pH inactivation of SARS-CoV-2 and SARS-CoV in virus spiked protein A eluates from a mAb purification process.

Biopharmaceutical manufacturing processes may include a low pH treatment step as a means of inactivating enveloped viruses. Small scale virus clearance studies are routinely performed using model enveloped viruses such as murine leukemia virus to assess inactivation at the pH range used in the downstream manufacturing process. Further, as a means of bioburden reduction, chromatography resins may be cleaned and stored using sodium hydroxide and this can also inactivate viruses. The susceptibility of SARS-CoV-2 and SARS-CoV to low pH conditions using protein A eluate derived material from a monoclonal antibody production process as well as high pH cleaning conditions was addressed. SARS-CoV-2 was effectively inactivated at pH 3.0, moderately inactivated at pH 3.4, but not inactivated at pH 3.8. Low pH was less effective at inactivating SARS-CoV. Both viruses were inactivated at a high pH of ca.13.4. These studies provide important information regarding the effectiveness of viral clearance and inactivation steps of novel coronaviruses when compared to other enveloped viruses.

The potential of patient-based nurse staffing - a queuing theory application in the neonatal intensive care setting.

Faced by a severe shortage of nurses and increasing demand for care, hospitals need to optimally determine their staffing levels. Ideally, nurses should be staffed to those shifts where they generate the highest positive value for the quality of healthcare. This paper develops an approach that identifies the incremental benefit of staffing an additional nurse depending on the patient mix. Based on the reasoning that timely fulfillment of care demand is essential for the healthcare process and its quality in the critical care setting, we propose to measure the incremental benefit of staffing an additional nurse through reductions in time until care arrives (TUCA). We determine TUCA by relying on queuing theory and parametrize the model with real data collected through an observational study. The study indicates that using the TUCA concept and applying queuing theory at the care event level has the potential to improve quality of care for a given nurse capacity by efficiently trading situations of high versus low workload.

Referral rate and false-positive rates in a hearing screening program among high-risk newborns.

AIM: More studies exploring referral rates and false-positive rates are needed to make hearing screening programs in newborns better and cost-effective. Our aim was to study the referral and false-positivity rates among high-risk newborns in our hearing screening program and to analyze the factors potentially associated with false-positive hearing screening test results. METHODS: A retrospective cohort study was done among the newborns hospitalized at a university hospital from January 2009 to December 2014 that underwent hearing screening with a two-staged AABR screening protocol. Referral rates and false-positivity rates were calculated and possible risk factors for false-positivity were analyzed. RESULTS: 4512 newborns were screened for hearing loss in the neonatology department. The referral rate for the two-staged AABR-only screening was 3.8% with false-positivity being 2.9%. Our study showed that the higher the birthweight or gestational age of the newborn, the lower the odds of the hearing screening results being false-positive, and the higher the chronological age of the infant at the time of screening, the higher the odds of the results being false-positive. Our study did not show a clear association between the mode of delivery or gender and false-positivity. CONCLUSION: Among high-risk infants, prematurity and low-birthweight increased the rate of false-positivity in the hearing screening, and the chronological age at the time of the test seems to be significantly associated with false-positivity.

Mueller Matrix Microscopy for In Vivo Scar Tissue Diagnostics and Treatment Evaluation.

Scars usually do not show strong contrast under standard skin examination relying on dermoscopes. They usually develop after skin injury when the body repairs the damaged tissue. In general, scars cause multiple types of distress such as movement restrictions, pain, itchiness and the psychological impact of the associated cosmetic disfigurement with no universally successful treatment option available at the moment. Scar treatment has significant economic impact as well. Mueller matrix polarimetry with integrated autofocus and automatic data registration can potentially improve scar assessment by the dermatologist and help to make the evaluation of the treatment outcome objective. Polarimetry can provide new physical parameters for an objective treatment evaluation. We show that Mueller matrix polarimetry can enable strong contrast for in vivo scar imaging. Additionally, our results indicate that the polarization stain images obtained form there could be a useful tool for dermatology. Furthermore, we demonstrate that polarimetry can be used to monitor wound healing, which may help prevent scarring altogether.

Real-time stimulated Raman spectroscopy with a non-collinear optical parametric oscillator.

Ultrafast detection of microplastic particles is becoming a vital problem, as these particles are found in water sources worldwide. Ideally, a live analysis in flow is desirable to directly monitor the water quality for contaminations. Therefore, coherent Raman spectroscopy techniques require fast and broadband tunable lasers to address all relevant spectral regions of the investigated samples. In our work, we combine a high power non-collinear optical parametric oscillator with a real-time stimulated Raman scattering spectroscopy setup. The light source is continously tunable from 700 nm to 1030 nm in less than 10 ms, delivering an average output power of more than 500 mW with sub-ps pulses. We show the immediate observation of mixing processes and the detection of microplastic particles in water solution with a spectral window of more than 2000 cm-1.

Developmental outcome of extremely preterm infants is improved after less invasive surfactant application: Developmental outcome after LISA.

AIM: The aim of this study was to evaluate neurocognitive outcome at 24 months of corrected age after less invasive surfactant application (LISA) in preterm infants born at 23-26 weeks of gestational age. METHODS: Surviving participants of a LISA trial conducted in 13 German level III neonatal intensive care units were reviewed for assessment of developmental outcome, hearing and vision problems, growth and rehospitalisation days. Maternal depression, breastfeeding rates and socio-economic factors were evaluated as potentially confounding factors. RESULTS: In total, 156/182 infants took part in the study, 78 had received surfactant via LISA and 78 via endotracheal intubation. 22% of LISA infants compared to 42% of intubated infants had a psychomotor development index (PDI) <70 (0.012). A significant difference in mental development index (MDI) was observed in the stratum of more mature infants (25 and 26 weeks of GA). For this group, MDI < 70 was observed in 4% of LISA infants vs 21% of intubated infants (P = 0.008). CONCLUSION: At 24 months of age, the LISA-treated infants scored less often PDI < 70 and had similar results in MDI. Infants born at 25 and 26 weeks treated with LISA had lower rates of severe disability. LISA is safe and may be superior.

Fiber Optic Sensors Embedded in Textile-Reinforced Concrete for Smart Structural Health Monitoring: A Review.

The last decade has seen rapid developments in the areas of carbon fiber technology, additive manufacturing technology, sensor engineering, i.e., wearables, and new structural reinforcement techniques. These developments, although from different areas, have collectively paved way for concrete structures with non-corrosive reinforcement and in-built sensors. Therefore, the purpose of this effort is to bridge the gap between civil engineering and sensor engineering communities through an overview on the up-to-date technological advances in both sectors, with a special focus on textile reinforced concrete embedded with fiber optic sensors. The introduction section highlights the importance of reducing the carbon footprint resulting from the building industry and how this could be effectively achieved by the use of state-of-the-art reinforcement techniques. Added to these benefits would be the implementations on infrastructure monitoring for the safe operation of structures through their entire lifespan by utilizing sensors, specifically, fiber optic sensors. The paper presents an extensive description on fiber optic sensor engineering that enables the incorporation of sensors into the reinforcement mechanism of a structure at its manufacturing stage, enabling effective monitoring and a wider range of capabilities when compared to conventional means of structural health monitoring. In future, these developments, when combined with artificial intelligence concepts, will lead to distributed sensor networks for smart monitoring applications, particularly enabling such distributed networks to be implemented/embedded at their manufacturing stage.

Effect of image artefacts on phase conjugation with spectral domain optical coherence tomography.

Recently the acquisition of the time-resolved reflection matrix was demonstrated based on spectral domain optical coherence tomography. In principle, the matrix describes the linear dependence of the OCT signal received from different depths on the field which is incident to the scattering sample. Knowledge of the matrix, hence, enables beam shaping to selectively enhance the received signal, for example to increase the penetration depth when imaging turbid media. We investigate the impact of image artefacts on the approach. Phase conjugation is shown to enhance the OCT signal, but not autocorrelation and mirror artefacts. Imaging applications are demonstrated indicating the potential for future in-vivo studies on biotissues.

Two-year outcome data suggest that less invasive surfactant administration (LISA) is safe. Results from the follow-up of the randomized controlled AMV (avoid mechanical ventilation) study.

Less invasive surfactant administration (LISA) is a method to deliver surfactant to spontaneously breathing premature infants via a thin catheter. Here we report the two-year outcome from the AMV (avoid mechanical ventilation) study, the first randomized controlled trial on this mode of surfactant delivery. No statistically significant differences in weight, length or neurodevelopmental outcome (Bayley II scores) were found between the LISA intervention group (n = 95) and the control group (n = 84) that received standard treatment.Conclusion: No differences in outcome were observed at 2 years. LISA seems safe in that aspect. What is Known: • LISA is a method that is in increasing use for surfactant delivery to spontaneously breathing infants. LISA reduces the need for mechanical ventilation. What is New: • Outcome data at 2 years from the first randomized study with LISA raise no safety concerns in comparison to a group of infants that received standard treatment.

Delivery room skin-to-skin contact for preterm infants-A randomized clinical trial.

AIM: To investigate the effects of 60 minutes delivery room skin-to-skin contact (DR-SSC) compared with 5 minutes visual contact (VC) on mother-child interaction (MCI), salivary cortisol, maternal depression, stress and bonding at 6 months corrected age. METHODS: A single-centre randomized controlled trial conducted in a German level III NICU. Eighty-eight preterm infants (25-32 weeks of gestational age) were randomized after initial stabilization to either 60 minutes DR-SSC or 5 minutes VC. Forty-five infants were allocated to DR-SSC, 43 to VC. RESULTS: Delivery room skin-to-skin contact dyads showed a higher quantity of maternal motoric (18 vs 15, P = .030), infant's vocal (7 vs 5, P = .044) and motoric (20 vs 15, P = .032) responses. Moreover, the combined score of maternal and infant responsive behaviour was higher (86 vs 71, P = .041) in DR-SSC dyads. DR-SSC mothers had lower risk of both, early postpartum depression (15% vs 45%, P = .003) and impaired bonding (Score 3 vs 5, P = .031). CONCLUSION: In addition to regular intermittent kangaroo mother care, DR-SSC promotes MCI and decreases risk of maternal depression and bonding problems. Thus, DR-SSC may have positive effects on preterm development.

Wavefront Shaping Concepts for Application in Optical Coherence Tomography-A Review.

Optical coherence tomography (OCT) enables three-dimensional imaging with resolution on the micrometer scale. The technique relies on the time-of-flight gated detection of light scattered from a sample and has received enormous interest in applications as versatile as non-destructive testing, metrology and non-invasive medical diagnostics. However, in strongly scattering media such as biological tissue, the penetration depth and imaging resolution are limited. Combining OCT imaging with wavefront shaping approaches significantly leverages the capabilities of the technique by controlling the scattered light field through manipulation of the field incident on the sample. This article reviews the main concepts developed so far in the field and discusses the latest results achieved with a focus on signal enhancement and imaging.

All-Optical Planar Polymer Waveguide-Based Biosensor Chip Designed for Smartphone-Assisted Detection of Vitamin D.

An all-optical plasmonic sensor platform designed for smartphones based on planar-optical waveguide structures integrated in a polymer chip is reported for the first time. To demonstrate the applicability of the sensor system for biosensing purposes, the detection of 25-hydroxyvitamin D (25OHD) in human serum samples using an AuNP-enhanced aptamer-based assay was demonstrated. With the aid of the developed assay sensitivity of 0.752 pixel/nM was achieved for 25OHD concentrations ranging from 0-100 nM. The waveguide structure of the sensor enables miniaturisation and parallelisation, thus, demonstrates the potential for simultaneous detection of various analytes including biomarkers. The entire optical arrangement can be integrated into a single polymer chip which allows for large scale and cost-efficient sensor fabrication. The broad utilization and access of smartphone electronics make the proposed design most attractive for its wider use in lab-on-chip applications.

SPR Biosensor Based on Polymer Multi-Mode Optical Waveguide and Nanoparticle Signal Enhancement.

We present a surface plasmon resonance (SPR) biosensor that is based on a planar-optical multi-mode (MM) polymer waveguide structure applied for the detection of biomolecules in the lower nano-molar (nM) range. The basic sensor shows a sensitivity of 608.6 nm/RIU when exposed to refractive index changes with a measurement resolution of 4.3 × 10-3 RIU. By combining the SPR sensor with an aptamer-functionalized, gold-nanoparticle (AuNP)-enhanced sandwich assay, the detection of C-reactive protein (CRP) in a buffer solution was achieved with a response of 0.118 nm/nM. Due to the multi-mode polymer waveguide structure and the simple concept, the reported biosensor is well suited for low-cost disposable lab-on-a-chip applications and can be used with rather simple and economic devices. In particular, the sensor offers the potential for fast and multiplexed detection of several biomarkers on a single integrated platform.

Experimental and theoretical study of the formation process of photopolymer based self-written waveguides.

The realization of optical interconnects between multimode (MM) optical fibers and waveguides based on a self-writing process in photopolymer media represents an efficient approach for fast and easy-to-implement connection of light-guiding elements. When light propagates through photopolymer media, it modulates the material properties of the media and confines the spreading of the light beam to create a waveguide along the beam propagation direction. This self-writing process can be realized with a single photopolymer medium and is also suited to connect optical fibers or waveguides with active elements such as light sources and detectors. Numerical simulations of the underlying light-induced polymerization process is carried out by using a diffusion based material model which takes account both monomer diffusion and its conversion to polymer chains in regions exposed to light fields. In this work experimental results obtained from a one-polymer approach are validated with theoretical predictions from the diffusion model. The study involved the demonstration of temporal dynamics and transmittance from self-written waveguide (SWW) couplers during the self-writing process. The measured attenuation coefficient from experiment αexperiment = (8.43 ± 0.3) × 10-5 dB/µm showed good agreement with the theoretically predicted attenuation coefficient αsimulation = 7.93 × 10-5 dB/µm, thus demonstrating a successful application of the diffusion model to epoxy based acrylate SWWs. For comparison, attenuation measurements between optical fibers with SWWs as interconnects and one without SWW, i.e. with an air gap in between, were performed. The obtained results reveal that the theoretical approach correctly describes the waveguide formation process so that in the next step the studies can be extended towards including further relevant parameters such as temperature.

Iterative wavefront correction for complex spectral domain optical coherence tomography.

We propose a compact setup for wavefront manipulation in spectral domain optical coherence tomography (OCT). The system can easily be implemented into existing free-space OCT setups through modification of the source path only. We demonstrate complex-valued OCT signal acquisition based on phase shifting combined with iterative optical wavefront shaping, which locally enhances the OCT signal acquired from within a scattering sample. The system lends itself to future imaging studies in strongly scattering media such as biological tissue.

Grating assisted glass fiber coupler for mode selective co-directional coupling.

To keep pace with the increasing demand of transmission capacity, space division multiplexing technologies are currently intensively investigated. In this context, mode selective glass fiber couplers are of great interest due to their compatibility with existing glass fiber networks. In this work, we present a novel type of mode selective glass fiber coupler for co-directional coupling based on fiber gratings and fused asymmetric fibers. The achieved mode selective coupling efficiency agrees well with numerical simulations performed for comparison. The benefits of the grating approach are a lower mode crosstalk and a simple adaption of the propagation constants through changing of the grating-period.

Soliton Molecules with Two Frequencies.

We demonstrate a peculiar mechanism for the formation of bound states of light pulses of substantially different optical frequencies, in which pulses are strongly bound across a vast frequency gap. This is enabled by a propagation constant with two separate regions of anomalous dispersion. The resulting soliton compound exhibits moleculelike binding energy, vibration, and radiation and can be understood as a mutual trapping providing a striking analogy to quantum mechanics. The phenomenon constitutes an intriguing case of two light waves mutually affecting and controlling each other.

Monte Carlo simulation of the influence of internal optical absorption on the external Raman signal for biological samples.

Proper understanding of Raman spectroscopic signals from biological samples requires the quantification of internal signal absorption and its effect on the Raman spectra detected outside the samples under study. In this paper, we describe an efficient Monte Carlo method to simulate Raman scattering in biological tissues and solutions and compare the findings with experimental results obtained in samples with different absorber concentrations and optical properties. As an illustrative example, we focus on solutions of beta-carotene (bCar) in ethanol with different concentrations of absorber (ink) added. We find good agreement between simulation and experiment, thus indicating a way to quantify the influence of internal signal absorption in Raman measurements.

Prevalence and risk factors for hearing loss in high-risk neonates in Germany.

AIM: Hearing loss in infants is often diagnosed late, despite universal screening programmes. Risk factors of hearing impairment in high-risk neonates, identified from population-based studies, can inform policy around targeted screening. Our aim was to determine the prevalence and the risk factors of hearing loss in a high-risk neonatal population. METHODS: This was a retrospective cohort study of neonates hospitalised at the University Hospital Cologne, Germany from January 2009 to December 2014 and were part of the newborn hearing screening programme. Multivariable regression analyses using the lasso approach was performed. RESULTS: Data were available for 4512 (43% female) neonates with a mean gestational age at birth of 35.5 weeks. The prevalence of hearing loss was 1.6%, and 42 (0.9%) neonates had permanent hearing loss. Craniofacial anomalies, hyperbilirubinaemia requiring exchange transfusion, oxygen supplementation after 36 weeks of gestation and hydrops fetalis showed associations with permanent hearing loss. CONCLUSION: Our findings of risk factors for hearing loss were consistent with other studies. However, some commonly demonstrated risk factors such as perinatal infections, meningitis, sepsis and ototoxic drugs did not show significant associations in our cohort. Targeted screening based on risk factors may help early identification of hearing loss in neonates.

Raman Sensing and Its Multimodal Combination with Optoacoustics and OCT for Applications in the Life Sciences.

Currently, many optical modalities are being investigated, applied, and further developed for non-invasive analysis and sensing in the life sciences. To befit the complexity of the study objects and questions in this field, the combination of two or more modalities is attempted. We review our work on multimodal sensing concepts for applications ranging from non-invasive quantification of biomolecules in the living organism to supporting medical diagnosis showing the combined capabilities of Raman spectroscopy, optical coherence tomography, and optoacoustics.