Soft phenotyping for sepsis via EHR time-aware soft clustering.

OBJECTIVE: Sepsis is one of the most serious hospital conditions associated with high mortality. Sepsis is the result of a dysregulated immune response to infection that can lead to multiple organ dysfunction and death. Due to the wide variability in the causes of sepsis, clinical presentation, and the recovery trajectories, identifying sepsis sub-phenotypes is crucial to advance our understanding of sepsis characterization, to choose targeted treatments and optimal timing of interventions, and to improve prognostication. Prior studies have described different sub-phenotypes of sepsis using organ-specific characteristics. These studies applied clustering algorithms to electronic health records (EHRs) to identify disease sub-phenotypes. However, prior approaches did not capture temporal information and made uncertain assumptions about the relationships among the sub-phenotypes for clustering procedures. METHODS: We developed a time-aware soft clustering algorithm guided by clinical variables to identify sepsis sub-phenotypes using data available in the EHR. RESULTS: We identified six novel sepsis hybrid sub-phenotypes and evaluated them for medical plausibility. In addition, we built an early-warning sepsis prediction model using logistic regression. CONCLUSION: Our results suggest that these novel sepsis hybrid sub-phenotypes are promising to provide more accurate information on sepsis-related organ dysfunction and sepsis recovery trajectories which can be important to inform management decisions and sepsis prognosis.

Expression of Shh, Gli1, and Cyr61 in Gastric Cancer Predicts Overall Survival of Patients: A Retrospective Study.

OBJECTIVE: This study aimed to evaluate the expression levels of Shh, Gli1, and Cyr61 proteins in gastric cancer tissues and analyze the relationship between these three proteins and the clinicopathological factors and prognosis of patients. METHODS: This was a retrospective study. Four hundred gastric cancer tissue specimens from patients who underwent radical gastrectomy in Zhangye People's Hospital affiliated to Hexi University between February 2013 and February 2021 underwent immunohistochemical analysis. RESULTS: The positive expression rates of Shh, Gli1, and Cyr61 in gastric cancer tissues were 55.5%, 56.5%, and 64.5%, respectively. The expressions of Shh, Gli1, and Cyr61 in gastric cancer tissues were significantly correlated with tumor size, depth of invasion, and degree of differentiation (P < .05). The expression of Shh protein was positively correlated with the expression of Gli1 protein (P < .01), and the expression of Gli1 protein was positively correlated with the expression of Cyr61 protein (P < .01). Univariate and multivariate analyses showed that the expression of Shh, Gli1, and Cyr61 could predict the prognosis of patients (P < .05). Receiver operating characteristic curve analysis combined with TNM staging could better predict the three-year overall survival of patients (P < .05). CONCLUSION: Shh, Gli1, and Cyr61 proteins are significantly expressed in gastric cancer tissues and are risk factors for the prognosis of patients with gastric cancer.

Ultra-low-power four-wave mixing wavelength conversion in high-Q chalcogenide microring resonators.

A compact Ge11.5As24Se64.5 chalcogenide microring resonator is fabricated with an intrinsic quality factor of 3.0×105 in the telecom band. By taking advantage of the strong nonlinearity and cavity enhancement, highly efficient wavelength conversion via four-wave mixing is demonstrated using a microring resonator. Conversion efficiency of -33.7dB is obtained by using an ultra-low pump power of 63.8 µW. This work shows that Ge11.5As24Se64.5 chalcogenide microring devices are promising for quantum photonics.

CMOS compatible fabrication of micro, nano convex silicon lens arrays by conformal chemical vapor deposition.

We present a novel CMOS-compatible fabrication technique for convex micro-nano lens arrays (MNLAs) with high packing density on the wafer scale. By means of conformal chemical vapor deposition (CVD) of hydrogenated amorphous silicon (a-Si:H) following patterning of silicon pillars via electron beam lithography (EBL) and plasma etching, large areas of a close packed silicon lens array with the diameter from a few micrometers down to a few hundred nanometers was fabricated. The resulting structure shows excellent surface roughness and high uniformity. The optical focusing properties of the lenses at infrared wavelengths were verified by experimental measurements and numerical simulation. This approach provides a feasible solution for fabricating silicon MNLAs compatible for next generation large scale, miniaturized optical imaging detectors and related optical devices.

Experimental demonstration of linearly polarized 2-10 µm supercontinuum generation in a chalcogenide rib waveguide.

This Letter reports the production of a supercontinuum extending from ≈2 µm to >10 µm generated using a chalcogenide buried rib waveguide pumped with 330 femtosecond pulses at 4.184 µm. This is, to the best of our knowledge, the broadest mid-infrared supercontinuum generated in any planar waveguide platform. Because the waveguide is birefringent, quasi-single-mode, and uses an optimized dispersion design, the supercontinuum is linearly polarized with an extinction ratio >100. Dual beam spectrophotometry is performed easily using this source.

Multi-milliwatt mid-infrared supercontinuum generation in a suspended core chalcogenide fiber.

A low-loss suspended core As(38)Se(62) fiber with core diameter of 4.5 µm and a zero-dispersion wavelength of 3.5 µm was used for mid-infrared supercontinuum generation. The dispersion of the fiber was measured from 2.9 to 4.2 µm and was in good correspondence with the calculated dispersion. An optical parametric amplifier delivering 320 fs pulses with a peak power of 14.8 kW at a repetition rate of 21 MHz was used to pump 18 cm of suspended core fiber at different wavelengths from 3.3 to 4.7 µm. By pumping at 4.4 µm with a peak power of 5.2 kW coupled to the fiber a supercontinuum spanning from 1.7 to 7.5 µm with an average output power of 15.6 mW and an average power >5.0 µm of 4.7 mW was obtained.

High-resolution chalcogenide fiber bundles for infrared imaging.

An ordered chalcogenide fiber bundle with a high resolution for infrared imaging was fabricated using a stack-and-draw approach. The fiber bundle consisted of about 810,000 single fibers with an As2S3 glass core of 9 µm in diameter and a polyetherimide (PEI) polymer cladding of 10 µm in diameter. The As2S3/PEI fibers showed good transparency in the 1.5-6.5 µm spectral region. It presented a resolution of ∼45 lp/mm and a crosstalk of ∼2.5%. Fine thermal images of a hot soldering iron tip were delivered through the fiber bundle.

1.8-10 µm mid-infrared supercontinuum generated in a step-index chalcogenide fiber using low peak pump power.

By pumping an 11-cm-long step-index chalcogenide fiber with ∼330 fs pulses at 4.0 µm from an optical parametric amplifier, mid-infrared supercontinuum generation spanning from ∼1.8 to ∼10 µm within a dynamic range of ±15 dB has been demonstrated at a relatively low power threshold of ∼3000 W.

Negligible nonlinear absorption in hydrogenated amorphous silicon at 1.55 µm for ultra-fast nonlinear signal processing.

Three-photon absorption (3PA) has been observed as the dominant mechanism for nonlinear absorption in wide-bandgap hydrogenated amorphous silicon (a-Si:H-W) at 1.55 µm. The nonlinear index n2 and 3PA coefficient were measured to be 22 × 10(-17)m(2)/W and 5.0 × 10(-26) m(3)/W(2) respectively at 1.55 µm by using the z-scan method. This indicates that the figure of merit (FOM) of this material is intensity dependent. A value FOM>60 is predicted at intensities below 0.5 GW/cm(2) which is the maximum practical intensity for high-bit-rate (>160 GB/s) alloptical signal processing. The nonlinear phase change in a-Si:H-W has been compared with other common nonlinear materials (c-Si, As(2)S(3), Ge(11.5)As(24)Se(64.5)) for a 2 cm long waveguide with a-Si:H-W showing the greatest potential for integrated devices for all-optical processing with a high nonlinear index and negligible nonlinear absorption at intensities < 0.5 GW/cm(2).

Low-loss chalcogenide waveguides for chemical sensing in the mid-infrared.

We report the characteristics of low-loss chalcogenide waveguides for sensing in the mid-infrared (MIR). The waveguides consisted of a Ge11.5As24Se64.5 rib waveguide core with a 10nm fluoropolymer coating on a Ge11.5As24S64.5 bottom cladding and were fabricated by thermal evaporation, photolithography and ICP plasma etching. Over most of the functional group band from 1500 to 4000 cm⁻¹ the losses were < 1 dB/cm with a minimum of 0.3 dB/cm at 2000 cm⁻¹. The basic capabilities of these waveguides for spectroscopy were demonstrated by measuring the absorption spectrum of soluble Prussian blue in Dimethyl Sulphoxide.

Hybrid waveguide from As2S3 and Er-doped TeO2 for lossless nonlinear optics.

The fabrication and characterization of loss-compensated dispersion-engineered nonlinear As(2)S(3) on Er:TeO2 waveguides is reported for the first time, to the best of our knowledge. The hybrid waveguide is a strip loaded structure made from an Er-doped TeO2 slab and an etched As(2)S(3) strip. Almost complete loss compensation is demonstrated with 1480 nm pumping and a fully lossless waveguide with high nonlinear coefficient can be achieved with higher 1480 nm pump power.

Photonic crystal nanocavities fabricated from chalcogenide glass fully embedded in an index-matched cladding with a high Q-factor (>750,000).

We have designed and fabricated a 2-D photonic crystal hetero-structure cavity in the chalcogenide glass Ge(11.5)As(24)Se(64.5) that is fully embedded in a cladding with refractive index of 1.44. The low index contrast of this structure (≈1.21) means that high-Q resonances cannot be obtained using standard hetero-structure cavity designs based on W1 waveguides. We show that reducing the waveguide width can substantially improve light confinement, leading to high-Q resonances in a hetero-structure cavity. Numerical simulations indicate intrinsic Q(v) > 10(7) are possible with this approach. Experimentally, an optical cavity with a high intrinsic Q(v)>7.6 x 10(5) was achieved in a structure with a theoretical Q(v) = 1.7 x 10(6).

Polarization-independent chalcogenide glass nanowires with anomalous dispersion for all-optical processing.

We demonstrate the design and fabrication of square Ge11.5As24Se64.5 (Ge11) nonlinear nanowires fully embedded in a silica cladding for polarization independent (P-I) nonlinear processing. We observed similar performance for FWM using both TE and TM modes confirming that a near P-I operation was obtained. In addition we find that the supercontinuum spectrum that can be generated in the nanowires using 1ps pulse pulses with around 30W peak power was independent of polarization.

Supercontinuum generation in the mid-infrared from a dispersion-engineered As2S3 glass rib waveguide.

We report the generation of a mid-infrared supercontinuum created by ≈7.5 ps duration pulses at 3260 nm passing through a dispersion engineered As(2)S(3) rib waveguide. The threshold for a 6.6 cm long waveguide was around 800 W and at 1700 W the spectrum extended from ≈2.9-4.2 µm and was limited on the long wavelength side by absorption in the cladding of this particular waveguide.

A direct comparison of azide and nitrile vibrational probes.

The synthesis of 2'-azido-5-cyano-2'-deoxyuridine, N(3)CNdU (1), from trityl-protected 2'-amino-2'-deoxyuridine was accomplished in four steps with a 12.5% overall yield. The IR absorption positions and profiles of the azide and nitrile group of N(3)CNdU were investigated in 14 different solvents and water/DMSO solvent mixtures. The azide probe was superior to the nitrile probe in terms of its extinction coefficient, which is 2-4 times larger. However, the nitrile IR absorbance profile is generally less complicated by accidental Fermi resonance. The IR frequencies of both probes undergo a substantial red shift upon going from water to aprotic solvents such as THF or DMSO. DFT calculations supported the hypothesis that the molecular origin of the higher observed frequency in water is primarily due to hydrogen bonds between the probes and water molecules.

2D IR photon echo of azido-probes for biomolecular dynamics.

The vibrations in the azido-, N(3), asymmetric stretching region of 2'-azido-2'-deoxyuridine (N(3)dU) are examined by two-dimensional infrared spectroscopy. In water and tetrahydrofuran (THF), the spectra display a single sharp diagonal peak that shows solvent sensitivity. The frequency-frequency correlation time in water is 1.5 ps, consistent with H-bond making and breaking dynamics. The 2D IR spectrum is reproduced for N(3)dU in water based on a model correlation function and known linear response functions. Its large extinction coefficient, vibrational frequency outside the protein and nucleic acid IR absorption, and sensitivity to water dynamics render -N(3) a very useful probe for 2D IR and other nonlinear IR studies: its signal is ca. 100 times that of nitriles.

Determining the Covertness of COVID-19 - Wuhan, China, 2020.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has been going on for over a year and has reemerged in several regions. Therefore, understanding the covertness of COVID-19 is critical to more precisely estimating the pandemic size, especially the population of hidden carriers (those with very mild or no symptoms). METHODS: A stochastic dynamic model was proposed to capture the transmission mechanism of COVID-19 and to depict the covertness of COVID-19. The proposed model captured unique features of COVID-19, changes in the diagnosis criteria, and escalating containment measures. RESULTS: The model estimated that, for the epidemic in Wuhan, 79.8% (76.7%-82.7%) of the spread was caused by hidden carriers. The overall lab-confirmation rate in Wuhan up until March 8, 2020 was 0.17 (0.15-0.19). The diagnostic rate among patients with significant symptoms went up to 0.82 on March 8, 2020 from 0.43 on January 1, 2020 with escalating containment measures and nationwide medical supports. The probability of resurgence could be as high as 0.72 if containment measures were lifted after zero new reported (lab-confirmed or clinically confirmed) cases in a consecutive period of 14 days. This probability went down to 0.18 and 0.01 for measures lifted after 30 and 60 days, respectively. DISCUSSION: Consistent with the cases detected in Wuhan in mid-May, 2020, this study suggests that much of the COVID-19 pandemic is underreported and highly covert, which suggests that strict measures must be enforced continuously to contain the spread of the pandemic.

Transmission Dynamics, Heterogeneity and Controllability of SARS-CoV-2: A Rural-Urban Comparison.

Few studies have examined the transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in rural areas and clarified rural-urban differences. Moreover, the effectiveness of non-pharmaceutical interventions (NPIs) relative to vaccination in rural areas is uncertain. We addressed this knowledge gap through using an improved statistical stochastic method based on the Galton-Watson branching process, considering both symptomatic and asymptomatic cases. Data included 1136 SARS-2-CoV infections of the rural outbreak in Hebei, China, and 135 infections of the urban outbreak in Tianjin, China. We reconstructed SARS-CoV-2 transmission chains and analyzed the effectiveness of vaccination and NPIs by simulation studies. The transmission of SARS-CoV-2 showed strong heterogeneity in urban and rural areas, with the dispersion parameters k = 0.14 and 0.35, respectively (k < 1 indicating strong heterogeneity). Although age group and contact-type distributions significantly differed between urban and rural areas, the average reproductive number (R) and k did not. Further, simulation results based on pre-control parameters (R = 0.81, k = 0.27) showed that in the vaccination scenario (80% efficacy and 55% coverage), the cumulative secondary infections will be reduced by more than half; however, NPIs are more effective than vaccinating 65% of the population. These findings could inform government policies regarding vaccination and NPIs in rural and urban areas.

Dispersion engineered Ge11.5As24Se64.5 nanowires with a nonlinear parameter of 136 W⁻¹m⁻¹ at 1550 nm.

We have fabricated 630 × 500 nm nanowires from Ge(11.5)As(24)Se(64.5) chalcogenide glass by electron beam lithography (EBL) and inductively coupled plasma (ICP) etching. The loss of the nanowire was measured to be 2.6 dB/cm for the fundamental TM mode. The nonlinear coefficient (γ) was determined to be ≈136 ± 7 W(-1)m(-1) at 1550 nm by both CW four-wave-mixing (FWM) and modeling. Supercontinuum (SC) was produced in an 18 mm long nanowire pumped by 1 ps pulses with peak power of 25 W.