Ratiometric Temperature Sensing Using Highly Coupled Seven-Core Fibers.

In this paper, a ratiometric approach to sensing temperature variations is shown using specialty fiber optic devices. We analyzed the transmission response of cascaded segments of multicore fibers (MCFs), and dissimilar lengths were found to generate an adequate scheme for ratiometric operation. The perturbation of optical parameters in the MCFs translates to a rich spectral behavior in which some peaks increase their intensity while others decrease their intensity. Thus, by selecting opposite-behavior peaks, highly sensitive ratiometric measurements that provide robustness against spurious fluctuations can be performed. We implemented this approach using seven-core fiber (SCF) segments of 5.8 cm and 9.9 cm. To test the system's response under controlled perturbations, we heated one of the segments from ambient temperature up to 150 °C. We observed defined peaks with opposite behavior as a function of temperature. Two pairs of peaks within the interrogation window were selected to perform ratiometric calculations. Ratiometric measurements exhibited sensitivities 6-14 times higher than single-wavelength measurements. A similar trend with enhanced sensitivity in both peak pairs was obtained. In contrast to conventional interferometric schemes, the proposed approach does not require expensive facilities or micrometric-resolution equipment. Moreover, our approach has the potential to be realized using commercial splicers, detectors, and filters.

All-Fiber Measurement of Surface Tension Using a Two-Hole Fiber.

An all-fiber approach is presented to measure surface tension. The experimental realization relies on the use of a specialty fiber, a so-called two-hole fiber (THF), which serves a two-fold purpose: providing a capillary channel to produce bubbles while having the means to measure the power reflected at the end facet of the fiber core. We demonstrate that provided a controlled injection of gas into the hollow channels of the THF, surface tension measurements are possible by simply tracking the Fresnel reflection at the distal end of the THF. Our results show that the characteristic times involved in the bubble formation process, from where the surface tension of the liquids under test is retrieved, can be measured from the train of pulses generated by the continuous formation and detachment of bubbles.

Non-Linear Diffusion and Power Law Properties of Heterogeneous Systems: Application to Financial Time Series.

In this work, we show that it is possible to obtain important ubiquitous physical characteristics when an aggregation of many systems is taken into account. We discuss the possibility of obtaining not only an anomalous diffusion process, but also a Non-Linear diffusion equation, that leads to a probability distribution, when using a set of non-Markovian processes. This probability distribution shows a power law behavior in the structure of its tails. It also reflects the anomalous transport characteristics of the ensemble of particles. This ubiquitous behavior, with a power law in the diffusive transport and the structure of the probability distribution, is related to a fast fluctuating phenomenon presented in the noise parameter. We discuss all the previous results using a financial time series example.

Emerging pollutant treatments in wastewater: Cases of antibiotics and hormones.

Because of the intensive use of pharmaceutical substances in human life, studies on the detection of these chemical compounds and their metabolites as pollutants in water bodies are continuously reported. Some pharmaceutical agents are associated with adverse effects to aquatic life, even at very low concentrations (ng L-1 to µg L-1). For instance, the presence of antibiotics and hormones has been associated with increasing proliferation of antibiotic resistant pathogens and feminization and masculinization of some aquatic organisms. Currently, new attempts are being made to minimize or fully remove these types of pollutants from aquatic systems to protect the environment and human health. In this regard, physicochemical and biological treatments are among the most promising technologies for the treatment of wastewater containing pharmaceutical pollutants. These treatments are green alternatives for the degradation of hazardous organic compounds into nontoxic by-products. Here, we review some of the physicochemical and biological treatment methods used for the removal of the most extensively used antibiotics and hormones. Enzymatic oxidation, photocatalysis and electrochemical oxidation are described in terms of the aforementioned pharmaceutically active compounds (PhACs). The use of membrane technologies to separate different groups of antibiotics and hormones prior to biologic or physicochemical treatment methods is also addressed.

Highly Sensitive Liquid Core Temperature Sensor Based on Multimode Interference Effects.

A novel fiber optic temperature sensor based on a liquid-core multimode interference device is demonstrated. The advantage of such structure is that the thermo-optic coefficient (TOC) of the liquid is at least one order of magnitude larger than that of silica and this, combined with the fact that the TOC of silica and the liquid have opposite signs, provides a liquid-core multimode fiber (MMF) highly sensitive to temperature. Since the refractive index of the liquid can be easily modified, this allows us to control the modal properties of the liquid-core MMF at will and the sensor sensitivity can be easily tuned by selecting the refractive index of the liquid in the core of the device. The maximum sensitivity measured in our experiments is 20 nm/°C in the low-temperature regime up to 60 °C. To the best of our knowledge, to date, this is the largest sensitivity reported for fiber-based MMI temperature sensors.

Self-mixing sensing system based on uncooled vertical-cavity surface-emitting laser array: linking multichannel operation and enhanced performance.

We compare the performance of a self-mixing (SM) sensing system based on an uncooled monolithic array of 24×1 vertical-cavity surface-emitting lasers (VCSELs) in two modes of operation: single active channel and the concurrent multichannel operation. We find that the signal-to-noise ratio of individual SM sensors in a VCSEL array is markedly improved by multichannel operation, as a consequence of the increased operational temperature of the sensors. The performance improvement can be further increased by manufacturing VCSEL arrays with smaller pitch. This has the potential to produce an imaging system with high spatial and temporal resolutions that can be operated without temperature stabilization.

Designing a gelatin/chitosan/hyaluronic acid biopolymer using a thermophysical approach for use in tissue engineering.

Cell culture on biopolymeric scaffolds has provided treatments for tissue engineering. Biopolymeric mixtures based on gelatin (Ge), chitosan (Ch) and hyaluronic acid (Ha) have been used to make scaffolds for wound healing. Thermal and physical properties of scaffolds prepared with Ge, Ch and Ha were characterized. Thermal characterization was made by using differential scanning calorimetry (DSC), and physical characterization by gas pycnometry and scanning electron microscopy. The effects of Ge content and cross-linking on thermophysical properties were evaluated by means of a factorial experiment design (central composite face centered). Gelatin content was the main factor that affects the thermophysical properties (microstructure and thermal transitions) of the scaffold. The effect of Ge content of the scaffolds for tissue engineering was studied by seeding skin cells on the biopolymers. The cell attachment was not significantly modified at different Ge contents; however, the cell growth rate increased linearly with the decrease of the Ge content. This relationship together with the thermophysical characterization may be used to design scaffolds for tissue engineering.

Real-World Analysis of Nivolumab and Atezolizumab Efficacy in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer.

Nivolumab (anti-PD-1 antibody) and atezolizumab (anti-PD-L1 antibody) have shown superior survival outcomes and improved adverse effects compared to standard chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. However, the efficacy of both treatments has not been directly compared in clinical trials. This retrospective, single-centre study was performed from June 2015 to December 2020 and included a cohort of 158 previously treated patients with stage IV or recurrent NSCLC who received PD-1 (nivolumab) (n = 89) or PD-L1 (atezolizumab) (n = 69) inhibitors at the Virgen del Rocío Hospital in Seville. The objective response rate (ORR) was 22.5% in the nivolumab group and 14.5% in the atezolizumab group (p = 0.140). Multivariate analysis did not show significant differences between the two groups for PFS and OS (PFS hazard ratio (HR): 0.80, 95% confidence interval (CI): 0.55−1.17, p = 0.260; OS HR: 0.79, 95% CI: 0.52−1.21, p = 0.281). Adverse events of all grades occurred in 68 patients in the nivolumab group (76.4%) and in 34 patients in the atezolizumab group (49.3%) (p < 0.001). Atezolizumab and nivolumab did not show statistically significant differences in survival outcomes in patients with NSCLC, even when stratified by histological subtype (squamous versus nonsquamous). However, the safety analysis suggested a more favourable toxicity profile for atezolizumab.

A review of cardiac troponin I detection by surface enhanced Raman spectroscopy: Under the spotlight of point-of-care testing.

Cardiac troponin I (cTnI) is a biomarker widely related to acute myocardial infarction (AMI), one of the leading causes of death around the world. Point-of-care testing (POCT) of cTnI not only demands a short turnaround time for its detection but the highest accuracy levels to set expeditious and adequate clinical decisions. The analytical technique Surface-enhanced Raman spectroscopy (SERS) possesses several properties that tailor to the POCT format, such as its flexibility to couple with rapid assay platforms like microfluidics and paper-based immunoassays. Here, we analyze the strategies used for the detection of cTnI by SERS considering POCT requirements. From the detection ranges reported in the reviewed literature, we suggest the diseases other than AMI that could be diagnosed with this technique. For this, a section with information about cardiac and non-cardiac diseases with cTnI release, including their release kinetics or cut-off values are presented. Likewise, POCT features, the use of SERS as a POCT technique, and the biochemistry of cTnI are discussed. The information provided in this review allowed the identification of strengths and lacks of the available SERS-based point-of-care tests for cTnI and the disclosing of requirements for future assays design.

A Review on SERS-Based Detection of Human Virus Infections: Influenza and Coronavirus.

The diagnosis of respiratory viruses of zoonotic origin (RVsZO) such as influenza and coronaviruses in humans is crucial, because their spread and pandemic threat are the highest. Surface-enhanced Raman spectroscopy (SERS) is an analytical technique with promising impact for the point-of-care diagnosis of viruses. It has been applied to a variety of influenza A virus subtypes, such as the H1N1 and the novel coronavirus SARS-CoV-2. In this work, a review of the strategies used for the detection of RVsZO by SERS is presented. In addition, relevant information about the SERS technique, anthropozoonosis, and RVsZO is provided for a better understanding of the theme. The direct identification is based on trapping the viruses within the interstices of plasmonic nanoparticles and recording the SERS signal from gene fragments or membrane proteins. Quantitative mono- and multiplexed assays have been achieved following an indirect format through a SERS-based sandwich immunoassay. Based on this review, the development of multiplex assays that incorporate the detection of RVsZO together with their specific biomarkers and/or secondary disease biomarkers resulting from the infection progress would be desirable. These configurations could be used as a double confirmation or to evaluate the health condition of the patient.

Correlation of peripheral blood biomarkers with clinical outcomes in NSCLC patients with high PD-L1 expression treated with pembrolizumab.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are currently the standard therapy in advanced non-small cell lung cancer (NSCLC); however, there is no well-established prognostic biomarker. We investigated the relationship between survival outcomes and three peripheral blood biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), as well as a new score termed the risk blood biomarker (RBB), calculated from the combination of the neutrophil-monocyte-to-lymphocyte ratio (NMLR) and white blood cell count (WBC). METHODS: This study included patients with stage IV or recurrent NSCLC confirmed with programmed death ligand 1 (PD-L1) expression ≥50% who received pembrolizumab monotherapy as first-line treatment at the Virgen del Rocío University Hospital in Seville, Spain. To establish the relationship between baseline peripheral blood biomarkers and survival outcomes, progression free survival (PFS) and overall survival (OS), we used the Kaplan-Meier method and multivariable Cox regression models. RESULTS: A total of 51 patients were included in this study. In multivariate analysis, baseline NLR and PLR showed a strong association with PFS [NLR hazard ratio (HR): 0.19, 95% confidence interval (CI): 0.09-0.44, P<0.001; PLR HR: 0.46, 95% CI: 0.23-0.92, P=0.03] and OS (NLR HR: 0.07, 95% CI: 0.02-0.19, P<0.001; PLR HR: 0.29, 95% CI: 0.13-0.67, P=0.004), and the MLR was associated with OS (MLR HR: 0.34, 95% CI: 0.15-0.76, P=0.01). According to the RBB score, groups with lower scores were associated with superior PFS (group 0: HR: 0.16, 95% CI: 0.06-0.41, P<0.001 and group 1: HR: 0.29, 95% CI: 0.12-0.73, P=0.01) and OS (group 0: HR: 0.04, 95% CI: 0.01-0.17, P<0.001 and group 1: HR: 0.15, 95% CI: 0.05-0.42, P<0.001). CONCLUSIONS: Low baseline NLR, MLR and PLR are significantly associated with better PFS, and low baseline NLR and PLR are associated with better OS. Additionally, we identified three subgroups of patients using the RBB score, and low scores were associated with improved survival outcomes and response to therapy.

Vernier effect using in-line highly coupled multicore fibers.

We demonstrate optical fiber sensors based on highly coupled multicore fibers operating with the optical Vernier effect. The sensors are constructed using a simple device incorporating single-mode fibers (SMFs) and a segment of a multicore fiber. In particular, we evaluated the performance of a sensor based on a seven-core fiber (SCF) spliced at both ends to conventional SMFs, yielding a versatile arrangement for realizing Vernier-based fiber sensors. The SMF-SCF-SMF device can be fabricated using standard splicing procedures and serve as a "building block" for both, reflection and transmission sensing configurations. As demonstrated with our experimental results, the Vernier arrangements can yield a ten-fold increase in sensitivity for temperature measurements compared to a conventional single SMF-SCF-SMF device, thereby confirming the enhanced sensitivity that can be attained with this optical effect. Furthermore, through theoretical analysis, we obtain the relevant parameters that must be optimized in order to achieve an optimal sensitivity for a specific application. Our findings thus provide the necessary guidelines for constructing Vernier-based sensors with all-fiber devices based on highly coupled multicore optical fibers, which constitutes an ideal framework to develop highly sensitive fiber sensors for different applications.

The effect of an autologous cellular gel-matrix integrated implant system on wound healing.

BACKGROUND: This manuscript reports the production and preclinical studies to examine the tolerance and efficacy of an autologous cellular gel-matrix integrated implant system (IIS) aimed to treat full-thickness skin lesions. METHODS: The best concentration of fibrinogen and thrombin was experimentally determined by employing 28 formula ratios of thrombin and fibrinogen and checking clot formation and apparent stability. IIS was formed by integrating skin cells by means of the in situ gelification of fibrin into a porous crosslinked scaffold composed of chitosan, gelatin and hyaluronic acid. The in vitro cell proliferation within the IIS was examined by the MTT assay and PCNA expression. An experimental rabbit model consisting of six circular lesions was utilized to test each of the components of the IIS. Then, the IIS was utilized in an animal model to cover a 35% body surface full thickness lesion. RESULTS: The preclinical assays in rabbits demonstrated that the IIS was well tolerated and also that IIS-treated rabbit with lesions of 35% of their body surface, exhibited a better survival rate (p = 0,06). CONCLUSION: IIS should be further studied as a new wound dressing which shows promising properties, being the most remarkable its good biological tolerance and cell growth promotion properties.

Vegetation pattern formation in a fog-dependent ecosystem.

Vegetation pattern formation is a striking characteristic of several water-limited ecosystems around the world. Typically, they have been described on runoff-based ecosystems emphasizing local interactions between water, biomass interception, growth and dispersal. Here, we show that this situation is by no means general, as banded patterns in vegetation can emerge in areas without rainfall and in plants without functional root (the Bromeliad Tillandsia landbeckii) and where fog is the principal source of moisture. We show that a simple model based on the advection of fog-water by wind and its interception by the vegetation can reproduce banded patterns which agree with empirical patterns observed in the Coastal Atacama Desert. Our model predicts how the parameters may affect the conditions to form the banded pattern, showing a transition from a uniform vegetated state, at high water input or terrain slope to a desert state throughout intermediate banded states. Moreover, the model predicts that the pattern wavelength is a decreasing non-linear function of fog-water input and slope, and an increasing function of plant loss and fog-water flow speed. Finally, we show that the vegetation density is increased by the formation of the regular pattern compared to the density expected by the spatially homogeneous model emphasizing the importance of self-organization in arid ecosystems.

Study on the 3D printability of poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(lactic acid) blends with chain extender using fused filament fabrication.

In this study, the 3D printability of a series of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/poly(lactic acid) (PLA) blends were investigated using fused filament fabrication (FFF). The studied blends suffered from poor 3D printability due to differences in compatibility and low thermal resistance. These shortcomings were addressed by incorporating a functionalized styrene-acrylate copolymer with oxirane moieties as a chain extender (CE). To enhance mechanical properties, the synergistic effect of 3D printing parameters such as printing temperature and speed, layer thickness and bed temperature were explored. Rheological analysis showed improvement in the 3D printability of PHBV:PLA:CE blend by allowing a higher printing temperature (220 °C) and sufficient printing speed (45 mm s-1). The surface morphology of fractured tensile specimens showed good bonding between layers when a bed temperature of 60 °C was used and a layer thickness of 0.25 mm was designed. The optimized printing samples shown higher storage modulus and strength, resulting in stiffer and stronger parts. The crystallinity, morphology and performance of the 3D printed products were correlated to share key methods to improve the 3D printability of PHBV:PLA based blends which may be implemented in other biopolymer blends, and further highlight how process parameters enhance the mechanical performance of 3D printed products.

Indirect Quantification of Glyphosate by SERS Using an Incubation Process With Hemin as the Reporter Molecule: A Contribution to Signal Amplification Mechanism.

The indirect determination of the most used herbicide worldwide, glyphosate, was achieved by the SERS technique using hemin chloride as the reporter molecule. An incubation process between hemin and glyphosate solutions was required to obtain a reproducible Raman signal on SERS substrates consisting of silicon decorated with Ag nanoparticles (Si-AgNPs). At 780 nm of excitation wavelength, SERS spectra from hemin solutions do not show extra bands in the presence of glyphosate. However, the hemin bands increase in intensity as a function of glyphosate concentration. This allows the quantification of the herbicide using as marker band the signal associated with the ring breathing mode of pyridine at 745 cm-1. The linear range was from 1 × 10-10 to 1 × 10-5 M and the limit of detection (LOD) was 9.59 × 10-12 M. This methodology was successfully applied to the quantification of the herbicide in honey. From Raman experiments with and without silver nanoparticles, it was possible to state that the hemin is the species responsible for the absorption in the absence or the presence of the herbicide via vinyl groups. Likewise, when the glyphosate concentration increases, a subtle increase occurs in the planar orientation of the vinyl group at position 2 in the porphyrin ring of hemin over the silver surface, favoring the reduction of the molecule. The total Raman signal of the hemin-glyphosate incubated solutions includes a maximized electromagnetic contribution by the use of the appropriate laser excitation, and chemical contributions related to charge transfer between silver and hemin, and from resonance properties of Raman scattering of hemin. Incubation of the reporter molecule with the analyte before the conjugation with the SERS substrate has not been explored before and could be extrapolated to other reporter-analyte systems that depend on a binding equilibrium process.

Nonequilibrium evolution of volatility in origination and extinction explains fat-tailed fluctuations in Phanerozoic biodiversity.

Fluctuations in biodiversity, large and small, pervade the fossil record, yet we do not understand the processes generating them. Here, we extend theory from nonequilibrium statistical physics to describe the fat-tailed form of fluctuations in Phanerozoic marine invertebrate richness. Using this theory, known as superstatistics, we show that heterogeneous rates of origination and extinction between clades and conserved rates within clades account for this fat-tailed form. We identify orders and families as the taxonomic levels at which clades experience interclade heterogeneity and within-clade homogeneity of rates, indicating that families are subsystems in local statistical equilibrium, while the entire system is not. The separation of timescales between within-clade background rates and the origin of major innovations producing new orders and families allows within-clade dynamics to reach equilibrium, while between-clade dynamics do not. The distribution of different dynamics across clades is consistent with niche conservatism and pulsed exploration of adaptive landscapes.

Developmental autonomy and somatic niche construction promotes robust cell fate decisions.

During the course of development cells undergo division producing a variety of cell types. Proliferation and differentiation are dependent on both genetic programs, encoded by the cellular genome, and environmental cues produced by the local cellular environment imposing local selection pressures on cells. We explore the role that cellular signals play over a large range of potential parameter regimes, in minimizing developmental error: errors in differentiation where an inappropriate proportion of differentiated daughter cells are generated. We find that trophic factors produced by the population of dividing cells can compensate for increased error rates when signals act through a form of positive feedback--survival signals. We operationalize these signals as the somatic niche and refer to their production as somatic niche construction. We find that tissue development switches to an autonomous state, independent of cellular signals, when errors are unmanageably high or density regulation is very strong. A signal-selective regime--strong niche dependence--is favored at low to intermediate error, assuming compartmentalized density dependence.

The evolution of developmental patterning under genetic duplication constraints.

Of considerable interest are the evolutionary and developmental origins of complex, adaptive structures and the mechanisms that stabilize these structures. We consider the relationship between the evolutionary process of gene duplication and deletion and the stability of morphogenetic patterns produced by interacting activators and inhibitors. We compare the relative stability of patterns with a single activator and inhibitor (two-dimensional system) against a 'redundant' system with two activators or two inhibitors (three-dimensional system). We find that duplication events can both expand and contract the space of patterns. We study developmental robustness in terms of stochastic escape times from this space, also known as a 'canalization potential'. We embed the output of pattern formation into an explicit evolutionary model of gene duplication, gene loss and variation in the steepness of the canalization potential. We find that under all constant conditions, the system evolves towards a preference for steep potentials associated with low phenotypic variability and longer lifespans. This preference leads to an overall decrease in the density of redundant genotypes as developmental robustness neutralizes the advantages of genetic robustness.

Analysis and measurements of magnetic field exposures for healthcare workers in selected MR environments.

There are concerns about workers repeatedly exposed to magnetic fields exceeding regulatory limits with respect to modern magnetic resonance imaging (MRI). As a result, there is need for an ambulatory magnetic field dosimeter capable of measuring these fields in and around an MRI scanner in order to evaluate the regulatory guidelines and determine any underlying exposure risks. This study presents results of tri-axial measurements using an ambulatory magnetic field dosimeter worn by workers during normal working shifts. We recorded and analyzed magnetic field exposures in and around 1.5 T, 2 T, and 4 T magnets during routine patient procedures. The data was integrated and averaged over time and evaluated against the latest exposure standards. Time-varying magnetic fields occur when individuals move through spatially non-uniform static magnetic fields or during gradient-pulsed magnetic fields or a combination of both. Our previous numerical analysis shows that at certain positions surrounding the MRI scanner ends, such fields may induce current densities and electric fields that may exceed the relevant EU, ICNIRP, and IEEE standards. A high-speed acquisition version of the dosimeter measured gradient- pulsed fields at positions accessible by MRI workers near the scanner ends, and the results were evaluated and compared against the numerical simulations and the standards. Our measurements confirm that workers can be exposed to magnetic fields exceeding the guidelines at positions near the gradient coil ends during clinical imaging and a high degree of correlation exists with the numerical results. While the time-weighted average magnetic field exposures in 1.5 T, 2 T, and 4 T were all within the regulatory limits during static magnetic field measurements, the peak limits for the head can be exceeded in some circumstances. This study presents a small number of routine shifts of data that provide indicative results of magnetic field exposure in real situations.