Particles in Exhaled Air (PExA): Clinical Uses and Future Implications.

Access to distal airway samples to assess respiratory diseases is not straightforward and requires invasive procedures such as bronchoscopy and bronchoalveolar lavage. The particles in exhaled air (PExA) device provides a non-invasive means of assessing small airways; it captures distal airway particles (PEx) sized around 0.5-7 µm and contains particles of respiratory tract lining fluid (RTLF) that originate during airway closure and opening. The PExA device can count particles and measure particle mass according to their size. The PEx particles can be analysed for metabolites on various analytical platforms to quantitatively measure targeted and untargeted lung specific markers of inflammation. As such, the measurement of distal airway components may help to evaluate acute and chronic inflammatory conditions such as asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, and more recently, acute viral infections such as COVID-19. PExA may provide an alternative to traditional methods of airway sampling, such as induced sputum, tracheal aspirate, or bronchoalveolar lavage. The measurement of specific biomarkers of airway inflammation obtained directly from the RTLF by PExA enables a more accurate and comprehensive understanding of pathophysiological changes at the molecular level in patients with acute and chronic lung diseases.

Towards quantifying biomarkers for respiratory distress in preterm infants: Machine learning on mid infrared spectroscopy of lipid mixtures.

Neonatal respiratory distress syndrome (nRDS) is a challenging condition to diagnose which can lead to delays in receiving appropriate treatment. Mid infrared (IR) spectroscopy is capable of measuring the concentrations of two diagnostic nRDS biomarkers, lecithin (L) and sphingomyelin (S) with the potential for point of care (POC) diagnosis and monitoring. The effects of varying other lipid species present in lung surfactant on the mid IR spectra used to train machine learning models are explored. This study presents a lung lipid model of five lipids present in lung surfactant and varies each in a systematic approach to evaluate the ability of machine learning models to predict the lipid concentrations, the L/S ratio and to quantify the uncertainty in the predictions using the jackknife + -after-bootstrap and variant bootstrap methods. We establish the L/S ratio can be determined with an uncertainty of approximately ±0.3 mol/mol and we further identify the 5 most prominent wavenumbers associated with each machine learning model.

Pulmonary Surfactant in Adult ARDS: Current Perspectives and Future Directions.

Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults, leading to the requirement for mechanical ventilation and poorer outcomes. Dysregulated surfactant metabolism and function are characteristic of ARDS. A combination of alveolar epithelial damage leading to altered surfactant synthesis, secretion, and breakdown with increased functional inhibition from overt alveolar inflammation contributes to the clinical features of poor alveolar compliance and alveolar collapse. Quantitative and qualitative alterations in the bronchoalveolar lavage and tracheal aspirate surfactant composition contribute to ARDS pathogenesis. Compared to neonatal respiratory distress syndrome (nRDS), replacement studies of exogenous surfactants in adult ARDS suggest no survival benefit. However, these studies are limited by disease heterogeneity, variations in surfactant preparations, doses, and delivery methods. More importantly, the lack of mechanistic understanding of the exact reasons for dysregulated surfactant remains a significant issue. Moreover, studies suggest an extremely short half-life of replaced surfactant, implying increased catabolism. Refining surfactant preparations and delivery methods with additional co-interventions to counteract surfactant inhibition and degradation has the potential to enhance the biophysical characteristics of surfactant in vivo.

Prediction of Neonatal Respiratory Distress Biomarker Concentration by Application of Machine Learning to Mid-Infrared Spectra.

The authors of this study developed the use of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) combined with machine learning as a point-of-care (POC) diagnostic platform, considering neonatal respiratory distress syndrome (nRDS), for which no POC currently exists, as an example. nRDS can be diagnosed by a ratio of less than 2.2 of two nRDS biomarkers, lecithin and sphingomyelin (L/S ratio), and in this study, ATR-FTIR spectra were recorded from L/S ratios of between 1.0 and 3.4, which were generated using purified reagents. The calibration of principal component (PCR) and partial least squares (PLSR) regression models was performed using 155 raw baselined and second derivative spectra prior to predicting the concentration of a further 104 spectra. A three-factor PLSR model of second derivative spectra best predicted L/S ratios across the full range (R2: 0.967; MSE: 0.014). The L/S ratios from 1.0 to 3.4 were predicted with a prediction interval of +0.29, -0.37 when using a second derivative spectra PLSR model and had a mean prediction interval of +0.26, -0.34 around the L/S 2.2 region. These results support the validity of combining ATR-FTIR with machine learning to develop a point-of-care device for detecting and quantifying any biomarker with an interpretable mid-infrared spectrum.

Broadband 2 × 2 multimode interference coupler for mid-infrared wavelengths.

Beam splitters are core components of photonic integrated circuits and are often implemented with multimode interference couplers. While these devices offer high performance, their operational bandwidth is still restrictive for sensing applications in the mid-infrared wavelength range. Here we experimentally demonstrate a subwavelength-structured 2×2 multimode interference coupler with high performance in the 3.1-3.7µm range, doubling the bandwidth of a conventional device.

Study of waveguide background at visible wavelengths for on-chip nanoscopy.

On-chip super-resolution optical microscopy is an emerging field relying on waveguide excitation with visible light. Here, we investigate two commonly used high-refractive index waveguide platforms, tantalum pentoxide (Ta2O5) and silicon nitride (Si3N4), with respect to their background with excitation in the range 488-640 nm. The background strength from these waveguides were estimated by imaging fluorescent beads. The spectral dependence of the background from these waveguide platforms was also measured. For 640 nm wavelength excitation both the materials had a weak background, but the background increases progressively for shorter wavelengths for Si3N4. We further explored the effect of the waveguide background on localization precision of single molecule localization for direct stochastic optical reconstruction microscopy (dSTORM). An increase in background for Si3N4 at 488 nm is shown to reduce the localization precision and thus the resolution of the reconstructed images. The localization precision at 640nm was very similar for both the materials. Thus, for shorter wavelength applications Ta2O5 is preferable. Reducing the background from Si3N4 at shorter wavelengths via improved fabrication will be worth pursuing.

Extraordinary evanescent field confinement waveguide sensor for mid-infrared trace gas spectroscopy.

Nanophotonic waveguides are at the core of a great variety of optical sensors. These structures confine light along defined paths on photonic chips and provide light-matter interaction via an evanescent field. However, waveguides still lag behind free-space optics for sensitivity-critical applications such as trace gas detection. Short optical pathlengths, low interaction strengths, and spurious etalon fringes in spectral transmission are among the main reasons why on-chip gas sensing is still in its infancy. In this work, we report on a mid-infrared integrated waveguide sensor that successfully addresses these drawbacks. This sensor operates with a 107% evanescent field confinement factor in air, which not only matches but also outperforms free-space beams in terms of the per-length optical interaction. Furthermore, negligible facet reflections result in a flat spectral background and record-low absorbance noise that can finally compete with free-space spectroscopy. The sensor performance was validated at 2.566 µm, which showed a 7 ppm detection limit for acetylene with only a 2 cm long waveguide.

A general model for taper coupling of multiple modes of whispering gallery resonators and application to analysis of coupling-induced Fano interference in a single cavity.

In this paper, we give a general model for analysis of multimode Whispering Gallery Mode (WGM) resonators coupled to multimode tapered fibers based on the coupled-mode theory. Such formulation takes into account the asymmetry of the taper-resonator coupling. Simulations for a microsphere show that the tapered fiber coupling mechanism induces cross-coupling between coherent orthonormal WGMs. We show that the degree of such cross-coupling depends basically on the fiber diameter, air-gap between the taper and resonator, intrinsic losses and eccentricity. The WGM cross-coupling affects the total transmission and spectral line-shape of the internal powers resulting in a controllable transformation of the line-shape to non-Lorentzian spectra. This analysis can be utilized to precisely determine the output and intra-cavity intensity of multimode microresonators, which is important in lasers, nonlinear optical signal generation and realization of optical delays.

Effects of participatory learning and action with women's groups, counselling through home visits and crèches on undernutrition among children under three years in eastern India: a quasi-experimental study.

BACKGROUND: India faces a high burden of child undernutrition. We evaluated the effects of two community strategies to reduce undernutrition among children under 3 years in rural Jharkhand and Odisha, eastern India: (1) monthly Participatory Learning and Action (PLA) meetings with women's groups followed by home visits; (2) crèches for children aged 6 months to 3 years combined with monthly PLA meetings and home visits. METHODS: We tested these strategies in a non-randomised, controlled study with baseline and endline cross-sectional surveys. We purposively selected five blocks of Jharkhand and Odisha, and divided each block into three areas. Area 1 served as control. In Area 2, trained local female workers facilitated PLA meetings and offered counselling to mothers of children under three at home. In Area 3, workers facilitated PLA meetings, did home visits, and crèches with food and growth monitoring were opened for children aged 6 months to 3 years. We did a census across all study areas and randomly sampled 4668 children under three and their mothers for interview and anthropometry at baseline and endline. The evaluation's primary outcome was wasting among children under three in areas 2 and 3 compared with area 1, adjusted for baseline differences between areas. Other outcomes included underweight, stunting, preventive and care-seeking practices for children. RESULTS: We interviewed 83% (3868/4668) of mothers of children under three sampled at baseline, and 76% (3563/4668) at endline. In area 2 (PLA and home visits), wasting among children under three was reduced by 34% (adjusted Odds Ratio [aOR]: 0.66, 95%: 0.51-0.88) and underweight by 25% (aOR: 0.75, 95% CI: 0.59-0.95), with no change in stunting (aOR: 1.23, 95% CI: 0.96-1.57). In area 3, (PLA, home visits, crèches), wasting was reduced by 27% (aOR: 0.73, 95% CI: 0.55-0.97), underweight by 40% (aOR: 0.60, 95% CI: 0.47-0.75), and stunting by 27% (aOR: 0.73, 95% CI: 0.57-0.93). CONCLUSIONS: Crèches, PLA meetings and home visits reduced undernutrition among children under three in rural eastern India. These interventions could be scaled up through government plans to strengthen home visits and community mobilisation with Accredited Social Health Activists, and through efforts to promote crèches. TRIAL REGISTRATION: The evaluation was registered retrospectively with Current Controlled Trials as ISCRTN89911047 on 30/01/2019.

Design of rare-earth-doped microbottle lasers.

Coupling strength in taper-coupled microbottle resonators can be tuned by offsetting the taper along the resonator profile, similar to controlling the air-gap in microsphere excitation, and hence, achieve desired coupling characteristics for a specific mode. Such flexibility makes microbottles attractive and adaptable laser cavities. In this paper, lasing characteristics of Yb3+-doped microbottle laser (MBL) coupled to tapered fiber are theoretically investigated. It is demonstrated that desired lasing characteristics for a particular mode are achievable by controlling the taper-resonator coupling, intrinsic quality factor (Q) and dopant concentration. Although, high Q whispering gallery cavities provide high internal powers, which is favorable especially for low gain materials, they lack high output powers. Hence, care should be taken in designing MBLs to attain the highest possible output power. Here, we address such issues, and optimized the required resonator parameters (for both pump and signal) for a low threshold pump power, high efficiency and desired lasing wavelength.

Chalcogenide glass waveguides with paper-based fluidics for mid-infrared absorption spectroscopy.

We demonstrate the integration of paper fluidics with mid-infrared (MIR) chalcogenide waveguides to introduce liquid samples to the waveguide evanescent field for analysis. Spectroscopy of model analytes (water and isopropyl alcohol) having well-defined mid-IR absorptions, on a ZnSe rib waveguide fabricated on silicon, is demonstrated in the wavelength range of 2.6-3.7 µm, showing their O-H and C-H stretching absorptions. The results are compared with a theoretical waveguide model, achieving good agreement. It is concluded that the presence of paper in the evanescent field does not interfere with the waveguide measurements, opening up opportunities to combine low-cost paper-based fluidics and integrated photonic technologies.

Denying access of Particularly Vulnerable Tribal Groups to contraceptive services: a case study among the Baiga community in Chhattisgarh, India.

Baigas are a Particularly Vulnerable Tribal Group (PVTG), categorised as the most vulnerable amongst indigenous communities in India. As a strategy to stall their decreasing population, due mainly to high mortality, in 1979 the government restricted their access to permanent contraceptive methods, and this is enforced as a "ban". Using a case study design with mixed methods, this study aims to understand the experiences and perceptions of Baigas in Chhattisgarh in accessing contraceptive services. Data was collected through: a household survey (n = 289) in 13 habitations; individual interviews and group discussions with Baiga men and women and health service providers; and anthropometry. The Baiga suffer poor nutritional status and poverty, out of proportion with district and state averages. Of the women interviewed, 61.3% have had four or more pregnancies and 61.3% have experienced the loss of child at least once during pregnancy or later. Baiga women's forehead tattoo, a marker of their identity, is used to deny them contraceptive services. Baiga women either have to travel to the neighbouring state to avail themselves of services, or lie about their identity. They are usually unable to access even the temporary methods. This coercive policy has led to their further impoverishment. Baigas have been demanding the right to contraceptive services. Denying contraceptive services is a violation of reproductive and human rights and the right to self-determination and bodily autonomy.

Germanium-on-silicon waveguides operating at mid-infrared wavelengths up to 8.5 µm.

We report transmission measurements of germanium on silicon waveguides in the 7.5-8.5 µm wavelength range, with a minimum propagation loss of 2.5 dB/cm at 7.575 µm. However, we find an unexpected strongly increasing loss at higher wavelengths, potential causes of which we discuss in detail. We also demonstrate the first germanium on silicon multimode interferometers operating in this range, as well as grating couplers optimized for measurement using a long wavelength infrared camera. Finally, we use an implementation of the "cut-back" method for loss measurements that allows simultaneous transmission measurement through multiple waveguides of different lengths, and we use dicing in the ductile regime for fast and reproducible high quality optical waveguide end-facet preparation.

Fabrication and characterization of high-contrast mid-infrared GeTe4 channel waveguides.

We report the fabrication and characterization of high index contrast (Δn≈0.9) GeTe4 channel waveguides on ZnSe substrate for evanescent-field-based biosensing applications in the mid-IR spectral region. GeTe4 films were deposited by RF sputtering and characterized for their structure, composition, transparency, and dispersion. The lift-off technique was used to pattern the waveguide channels. Waveguiding from 2.5-3.7 and 6.4-7.5 µm was demonstrated, and mode intensity profile and estimated propagation losses are given for the 3.5 µm wavelength.

Packaged, high-Q, microsphere-resonator-based add-drop filter.

In this Letter a packaged add-drop filter composed of a silica microsphere resonator and two fiber tapers is demonstrated theoretically and experimentally. A two-step fabrication process using an UV curable polymer is shown to stabilize the microsphere resonator with a diameter of 153 µm coupled to two tapered microfibers with diameters of 1.5 µm which are used as add and drop ports. A high loaded quality factor (Q-factor) of 0.9×10(5) and a free spectral range (FSR) of about 104 pm are obtained at around 1550 nm from the microsphere for the parallel coupling tapered fibers in the add-drop configuration. This device has a range of advantages, such as ease of fabrication, low-cost, and compatibility with traditional and commercial fiber systems.

Continuous-wave and Q-switched Tm-doped KY(WO4)2 planar waveguide laser at 1.84 µm.

High-quality monoclinic planar waveguide crystals of Tm-doped KY(WO4)2 codoped with Gd3+ and Lu3+ were grown by liquid-phase epitaxy. For the first time, planar waveguide lasing was demonstrated in a monolithic cavity in the 2 µm spectral range. The laser was operated in the Q-switched mode using a Cr2+:ZnSe crystal as saturable absorber and in the continuous-wave regimes. The Q-switched planar waveguide laser delivered pulse energies up to 120 nJ at a repetition rate of 7 kHz.

Integrated Nd-doped borosilicate glass microsphere laser.

A neodymium-doped BK7 glass microsphere laser integrated with a planar ion-exchanged waveguide pumped at 0.8 µm has been demonstrated. The pump radiation was launched by evanescent coupling from the waveguide, and the signal radiation was coupled out through the same waveguide, offering the potential for robustly assembled fully integrated active optical circuits. The dependence of the lasing spectra on pump power and wavelength were studied in detail to clarify the whispering-gallery-mode behavior at the pump and lasing wavelengths.

Optical excitation and probing of whispering gallery modes in bottle microresonators: potential for all-fiber add-drop filters.

We have investigated the optical excitation and probing of bottle microresonators experimentally, using fiber tapers. The channel-dropping characteristics of such devices are shown to depend on the excitation configuration. In addition, the axial leakage behavior of these microresonators is characterized.

Mirrorless buried waveguide laser in monoclinic double tungstates fabricated by a novel combination of ion milling and liquid phase epitaxy.

Buried channel waveguides were fabricated by liquid phase epitaxial growth of a lattice-matched KY(0.58)Gd(0.22)Lu(0.17)Tm(0.03)(WO4)2 film on a microstructured KY(WO4)2 substrate. Channels were transferred to the substrates by standard photolithography and Ar-ion milling. The bottom and sidewalls of the milled channels were smooth enough (rms roughness = 70 nm and 20 nm, respectively) to favour the epitaxial growth of the active layer without defects at the boundary of substrate/epitaxial layer. The refractive index contrast was sufficient to enable light confinement and guided modes with low scattering losses were observed at wavelengths between 1440 nm and 1640 nm. CW laser operation at 1840 nm at room temperature was observed with feedback provided only by Fresnel reflection at the end faces, with slope efficiencies of 4% and 9% for TE and TM polarizations, respectively.

Selective excitation of whispering gallery modes in a novel bottle microresonator.

Selective excitation of spheroidal whispering gallery modes and bottle modes in a robust bottle microresonator fabricated straightforwardly from a short section of optical fiber is demonstrated. Characteristic resonance spectra of long-cavity bottle modes were obtained by using a tapered fiber to excite evanescently bottle microresonator at different points along its axis. Compared to bare-fiber cylindrical resonators, the bottle microresonator results in a 35x increase of the observed Q factor.