepatitis B vaccine outcomes in children delivered by mothers with chronic hepatitis B.

AIM: We compared the vaccine effectiveness of monovalent and combination hepatitis B vaccine regimens in infants born to chronic hepatitis B carrier mothers. METHODS: An observational cohort of neonates was recruited over 78 months from two public hospital maternity units in Singapore. We enrolled term infants, born to chronic hepatitis B surface antigen-positive mothers regardless of their hepatitis Be antigen status, who completed the hepatitis B virus (HBV) vaccination programme in Singapore. Infants born to mothers on antiviral therapy, or with concurrent hepatitis C or human immunodeficiency virus infection were excluded. All infants received hepatitis B immunoglobulin at birth. One group received three doses of monovalent hepatitis B vaccine (0, 1, 6 months) (regimen A). The other group received two doses of monovalent vaccine, followed by one dose combination vaccine DTaP-IPV-Hib-HBV (0, 1, 6 months) (regimen B). Vaccine effectiveness was determined by immunoprophylaxis failure leading to HBV vertical transmission. Immunogenicity was assessed by hepatitis B surface antibody (anti-HBs) levels at 9 months of age. RESULTS: Total of 177 term neonates received regimen A and 115 received regimen B. Immunoprophylaxis failure rate was low, 2.3 and 2.6% (P = 1.00) in regimen A and B, respectively. Mean anti-HBs titres were similar at 643 ± 374 and 561 ± 396 IU/L (P = 0.08) for regimen A and B, respectively. CONCLUSION: Hepatitis B vaccine regimens using monovalent or combination vaccine for the third dose showed similarly high vaccine effectiveness and low immunoprophylaxis failure rate in term infants born to chronic hepatitis B carrier mothers.

Validation of a Natural Language Processing Algorithm for Detecting Infectious Disease Symptoms in Primary Care Electronic Medical Records in Singapore.

BACKGROUND: Free-text clinical records provide a source of information that complements traditional disease surveillance. To electronically harness these records, they need to be transformed into codified fields by natural language processing algorithms. OBJECTIVE: The aim of this study was to develop, train, and validate Clinical History Extractor for Syndromic Surveillance (CHESS), an natural language processing algorithm to extract clinical information from free-text primary care records. METHODS: CHESS is a keyword-based natural language processing algorithm to extract 48 signs and symptoms suggesting respiratory infections, gastrointestinal infections, constitutional, as well as other signs and symptoms potentially associated with infectious diseases. The algorithm also captured the assertion status (affirmed, negated, or suspected) and symptom duration. Electronic medical records from the National Healthcare Group Polyclinics, a major public sector primary care provider in Singapore, were randomly extracted and manually reviewed by 2 human reviewers, with a third reviewer as the adjudicator. The algorithm was evaluated based on 1680 notes against the human-coded result as the reference standard, with half of the data used for training and the other half for validation. RESULTS: The symptoms most commonly present within the 1680 clinical records at the episode level were those typically present in respiratory infections such as cough (744/7703, 9.66%), sore throat (591/7703, 7.67%), rhinorrhea (552/7703, 7.17%), and fever (928/7703, 12.04%). At the episode level, CHESS had an overall performance of 96.7% precision and 97.6% recall on the training dataset and 96.0% precision and 93.1% recall on the validation dataset. Symptoms suggesting respiratory and gastrointestinal infections were all detected with more than 90% precision and recall. CHESS correctly assigned the assertion status in 97.3%, 97.9%, and 89.8% of affirmed, negated, and suspected signs and symptoms, respectively (97.6% overall accuracy). Symptom episode duration was correctly identified in 81.2% of records with known duration status. CONCLUSIONS: We have developed an natural language processing algorithm dubbed CHESS that achieves good performance in extracting signs and symptoms from primary care free-text clinical records. In addition to the presence of symptoms, our algorithm can also accurately distinguish affirmed, negated, and suspected assertion statuses and extract symptom durations.

Revealing hidden scenes by photon-efficient occlusion-based opportunistic active imaging.

The ability to see around corners, i.e., recover details of a hidden scene from its reflections in the surrounding environment, is of considerable interest in a wide range of applications. However, the diffuse nature of light reflected from typical surfaces leads to mixing of spatial information in the collected light, precluding useful scene reconstruction. Here, we employ a computational imaging technique that opportunistically exploits the presence of occluding objects, which obstruct probe-light propagation in the hidden scene, to undo the mixing and greatly improve scene recovery. Importantly, our technique obviates the need for the ultrafast time-of-flight measurements employed by most previous approaches to hidden-scene imaging. Moreover, it does so in a photon-efficient manner (i.e., it only requires a small number of photon detections) based on an accurate forward model and a computational algorithm that, together, respect the physics of three-bounce light propagation and single-photon detection. Using our methodology, we demonstrate reconstruction of hidden-surface reflectivity patterns in a meter-scale environment from non-time-resolved measurements. Ultimately, our technique represents an instance of a rich and promising new imaging modality with important potential implications for imaging science.

Efficient generation and characterization of spectrally factorable biphotons.

Spectrally unentangled biphotons with high single-spatiotemporal-mode purity are highly desirable for many quantum information processing tasks. We generate biphotons with an inferred heralded-state spectral purity of 99%, the highest to date without any spectral filtering, by pulsed spontaneous parametric downconversion in a custom-fabricated periodically-poled KTiOPO4 crystal under extended Gaussian phase-matching conditions. To efficiently characterize the joint spectral intensity of the generated biphotons at high spectral resolution, we employ a commercially available dispersion compensation module (DCM) with a dispersion equivalent to 100 km of standard optical fiber and with an insertion loss of only 2.8 dB. Compared with the typical method of using two temperature-stabilized equal-length fibers that incurs an insertion loss of 20 dB per fiber, the DCM approach achieves high spectral resolution in a much shorter measurement time. Because the dispersion amount and center wavelengths of DCMs can be easily customized, spectral characterization in a wide range of quantum photonic applications should benefit significantly from this technique.

Unity-Efficiency Parametric Down-Conversion via Amplitude Amplification.

We propose an optical scheme, employing optical parametric down-converters interlaced with nonlinear sign gates (NSGs), that completely converts an n-photon Fock-state pump to n signal-idler photon pairs when the down-converters' crystal lengths are chosen appropriately. The proof of this assertion relies on amplitude amplification, analogous to that employed in Grover search, applied to the full quantum dynamics of single-mode parametric down-conversion. When we require that all Grover iterations use the same crystal, and account for potential experimental limitations on crystal-length precision, our optimized conversion efficiencies reach unity for 1≤n≤5, after which they decrease monotonically for n values up to 50, which is the upper limit of our numerical dynamics evaluations. Nevertheless, our conversion efficiencies remain higher than those for a conventional (no NSGs) down-converter.

Serologic Responses After Hepatitis B Vaccination in Preterm Infants Born to Hepatitis B Surface Antigen-Positive Mothers: Singapore Experience.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends a 4-dose vaccination schedule for preterm low birth weight infants (<2 kg) and a 3-dose vaccination schedule for preterm infants (≥2 kg) born to hepatitis B surface antigen (HBsAg)-positive mothers. However, data remain limited for these high-risk infants, and the optimal dosing schedule in Asia is not well established. AIM: The aim of this study was to evaluate the serologic vaccine responses in preterm infants born to HBsAg-positive mothers using current vaccination guidelines. METHODS: Preterm babies of gestation less than 37 completed weeks born to HBsAg-positive mothers were prospectively recruited during 6 years (June 2009 to December 2015) and retrospectively recruited via convenience sampling in 2 years (June 2013 to April 2015) in 2 tertiary pediatric centers. The preterm infants were given 4 or 3 vaccine doses as per ACIP 2005 guidelines. Vaccine response was defined as achieving hepatitis B surface antibody values of >10 IU/L [Abbott Architect (Abbott Laboratories, Chicago, IL)] at 9 months of chronologic age. RESULTS: A total of 24 preterm infants were recruited. Four had a birth weight <2 kg. Of 23 surviving infants, all were negative for HBsAg. One baby (4.5%) did not achieve adequate vaccine response. All 4 infants with birth weight <2 kg achieved seroprotective values. CONCLUSION: The current ACIP-recommended vaccination schedule results in adequate antibody responses in preterm infants of HBsAg-positive mothers.

Photon-efficient imaging with a single-photon camera.

Reconstructing a scene's 3D structure and reflectivity accurately with an active imaging system operating in low-light-level conditions has wide-ranging applications, spanning biological imaging to remote sensing. Here we propose and experimentally demonstrate a depth and reflectivity imaging system with a single-photon camera that generates high-quality images from ∼1 detected signal photon per pixel. Previous achievements of similar photon efficiency have been with conventional raster-scanning data collection using single-pixel photon counters capable of ∼10-ps time tagging. In contrast, our camera's detector array requires highly parallelized time-to-digital conversions with photon time-tagging accuracy limited to ∼ns. Thus, we develop an array-specific algorithm that converts coarsely time-binned photon detections to highly accurate scene depth and reflectivity by exploiting both the transverse smoothness and longitudinal sparsity of natural scenes. By overcoming the coarse time resolution of the array, our framework uniquely achieves high photon efficiency in a relatively short acquisition time.

Computational multi-depth single-photon imaging.

We present an imaging framework that is able to accurately reconstruct multiple depths at individual pixels from single-photon observations. Our active imaging method models the single-photon detection statistics from multiple reflectors within a pixel, and it also exploits the fact that a multi-depth profile at each pixel can be expressed as a sparse signal. We interpret the multi-depth reconstruction problem as a sparse deconvolution problem using single-photon observations, create a convex problem through discretization and relaxation, and use a modified iterative shrinkage-thresholding algorithm to efficiently solve for the optimal multi-depth solution. We experimentally demonstrate that the proposed framework is able to accurately reconstruct the depth features of an object that is behind a partially-reflecting scatterer and 4 m away from the imager with root mean-square error of 11 cm, using only 19 signal photon detections per pixel in the presence of moderate background light. In terms of root mean-square error, this is a factor of 4.2 improvement over the conventional method of Gaussian-mixture fitting for multi-depth recovery.

Classical imaging with undetected photons.

Barreto Lemos et al. [Nature 512, 409-412 (2014)] reported an experiment in which a non-degenerate parametric downconverter and a non-degenerate optical parametric amplifier--used as a wavelength-converting phase conjugator--were employed to image object transparencies in a manner akin to ghost imaging. Their experiment, however, relied on single-photon detection, rather than the photon-coincidence measurements employed in ghost imaging with a parametric downconverter source. More importantly, their system formed images despite the photons that passed through the object never being detected. Barreto Lemos et al. interpreted their experiment as a quantum imager, as assuredly it is, owing to its downconverter's emitting entangled signal and idler beams. We show, however, that virtually all the features of their setup can be realized in a quantum-mimetic fashion using classical-state light, specifically a pair of bright pseudothermal beams possessing a phase-sensitive cross correlation. Owing to its much higher signal-to-noise ratio, our bright-source classical imager could greatly reduce image-acquisition time compared to that of Barreto Lemos et al.'s quantum system, while retaining the latter's ability to image with undetected photons.